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Diagnostic procedures for Parkinson's disease dementia: Recommendations from the Movement Disorder Society Task Force
Abstract
A preceding article described the clinical features of Parkinson's disease dementia (PD-D) and proposed clinical diagnostic criteria for "probable" and "possible" PD-D. The main focus of this article is to operationalize the diagnosis of PD-D and to propose practical guidelines based on a two level process depending upon the clinical scenario and the expertise of the evaluator involved in the assessment. Level I is aimed primarily at the clinician with no particular expertise in neuropsychological methods, but who requires a simple, pragmatic set of tests that are not excessively time-consuming. Level I can be used alone or in concert with Level II, which is more suitable when there is the need to specify the pattern and the severity on the dementia of PD-D for clinical monitoring, research studies or pharmacological trials. Level II tests can also be proposed when the diagnosis of PD-D remains uncertain or equivocal at the end of a Level I evaluation. Given the lack of evidence-based standards for some tests when applied in this clinical context, we have tried to make practical and unambiguous recommendations, based upon the available literature and the collective experience of the Task Force. We accept, however, that further validation of certain tests and modifications in the recommended cut off values will be required through future studies.
... The diagnosis of PD with cognitive impairment and dementia, including executive and visuospatial deficits [11], is generally based on a level II neuropsychological assessment. Apart from neuropsychological tests, regular examinations include blood testing and brain imaging techniques, such as magnetic resonance imaging (MRI) [12,13]. However, the entire procedure of cognitive examination is often time-consuming and requires the involvement of multiple medical personnel [12,13]. ...
... Apart from neuropsychological tests, regular examinations include blood testing and brain imaging techniques, such as magnetic resonance imaging (MRI) [12,13]. However, the entire procedure of cognitive examination is often time-consuming and requires the involvement of multiple medical personnel [12,13]. Hence, reliable biomarkers that could facilitate diagnosis and enable rapid distinction between PD patients with and without cognitive impairments are an unmet need. ...
... It has been reported that miRNAs exist not only in the cytoplasm but also in extracellular areas, such as cerebrospinal fluid, blood and other biofluids [16,17]. Circulating miRNAs may travel across the blood-brain barrier (BBB) due to their short sequence length [13]. Various studies have shown an association between miRNAs and neurodegenerative diseases, including Alzheimer's disease (AD) and PD [18][19][20], and patients with cognitive decline [21,22]. ...
The early detection of cognitive decline and timely non-pharmacological management or drug therapy are extremely important in providing care for Parkinson’s disease with dementia (PDD). In this study, we first conducted a discovery study to identify six plasma microRNAs that may allow for the differentiation of PD with or without mild cognitive impairment via NGS. A total of 120 participants were further recruited in a validation cohort and divided into four subgroups, namely, normal controls (HC), PD with no dementia (PDND), PD with mild cognitive impairment (PD-MCI) and PDD. Among the six candidates, miR-203a-3p was successfully detected in the plasma of the validation cohort using droplet digital PCR (ddPCR). Our results show that the ratio of miR-203a-3p/miR-16-5p observed in PDD was significantly increased compared to in PD-MCI (p < 0.001) and PDND (p = 0.041). Moreover, the ratio of miR-203a-3p/miR-16-5p showed a significant correlation with MoCA scores (r = -0.237, p = 0.024) in patients with PD (PwP). The ROC curve of the logistic regression model, consisting of the variables of age, the ratio of miR-203a-3p/miR-16-5p and the UPDRS III score, also demonstrated an average AUC of 0.883 via 5-fold cross-validation. In conclusion, the ratio of miR-203a-3p/miR-16-5p may serve as a potential biomarker for distinguishing cognitive dysfunction from PwP.
... The diagnosis of PD with cognitive impairment and dementia, including executive and visuospatial deficits [11], is generally based on Level II neuropsychological assessment. Apart from neuropsychological tests, regular examinations includes blood testing and brain imaging such as Magnetic Resonance Imaging (MRI) [12,13]. However, the entire procedure of cognitive examination is often time-consuming and requires the involvement of multiple medical personnel [12,13]. ...
... Apart from neuropsychological tests, regular examinations includes blood testing and brain imaging such as Magnetic Resonance Imaging (MRI) [12,13]. However, the entire procedure of cognitive examination is often time-consuming and requires the involvement of multiple medical personnel [12,13]. Hence, reliable biomarkers that could facilitate the diagnosis and provide quick distinction between PD patients with and without cognitive impairments are the unmet need. ...
... It was reported that miRNA exist not only in cytoplasm but also in extracellular area such as cerebrospinal fluid, blood and other biofluids [16,17]. The circulating miRNAs may travel across the blood-brain barrier (BBB) due to their short sequence length [13]. Various studies have shown the association between miRNAs and neurodegenerative diseases, including Alzheimer's disease (AD) and PD [18][19][20] and also for patients with cognitive decline [21,22]. ...
Early detection of cognitive decline and in-time non-pharmacological management or drug therapy are extremely important in providing care for Parkinson’s disease with dementia (PDD). In this study, we firstly conducted a discovery study to identify 6 plasma microRNAs that may differentiate PD with or without mild cognitive impairment via NGS sequencing. Total 120 participants were further recruited in validation cohort and divided into 4 subgroups, including normal controls (HC), PD with no dementia (PDND), PD with mild cognitive impairment (PD-MCI) and PDD. Among the 6 candidates, miR-203a-3p was successfully detected in the plasma of the validation cohort using droplet digital PCR (ddPCR). Our results showed that the ratio of miR-203a-3p/miR-16-5p observed in PDD was significantly increased compared to PD-MCI (p < 0.001) and PDND (p = 0.041). Moreover, the ratio of miR-203a-3p/miR-16-5p showed a significant correlation with MoCA scores (r = -0.237, p = 0.024) in patients with PD (PwP). The ROC curve of the logistic regression model, consisting variates of age, the ratio of miR-203a-3p/miR-16-5p and the score of UPDRS III, also demonstrated an average AUC of 0.883 by 5-fold cross-validation. In conclusion, the ratio of miR-203a-3p/miR-16-5p may serve as a potential biomarker for distinguishing cognitive dysfunction from PwP.
... Patients presenting with dementia according to current PDD criteria [16] at baseline were excluded from the study. Specifically, PDD level II MDS diagnostic criteria were applied: i.) Scores 1.5 standard deviation below group norms or previous defined cut-off scores for the MMSE items in at least 2 of the following cognitive domains: attention (Trail Making Test A; Serial 7's of the MMSE (0-5), at least two incorrect responses [16,17]), executive functions (Clock drawing, inability to insert the correct clock face numbers and/or the clock hands pointing to the correct time: <6/10 score [17,18], Trail Making B), visuospatial function (Rey Complex figure and Drawing of the MMSE pentagons (0-1) [16,17], memory (short story recall and recall of the Rey complex figure), or language abilities (semantic fluency, MMSE language cumulative score for naming (0-2), repetition (0-1) and writing (0-1), at least two incorrect responses [17]); ii.) Self-reported cognitive decline with insidious onset and slow progression; iii.) Self-reported impairment of non-motor activities of daily living (ADL) by the Basic Activities of Daily Living (ADL, cut-off <1 points) and Instrumental Activities of Daily Living (IADL, cut-off <1 points) not depending on motor function. ...
... Patients presenting with dementia according to current PDD criteria [16] at baseline were excluded from the study. Specifically, PDD level II MDS diagnostic criteria were applied: i.) Scores 1.5 standard deviation below group norms or previous defined cut-off scores for the MMSE items in at least 2 of the following cognitive domains: attention (Trail Making Test A; Serial 7's of the MMSE (0-5), at least two incorrect responses [16,17]), executive functions (Clock drawing, inability to insert the correct clock face numbers and/or the clock hands pointing to the correct time: <6/10 score [17,18], Trail Making B), visuospatial function (Rey Complex figure and Drawing of the MMSE pentagons (0-1) [16,17], memory (short story recall and recall of the Rey complex figure), or language abilities (semantic fluency, MMSE language cumulative score for naming (0-2), repetition (0-1) and writing (0-1), at least two incorrect responses [17]); ii.) Self-reported cognitive decline with insidious onset and slow progression; iii.) Self-reported impairment of non-motor activities of daily living (ADL) by the Basic Activities of Daily Living (ADL, cut-off <1 points) and Instrumental Activities of Daily Living (IADL, cut-off <1 points) not depending on motor function. ...
... Patients presenting with dementia according to current PDD criteria [16] at baseline were excluded from the study. Specifically, PDD level II MDS diagnostic criteria were applied: i.) Scores 1.5 standard deviation below group norms or previous defined cut-off scores for the MMSE items in at least 2 of the following cognitive domains: attention (Trail Making Test A; Serial 7's of the MMSE (0-5), at least two incorrect responses [16,17]), executive functions (Clock drawing, inability to insert the correct clock face numbers and/or the clock hands pointing to the correct time: <6/10 score [17,18], Trail Making B), visuospatial function (Rey Complex figure and Drawing of the MMSE pentagons (0-1) [16,17], memory (short story recall and recall of the Rey complex figure), or language abilities (semantic fluency, MMSE language cumulative score for naming (0-2), repetition (0-1) and writing (0-1), at least two incorrect responses [17]); ii.) Self-reported cognitive decline with insidious onset and slow progression; iii.) Self-reported impairment of non-motor activities of daily living (ADL) by the Basic Activities of Daily Living (ADL, cut-off <1 points) and Instrumental Activities of Daily Living (IADL, cut-off <1 points) not depending on motor function. ...
Introduction: Brain hypometabolism patterns have been previously associated with cognitive decline in Parkinson's disease (PD). Our aim is to evaluate the impact of single-subject fluorodeoxyglucose (FDG)-PET brain hypometabolism on long-term cognitive and motor outcomes in PD.
Methods: Forty-nine non-demented PD patients with baseline brain FDG-PET data underwent an extensive clinical follow-up for 8 years. The ability of FDG-PET to predict long-term cognitive and motor progression was evaluated using Cox regression and mixed ANCOVA models.
Results: Participants were classified according to FDG-PET pattern in PD with typical (n = 26) and atypical cortical metabolism (n = 23). Patients with atypical brain hypometabolic patterns showed higher incidence of dementia (60% vs 3%; HR = 18.3), hallucinations (56% vs 7%, HR = 7.3) and faster motor decline compared to typical pattern group.
Conclusion: This study argues for specific patterns of FDG-PET cortical hypometabolism in PD as a prognostic marker for long term cognitive and motor outcomes at single-subject level.
... During the follow-up period, patients were diagnosed with PDD if they fulfilled the clinical criteria for probable PDD based on the Movement Disorder Society Task Force guidelines 14,44 . After diagnosis of PD, patients visited the outpatient clinic at 3-month intervals, and at every visit, they or their caregivers were asked questions regarding their daily functioning. ...
... After diagnosis of PD, patients visited the outpatient clinic at 3-month intervals, and at every visit, they or their caregivers were asked questions regarding their daily functioning. Additionally, all patients underwent serial cognitive assessment using the Korean version of the Mini-Mental State Examination (K-MMSE) and Clock Drawing Test with a one-year interval (Level I tests) 44 . In case of definite cognitive decline or evidence of impairments in daily life due to cognitive changes (Level I 45 ), most patients underwent the SNSB to identify the pattern of cognitive deficits and diagnose PDD at Level II 44,46 . ...
... Additionally, all patients underwent serial cognitive assessment using the Korean version of the Mini-Mental State Examination (K-MMSE) and Clock Drawing Test with a one-year interval (Level I tests) 44 . In case of definite cognitive decline or evidence of impairments in daily life due to cognitive changes (Level I 45 ), most patients underwent the SNSB to identify the pattern of cognitive deficits and diagnose PDD at Level II 44,46 . ...
Cognitive impairment in Parkinson’s disease (PD) severely affects patients’ prognosis, and early detection of patients at high risk of dementia conversion is important for establishing treatment strategies. We aimed to investigate whether multiparametric MRI radiomics from basal ganglia can improve the prediction of dementia development in PD when integrated with clinical profiles. In this retrospective study, 262 patients with newly diagnosed PD (June 2008–July 2017, follow-up >5 years) were included. MRI radiomic features (n = 1284) were extracted from bilateral caudate and putamen. Two models were developed to predict dementia development: (1) a clinical model—age, disease duration, and cognitive composite scores, and (2) a combined clinical and radiomics model. The area under the receiver operating characteristic curve (AUC) were calculated for each model. The models’ interpretabilities were studied. Among total 262 PD patients (mean age, 68 years ± 8 [standard deviation]; 134 men), 51 (30.4%), and 24 (25.5%) patients developed dementia within 5 years of PD diagnosis in the training (n = 168) and test sets (n = 94), respectively. The combined model achieved superior predictive performance compared to the clinical model in training (AUCs 0.928 vs. 0.894, P = 0.284) and test set (AUCs 0.889 vs. 0.722, P = 0.016). The cognitive composite scores of the frontal/executive function domain contributed most to predicting dementia. Radiomics derived from the caudate were also highly associated with cognitive decline. Multiparametric MRI radiomics may have an incremental prognostic value when integrated with clinical profiles to predict future cognitive decline in PD.
... The diagnosis of both PD-MCI and PDD, defined by the Movement Disorders Society (MDS) criteria, requires: (1) progressive cognitive decline in an individual with PD that does not interfere or interferes significantly with functional independence, respectively; and (2) the exclusion of other potential causes of CI, such as medication side effects, vascular disease, delirium, or other mental illnesses [7,8]. Two levels of certainty have been defined for PD-MCI and PDD (Table 1): Level I necessitates an altered screening test, such as the PD-Cognitive Rating Scale, Montreal Cognitive Assessment, or Mattis Dementia Rating Scale; Level II requires impairment on at least two out of ten neuropsychological tests, including two tests of five different domains (attention and working memory, executive, language, memory, and visuospatial) [7,9]. It is worth noting that since 2015, the MDS diagnostic criteria for PD allow the inclusion of early-onset dementia, overlapping with the dementia Table 1 Updated clinical criteria for the diagnosis of PD-MCI and PDD MMSE Mini-Mental State Examination, PD Parkinson's disease, PDD Parkinson's disease dementia, PD-MCI Parkinson's disease-mild cognitive impairment *Abnormal corresponds to z-score − 1 to − 2 (not explicitly specified) or decline on serial neuropsychological assessments or decline from estimated premorbid functioning PD-MCI (according to [7]) Probable PDD (according to [8]) ...
... According to [7] According to [9] Certainty level I Abbreviated assessment (e.g. global cognitive scale, limited battery of neuropsychological tests) with Lewy bodies (DLB) criteria [10,11]. ...
Parkinson’s disease (PD) is a neurodegenerative condition that is frequently associated with cognitive disorders. These can arise directly from the primary disease, or be triggered by external factors in susceptible individuals due to PD or other predisposing factors. The cognitive disorders encompass PD-associated cognitive impairment (PD-CI), delirium, PD treatment-associated cognitive side effects, cognitive non-motor fluctuations, and PD-associated psychosis. Accurate diagnosis of delirium is crucial because it often stems from an underlying disease that may be severe and require specific treatment. However, overlapping molecular mechanisms are thought to be involved in both delirium and PD, leading to similar clinical symptoms. Additionally, there is a bidirectional interaction between delirium and PD-CI, resulting in frequent concurrent processes that further complicate diagnosis. No reliable biomarker is currently available for delirium, and the diagnosis is primarily based on clinical criteria. However, the screening tools validated for diagnosing delirium in the general population have not been specifically validated for PD. Our review addresses the current challenges in the diagnosis of these cognitive disorders and highlights existing gaps within this field.
... [1][2][3][4] For the diagnosis of MCI or dementia in PD, the Movement Disorders Society (MDS) Task Force has proposed the following two sets of tests: a practical set (Level I) for screening cognitive impairment, and a second set (Level II) consisting of comprehensive neuropsychological tests that assess individual cognitive domains. 5,6 The Montreal Cognitive Assessment (MoCA), originally developed as a screening measure for MCI in the general population, 7 is recommended as a Level I test due to its reliability and validity. 6,8 The selection of an optimal cutoff for a diagnostic screening test hinges on balancing sensitivity and specificity to suit the requirements of a particular study or clinical context. ...
... Secondly, cognitive diagnoses in our study were determined using a gold standard method, namely comprehensive neuropsychological assessments, as recommended by the MDS Task Force. 5,6 This approach likely led to more accurate cognitive diagnoses compared to other studies. Notably, cognitive diagnosis using machine learning tests demonstrated higher specificity than when using age-and education-adjusted cutoffs. ...
Background and objectives:
The Montreal Cognitive Assessment (MoCA) is recommended for general cognitive evaluation in Parkinson's Disease (PD). However, age- and education-adjusted cutoffs specifically for PD have not been developed and systematically validated across PD cohorts with diverse education levels.
Methods:
This retrospective analysis utilized data from 1,293 Korean patients with PD, where cognitive diagnoses were determined through comprehensive neuropsychological assessments. Age- and education-adjusted cutoffs were formulated based on 1,202 patients with PD. To identify the optimal machine learning model, clinical parameters and MoCA domain scores from 416 patients with PD were used. Comparative analyses between machine learning and different cutoffs were conducted on an additional 91 consecutive patients with PD.
Results:
The cutoffs for cognitive impairment decrease with advancing age within the same education level. Similarly, lower education levels within the same age group correspond to lower cutoffs. For individuals aged 60-80, cutoffs were set as follows: 25 or 24 for those with over 12 years of education, 23 or 22 for 10-12 years, and 21 or 20 for 7-9 years. Comparisons between age- and education-adjusted cutoffs and the machine learning method showed comparable accuracies. The cutoff method demonstrated higher sensitivity (0.8627), whereas machine learning achieved higher specificity (0.8250).
Conclusions:
Both the age- and education-adjusted cutoff method and machine learning demonstrated high effectiveness in detecting cognitive impairment in PD. This study highlights the necessity of tailored cutoffs and suggests the potential of machine learning to enhance cognitive assessments in PD.
... The MMSE scale was corrected by education level and was generally applicable to people of all cultural levels [23,24]. Thus, in this study, we used the recommended cutoff score of 27/30 of the MMSE as an objective cognitive measure [25]. At the same time, considering the ceiling oor of it, we aimed to capture PD-SCD using a newly established indicator. ...
... All of the patients were diagnosed with idiopathic PD according to the International Parkinson's and Movement Disorder Society (MDS) clinical diagnostic criteria. According to the guidelines for the diagnosis of dementia in PD published by the MDS, MMSE ≥ 27 was de ned as objective cognitive test normal [25].The following are the inclusion criteria: 1) those with an MMSE score ≥ 27, 2) those with an education level ≤ 12, 3) those who had the ability to collaborate with the researchers on their own, and 4) those who were able to communicate, write, and read. Patients were excluded based on the following criteria: 1) those who diagnosed dementia, 2) a diagnose of secondary Parkinson's disease, 3) those with brain disorders (e. g., cerebral infarction, cerebral hemorrhage, or brain tumor), and 4) those with serious psychiatric diseases (e. g., Hamilton Anxiety Scale (HAMA) ≥ 21[26], Hamilton Depression Scale (HAMD) ≥ 17 [27], or obsessive-compulsive disorder). ...
Subjective Cognitive Decline (SCD), refers to self-reported cognitive decline with normal global cognition. We aimed to capture SCD among low educated patients with Parkinson’s disease (PD) by a newly established indicator. There were total of 64 PD patients with low education levels (education ≤ 12 years) recruited in this study. The presence of SCD was determined based on a Unified Parkinson’s Disease Rating Scale Part I (1.1) score ≥ 1. The prevalence of SCD in PD patients was 43.75% (28/64). Low educated PD-SCD patients had higher scores on the Non-Motor Symptoms Scale (NMSS), Parkinson’s Fatigue Scale (PFS), Epworth Sleepiness Scale (ESS), as well as higher scores on the UPDRS-I and UPDRS-II, compared to PD patients without SCD. Multivariate binary regression confirmed the significant association between PD-SCD and MoCA-executive abilities/attention/language. A score of 12 or less on the combined index had a sensitivity of 73.9% and a specificity of 76.2% for diagnosing PD-SCD. Most importantly, the newly combined index can help capture these low educated PD-SCD patients, with an AUC of 0.867, and is expected to assist clinicians in earlier identification of PD patients.
... The diagnostic procedure included movement disorder society PDD criteria, DLB consortium criteria, National Institute of neurological disorders and stroke association criteria and FTD consortium new highly sensitive revised criteria (4,7,12,(15)(16)(17)(18). The final diagnosis was made by the neurologist. ...
... The date on which the patients with PD or their caregivers reported that LID occurred during on-time or the date on which LID was first observed during on-time in the clinic was regarded as the date of LID occurrence. Patients were diagnosed with PD dementia if they fulfilled the clinical criteria of probable PD dementia based on the Movement Disorder Society Task Force guideline (level I testing) with evidence of abnormal activities of daily living [20]. The impairment of cognitive decline on activities of daily living was judged both clinically and with the activities of daily living scale [21]. ...
Background
Parkinson’s disease (PD) manifests as a wide variety of clinical phenotypes and its progression varies greatly. However, the factors associated with different disease progression remain largely unknown.
Methods
In this retrospective cohort study, we enrolled 113 patients who underwent ¹⁸F-FP-CIT PET scan twice. Given the negative exponential progression pattern of dopamine loss in PD, we applied the natural logarithm to the specific binding ratio (SBR) of two consecutive ¹⁸F-FP-CIT PET scans and conducted linear mixed model to calculate individual slope to define the progression rate of nigrostriatal degeneration. We investigated the clinical and dopamine transporter (DAT) availability patterns associated with the progression rate of dopamine depletion in each striatal sub-region.
Results
More symmetric parkinsonism, the presence of dyslipidemia, lower K-MMSE total score, and lower anteroposterior gradient of the mean putaminal SBR were associated with faster progression rate of dopamine depletion in the caudate nucleus. More symmetric parkinsonism and lower anteroposterior gradient of the mean putaminal SBR were associated with faster depletion of dopamine in the anterior putamen. Older age at onset, more symmetric parkinsonism, the presence of dyslipidemia, and lower anteroposterior gradient of the mean putaminal SBR were associated with faster progression rate of dopamine depletion in the posterior putamen. Lower striatal mean SBR predicted the development of LID, while lower mean SBR in the caudate nuclei predicted the development of dementia.
Discussion
Our results suggest that the evaluation of baseline clinical features and patterns of DAT availability can predict the progression of PD and its prognosis.
... Patient demographics are detailed in Table 1. No participants satisfied MDS criteria for PD dementia [40], patients were also not on psychiatric medication, and had no major affective symptoms assessed by the DSM-V [41]. However, five participants did score above 8 on the anxiety component of the HADS, indicating mild anxiety. ...
Background
Freezing of gait (FOG) in Parkinson’s disease (PD) has a poorly understood pathophysiology, which hinders treatment development. Recent work showed a dysfunctional fronto-striato-limbic circuitry at rest in PD freezers compared to non-freezers in the dopamine “OFF” state. While other studies found that dopaminergic replacement therapy alters functional brain organization in PD, the specific effect of dopamine medication on fronto-striato-limbic functional connectivity in freezers remains unclear.
Objective
To evaluate how dopamine therapy alters resting state functional connectivity (rsFC) of the fronto-striato-limbic circuitry in PD freezers, and whether the degree of connectivity change is related to freezing severity and anxiety.
Methods
Twenty-three PD FOG patients underwent MRI at rest (rsfMRI) in their clinically defined “OFF” and “ON” dopaminergic medication states. A seed-to-seed based analysis was performed between a priori defined limbic circuitry ROIs. Functional connectivity was compared between OFF and ON states. A secondary correlation analyses evaluated the relationship between Hospital Anxiety and Depression Scale (HADS)-Anxiety) and FOG Questionnaire with changes in rsFC from OFF to ON.
Results
PD freezers’ OFF compared to ON showed increased functional coupling between the right hippocampus and right caudate nucleus, and between the left putamen and left posterior parietal cortex (PPC). A negative association was found between HADS-Anxiety and the rsFC change from OFF to ON between the left amygdala and left prefrontal cortex, and left putamen and left PPC.
Conclusion
These findings suggest that dopaminergic medication partially modulates the frontoparietal-limbic-striatal circuitry in PD freezers, and that the influence of medication on the amygdala, may be related to clinical anxiety in freezer.
... As for specific tools for this assessment, it is recommended to include broad measurements of cognitive functioning, such as executive functions (working memory, attention, conceptualization, set activation, set-shifting, and set maintenance), instrumental functions (language, visuo-constructive, visuospatial, visuo-perceptive), and memory. 63 A comprehensive assessment of global cognitive ability in PD can be obtained with the Mattis Dementia Rating Scale (MDRS), which is considered one of the appropriate scales to evaluate the loss of global intellectual capacities, especially for subcortical degenerative disease. 64 This scale provides cut-off scores that allow for a psychometric distinction between demented and non-demented patients, however, it may have reduced sensitivity in younger patients being considered for DBS. ...
Deep brain stimulation (DBS) is recognized as an established therapy for Parkinson's disease (PD) and other movement disorders in the light of the developments seen over the past three decades. Long-term efficacy is established for PD with documented improvement in the cardinal motor symptoms of PD and levodopa-induced complications, such as motor fluctuations and dyskinesias. Timing of patient selection is crucial to obtain optimal benefits from DBS therapy, before PD complications become irreversible. The objective of this first part review is to examine the fundamental concepts of DBS for PD in clinical practice, discussing the historical aspects, patient selection, potential effects of DBS on motor and non-motor symptoms, and the practical management of patients after surgery.
Resumo
Nas últimas três décadas, a estimulação cerebral profunda (ECP) se tornou um tratamento bem estabelecido para doença de Parkinson (DP) e outros transtornos do movimento. A eficácia a longo prazo na DP foi bem documentada para a melhora dos sintomas motores cardinais da DP e das complicações induzidas pelo uso do levodopa, como as flutuações motoras e as discinesias. O momento da seleção do paciente é crucial para se obter os benefícios ideais da ECP, antes que as complicações da DP se tornem irreversíveis. O objetivo desta primeira parte da revisão é examinar os conceitos fundamentais da ECP na prática clínica, discutindo os aspectos históricos, a seleção de pacientes, os potenciais efeitos da ECP nos sintomas motores e não motores da doença e o manejo prático dos pacientes após a cirurgia.
... The results of this report are interpreted to signify memory loss as the cortex and hippocampus are the epicenters of cognition and memory. Motor abnormalities and cognitive disturbances have been reported to go hand in hand in people suffering from PD (Burton, McKeith et al., 2004;Dubois, Burn et al., 2007). Moreover, along with α-synuclein pathology in the cortex and striatum, amyloid and tau pathology also occur in PD responsible for synaptic dysfunction and dementia (Schulz-Schaeffer, 2010;Irwin, Lee et al., 2013). ...
Alzheimer's disease (AD) is the most common type of dementia accounting for 90% of cases; however, frontotemporal dementia, vascular dementia, etc. prevails only in a minority of populations. The term dementia is defined as loss of memory which further takes several other categories of memories like working memory, spatial memory, fear memory, and long-term, and short-term memory into consideration. In this review, these memories have critically been elaborated based on context, duration, events, appearance, intensity, etc. The most important part and purpose of the review is the various pathological cascades as well as molecular levels of targets of AD, which have extracellular amyloid plaques and intracellular hyperphosphorylated tau protein as major disease hallmarks. There is another phenomenon that either leads to or arises from the above-mentioned hallmarks, such as oxidative stress, mitochondrial dysfunction, neuroinflammation, cholinergic dysfunction, and insulin resistance. Several potential drugs like antioxidants, anti-inflammatory drugs, acetylcholinesterase inhibitors, insulin mimetics or sensitizers, etc. studied in various previous preclinical or clinical reports were put as having the capacity to act on these pathological targets. Additionally, agents directly or indirectly targeting amyloid and tau were also discussed. This could be further investigated in future research.
Keywords: Memory; Dementia; Alzheimer’s disease; Oxidative stress; Mitochondrial dysfunction; Neuroinflammation; Brain insulin resistance
... The initial sample comprised 216 PD and 87 HC individuals, previously described in Monté-Rubio et al. 31 . The PD patients included in this sample fulfilled the UK PD Society Brain Bank diagnostic criteria for PD and were classified as non-demented according to the Level I for PD dementia diagnosis from the Movement Disorder Society Task Force on Dementia in Parkinson's Disease 32,33 . After preprocessing, we excluded 5 PD and 1 HC due to segmentation problems; see the MRI preprocessing section below. ...
Clinical, cognitive, and atrophy characteristics depending on sex have been previously reported in Parkinson’s disease (PD). However, though sex differences in cortical gray matter measures in early drug naïve patients have been described, little is known about differences in cortical thickness (CTh) as the disease advances. Our multi-site sample comprised 211 non-demented PD patients (64.45% males; mean age 65.58 ± 8.44 years old; mean disease duration 6.42 ± 5.11 years) and 86 healthy controls (50% males; mean age 65.49 ± 9.33 years old) with available T1-weighted 3 T MRI data from four international research centers. Sex differences in regional mean CTh estimations were analyzed using generalized linear models. The relation of CTh in regions showing sex differences with age, disease duration, and age of onset was examined through multiple linear regression. PD males showed thinner cortex than PD females in six frontal (bilateral caudal middle frontal, bilateral superior frontal, left precentral and right pars orbitalis), three parietal (bilateral inferior parietal and left supramarginal), and one limbic region (right posterior cingulate). In PD males, lower CTh values in nine out of ten regions were associated with longer disease duration and older age, whereas in PD females, lower CTh was associated with older age but with longer disease duration only in one region. Overall, male patients show a more widespread pattern of reduced CTh compared with female patients. Disease duration seems more relevant to explain reduced CTh in male patients, suggesting worse prognostic over time. Further studies should explore sex-specific cortical atrophy trajectories using large longitudinal multi-site data.
... In addition, the Unified Parkinson's Disease Rating Scale (UPDRS) part III was used to evaluate the motor functions of PDND, PD-MCI, and PDD. PD-MCI and PDD achieved the criteria of the Montreal Cognitive Assessment (MoCA), a level I cognitive assessment proposed by the MDS Task Force [4,10]. The levodopa equivalent daily dose (LEDD) was calculated for PD patients via the LEDD conversion factor [60]. ...
The early detection of cognitive decline in Parkinson’s disease is important for providing drug therapy and non-pharmacological management. The circulating microRNAs present in plasma are promising biomarkers of PD with dementia (PDD) due to their critical roles in synaptic plasticity and the regulation of neurodegeneration-associated proteins. In this study, we aimed to identify plasma microRNAs that may differentiate PD with or without cognitive impairment. Global microRNA expression was obtained from a discovery set of 123 participants who were divided into four groups, namely normal controls (HC), PD with no dementia (PDND), PD with mild cognitive impairment (PD-MCI), and PDD, using next-generation sequencing. The BOLD selector was used for microRNA candidate selection. Six miRNAs, namely miR-203a-3p, miR-626, miR-662, miR-3182, miR-4274, and miR-4295, were clustered as potential candidates for use in identifying PDND from PD-MCI. Another independent cohort of 120 participants was further recruited in a validation step in order to detect candidate microRNAs via droplet digital PCR (ddPCR), which was used for its high sensitivity in detecting low miRNA concentrations. Our results show that the ratio of miR-203a-3p/miR-16-5p, in which miR-16-5p was used as a reference control miRNA, was significantly increased in PDD compared to that seen in PD-MCI and PDND individually, and was negatively correlated with the MoCA scores (r = −0.237, p = 0.024) in patients with PD. However, there was no significant difference in the ratio of miR-203a-3p/miR-16-5p between HC and PDND, PD-MCI, or PDD individually. The ROC curve of the logistic regression model, factoring in the variables of age, the ratio of miR-203a-3p/miR-16-5p, and the UPDRS III score, demonstrated an AUC of 0.883. Our findings suggest that the ratio of miR-203a-3p/miR-16-5p, used with age and motor score, could be a predictor of dementia among PD patients.
... Such cognitive tests should be short, simple to perform, sensitive to subtle changes in cognition, not confounded by motor and visual problems, and able to assess a full range of cognitive domains. Some global cognitive screening tools that have been developed for patients with neurocognitive disorders are the Montreal Cognitive Assessment (MoCA) and Visual Cognitive Assessment Test (VCAT), among others [4,7,[9][10][11][12][13]. ...
Background: Cognitive assessments for patients with neurocognitive disorders are mostly measured by the Montreal Cognitive Assessment (MoCA) and Visual Cognitive Assessment Test (VCAT) as screening tools. These cognitive scores are usually left-skewed and the results of the association analysis might not be robust. This study aims to study the distribution of the cognitive outcomes and to discuss potential solutions. Materials and Methods: In this retrospective cohort study of individuals with subjective cognitive decline or mild cognitive impairment, the inverse-transformed cognitive outcomes are modelled using different statistical distributions. The robustness of the proposed models are checked under different scenarios: with intercept-only, models with covariates, and with and without bootstrapping. Results: The main results were based on the VCAT score and validated via the MoCA score. The findings suggested that the inverse transformation method improved the modelling the cognitive scores compared to the conventional methods using the original cognitive scores. The association of the baseline characteristics (age, gender, and years of education) and the cognitive outcomes were reported as estimates and 95% confidence intervals. Bootstrap methods improved the estimate precision and the bootstrapped standard errors of the estimates were more robust. Cognitive outcomes were widely analysed using linear regression models with the default normal distribution as a conventional method. We compared the results of our suggested models with the normal distribution under various scenarios. Goodness-of-fit measurements were compared between the proposed models and conventional methods. Conclusions: The findings support the use of the inverse transformation method to model the cognitive outcomes instead of the original cognitive scores for early-stage neurocognitive disorders where the cognitive outcomes are left-skewed.
... Cognitive assessment was administered by neuropsychologists with experience in movement disorders to determine patients' cognitive status according to the MDS Task Force Level II diagnostic criteria for PDD (Emre et al. 2007) and PD-MCI (Dubois et al. 2007;Litvan et al. 2012). For further details on the cognitive tests adopted see Fiorenzato et al. (2019). ...
A key distinguishing factor between mild cognitive impairment (MCI) and dementia in Parkinson’s disease (PD) lies in the notable decrease in functioning due to cognitive impairment. The Parkinson’s Disease-Cognitive Functional Rating Scale (PD-CRFS) was developed to assess functional limitations caused by cognitive impairment, while reducing the influence of motor impairment. The aim of this multicenter study was to (i) validate the Italian version of the PD-CFRS in PD, (ii) determine optimal cut-off scores for detecting MCI and dementia in PD, (iii) compare its performances with the most established functional assessment tool (IADL). Six hundred and sixty nine PD participants were recruited from 4 Italian Movement Disorders centers (Venice, Milan, Gravedona, and Salerno). They underwent Level-II cognitive evaluation, which resulted in 282 PD-NC, 310 PD-MCI, and 77 PDD. The PD-CFRS’s psychometric and clinimetric properties, applicability, and responsiveness were analyzed. The PD-CFRS showed high acceptability. Floor and ceiling effects were acceptable. It also displayed strong internal consistency (Cronbach’s α = 0.738), and test–retest reliability (ICC = .854). The PD-CFRS demonstrated higher coefficient of variation to detect dysfunction in PD-MCI patients in comparison to the IADL scale (PD-CFRS 96% vs IADL 22.5%). Convergent validity with the IADL was r = − 0.638 and − 0.527 in males and females, respectively. PD-CFRS total score negatively correlated with global cognition (MoCA corrected score r = − 0.61; p < 0.001). A cut-off score > 6.5 identified PDD with a sensitivity of 90% and specificity of 88% (AUC = .959). A cut-off value of > 1 detected PD-MCI with a sensitivity of 68% and specificity of 69% (AUC = .695). The Italian version of the PD-CFRS demonstrated to be an easy, valid and reliable tool that properly captures functional impairment due to cognitive decline in PD. It also proved to be particularly effective in the advanced stages of PD, and would be a useful support for the diagnosis of PD-MCI and PDD.
... Neurological examination included Unified Parkinson's Disease Rating Scale (UPDRS), and Hoehn and Yahr scale scores [19]. Neuropsychological assessment included the Mattis dementia rating scale (MDRS), rated on 144 [20], a score ≤ 135 being used as a threshold to define cognitive impairment, as previously proposed [21]. MDRS includes 5 sub-scores: attention, initiation (both rated on 37), construction (rated on 6), concept (rated on 39), and memory (rated on 25). ...
Background
The long-term prognosis of impulsive compulsive disorders (ICD) remains poorly studied in Parkinson’s disease (PD).
Objective
Evaluating the natural history of ICD and its impact on PD symptoms including cognition and treatment adjustments.
Materials and methods
We assessed PD patients at baseline (BL) with (BL-ICD+) or without (BL-ICD-) ICD despite dopamine agonist (DA) exposure of > 300 mg levodopa-equivalent daily dose for > 12 months at baseline and after more than two years of follow-up. ICD were assessed using the Ardouin’s Scale of Behaviors in PD (ASBPD), cognition using the Mattis scale, and PD symptoms using the UPDRS score. Treatment adjustments, DA withdrawal-associated symptoms, and ICDs social consequences were recorded.
Results
149 patients were included (78 cases and 71 controls), mean duration of follow-up was 4.4 ± 1 years. At baseline, psychiatric disorders were more common among BL-ICD + (42.3 vs 12.3% among BL-ICD-, p < 0.01). At follow-up, 53.8% of BL-ICD + were not ICD-free while 21.1% of BL-ICD- had developed ICD. BL-ICD + more frequently experienced akinesia (21.8 vs 8.5%, p = 0.043) and rigidity worsening (11.5 vs 1.4%, p = 0.019) following therapeutic modifications. Decision to decrease > 50% DA doses (12.8 vs 1.4%, p = 0.019) or to withdraw DA (19.2 vs 5.6%, p = 0.025) was more frequently considered among BL-ICD+ . At follow-up, the prevalence of cognitive decline was lower among BL-ICD + (19.2 vs 37.1%, p = 0.025).
Conclusion
ICDs were associated with increased psychiatric burden at baseline and better cognitive prognosis. Most patients were still showing ICDs at the follow-up visit, suggesting ICD to be considered as a chronic, neuropsychiatric disorder.
... Global cognitive status was addressed using the Parkinson's Disease-Cognitive Rating Scale (PD-CRS). Cutoff scores were used to categorize participants as follows: PD dementia (PDD) with PD-CRS ≤ 64; PD-Mild Cognitive Impairment (PD-MCI) with PD-CRS ≤ 81 and ≥ 65; and PD normal cognition with PD-CRS ≥ 82 (Dubois et al. 2007;Pagonabarraga et al. 2008;Litvan et al. 2012). Neuropsychiatric symptoms were assessed using the Starkstein Apathy Scale (SAS) for apathy, and the Hospital Anxiety and Depression Scale (HADS) for depression and anxiety. ...
Hypomimia is a frequent manifestation in Parkinson's disease (PD) that can affect interpersonal relationships and quality of life. Recent studies have suggested that hypomimia is not only related to motor dysfunction but also to impairment in emotional processing networks. Therefore, we hypothesized that the severity of hypomimia could be associated with performance on a task aimed at assessing facial emotion recognition. In this study, we explored the association between hypomimia, recognition of facial expressions of basic emotions using the Ekman 60 Faces Test (EF), and brain correlates of both hypomimia and performance on the EF. A total of 94 subjects underwent clinical assessments (neurological and neuropsychological examinations), and 56 of them participated in the neuroimaging study. We found significant correlation between hypomimia, EF Disgust (r = −0.242, p = 0.022) and EF Happiness (r = −0.264, p = 0.012); an independent reduction in Cortical Thickness (Cth) in the postcentral gyrus, insula, middle and superior temporal gyri, supramarginal gyrus, banks of the superior temporal sulcus, bilateral fusiform gyri, entorhinal cortex, parahippocampal gyrus, inferior and superior parietal cortex, and right cuneus and precuneus; and multiple correlations between negative emotions such as EF Disgust or EF Anger and a reduced Cth in fronto-temporo-parietal regions. In conclusion, these results suggest that the association between hypomimia and emotion recognition deficits in individuals with PD might be mediated by shared circuits, supporting the concept that hypomimia is not only the result of the dysfunction of motor circuits, but also of higher cognitive functions.
... As for the predictive value of SCCs with objective cognitive decline, over a mean follow-up period of 3.16 years (range: 1-7.5 years), data from five studies for 435 patients [11][12][13][14]60 established that cognitively healthy patients with SCCs had an RR of 2.71 [95% CI: 1.82; 4.04] to progress to objective cognitive decline (ie, PD-MCI or PD-dementia diagnosed based on the Level I testing procedures). 3,61 The heterogeneity statistic I 2 is 0.00, and its 95% CI ranges from 0.00% to 79.2%, denoting potentially unimportant to substantial heterogeneity. ...
Background
Subjective cognitive complaints (SCCs) in Parkinson's disease (PD) are reported frequently, but their prevalence and association with changes on objective testing are not fully known.
Objective
We aimed to determine the prevalence, clinical correlates, and predictive value of SCCs in PD.
Methods
We conducted a systematic review and meta‐analysis. From 204 abstracts, we selected 31 studies (n = 3441 patients), and from these, identified the prevalence, clinical features, associations with neuropsychiatric symptoms, and predictive values of SCCs in PD.
Results
The meta‐analysis showed an SCC prevalence of 36%. This prevalence, however, was significantly moderated by study heterogeneity regarding female sex, disease severity, levodopa equivalent daily dosage, exclusion from the overall sample of patients with objective cognitive impairment, and measurement instrument. SCC prevalence did not differ between de novo and treated PD patients. SCCs were weakly and negligibly associated with cognitive changes on objective testing in cross‐sectional studies. However, in cognitively healthy patients, SCCs had a risk ratio of 2.71 for later cognitive decline over a mean follow‐up of 3.16 years. Moreover, SCCs were moderately related to co‐occurring symptoms of depression, anxiety, or apathy and were more strongly related to these neuropsychiatric symptoms than objective cognitive functioning.
Conclusion
Our analyses suggest that SCCs in patients with and without objective cognitive impairment are frequent, occurring in more than one third of PD patients. Establishing uniform measurement instruments for identifying PD‐related SCCs is critical to understand their implications. Even in cases lacking evidence of objective cognitive impairment and where SCCs might reflect underlying neuropsychiatric symptoms, the possibility of later cognitive deterioration should not be excluded. Therefore, SCCs in PD patients warrant close monitoring for opportunities for targeted and effective interventions. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
... The study included a total of 288 patients with probable AD dementia [14], 514 with mild cognitive impairment (MCI) based on the National Institute on Aging-Alzheimer's Association criteria [15], 77 with subjective cognitive decline (SCD) according to the guideline established by Jessen et al. [16], and 157 with other neurodegenerative diseases (OND) including frontotemporal dementia [17,18], corticobasal syndrome [19], Parkinson's disease dementia [20], progressive nuclear palsy [21], and individuals with postponed diagnoses. ...
Background
Alzheimer’s disease (AD) is characterized by amyloid-β (Aβ) plaque accumulation and neurofibrillary tangles in the brain. Emerging evidence has suggested potential interactions between the brain and periphery, particularly the liver, in regulating Aβ homeostasis.
Objective
This study aimed to investigate the association of serum liver enzymes with brain amyloidopathy and cognitive performance in patients with complaints of cognitive decline.
Methods
A total of 1,036 patients (mean age 74 years, 66.2% female) with subjective cognitive decline, mild cognitive impairment, AD dementia, and other neurodegenerative diseases were included using the Smart Clinical Data Warehouse. Amyloid positron emission tomography (PET) imaging, comprehensive neuropsychological evaluations, and measurements of liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin, and albumin, were assessed. After propensity score matching, logistic and linear regression analyses were used to investigate the associations between liver enzymes, amyloid status, and cognitive performance. Additionally, a machine learning approach was used to assess the classification performance of liver enzymes in predicting amyloid PET positivity.
Results
Lower ALT levels and higher AST-to-ALT ratios were significantly associated with amyloid PET positivity and AD diagnosis. The AST-to-ALT ratio was also significantly associated with poor memory function. Machine learning analysis revealed that the classification performance of amyloid status (AUC = 0.642) for age, sex, and apolipoprotein E ɛ4 carrier status significantly improved by 6.2% by integrating the AST-to-ALT ratio.
Conclusions
These findings highlight the potential association of liver function on AD and its potential as a diagnostic and therapeutic implications.
... Major depression, delirium, or other disorders that would obscure the diagnosis must be absent. Level II consists of an extensive assessment of four compartments: global cognitive efficiency, subcortical-frontal characteristics of D-PD, cortical characteristics of D-PD (language, visuo-constructive, visuo-spatial, visuo-perceptual) and neuropsychiatric characteristics of D-PD (apathy, depression, visual hallucinations, psychosis) [76]. ...
Background: Parkinson’s disease (PD) affects more than 1% of the population aged over 65 years and manifests with both motor symptoms – bradykinesia, rest tremor, rigidity, and non-motor symptoms. Cognitive impairment and dementia are recognized non-motor symptoms that can significantly affect the quality of life of both the patient and caregivers and are a risk factor for institutionalization in nursing homes and a risk factor for early mortality. Cognitive impairment is frequent in Parkinson’s disease (PD) that can develop even before the diagnosis of Parkinson’s disease based on its motor features. Conclusions: There are several clinical, molecular, and imaging factors that constitute risk factors for the development of Parkinson’s disease dementia, in which basal cholinergic and prefrontal dopaminergic systems are involved. Histological changes are Lewy-body, Alzheimer, but also vascular pathology. Clinically can be distinguished subjective cognitive decline, mild cognitive impairment and, subsequently, Parkinson’s disease dementia. There are no remedies with a proven effect to prevent the occurrence of cognitive decline in PD. The only approved drug for already developed D-PD is the cholinesterase inhibitor – donepezil. Non-pharmacological interventions are thought to be beneficial. A multidisciplinary approach to cognitive impairment is recommended, with specific pharmaceutical treatment of the cognitive disorder and comorbidities, and appropriate rehabilitation.
... The reasons might be that MMSE takes only about 7-8 minutes while MoCA takes 10-12 minutes to administer, whichthis is an important factor for its use in in-patient settings while MoCA is difficult to use in patients with moderate-tosevere impairments. Some research reports MMSE as useful in detecting cognitive deterioration in patients with Pd [62] while other recommends the use of MoCA [63,64,65] but these studies were conducted with small sample sizes, therefore no conclusions can be drawn until more studies are conducted with stronger methodological bases [66]. ...
Introduction
Patients with Parkinson’s disease are often prescribed physical therapy. Physiotherapists often assist Parkinson’s disease patients with assessment and treatment, but little is known about the assessment tools and interventions they use. Additionally, physical therapists do not consistently integrate standard outcome measures and treatment procedures into their practices. Consequently, this study was carried out to determine physical therapists’ preferences for assessment and treatment of Parkinson’s disease.
Methods
Five hundred questionnaires were distributed to physiotherapists working in clinical settings. Overall, 446 physiotherapists responded to the survey and returned the questionnaires. Questionnaires with incomplete information were excluded from the survey. In total, 418 physiotherapists participated in the study, of whom 324 saw PD patients in their clinical practice.
Results
Overall, 446 physiotherapists responded to the survey and returned the questionnaires. Questionnaires with incomplete information were excluded from the survey. In total, 418 physiotherapists participated in the study, of whom 324 saw PD patients in their clinical practice. Study participants included 43.8% male PTs and 56.2% female PTs with an average age of 30.02 ± 5.38 years. The Berg balance scale for balance assessment was preferred by 220 (67.9%), the Mini Mental State Examination for cognitive assessment was preferred by 317 (97.8%), and the Unified Parkinson’s Disease Rating Scale was preferred by 168 (51.85%) PTs. Neurological PTs employed PNF (proprioceptive neuromuscular facilitation) to decrease stiffness, and exercise and task-focused training for functional training. Virtual Reality and Motor Imagery were also known by 56.6% and 62.4% of PTs, respectively, although only 4.8% and 1.85% used them.
Conclusions
Study results revealed that most physiotherapists follow routine assessment and treatment protocols and do not implement innovative technology in the physical rehabilitation of patients with Parkinson’s disease.
... Such cognitive tests should be short, simple to perform, sensitive to subtle changes in cognition, not confounded by motor and visual problems, and able to assess a full range of cognitive domains. Some global cognitive screening tools that have been developed for patients with neurocognitive disorders are the Montreal Cognitive Assessment (MoCA) and Visual Cognitive Assessment Test (VCAT) among others [4,7,[9][10][11][12][13]. ...
Background: Cognitive for patients with neurocognitive disorders are mostly measured by Montreal Cognitive Assessment (MoCA) and Visual Cognitive Assessment Test (VCAT) as screening tools. These cognitive scores are usually left skewed and the results of association analysis might not be robust. This study aims to study the distribution of the cognitive outcomes and to discuss potential solutions. Materials and Methods: The inverse transformed cognitive outcomes are modelled using different statistical distributions. Robustness of the proposed models are checked under different scenarios: with intercept only, models with covariate, with and without bootstrapping. Results: Main results were based on VCAT score, and validated via MoCA score. Findings suggested that the inverse transformation method improves modelling the cognitive scores compared to the conventional methods using the original cognitive scores. Association of baseline characteristics (age, gender and years of education) and the cognitive outcomes were reported as estimates and 95% confidence intervals. Bootstrap methods improved the estimate precision and the bootstrapped standard errors of the estimates are more robust. Cognitive outcomes are widely analyzed using linear regression models with default normal distribution as a conventional method. We compared the results of our suggested models with the normal distribution under various scenarios. Goodness-of-fit measurements were compared between proposed models and conventional methods. Conclusions: The findings support the use of the inverse transformation method to model the cognitive outcomes instead of the original cognitive scores for early stage neurocognitive disorders where the cognitive outcomes are left skewed.
... Dementia typically manifests later in life, is characterized by global abnormalities that prevent functional independence, and generally occurs into three groups (11). ...
Background/Aim: The primary objective of this research was to evaluate the findings and conclusions presented in existing literature articles pertaining to mental illnesses in patients with Parkinson’s disease. Patients and Methods: The study used a patients and methods approach. The study also comprised studies and papers that provided information on clinical aspects, as well as links and correlations between Parkinson’s disease and mental illnesses. Results: Symptoms of mental disorders are extremely prevalent in PD, but they are frequently undetected, undertreated, and overlooked if not evaluated precisely. Neuropsychiatric disorders of Parkinson’s disease divide into a number of major groups: anxiety and mood disorders, psychosis, behavioral modifications such as sexual disorders, impulse control disorders, dopaminergic medication abuse, and sleeping disorders. Conclusion: The majority of mental health conditions in PD are treatable, and failure to do so has a negative impact. Numerous investigations demonstrate that psychiatric symptoms influence the quality of life more than motor manifestations. Depression seems to be associated with deterioration in cognitive performance, tasks associated with everyday living, and motor performance and might have the greatest influence on the quality of life in PD. Psychosis is the leading cause of caretaker concern and a significant predictor of nursing residence relocation. The objective of therapy for mental illnesses in PD ought to include remission; inadequate treatment must be avoided.
... The diagnosis of PD and Parkinson's disease dementia (PDD) was based on the clinical diagnostic criteria of the Movement Disorder Society for Parkinson's disease 23 and the recommendations of the MDS Task Force for the diagnosis of PDD. 24 Dementia with Lewy bodies (DLB) was diagnosed by using consensus criteria for clinical diagnosis developed by the DLB Consortium 25 , and probable Alzheimer's disease (AD) was defined using the criteria of the National Institute on Aging and the Alzheimer's Association (NIA-AA). 26 The sample size was calculated using the mean ± standard deviation (SD) from the reference literature. ...
Objective: We explored whether plasma α-syn be used as a potential biomarker for synucleinopathies. Materials and Methods: α-syn levels in plasma from 54 Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) patents, 31 Alzheimer’s disease dementia (AD), and 29 controls were measured by enzymelinked immunosorbent assay (ELISA). Results: The mean age of the synucleinopathies group, the AD group, and the normal controls was 72.70, 74.26, and 62 years old. The median plasma α-syn levels in the synucleinopathies group, AD group and controls were 9.72 (4.41-25.30), 16.78 (7.68-51.41) and 16.65 (10.37-32.72) ng/ml, respectively (Independent-Samples Kruskal-Wallis test, p = 0.026). The α-syn levels in the synucleinopathies group were lower than those of AD and controls. There was a fair correlation between plasma α-syn levels and the sum of the Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 (spearman correlation coefficient r = -0.261, p = 0.021) but not with cognition measured by Thai Mental Status Examination (TMSE). The area under the receiver operating characteristic curve (ROC) was 0.710 between the PDD and DLB vs non synucleinopathies group (AD and normal controls) (SE = 0.052, p ≤ 0.001). At the cut-off levels of 11.4 ng/ml indicated a sensitivity of 58% (95% CI 43.21-71.81%), specificity of 84.78% (95% CI 71.13-93.66%), positive predictive value (PPV) of 80.56%, a negative predictive value (NPV) of 65% and a precision of 70.83%. Conclusion: The present results suggest that plasma α-syn could be a potential biomarker to differentiate synucleinopathies from Alzheimer’s disease and the elderly with normal cognition.
... All participants underwent comprehensive assessments, including physical and neurological examinations, laboratory tests, APOE genotyping, neuropsychological assessments, brain magnetic resonance imaging, and amyloid positron emission tomography (PET) imaging. We excluded individuals who had not undergone liver function tests within 1 year of their amyloid PET imaging date as well as those with concomitant medical conditions, such as hepatocellular carcinoma and liver cirrhosis (which could signi cantly affect liver function) or other neurodegenerative disorders, including frontotemporal dementia [20,21], corticobasal syndrome [22], Parkinson's disease dementia [23], and progressive nuclear palsy [24]. Additionally, participants with outliers in liver function parameters exceeding the interquartile range by four times, which could lead to a signi cant impairment in liver function, were excluded. ...
Background
Alzheimer’s disease (AD) is a complex neurodegenerative disorder influenced by various factors, including liver function, which may impact the clearance of amyloid-β (Aβ) in the brain. This study aimed to explore how the apolipoprotein E (APOE) ε4 allele, a well-known genetic risk factor for AD, affects the relationship of liver function markers with AD pathology and cognition.
Methods
Using two independent cohorts, the Hallym University Medical Center and the Alzheimer’s Disease Neuroimaging Initiative, logistic and linear regression models were used to investigate the associations of liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, total bilirubin, and albumin) with AD diagnosis, amyloid positron emission tomography (PET) burden, cerebrospinal fluid biomarkers for AD (Aβ42, total tau, and phosphorylated tau181]), and cognitive performance. Mediation analyses were conducted to assess whether age and amyloid PET burden mediated these associations.
Results
Only in the APOE ε4 carrier group, a high AST to ALT ratio and low ALT levels were significantly associated with AD diagnosis, increased amyloid PET burden, poor cognitive function at the last visit, and faster longitudinal decline in cognitive function in both cohorts. However, no such relationship was observed in the APOE ε4 non-carrier group. In particular, the AST to ALT ratio was associated with cerebrospinal fluid Aβ42 levels exclusively in the APOE ε4 carrier group in the Alzheimer's Disease Neuroimaging Initiative cohort but not with phosphorylated tau181 or total tau levels. Moreover, mediation analyses in both cohorts revealed that age played a mediating role in the associations between these liver enzymes and amyloid PET burden or AD diagnosis, exclusively in the APOE ε4 non-carrier group, but not in the APOE ε4 carrier group. The association between these liver enzymes and AD diagnosis was mediated by the amyloid PET burden, but this mediation effect was only evident in the APOE ε4 carrier group.
Conclusions
This study provides valuable insights into the significant influence of the APOE ε4 allele on the intricate relationships of liver enzymes with Aβ-related pathogenesis and cognition in AD. Further research is required to elucidate the underlying mechanisms and potential therapeutic implications of these findings.
... [28] Exclusion criteria were: (i) dementia according to the neuropsychological assessment, [29] or the recommendations of the Movement Disorder Society Task Force for PD; [30] (ii) a major psychiatric disorder (including bipolar disorder, untreated major depression, schizophrenia) according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; [29] (iii) history of stroke, or cerebrovascular disease; and (iv) PSG date > 6 months from the clinical visit. Individuals were taking their usual medication during the study. ...
Background: Clinical and neuroanatomical correlates of daytime sleepiness in Parkinson’s disease remain inconsistent in the literature.
Objectives: Two studies were conducted. The first study evaluated the interrelation between non-motor and motor symptoms associated with daytime sleepiness in Parkinson’s disease. The second study identified the neuroanatomical substrates associated with daytime sleepiness in Parkinson’s disease using magnetic resonance imaging.
Methods: Seventy-seven participants with Parkinson’s disease were included in the first study. They completed extensive clinical and cognitive testing in addition to a polysomnographic recording. Principal component analysis was performed to evaluate the interrelation between daytime sleepiness and clinical symptoms and to discriminate between individuals with (n=25) and without (n=52) excessive daytime sleepiness on the components identified. In the second study, 29 individuals with Parkinson’s disease also underwent MRI acquisition of T1-weighted images. Vertex-based cortical and subcortical surface analysis, deformation-based morphometry, and voxel-based morphometry were performed to assess the association between daytime sleepiness severity and structural brain changes in participants.
Results: Individuals with excessive daytime sleepiness showed a higher score on a component including higher dosage of dopaminergic agonist, motor symptoms severity, shorter sleep latency, and greater sleep efficiency. Moreover, increased daytime sleepiness severity was associated with a larger surface area in the right insula, contracted surfaces in the right putamen and right lateral amygdala, and a larger surface in the right posterior amygdala.
Conclusion: Daytime sleepiness in Parkinson’s disease was associated with dopaminergic agonist dosage, motor impairment, and objective sleep measures. Moreover, neuroanatomical changes in cortical and subcortical regions related to vigilance, motor, and emotional states were associated with more severe daytime sleepiness.
... Participants were included in the present study based on their most recent clinical diagnosis or final pathological diagnosis of PD, PDD or DLB. A status of "case" for LBD-D was defined if the patient had a clinical diagnosis of DLB [5] or met the Movement Disorder Society task force PDD diagnostic criteria [29]. In detail, for PDD the criteria included: 1) scoring below the threshold for dementia on the Montreal Cognitive Assessment (MoCA score <21/30), 2) having cognitive deficits which are severe enough to interfere with activities of daily living (MDS-Unified Parkinson's disease Rating Scale (UPDRS) part I 1.1 ≥ 2 score), 3) and the absence of severe depression defined using the MDS-UPDRS (MDS-UPDRS part I 1.3 < 4). ...
Up to 80% of Parkinsons disease patients develop dementia, but time to dementia varies widely from motor symptom onset. Dementia with Lewy bodies presents with clinical features similar to Parkinsons disease dementia, but cognitive impairment precedes or coincides with motor onset. It remains controversial whether dementia with Lewy bodies and Parkinsons disease dementia are distinct conditions or represent part of a disease spectrum. The biological mechanisms underlying disease heterogeneity, in particular the development of dementia, remain poorly understood, but will likely be key to understanding disease pathways and ultimately therapy development. Previous genome-wide association studies in Parkinsons disease and dementia with Lewy bodies/Parkinsons disease dementia have identified risk loci differentiating patients from controls. We collated data for 7,804 patients of European ancestry from Tracking Parkinsons (PRoBaND), The Oxford Discovery Cohort, and AMP-PD. We conducted a discrete phenotype genome-wide association studies comparing Lewy body diseases with and without dementia to decode disease heterogeneity by investigating the genetic drivers of dementia in Lewy body diseases. We found that risk alleles rs429358 tagging APOEe4 and rs7668531 near the MMRN1 and SNCA-AS1 genes, increase the odds of developing dementia and that an intronic variant rs17442721 tagging LRRK2 G2019S, on chromosome 12 is protective against dementia. These results should be validated in autopsy confirmed cases in future studies.
... A score of less than 10 indicates severe impairment [24]. A diagnosis of PD with dementia is made upon the MDS recommendations [25]. Study participants are asked to return for re-evaluation to the clinic at 3-month intervals, because 3 months is the interval that is common in the NKUA movement disorder clinic where PD patients are examined. ...
1) Objective: We explore the predictive power of a novel stream of patient data, combining wearable devices and patient reported outcomes (PROs), using an AI-first approach to classify the health status of Parkinson's disease (PD), multiple sclerosis (MS) and stroke patients (collectively named PMSS). (2) Background: Recent studies acknowledge the burden of neurological disorders on patients and on the healthcare systems managing them. To address this, effort is invested in the digital transformation of health provisioning for PMSS patients. (3) Methods: We introduce the data collection journey within the ALAMEDA project, which continuously collects PRO data for a year through mobile applications and supplements them with data from minimally intrusive wearable devices (accelerometer bracelet, IMU sensor belt, ground force measuring insoles, and sleep mattress) worn for 1-2 weeks at each milestone. We present the data collection schedule and its feasibility, the mapping of medical predictor variables to wearable device capabilities and mobile application functionality. (4) Results: A novel combination of wearable devices and smartphone applications required for the desired analysis of motor, sleep, emotional and quality-of-life outcomes is introduced. AI-first analysis methods are presented that aim to uncover the prediction capability of diverse longitudinal and cross-sectional setups (in terms of standard medical test targets). Mobile application development and usage schedule facilitates the retention of patient engagement and compliance with the study protocol.
... Other dementias also have distinct clinical symptoms that relate to their underlying neuropathologic Proposed processes that may offer therapeutic targets to prevent or treat dementia. c Clinical consensus workup for the most common forms of dementia [1][2][3][4][5]. d Neuropathologic assessment identifies characteristic changes for each disease. ...
Neurodegenerative dementia can result from multiple underlying abnormalities, including neurotransmitter imbalances, protein aggregation, and other neurotoxic events. A major complication in identifying effective treatment targets is the frequent co-occurrence of multiple neurodegenerative processes, occurring either in parallel or sequentially. The path towards developing effective treatments for Alzheimer’s disease (AD) and other dementias has been relatively slow and until recently has focused on disease symptoms. Aducanumab and lecanemab, recently approved by the FDA, are meant to target disease structures but have only modest benefit on symptom progression and remain unproven in reversing or preventing dementia. A third, donanemab, appears more promising but awaits FDA approval. Ongoing trials include potential cognition enhancers, new combinations of known drugs for synergistic effects, prodrugs with less toxicity, and increasing interest in drugs targeting neuroinflammation or microbiome. Scientific and technological advances offer the opportunity to move in new therapy directions, such as modifying microglia to prevent or suppress underlying disease. A major challenge, however, is that underlying comorbidities likely influence the effectiveness of therapies. Indeed, the full range of comorbidity, today only definitively identified postmortem, likely contributes to failed clinical trials and overmedication of older adults, since it is difficult to exclude (during life) people unlikely to respond. Our current knowledge thus signals that a paradigm shift towards individualized and multimodal treatments is necessary to effectively advance the field of dementia therapeutics.
... The study included a total of 288 patients with probable AD dementia [13] and 533 with mild cognitive impairment (MCI) [14] based on the National Institute on Aging-Alzheimer's Association criteria, 58 with subjective cognitive decline (SCD) according to the guideline established by Jessen et al [15], and 157 with other neurodegenerative diseases including frontotemporal dementia [16,17], corticobasal syndrome [18], Parkinson's disease dementia [19], progressive nuclear palsy [20], and individuals with postponed diagnoses. ...
Background
Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) plaque accumulation and neurofibrillary tangles in the brain. Emerging evidence has suggested potential interactions between the brain and peripheral organs, particularly the liver, in regulating Aβ homeostasis. This study aimed to investigate the association of serum liver enzymes with brain amyloidopathy and cognitive performance as the precise relationship remains unclear.
Methods
This retrospective study analyzed data collected between November 2015 and June 2023 using a clinical big data analytic solution called the Smart Clinical Data Warehouse (CDW). A total of 1,036 patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD dementia, and other neurodegenerative diseases were included in the study. Amyloid positron emission tomography (PET) imaging, comprehensive neuropsychological evaluations, and measurements of liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, and albumin, were assessed. Logistic and linear regression analyses were used to investigate the associations between liver enzymes, amyloid status, and cognitive performance. Additionally, a machine learning approach was used to assess the classification performance of liver enzymes in predicting amyloid status.
Results
Lower ALT levels (OR, 0.976; 95% CI, 0.957–0.994; P = 0.031) and higher AST-to-ALT ratios (OR, 1.862; 95% CI, 1.397–2.521; P < 0.001) were significantly associated with amyloid PET positivity. The AST-to-ALT ratio wasalsosignificantly associated with poor memory function. Machine learning analysis revealed that the classification performance of amyloid status (area under the curve (AUC) = 0.642) for age, sex, and apolipoprotein E ε4 carrier status significantly improved by 6.2% by integrating the AST-to-ALT ratio.
Conclusions
The association of lower ALT levels and a higher AST-to-ALT ratio with amyloid status in the brain suggests potential implications of liver function in the Aβ pathogenesis of AD. Moreover, the AST-to-ALT ratio showed promising associations with memory function, and its integration with clinical information improved the classification performance of amyloid status in the brain.
... Trail Making Test (TMT) was another often used instrument. TMT could be affected by cognitive changes in PD [43]. The 39 items on self-administered PDQ-39 were divided into eight categories, one of which was the cognitive domain [44]. ...
Background:
Tai Ji (TJ) can improve cognitive function, which in turn brings life quality to Parkinson's disease (PD) patients. Cognitive function is thus important for PD patients. Analyzing the cognitive function and obtaining precise TJ exercise prescriptions are effective in treating PD patients.
Objectives:
The purpose of this review was to discuss the current Randomized Controlled Trials (RCTs) of TJ and cognitive function improvement in PD.
Materials and methods:
Databases, including PubMed, Web of Science, Scopus, Cochrane Library, EBSCOhost, Wan Fang, and CNKI, were searched. Cochrane systematic evaluation method was adopted wherein 6 RCTs met the final inclusion criteria.
Results:
Among the 6 included RCTs, 3 were of high quality, and the rest were of medium quality. Quantitative analysis exhibited that TJ intervention improved the cognitive function of PD patients. TJ promoted the global cognitive function (p < 0.05) and the executive function (p = 0.09) compared with the control. However there was no significant improvement in cognitive motor. TJ training intervention doses of two times a week with 45-60 min sessions over ≤12 weeks could improve the cognitive function of PD patients.
Conclusions:
TJ affects the cognitive function of PD patients. However, this effect may have a reduced or no significant impact as the disease increases. PD patients can choose TJ as an intervention for 45-60 min twice a week for at least 12 weeks to accomplish maximum improvement in cognitive function.
... PD was diagnosed according to the United Kingdom Parkinson's Disease Brain Bank diagnostic criteria. PD with mild cognitive impairment (MCI) and PDD were diagnosed according to the level II PD-MCI criteria (Litvan et al., 2011) and the clinical criteria of probable PDD, respectively (Dubois et al., 2007). DLB was diagnosed using the 2017 revised criteria (McKeith et al., 2017); all patients satisfied the probable DLB criteria. ...
Introduction
Concomitant amyloid pathology is not uncommon and contributes to the clinical characteristics of Lewy body disease (LBD). We investigated the effect of amyloid on striatal ¹⁸ F-FP-CIT uptake patterns in LBD, including Parkinson's disease (PD) and dementia with Lewy bodies.
Methods
We enrolled 125 patients with LBD who underwent ¹⁸ F-florbetaben positron emission tomography (PET) and ¹⁸ F-FP-CIT PET. Patients were divided into amyloid-positive and amyloid-negative groups. We investigated the effect of amyloid on striatal dopamine transporter (DAT) availability, depending on the type of LBD, using general linear models with interaction analysis after controlling for age, sex, education, deep white matter hyperintensity (WMH), periventricular WMH, and cognitive status.
Results
There was a significant interaction effect between the disease group and the presence of amyloid on DAT availability in the anterior putamen, posterior putamen, caudate, and ventral striatum. In the presence of amyloid, only the PD group exhibited decreased DAT availability in the anterior and posterior putamen. In both groups, the presence of amyloid was not associated with DAT availability in the caudate and ventral striatum. The presence of amyloid was not directly related to the worse parkinsonian motor symptoms in both groups. However, there was a significant indirect effect of amyloid on parkinsonian motor symptoms, which was mediated by anterior and posterior putaminal DAT availability in the PD group alone.
Discussion
This study demonstrates different amyloid-dependent or amyloid-independent ¹⁸ F-FP-CIT PET patterns in patients with LBD, suggesting distinctive interactions between α-synuclein and amyloid pathology based on the type of LBD.
Anxiety and postural control deficits may be related in people with Parkinson’s disease (PwPD). However, the association between anxiety levels and weight-shifting control remains ambiguous. This study investigated whether 1) weight-shifting control differed between PwPD with and without anxiety, and 2) the learning effect of weight-shifting differed between the two populations. Additionally, we evaluated cortical activities to investigate neural mechanisms underlying weight-shifting control. Twenty-eight PwPD (14 anxiety, 14 nonanxiety) participated in a 5-day weight-shifting study by coupling the bearing weight of their more-affected leg to a sinusoidal target at 0.25 Hz. We tested the weight-shifting control on day 1 (pretest), day 3 (posttest), and day 5 (retention test) with a learning session on day 3. The error and jerk of weight-shifting trajectory and the theta and gamma powers of electroencephalography in prefrontal, frontal, sensorimotor and parietal-occipital areas were measured. At the pretest, the anxiety group showed larger error and smaller jerk of weight-shifting with greater prefrontal theta, frontal gamma, and sensorimotor gamma powers than the nonanxiety group. Anxiety intensity was correlated positively with weight-shifting error and theta power but negatively with weight-shifting jerk. Reduced weight-shifting error with increased theta power after weight-shifting learning was observed in the nonanxiety group. However, the anxiety group showed decreased gamma power after weight-shifting learning without behavior change. Our findings suggest differential weight-shifting control and associated cortical activation between PwPD with and without anxiety. In addition, anxiety would deteriorate weight-shifting control and hinder weight-shifting learning benefits in PwPD, leading to less weight-shifting accuracy and correction.
Background: Alzheimer’s disease (AD) and Lewy body disease (LBD) are characterized by early and gradual worsening perturbations in speeded cognitive responses. Objective: Using simple and choice reaction time tasks, we compared two indicators of cognitive speed within and across the AD and LBD spectra: mean rate (average reaction time across trials) and inconsistency (within person variability). Methods: The AD spectrum cohorts included subjective cognitive impairment (SCI, n = 28), mild cognitive impairment (MCI, n = 121), and AD (n = 45) participants. The LBD spectrum included Parkinson’s disease (PD, n = 32), mild cognitive impairment in PD (PD-MCI, n = 21), and LBD (n = 18) participants. A cognitively unimpaired (CU, n = 39) cohort served as common benchmark. We conducted multivariate analyses of variance and discrimination analyses. Results: Within the AD spectrum, the AD cohort was slower and more inconsistent than the CU, SCI, and MCI cohorts. The MCI cohort was slower than the CU cohort. Within the LBD spectrum, the LBD cohort was slower and more inconsistent than the CU, PD, and PD-MCI cohorts. The PD-MCI cohort was slower than the CU and PD cohorts. In cross-spectra (corresponding cohort) comparisons, the LBD cohort was slower and more inconsistent than the AD cohort. The PD-MCI cohort was slower than the MCI cohort. Discrimination analyses clarified the group difference patterns. Conclusions: For both speed tasks, mean rate and inconsistency demonstrated similar sensitivity to spectra-related comparisons. Both dementia cohorts were slower and more inconsistent than each of their respective non-dementia cohorts.
Background and objective
Level of Education (LoE) is widely used as an indicator of cognitive reserve and is associated with risk of dementia. The aim of the present study was to know the influence of the LoE on the change in cognitive function (CF) in patients with Parkinson´s disease (PD).
Patients and Methods
Controls and PD patients from the Spanish cohort COPPADIS with a disease duration from symptoms onset ≤ 5 years, who were recruited from January/2016 to November/2017 (baseline visit; V0) and evaluated at 2 (V2), 4 (V4) and 5 (V5) years of follow-up were included. Regarding LoE, patients were classified as with primary, secondary and university studies. CF was assessed using the Parkinson´s Disease Cognitive Rating Scale (PD-CRS). General linear model (GLM) repeated measure was used to test for changes in the CF.
Results
Three hundred and ninety-nine PD patients (61.9 ± 8.9 years old; 58.4% males) and 207 controls (61 ± 8.3 years old; 49.8% males) were included. From V0 to V5, significant differences were observed in PD patients in global and fronto-subcortical (p < 0.0001 in all visits) between LoE groups but not in posterior-cortical (p > 0.05 in all visits) CF. LoE was associated with the change from V0 to V5 in the PD-CRS total score and fronto-subcortical sub-score (p < 0.0001) in PD patients but not in controls. Having primary studies was associated to PD dementia (PD-CRS < 65) at V5 (OR = 2.47; p = 0.035).
Conclusion
Change in cognitive function in Parkinson´s disease is influenced by the level of education.
Parkinson’s disease (PD) is the fastest growing neurological condition. The number of patients suffering from this condition is expected to double to 12 million by 2040. PD is commonly associated with cognitive impairment. About one-third of the patients develop dementia, and about a third have mild cognitive impairment (MCI). The timeline from the onset of motor symptoms to dementia is variable, although most patients who have PD for more than 10 years will likely have impairment secondary to dementia. Diagnosing Parkinson’s disease dementia involves excluding other conditions that mimic dementia and other potential etiologies of dementia. Executive, attentional, and visuospatial cognitive domains are typically affected, although the presentation can be quite heterogenous, with memory impairment being commonly found as well. Development of neuropsychiatric symptoms (NPSs) often parallels dementia and manifests as mood, anxiety, psychotic symptoms, apathy, aggression, and behavioral disturbances. Care for these patients is complex and difficult, and the optimal treatment strategy involving both pharmacological and non-pharmacological measures should be developed to target motor, cognitive, and behavioral symptoms.
Background
MicroRNAs (miRNAs) have pivotal roles in gene regulation. Circulating miRNAs have been developed as novel candidate non-invasive biomarkers for diagnosis, prognosis, and treatment response for diseases. However, miRNAs that have causal effects on Parkinson’s Disease (PD) remain largely unknown. To investigate the causal relationships between miRNAs and PD, here we conduct a Mendelian randomization (MR) study.
Methods
This study utilized the summary-level data of respective genome-wide association studies (GWAS) for 2083 miRNAs and seven PD-related outcomes to comprehensively reveal the causal associations between the circulating miRNAs and PD. Two-sample MR design was deployed and the causal effects were estimated with inverse variance weighted, MR-Egger, and weighted median. Comprehensively sensitive analyses were followed, including Cochran’s Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis, to validate the robustness of our results. Finally, we investigated the potential role of the MR significant miRNAs by predicting their target genes and functional enrichment analysis.
Results
Inverse variance weighted estimates suggested that two miRNAs, miR-205-5p (β = −0.46, 95%CI: −0.690 to −0.229, p = 9.3 × 10⁻⁵) and miR-6800-5p (β = −0.389, 95%CI: −0.575 to −0.202, p = 4.32 × 10⁻⁵), significantly decreased the rate of cognitive decline among PD patients. In addition, eight miRNAs were nominally associated with more than three PD-related outcomes each. No significant heterogeneity of instrumental variables or horizontal pleiotropy was found. Gene Ontology (GO) analysis showed that the targets of these causal miRNAs were significantly enriched in cell cycle, apoptotic, and aging pathways.
Conclusion
This MR study identified two miRNAs whose genetically regulated expression might have a causal role in the development of PD dementia. Our findings provided potential miRNA biomarkers to make better and early diagnoses and risk assessments of PD.
Parkinson’s disease (PD) leads to cognitive impairment. Widely used methods to assess cognition are the Clock Drawing Test (CDT) and the Mini-Mental State Examination (MMSE). Another option is the Vienna Visuo-Constructional Test 3.0 Screening (VVT-3.0). We studied the neuropsychological and demographic data of 45 healthy controls (HC) and 64 individuals diagnosed with PD (total N = 109) and compared the validity of each test by using receiver-operator characteristic (ROC) curves and logistic regression analyses. The ROC analyses of PD yielded areas under the curve (AUC) of 0.68 using VVT-3.0, 0.74 using MMSE, and 0.72 using CDT as predictors, respectively. The VVT-3.0 shows comparable validity to the more established measurement tools and MMSE und CDT and is easy to administer in a clinical setting.
Backgrounds
Numerous lines of evidence support the intricate interplay between Parkinson’s disease (PD) and the PINK1-dependent mitophagy process. This study aimed to evaluate differences in plasma PINK1 levels among idiopathic PD, PD syndromes (PDs), and healthy controls.
Methods
A total of 354 participants were included, consisting of 197 PD patients, 50 PDs patients, and 107 healthy controls were divided into two cohorts, namely the modeling cohort (cohort 1) and the validated cohort (cohort 2). An enzyme-linked immunosorbent assay (ELISA)-based analysis was performed on PINK1 and α-synuclein oligomer (Asy-no). The utilization of the area under the curve (AUC) within the receiver-operating characteristic (ROC) curves served as a robust and comprehensive approach to evaluate and quantify the predictive efficacy of plasma biomarkers alone, as well as combined models, in distinguishing PD patients from controls.
Results
PINK1 and Asy-no were elevated in the plasma of PD and PDs patients compared to healthy controls. The AUCs of PINK1 (0.771) and Asy-no (0.787) were supposed to be potentially eligible plasma biomarkers differentiating PD from controls but could not differentiate PD from PDs. Notably, the PINK + Asy-no + Clinical RBD model showed the highest performance in the modeling cohort and was comparable with the PINK1 + Clinical RBD in the validation cohort. Moreover, there is no significant correlation between PINK1 and UPDRS, MMSE, HAMD, HAMA, RBDQ-HK, and ADL scores.
Conclusion
These findings suggest that elevated PINK1 in plasma holds the potential to serve as a non-invasive tool for distinguishing PD patients from controls. Moreover, the outcomes of our investigation lend support to the plausibility of implementing a feasible blood test in future clinical translation.
Idiopathic Parkinson’s disease (iPD) is believed to have a heterogeneous pathophysiology, but molecular disease subtypes have not been identified. Here, we show that iPD can be stratified according to the severity of neuronal respiratory complex I (CI) deficiency, and identify two emerging disease subtypes with distinct molecular and clinical profiles. The CI deficient (CI-PD) subtype accounts for approximately a fourth of all cases, and is characterized by anatomically widespread neuronal CI deficiency, a distinct cell type-specific gene expression profile, increased load of neuronal mtDNA deletions, and a predilection for non-tremor dominant motor phenotypes. In contrast, the non-CI deficient (nCI-PD) subtype exhibits no evidence of mitochondrial impairment outside the dopaminergic substantia nigra and has a predilection for a tremor dominant phenotype. These findings constitute a step towards resolving the biological heterogeneity of iPD with implications for both mechanistic understanding and treatment strategies.
Purpose of the Report
Although early detection of individuals at risk of dementia conversion is important in patients with Parkinson’s disease (PD), there is still no consensus on neuroimaging biomarkers for predicting future cognitive decline. We aimed to investigate whether cerebral perfusion patterns on early-phase ¹⁸ F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane ( ¹⁸ F-FP-CIT) PET have the potential to serve as a neuroimaging predictor for early dementia conversion in patients with PD.
Materials and Methods
In this retrospective analysis, we enrolled 187 patients with newly diagnosed PD who underwent dual-phase ¹⁸ F-FP-CIT PET at initial assessment and serial cognitive assessments during the follow-up period (>5 years). Patients with PD were classified into 2 groups: the PD with dementia (PDD)-high-risk (PDD-H; n = 47) and the PDD-low-risk (PDD-L; n = 140) groups according to dementia conversion within 5 years of PD diagnosis. We explored between-group differences in the regional uptake in the early-phase ¹⁸ F-FP-CIT PET images. We additionally performed a linear discriminant analysis to develop a prediction model for early PDD conversion.
Results
The PDD-H group exhibited hypoperfusion in Alzheimer’s disease (AD)-prone regions (inferomedial temporal and posterior cingulate cortices, and insula) compared with the PDD-L group. A prediction model using regional uptake in the right entorhinal cortex, left amygdala, and left isthmus cingulate cortex could optimally distinguish the PDD-H group from the PDD-L group.
Conclusions
Regional hypoperfusion in the AD-prone regions on early-phase ¹⁸ F-FP-CIT PET can be a useful biomarker for predicting early dementia conversion in patients with PD.
Prevalence of Parkinson’s disease (PD) increases with age. The purpose of this study was to evaluate the eligibility criteria in randomized clinical trials (RCTs) in PD, especially those limiting the enrollment of older adults. We examined RCTs of pharmacological and non-pharmacological anti-parkinsonian interventions registered with ClinicalTrials.gov and started from 2013 through 2022. Primary outcome was proportion of RCTs with an upper age limit of 85 years of age or less. Secondary outcome was proportion of RCTs with other exclusion criteria. Associations between trial characteristics and the presence of the age limits were determined using logistic regression. Our study included 420 RCTs. Two hundred thirty-nine (57%) of these had an upper age limit of 85 years of age or less. Proportion of these trials significantly increased over time. The odds of the presence of an upper age limit were significantly associated with the investigational site location, phase, and timeframe for the primary endpoint assessment. Three hundred fifty-six (85%) trials had other eligibility criteria limiting the enrollment of older patients; these often (n = 285; 68%) included cognitive impairment. Overall, 386 (92%) RCTs either explicitly excluded older adults or had criteria indirectly limiting their enrollment. Underrepresentation of older patients in clinical trials in PD considerably reduces the generalizability of their results. Some eligibility criteria should be modified to enable the investigators to assess the benefits and harms of new therapeutic interventions in older adults. This problem is important in view of rapidly growing number of older patients with PD.
Background
Cognitive impairment is common in Parkinson’s disease (PD), but care needs and resource use for those with significant cognitive impairment are not well established.
Methods
675 participants with PD from the international Care of Late-Stage Parkinsonism (CLaSP) study were grouped into those without (n = 333, 49%) and with cognitive impairment (MMSE < 24/30 or diagnosis of dementia or Mild Cognitive Impairment; n = 342, 51%) and their clinical features, care needs and healthcare utilisation compared. The relationship between cognition and healthcare consultations was investigated through logistic regression.
Results
Cognitive impairment was associated with more motor and non-motor symptoms, less antiparkinsonian but higher rates of dementia and antipsychotic medication, worse subjective health status and greater caregiver burden. A considerable proportion did not have a pre-established cognitive diagnosis. Care needs were high across the whole sample but higher in the cognitive impairment group. Home care and care home use was higher in the cognitive impairment group. However, use of healthcare consultations was similar between the groups and significantly fewer participants with cognitive impairment had had recent PD Nurse consultations. Worse cognitive impairment was associated with lower frequency of recent PD nurse and multidisciplinary therapy consultation (physiotherapy, massage, occupational therapy, speech training and general nursing).
Conclusions
Those with cognitive impairment have more severe PD, higher care needs and greater social care utilisation than those with normal cognition, yet use of health care services is similar or less. Cognitive impairment appears to be a barrier to PD nurse and multidisciplinary therapy consultations. This challenges current models of care: alternative models of care may be required to serve this population.
Plain Language Summary
Parkinson’s disease is a long-term progressive health condition. Over time, many people with Parkinson’s develop problems with thinking and memory, called cognitive impairment. This can negatively impact the daily lives of the person with Parkinson’s and their caregiver. It is also thought to be a barrier to accessing healthcare. How people with Parkinson’s who have cognitive impairment use healthcare and detail of their care needs is not well known. We analysed data from a large sample of people with advanced Parkinson’s from six European countries to investigate their symptoms, care needs and healthcare use. We compared those with cognitive impairment to (342 people) to those without cognitive impairment (333 people). We found that those with cognitive impairment had more severe Parkinson’s across a range of symptoms compared to those without cognitive impairment. They also had more care needs, reported their health status to be worse, and their caregivers experienced greater strain from caring. Whilst use of other healthcare services was similar between the two groups, those with cognitive impairment were less likely to have recently seen a Parkinson’s nurse than those without cognitive impairment. Further analysis showed an association between cognitive impairment and not having seen a Parkinson’s nurse or therapist recently, taking psychiatric symptoms, functional disability and care home residence into account. Therapists included were physiotherapy, massage, occupational therapy, speech training and general nursing. These findings highlight unmet need. We suggest that healthcare should be more targeted to help this group of people, given their higher care needs.
Background
Freezing of gait (FOG), is associated with impairment of different cognitive functions. Previous studies hypothesized that FOG may be due to a loss of automaticity.
Research question
To explore whether FOG is associated with impairment in cognitive functions, focusing on retrograde procedural memory, the memory responsible for the automatic, implicit stored procedures that have been acquired in earlier life stages.
Methods
In this cross-sectional, case–control study, 288 people with typical Parkinson’s disease (PD) from the Luxembourg Parkinson’s Study were assigned to Freezers (FOG ⁺ ) and non-Freezers (FOG ⁻ ) based on the MDS-UPDRS 2.13 (self-reported FOG episodes) and 3.11 (FOG evaluated by clinicians during gait assessment). Both groups were matched on age, sex and disease duration. Global cognition (MoCA), retrograde procedural memory and visuo-constructive abilities (CUPRO), psychomotor speed and mental flexibility (TMT) were assessed. Furthermore, we repeated our analyses by additionally controlling for depression (BDI-I).
Results
Besides lower global cognition (MoCA; p = 0.007) and mental flexibility (TMT-B and Delta-TMT; p < 0.001), FOG ⁺ showed a lower performance in retrograde procedural memory (CUPRO-IS1; p < 0.001) compared to FOG ⁻ . After controlling additionally for depression, our main outcome variable CUPRO-IS1 remained significantly lower in FOG ⁺ ( p = 0.010).
Conclusion
Our findings demonstrated that besides lower global cognition and mental flexibility scores, FOG ⁺ showed lower performance in retrograde procedural memory compared to matched FOG-control patients, even when accounting for factors such as age, sex, disease duration or depression.
Significance
In the context of limited treatment options, especially for non-invasive therapeutic approaches, these insights on procedural memory and FOG may lead to new hypotheses on FOG etiology and consequently the development of new treatment options.
Cognitive impairment (CI) is a characteristic non-motor feature of Parkinson disease (PD) that poses a severe burden on the patients and caregivers, yet relatively little is known about its pathobiology. Cognitive deficits are evident throughout the course of PD, with around 25% of subtle cognitive decline and mild CI (MCI) at the time of diagnosis and up to 83% of patients developing dementia after 20 years. The heterogeneity of cognitive phenotypes suggests that a common neuropathological process, characterized by progressive degeneration of the dopaminergic striatonigral system and of many other neuronal systems, results not only in structural deficits but also extensive changes of functional neuronal network activities and neurotransmitter dysfunctions. Modern neuroimaging studies revealed multilocular cortical and subcortical atrophies and alterations in intrinsic neuronal connectivities. The decreased functional connectivity (FC) of the default mode network (DMN) in the bilateral prefrontal cortex is affected already before the development of clinical CI and in the absence of structural changes. Longitudinal cognitive decline is associated with frontostriatal and limbic affections, white matter microlesions and changes between multiple functional neuronal networks, including thalamo-insular, frontoparietal and attention networks, the cholinergic forebrain and the noradrenergic system. Superimposed Alzheimer-related (and other concomitant) pathologies due to interactions between α-synuclein, tau-protein and β-amyloid contribute to dementia pathogenesis in both PD and dementia with Lewy bodies (DLB). To further elucidate the interaction of the pathomechanisms responsible for CI in PD, well-designed longitudinal clinico-pathological studies are warranted that are supported by fluid and sophisticated imaging biomarkers as a basis for better early diagnosis and future disease-modifying therapies.
We propose a novel approach for the reconstruction of functional networks representing brain dynamics based on the idea that the co-participation of two brain regions in a common cognitive task should result in a drop in their identifiability, or in the uniqueness of their dynamics. This identifiability is estimated through the score obtained by Deep Learning models in supervised classification tasks; and therefore requires no a priori assumptions about the nature of such co-participation. The method is tested on EEG recordings obtained from Alzheimer‘s and Parkinson‘s Disease patients, and matched healthy volunteers, for eyes-open and eyes-closed resting state conditions; and the resulting functional networks are analysed through standard topological metrics. Both groups of patients are characterised by a reduction in the identifiability of the corresponding EEG signals, and by differences in the patterns that support such identifiability. Resulting functional networks are similar, but not identical to those reconstructed by using a correlation metric. Differences between control subjects and patients can be observed in network metrics like the clustering coefficient and the assortativity, in different frequency bands. Differences are also observed between eyes-open and closed conditions, especially for Parkinson‘s Disease patients.
Objectives
We investigated whether hippocampal perfusion changes are associated with cognitive decline, motor deficits, and the risk of dementia conversion in patients with Parkinson's disease (PD).
Methods
We recruited patients with newly diagnosed and non‐medicated PD and healthy participants who underwent dual‐phase ¹⁸ F‐N‐(3‐fluoropropyl)‐2β‐carboxymethoxy‐3β‐(4‐iodophenyl) nortropane ( ¹⁸ F‐FP‐CIT) positron emission tomography (PET) scans. Patients were classified into three groups according to hippocampal perfusion measured by standard uptake value ratios (SUVRs): 1) PD hippocampal hypoperfusion group (1 standard deviation [SD] below the mean hippocampal SUVR of healthy controls; PD‐hippo‐hypo), 2) PD hippocampal hyperperfusion group (1 SD above the mean; PD‐hippo‐hyper), and 3) the remaining patients (PD‐hippo‐normal). We compared the baseline cognitive performance, severity of motor deficits, hippocampal volume, striatal dopamine transporter (DAT) availability, and the risk of dementia conversion among the groups.
Results
We included 235 patients (PD‐hippo‐hypo: n = 21; PD‐hippo‐normal: n = 157; and PD‐hippo‐hyper: n = 57) and 48 healthy participants. Patients in PD‐hippo‐hypo group were older and had smaller hippocampal volumes than those in the other PD groups. PD‐hippo‐hypo group showed less severely decreased DAT availability in the putamen than the other groups despite similar severities of motor deficit. PD‐hippo‐hypo group had a higher risk of dementia conversion compared to PD‐hippo‐normal (hazard ratio, 2.59; p = 0.013) and PD‐hippo‐hyper (hazard ratio, 3.73; p = 0.006) groups, despite similar cognitive performance at initial assessment between groups.
Interpretation
Hippocampal hypoperfusion may indicate a reduced capacity to cope with neurodegenerative processes in terms of the development of motor deficits and cognitive decline in patients with PD.
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Idiopathic Parkinson's disease (iPD) is believed to have a heterogeneous pathophysiology, but molecular disease subtypes have not been identified. We show that iPD can be stratified according to the severity of neuronal respiratory complex I (CI) deficiency, and identify two emerging disease subtypes with distinct molecular and clinical profiles. The CI deficient (CI-PD) subtype accounts for approximately a fourth of all cases, and is characterized by anatomically widespread neuronal CI deficiency, a distinct cell type-specific gene expression profile, increased load of neuronal mtDNA deletions, and a predilection for non-tremor dominant motor phenotypes. In contrast, the non-CI deficient (nCI-PD) subtype exhibits no evidence of mitochondrial impairment outside the dopaminergic substantia nigra and has a predilection for a tremor dominant phenotype. These findings constitute a step towards resolving the biological heterogeneity of iPD with implications for both mechanistic understanding and treatment strategies.
Background and objective:
Patients with young-onset Parkinson's disease (YOPD) have a slower progression. Our aim was to analyze the change in cognitive function in YOPD compared to patients with a later onset and controls.
Patients and methods:
Patients with Parkinson's disease (PD) and controls from the COPPADIS cohort were included. Cognitive function was assessed with the Parkinson's Disease Cognitive Rating Scale (PD-CRS) at baseline (V0), 2-year ± 1 month (V2y), and 4-year ± 3 months follow-up (V4y). Regarding age from symptoms onset, patients were classified as YOPD (< 50 years) or non-YOPD (≥ 50). A score in the PD-CRS < 81 was defined as cognitive impairment (CI): ≤ 64 dementia; 65-80 mild cognitive impairment (MCI).
Results:
One-hundred and twenty-four YOPD (50.7 ± 7.9 years; 66.1% males), 234 non-YOPD (67.8 ± 7.8 years; 59.3% males) patients, and 205 controls (61 ± 8.3 years; 49.5% males) were included. The score on the PD-CRS and its subscore domains was higher at all visits in YOPD compared to non-YOPD patients and to controls (p < 0.0001 in all analysis), but no differences were detected between YOPD patients and controls. Only non-YOPD patients had significant impairment in their cognitive function from V0 to V4y (p < 0.0001). At V4y, the frequency of dementia and MCI was 5% and 10% in YOPD compared to 25.2% and 22.3% in non-YOPD patients (p < 0.0001). A lower score on the Parkinson's Disease Sleep Scale at baseline was a predictor of CI at V4y in YOPD patients (Adjusted R2 = 0.61; OR = 0.965; p = 0.029).
Conclusion:
Cognitive dysfunction progressed more slowly in YOPD than in non-YOPD patients.
To test the hypotheses that visuoperceptual and attentional ability are disproportionately impaired in patients having dementia with Lewy Bodies (DLB) compared with Alzheimer's disease (AD).
A comprehensive battery of neuropsychological tasks designed to assess working, episodic, and semantic memory, and visuoperceptual and attentional functions was given to groups of patients with DLB (n=10) and AD (n=9), matched for age, education, and mini mental state examination (MMSE), and to normal controls (n=17).
Both patient groups performed equally poorly on tests of episodic and semantic memory with the exception of immediate and delayed story recall, which was worse in the AD group. Digit span was by contrast spared in AD. The most striking differences were on tests of visuoperceptual/spatial ability and attention. Whereas patients with AD performed normally on several subtests of the visual object and space perception battery, the DLB group showed substantial impairments. In keeping with previous studies, the AD group showed deficits in selective attention and set shifting, but patients with DLB were more impaired on virtually every test of attention with deficits in sustained, selective, and divided attention.
Patients with DLB have substantially greater impairment of attention, working memory, and visuoperceptual ability than patients with AD matched for overall dementia severity. Semantic memory seems to be equally affected in DLB and AD, unlike episodic memory, which is worse in AD. These findings may have relevance for our understanding of the genesis of visual hallucinations, and the differential diagnosis of AD and DLB.
Attentional problems are common symptoms of brain impairment and are generally assessed by a number of psychological tests. However, clinicians do not always agree on the processes measured by these tests and validation of the tests is often inadequate. The present study used factor-analytic techniques to examine the construct validity of eight attention tests (Letter Cancellation, Serial Subtraction, Digit Span, Digit Symbol, Stroop Colour-Word, Trail Making, Symbol Digit Modality, and Knox Cube). These tests were administered to 125 university controls, 45 normal controls from the community, and 37 closed-head-injured patients. Each of the 13 measures from the eight tests were found to load on one of three components/factors (identified as visuo-motor scanning, sustained selective processing, and visual/auditory spanning) for the normal as well as the patient group. Comparison of the mean performances of the patients and their matched controls suggested that: (a) severe short-term patients were impaired on the visuo-motor scanning and visual/auditory spanning components; (b) severe long-term patients were impaired only on the visuo-motor scanning component; and (c) mild short-term patients were not impaired on any of the components. The implications of these findings for the measurement of attention are discussed.
Controlled learning with effective cued recall is needed to distinguish between genuine memory deficits due to impairment of specific memory processes and apparent memory deficits due to impairment of other cognitive processes, such as attention, that can limit memory. Effective cued recall is needed for accurate measurement of memory in the elderly because cued recall reveals learning not shown by free recall. When a search procedure was used to control processing for effective encoding and cued recall, nondemented elderly adults recalled all or nearly all 16 items on each trial. Decreased recall by demented patients even after they carried out the same effective processing showed genuine memory impairment that was not due to other cognitive deficits. Cued recall was better than either free recall or recognition in discriminating elderly persons with dementia from those without dementia and by itself accounted for 75 % of the variation in dementia status. Cued recall was especially useful for identifying patients with mild to moderate dementia who were not identified by free recall. It is proposed that elderly persons who have decreased cued recall of a 16‐item list after controlled learning have genuine memory impairment and therefore are likely to be demented because other causes of amnestic syndromes are relatively infrequent in the aged. Controlled learning with effective cued recall should be useful for screening of elderly persons for dementia.
38 elderly control Ss performed better than did 18 patients with moderate Alzheimer's disease (AD), 33 with severe AD, or 12 with Parkinson's dementia (PD) on all measures of the Rey Auditory Verbal Learning Test (RAVLT). The moderate-AD group performed better than did the severe-AD group on the 5 learning trials of List A. Unlike the controls and PD patients, both AD groups showed a greater recency than primacy effect, and both performed equally poorly on recall of List A after List B had been presented. The PD group showed poorer recall on List B than did the moderate-AD group but had better recognition scores than did both AD groups. These findings indicate that the RAVLT is useful in distinguishing between PD and AD. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
(
This reprinted article originally appeared in the Journal of Experimental Psychology,
1935, Vol 18, 643–662. The following abstract of the original article appeared in PA, Vol 10:1863.) In this study pairs of conflicting stimuli, both being inherent aspects of the same symbols, were presented simultaneously (a name of one color printed in the ink of another color—a word stimulus and a color stimulus). The difference in time for reading the words printed in colors and the same words printed in black is the measure of the interference of color stimuli on reading words. The difference in the time for naming the colors in which the words are printed and the same colors printed in squares is the measure of the interference of conflicting word stimuli on naming colors. The interference of conflicting color stimuli on the time for reading 100 words (each word naming a color unlike the ink-color of its print) caused an increase of 2.3 sec or 5.6% over the normal time for reading the same words printed in black. This increase is not reliable, but the interference of conflicting word stimuli on the time for naming 100 colors (each color being the print of a word which names another color) caused an increase of 47.0 sec or 74.3% of the normal time for naming colors printed in squares.… (PsycINFO Database Record (c) 2012 APA, all rights reserved)
There are no standardized diagnostic criteria for psychosis associated with Parkinson's disease (PDPsy). As part of an NIH sponsored workshop, we reviewed the existing literature on PDPsy to provide criteria that distinguish PDPsy from other causes of psychosis. Based on these data, we propose provisional criteria for PDPsy in the style of the Diagnostic and Statistical Manual of Mental Disorders IV-TR. PDPsy has a well-characterized temporal and clinical profile of hallucinations and delusions, which is different than the pattern seen in other psychotic disorders such as substance induced psychosis or schizophrenia. PDPsy is associated with a poor prognosis of chronic psychosis, nursing home placement, and death. Medications used to treat Parkinson's disease (PD) contribute to PDPsy but may not be sufficient or necessary contributors to PDPsy. PDPsy is associated with Lewy bodies pathology, imbalances of monoaminergic neurotransmitters, and visuospatial processing deficits. These findings suggest that PDPsy may result from progression of the disease process underlying PD, rather than a comorbid psychiatric disorder or drug intoxication. PDPsy is not adequately described by existing criteria for psychotic disorders. We established provisional diagnostic criteria that define a constellation of clinical features not shared by other psychotic syndromes. The criteria are inclusive and contain descriptions of the full range of characteristic symptoms, chronology of onset, duration of symptoms, exclusionary diagnoses, and associated features such as dementia. These criteria require validation and may be refined, but form a starting point for studies of the epidemiology and pathophysiology of PDPsy, and are a potential indication for therapy development. © 2007 Movement Disorder Society
Selected aspects of verbal memory and executive function were compared in 11 demented Parkinson's disease (PD) patients and 11 Alzheimer's disease (AD) patients with equally severe dementia, with 11 healthy controls matched for age and education. Semantic and episodic memory were impared in all patients compared with controls, but to a relatively greater degree in AD patients than in those with PD. In contrast, demented PD patients were relatively more compromised on executive tasks. These findings, taken in the context of the neuropathological and neurochemical overlap between demented PD and AD patients, suggest that differences in neurobehavioural patterns in patients with these diseases are relative, rather than absolute.
Reviews previous studies of immediate memory for digits in which exposure time per digit was 1 sec. 3 sec., and results could be derived as percentages correct at each numerosity level. The survey indicates that the channel capacity (>90% correct) of unpracticed adolescents and adults of average and above average intelligence is 6, 1. There is some evidence that, at exposure times of 1 sec/stimulus array, the span of apprehension falls within this same range. (PsycINFO Database Record (c) 2006 APA, all rights reserved).
Elderly control subjects (n = 38) performed better than did patients with moderate Alzheimer's disease (AD; n = 18), severe AD (n = 33), or Parkinson's dementia (PD; n = 12) on all measures of the Rey Auditory Verbal Learning Test (RAVLT). The moderate-AD group performed better than did the severe-AD group on the 5 learning trials of List A. Unlike the controls and PD patients, both AD groups showed a greater recency than primacy effect, and both performed equally poorly on recall of List A after List B had been presented. The PD group showed poorer recall on List B than did the moderate-AD group but had better recognition scores than did both AD groups
Objective.
—To report the distribution of Mini-Mental State Examination (MMSE) scores by age and educational level.Design.
—National Institute of Mental Health Epidemiologic Catchment Area Program surveys conducted between 1980 and 1984.Setting.
—Community populations in New Haven, Conn; Baltimore, Md; St Louis, Mo; Durham, NC; and Los Angeles, Calif.Participants.
—A total of 18 056 adult participants selected by probability sampling within census tracts and households.Main Outcome Measures.
—Summary scores for the MMSE are given in the form of mean, median, and percentile distributions specific for age and educational level.Results.
—The MMSE scores were related to both age and educational level. There was an inverse relationship between MMSE scores and age, ranging from a median of 29 for those 18 to 24 years of age, to 25 for individuals 80 years of age and older. The median MMSE score was 29 for individuals with at least 9 years of schooling, 26 for those with 5 to 8 years of schooling, and 22 for those with 0 to 4 years of schooling.Conclusions.
—Cognitive performance as measured by the MMSE varies within the population by age and education. The cause of this variation has yet to be determined. Mini-Mental State Examination scores should be used to identify current cognitive difficulties and not to make formal diagnoses. The results presented should prove to be useful to clinicians who wish to compare an individual patient's MMSE scores with a population reference group and to researchers making plans for new studies in which cognitive status is a variable of interest.(JAMA. 1993;269:2386-2391)
The concurrent validity of the Hamilton Rating Scale for Depression (HAMD-17) and the Montgomery-Åsberg Depression Rating Scale (MADRS) against the DSM-IV diagnosis ‘depressive disorder’ was assessed in patients with Parkinson's disease (PD). Sixty-three non-demented Parkinson's Disease (PD) patients who attended the outpatient department of an academic hospital were diagnosed according to a standardised research protocol. This protocol consisted of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) to establish the presence or absence of ‘depressive disorder’ according to the DSM-IV criteria, as well as the HAMD-17 and the MADRS. Receiver Operating Characteristics curves (ROC curves) were obtained and the positive and negative predictive values (PPV, NPV) were calculated for different cut-off scores. Maximum discrimination between depressed and non-depressed patients was reached at a cut-off score of 13/14 for the HAMD-17, and at 14/15 for the MADRS. At lower cut-offs, like 11/12 for the HAMD-17 and 14/15 for the MADRS, the high sensitivity and NPV make these scales good screening instruments. At higher cut-offs, such as 16/17 for the HAMD-17 and 17/18 for the MADRS, the high specificity and PPV make these instruments good diagnostic instruments. The diagnostics performance of the HAMD-17 is slightly better than that of the MADRS. This study shows that it is justified to use the HAMD-17 and the MADRS to measure depressive symptoms in both non-depressed and depressed PD patients, to diagnose depressive disorder in PD, and to dichotomize patient samples into depressed and non-depressed groups. Copyright © 2000 John Wiley & Sons, Ltd.
Sorting tasks, requiring the subject to respond selectively, first to one aspect of a situation and then to another, have traditionally been regarded as sensitive indicators of brain injury, but there has been little agreement concerning the effects of lesions in different areas of the brain on sorting behavior. Weigl,36 in 1927, found that braininjured patients performed more poorly than normal control subjects on a simple Color-Form sorting task, and he described a patient with bilateral frontal-lobe damage who had particular difficulty in shifting from one sorting principle to another. Goldstein,6 though rejecting any strict localization of intellectual function, also appears to stress the importance of the frontal lobes for spontaneous shifting, and this view has been further emphasized by such workers as Rylander29 and Halstead.9,10 Yet Teuber, Battersby, and Bender,34 studying men with penetrating missile wounds of the brain, found greater deficits on
Article abstract—Objective: To report the percentile distribution of Mini-Mental State Examination (MMSE) scores in older people by age, sex, and education level, estimated from longitudinal data, after correcting for loss due to dropout. Methods: The Cambridge City over 75 Cohort is a population-based study of a cohort of 2106 subjects age 75 years and older at study entry followed up over 9 years. At each of the four waves, cognitive function was assessed using MMSE. Based on these data, the relationship between age and MMSE score was modeled. Percentile distributions by age, sex, and education level were provided using inverse probability weighting to correct for dropouts. Results: Performance on MMSE was related to age in men and women. In women, at age 75, MMSE score ranged from 21 (10th percentile) to 29 (90th percentile). At age 95, the range was 10 (10th percentile) to 27 (90th percentile). The upper end of MMSE distribution was slightly modified with age, whereas the lower end of the distribution was very sensitive to age effect. A similar pattern was observed in both sexes. Conclusion: These findings provide norms for MMSE scores in subjects age 75 years and older from longitudinal population-based data. Such norms can be used as reference values to determine where an individual's score lies in relation to his or her age, sex, and education level. NEUROLOGY 2000;55:1609 -1613
This report describes normative data for the Boston Diagnostic Aphasia Examination, the “Parietal Lobe Battery” (Goodglass & Kaplan, 1972), and the Boston Naming Test (Kaplan, Goodglass, & Weintraub, 1978). These tests were administered to 147 neurologically normal adult males, who were right-handed and native English-speaking. For each age and education group, means, standard deviations, and the range are reported. The lowest score for each group is suggested as a cut-off below which impairment may be suspected. Differences among age and education groups are specified and briefly discussed.
The record blank enables the examiner to conduct the test without consulting the manual except for scoring and norms, and to record the responses for each item. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
"The Trail Making Test was administered to 200 patients with clear evidence of brain damage and to 84 Ss without anamnestic or clinical evidence of brain damage. The groups were comparable with respect to sex, CA, and… education. The results showed… significant differences in the performances of the two groups for Parts A and B of the test individually as well as for their total. Frequency distributions were given that may serve as preliminary norms for use in evaluating results obtained with individual Ss. Some comments were offered regarding possible reasons why the Trail Making Test differentiated the groups so well, relating known aspects of brain function to the structure and requirements of the test." (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Dementia has been increasingly more recognized to be a common feature in patients with Parkinson's disease (PD), especially in old age. Specific criteria for the clinical diagnosis of dementia associated with PD (PD-D), however, have been lacking. A Task Force, organized by the Movement Disorder Study, was charged with the development of clinical diagnostic criteria for PD-D. The Task Force members were assigned to sub-committees and performed a systematic review of the literature, based on pre-defined selection criteria, in order to identify the epidemiological, clinical, auxillary, and pathological features of PD-D. Clinical diagnostic criteria were then developed based on these findings and group consensus. The incidence of dementia in PD is increased up to six times, point-prevelance is close to 30%, older age and akinetic-rigid form are associated with higher risk. PD-D is characterized by impairment in attention, memory, executive and visuo-spatial functions, behavioral symptoms such as affective changes, hallucinations, and apathy are frequent. There are no specific ancillary investigations for the diagnosis; the main pathological correlate is Lewy body-type degeneration in cerebral cortex and limbic structures. Based on the characteristic features associated with this condition, clinical diagnostic criteria for probable and possible PD-D are proposed. © 2007 Movement Disorder Society
Thesis (Ph. D.)--George Peabody College for Teachers, 1933.
Milner's (1963) report of impaired performance on the Wisconsin Card Sorting Test (WCST) in a group of patients with frontal lobe lesions suggested that this test might be a useful one in the investigation of individual patients with suspected brain lesions. However, for many of our older hospital population the WCST was found to be too difficult and distressing, and also the inherent ambiguities associated with certain responses limited the test's usefulness for research purposes. Therefore, a simpler and less ambiguous modification was devised (MCS) and a new method of measuring perseverative errors proposed. In a group of 53 patients with unilateral cerebral lesions, those with frontal lobe lesions performed less well with the MCST and made a higher proportion of perseverative errors than those with lesions elsewhere: there were no laterality effects in either frontal or non-frontal groups. The usefulness of the MCST for detecting frontal lobe lesions in individual patients was established, and the use of cut-off scores briefly discussed.
The authors examined a consecutive series of 50 patients for the presence of apathy, depression, anxiety, and neuropsychological deficits using a neuropsychological battery that included a recently designed apathy scale. This scale was found to be reliable and valid in the diagnosis of apathy in patients with PD. Of patients in the study, 12% showed apathy as their primary psychiatric problem, and 30% were both apathetic and depressed. Patients with apathy (with or without depression), showed significantly more deficits in both tasks of verbal memory and time-dependent tasks. Results suggest that apathy is a frequent finding in PD, is significantly associated with specific cognitive impairments, and may have a different mechanism than depression.
To investigate differences in severity and specificity of cognitive impairment among various neurodegenerative diseases, we tested groups of patients presenting with senile dementia of the Alzheimer type (SDAT; 44), progressive supranuclear palsy (PSP; 45), Huntington's disease (HD; 35) and Parkinson's disease (PD; 164), with an extensive neuropsychological battery. We found dementia, as defined by a global intellectual performance 2 standard deviations lower than mean control values, in 93% of SDAT, 66% of HD, 58% of PSP, and 18% of PD patients. Specific features of cognitive impairment distinguished the four groups of patients once they were matched for level of intellectual deterioration: remote memory and linguistic disorders in SDAT, frontal lobe-like abnormalities in PSP, concentration and acquisition disorders in HD. There was no specific alteration in demented PD patients. This study demonstrates the frequency of dementia in predominantly subcortical degenerative diseases and indicates that "subcortical dementia," rather than being a homogeneous entity, should be divided into specific subtypes of cognitive impairment related to different underlying specific lesions of each disease.
To investigate differences in severity and specificity of cognitive impairment among various neurodegenerative diseases, we tested groups of patients presenting with senile dementia of the Alzheimer's type (SDAT) (n = 44), progressive supranuclear palsy (PSP) (n = 45), Huntington's disease (HD) (n = 35), and Parkinson's disease (PD) (n = 164), with an extensive neuropsychologic battery. We found dementia, as defined by a global intellectual performance 2 SD lower than mean control values, in 93% of patients with SDAT, 66% of patients with HD, 58% of patients with PSP, and 18% of patients with PD. Specific features of cognitive impairment distinguished the four groups of patients once they were matched for level of intellectual deterioration. This study shows the frequency of dementia in predominantly subcortical degenerative diseases and indicates that "subcortical dementia," rather than being a homogeneous entity, should be divided into specific subtypes of cognitive impairment related to different underlying pathology.
Current knowledge of cognitive dysfunction in Parkinson's disease (PD) has largely been obtained from studies of chronically treated patients in whom effects of disease chronicity, treatment, depression and dementia are confounding factors. Studies of untreated patients have examined few cognitive domains and relationships between cognition, depression and motor disability have been incompletely explored. Accordingly, we studied 60 consecutive patients with newly diagnosed, untreated, idiopathic PD and 37 matched, healthy control subjects; no subject had clinical dementia or depression. All subjects received tests of specific processes of memory and cognition, including working memory, verbal and non-verbal short- and long-term memory, language, visuospatial capacity, set-formation and shifting and sequencing. Patients also received quantitative global clinical measures of severity of dementia, depression and motor disability. The PD group as a whole showed deficits in immediate recall of verbal material, language production and semantic fluency, set-formation, cognitive sequencing and working memory and visuomotor construction. However, this group was unimpaired in immediate memory span, long-term forgetting, naming, comprehension and visual perception. Language deficits and more severe frontal lobe impairments were confined to those PD patients scoring abnormally on a Mini Mental State examination. Motor disability correlated strongly with severity of depression but weakly with cognitive impairment. Cognitive sequencing, set-formation and set-shifting deficits tended to associate with depression, but otherwise there was no association between cognition and depression. The results indicate dissociation of cognition and motor control in early PD which suggests that cognitive dysfunction is largely independent of frontostriatal dopamine deficiency underlying motor disability. Some, but not all, of the frontal lobe deficits of chronic disease are detectable in early, untreated PD. The pathogenesis of the cognitive deficits shown here appears to involve extrastriatal dopamine systems or non-dopaminergic pathology. Longitudinal study is necessary to determine whether increasing disease duration exacerbates the early cognitive deficits and affects new cognitive domains, in addition to producing increasing motor disability.
We have tested a simple and reliable measure of visuospatial ability in Alzheimer patients--the Clock Drawing Test. To determine the usefulness of this measure, we asked 67 Alzheimer patients and 83 normal controls to draw the face of a clock reading the time of 2:45. Six independent observers blindly evaluated the results with ratings from 10 (best) to 1 (worst). The mean performance score of Alzheimer subjects was 4.9 +/- 2.7 compared to 8.7 +/- 1.1 for normal controls (P less than .001). Inter-rater reliability for the clocks drawn by Alzheimer patients was highly significant (r = 0.86; P less than .001), and there was relatively little overlap between ratings for Alzheimer patients and normal controls. Furthermore, correlations were highly significant (P less than .001) between the mean score of clock drawings and three independent global measures of dementia severity. Although the Clock Drawing Test is certainly not a definitive indicator of Alzheimer's disease, the test is easy to administer and provides a useful measure of dementia severity for both research and office settings where sophisticated neuropsychological testing is not available.
Speech and language alterations were assessed in 51 patients with Parkinson's disease (PD) and 10 patients with dementia of the Alzheimer type (DAT). Thirty-five of the PD patients had no evidence of intellectual impairment on a conventional mental status questionnaire and 16 of the PD patients had dementia syndromes of comparable severity to the DAT patients. DAT produced significantly greater language disturbances, including anomia, decreased information content of spontaneous speech, and diminished word list generation. PD patients had significantly decreased phrase length, impaired speech melody, dysarthria, and agraphia. The results suggest that the dementia of PD is distinguishable from that of DAT:PD patients have prominent motor speech abnormalities, whereas DAT patients exhibit more profound language alterations.
The cognitive, memory and psychomotor performance of 67 patients with Parkinson's disease who had not received any antiparkinson medication was compared with the performance of 43 healthy subjects matched by age and education. The principal impairments in the patients were motor ones, evident in various tests such as general motor slowness and delayed initiation of movement, and they correlated with clinical rigidity and hypokinesia but not with tremor. The performance of the patients was inferior to that of the controls in memory tests involving the processing of information and learning (logical memory, associative learning) but not in less demanding tasks such as the retrieval of numbers. The total disability was due to a combined effect of aging and disease. A decrease of about 15% in the psychomotor and cognitive performance, related to aging alone, can be expected to occur between the ages of 50 and 70. The performance of the patients in memory tests and other tests evaluating cognitive capacity did not correlate either with their motor disability or with their mood. A possibility therefore exists that biological processes behind the cognitive decline and the motor disability are separate, even if they may occur simultaneously.
A type of pathological behavior, imitation behavior (IB), is newly described. In this behavior patients imitate the examiner's gestures, although not instructed to do so. Patients explain that they thought they had to imitate the examiner. IB is the first stage of utilization behavior (UB). Neuropsychological examination of 40 patients with IB, of 35 with UB, and of 50 disease controls demonstrates the existence of a frontal syndrome and two determining features of such behavior: dependence on (1) the social and (2) the physical environments. Loss of intellectual control was also required for the occurrence of such behavior. UB and/or IB were present in 96% of the 29 patients with focal lesions of the frontal lobes. Computed tomographic scans in 26 of these patients showed involvement of the inferior half of the anterior part of one or both frontal lobes. IB and UB are interpreted as release of parietal lobe activities, resulting from impairment of frontal lobe inhibition.
In two experiments with an Odd-Man-Out choice discrimination task, Parkinsonian subjects had difficulty in alternating between two rules on successive trials. The pattern of errors suggested that the difficulty arises from an instability of cognitive set rather than any loss of reasoning ability, perseveration or increased distractibility.
As part of a study of dementia, 162 normal volunteers in the age range of 65-84 years were given a battery of nine neuropsychological tests assessing temporal orientation, short-term memory, language functions, and visuoperceptive capacity. When compared to subjects less than 65 years of age, the groups showed little evidence of generalized decline in cognitive function before the age of 80 years. The 80-84 years subgroup showed a higher overall failure rate on the tests than the younger subgroups. Nevertheless, 70% of all subjects in the 80-84 years subgroup made no more than one failure on the nine tests. There were substantial differences among the tests in respect to their sensitivity to the effects of aging. The largest decline in performance was shown on tests of short-term visual memory, serial digit learning, and facial recognition. The other verbal, memory, and visuoperceptive tests were performed well up to the age of 80 years. The findings are interpreted as providing limited support for the hypothesis that normal aging does not necessarily involve a general decline in level of cognitive functioning. The clinical application of the tests that were sensitive or insensitive to the effects of aging is considered.
The goal of this study was to characterize the changes in cognition associated with the earliest, or preclinical, stages of dementia in Parkinson's disease (PD). We administered a comprehensive neuropsychological test battery to a group of initially nondemented PD patients participating in a longitudinal community-based epidemiologic study. We used Cox proportional hazards models to assess the relative risk of incident dementia associated with baseline scores on the neuropsychological tests. Baseline performance on two verbal fluency tasks (letter fluency and category fluency) was significantly and independently associated with incident dementia. Tests of memory, orientation, abstract reasoning, naming, and constructional skill were less sensitive predictors of subsequent dementia. The neuropsychological pattern characterizing the preclinical stages of dementia in PD differed from that described previously in preclinical Alzheimer's disease. Results suggest that poor performance on tests of verbal fluency may represent a distinct characteristic of the preclinical phase of dementia in PD.