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Cognitive impairments in advanced PD without dementia
Abstract
To determine the nature and frequency of cognitive impairments in nondemented patients with advanced PD and their relationship to other variables potentially predictive of neuropsychological performance.
The neuropsychological performance of nondemented, nondepressed patients with idiopathic PD (n = 61) was quantified with respect to clinically available normative data. The relationship of neuropsychological measures to motor symptoms, age, years of education, disease duration, age at disease onset, disease deterioration rate, and dopaminergic therapy was assessed.
Impairment was most frequent on measures sensitive to frontal lobe function (67% on Wisconsin Card Sorting Test number of categories, 30% on letter fluency, 30% on verbal learning). Poorer performance on multiple neuropsychological measures was related to greater overall motor abnormality (total Unified Parkinson's Disease Rating Scale score), increased bradykinesia on medication, older age, longer disease duration, and reduced education.
Even in the absence of dementia or depression, patients with advanced PD are likely to show clinically significant impairments on neuropsychological measures sensitive to changes in dorsolateral prefrontal regions participating in cognitive basal ganglia-thalamocortical circuits.
... There is a large body of literature relative to cognitive impairments in PD without dementia. The more consistently reported domains of impairment include: 1) impaired verbal fluency for semantic categories, phonemes and action words (Benito-Leon et al. 2011;Green et al. 2002;Elgh et al. 2009;Henry and Crawford 2004;Muslimovic et al. 2005;Pagonabarraga and Kulisevsky 2012;Rodriguez-Ferreiro et al. 2010) 2) impaired attention (e.g., activation, sustained, setshifting) (Elgh et al. 2009;Green et al. 2002;Muslimovic et al. 2005;Pagonabarraga and Kulisevsky 2012), 3) impaired working memory (Muslimovic et al. 2005) 4) impaired psychomotor speed (Elgh et al. 2009;Muslimovic et al. 2005) 5) impaired verbal and visual memory (Benito-Leon et al. 2011;Bohlhalter et al. 2009;Elgh et al. 2009;Ivory et al. 1999;Muslimovic et al. 2005;Pagonabarraga and Kulisevsky 2012) and 6) impaired visual construction/visual perceptual skills (Pagonabarraga and Kulisevsky, 2012). The cognitive impairments observed in PDD and DLB are similar to those reported in PD except that they are more ubiquitous in these disorders and more severe in impairment. ...
... There is a large body of literature relative to cognitive impairments in PD without dementia. The more consistently reported domains of impairment include: 1) impaired verbal fluency for semantic categories, phonemes and action words (Benito-Leon et al. 2011;Green et al. 2002;Elgh et al. 2009;Henry and Crawford 2004;Muslimovic et al. 2005;Pagonabarraga and Kulisevsky 2012;Rodriguez-Ferreiro et al. 2010) 2) impaired attention (e.g., activation, sustained, setshifting) (Elgh et al. 2009;Green et al. 2002;Muslimovic et al. 2005;Pagonabarraga and Kulisevsky 2012), 3) impaired working memory (Muslimovic et al. 2005) 4) impaired psychomotor speed (Elgh et al. 2009;Muslimovic et al. 2005) 5) impaired verbal and visual memory (Benito-Leon et al. 2011;Bohlhalter et al. 2009;Elgh et al. 2009;Ivory et al. 1999;Muslimovic et al. 2005;Pagonabarraga and Kulisevsky 2012) and 6) impaired visual construction/visual perceptual skills (Pagonabarraga and Kulisevsky, 2012). The cognitive impairments observed in PDD and DLB are similar to those reported in PD except that they are more ubiquitous in these disorders and more severe in impairment. ...
... The motor speech problems in PD negatively affect conversational discourse by altering listeners' perceptions of speakers with PD wherein listeners rate persons with PD as less interested, less involved, less happy, less friendly, and more anxious (Pitcairn et al. 1990;Jaywant and Pell 2010). While investigators have not explored specifically the phenomenon of motor speech problems in PDD and DLB, there is evidence to suggest that worsening motor impairment, including declining motor speech performance, is associated with risk of developing cognitive decline or dementia in PD (Burn et al. 2003;Elgh et al. 2009;Gago et al. 2009;Green et al. 2002;Verbaan et al. 2007;Locascio, Corkin, and Growdon 2003;Sollinger et al. 2010 ...
... Estas investigaciones han sugerido que los déficits cognoscitivos en la EP no reflejan problemas en el funcionamiento de los ganglios basales sino una desconexión a los lóbulos frontales. Se ha sugerido que las desconexiones fronto-talámicas explican la pérdida de espontaneidad e imaginación y la falta de iniciativa que presentan los pacientes con EP 31 . En un cuestionario de funciones cotidianas los pacientes con EP fueron clasificados diferentes a los normales en conductas relacionadas a la iniciativa, conductas estereotipadas, indiferencia, desinterés, dependencia social, y control intelectual. ...
... El enlentecimiento para dar respuestas y la tendencia a verbalizar pero no ejecutar movimientos correctos puede también dar evidencia del involucramiento de los lóbulos frontales en la EP. Existen también otras evidencias empíricas que señalan deficiencias en funciones mediadas por los lóbulos frontales, como son las respuestas demoradas y cambios en el set mental 31 . ...
... alteración en la secuenciación, trastornos en la formación de conceptos, dificultad en la inhibición de estímulos periféricos, tendencia a las alteraciones en el mantenimiento de la atención. Todo ello desencadena una conducta caracterizada por la lentificación de las tareas cognitivas, tanto en su aspecto de análisis aferente como en la ejecución, con un notable aumento en el tiempo de procesamiento de la información 31 . ...
... Different from the core features of MSA including autonomic dysfunction, parkinsonism or cerebellar ataxia, cognitive impairment in MSA is clinically heterogeneous and its neuropathological substrate remains uncertain. In addition, in contrast to increased awareness of cognitive impairment in Parkinson's disease (Green et al., 2002;Aarsland and Kurz, 2010), cognitive impairment has been underestimated and under-investigated as a clinical feature of MSA. Although the estimated prevalence of cognitive impairment in patients MSA varies depending on retrospective post-mortem studies with different settings, 22-37% of patients with pathologically proven MSA were reported to have developed some degree of cognitive impairment during the course of their illness (Wenning et al., 1997;Cykowski et al., 2015;Koga et al., 2015Koga et al., , 2017. ...
... The remaining 21% had other pathological conditions, mainly Parkinson's disease or progressive supranuclear palsy. These findings suggest that many studies of cognitive impairment using clinically diagnosed MSA patients may erroneously include Parkinson's disease or progressive supranuclear palsy cases, in which cognitive impairment is more prevalent (Green et al., 2002;Aarsland and Kurz, 2010;Brown et al., 2010;Miki et al., 2019). Therefore, differences in the criteria for cognitive impairment, other sampling criteria and clinical settings between our study and others are likely to contribute to discrepancies in the prevalence of cognitive impairment. ...
Recent post-mortem studies reported 22-37% of patients with multiple system atrophy can develop cognitive impairment. With the aim of identifying associations between cognitive impairment including memory impairment and α-synuclein pathology, 148 consecutive patients with pathologically proven multiple system atrophy were reviewed. Among them, 118 (79.7%) were reported to have had normal cognition in life, whereas the remaining 30 (20.3%) developed cognitive impairment. Twelve of them had pure frontal-subcortical dysfunction, defined as the presence of executive dysfunction, impaired processing speed, personality change, disinhibition or stereotypy; six had pure memory impairment; and 12 had both types of impairment. Semi-quantitative analysis of neuronal cytoplasmic inclusions in the hippocampus and parahippocampus revealed a disease duration-related increase in neuronal cytoplasmic inclusions in the dentate gyrus and cornu ammonis regions 1 and 2 of patients with normal cognition. In contrast, such a correlation with disease duration was not found in patients with cognitive impairment. Compared to the patients with normal cognition, patients with memory impairment (pure memory impairment: n = 6; memory impairment + frontal-subcortical dysfunction: n = 12) had more neuronal cytoplasmic inclusions in the dentate gyrus, cornu ammonis regions 1-4 and entorhinal cortex. In the multiple system atrophy mixed pathological subgroup, which equally affects the striatonigral and olivopontocerebellar systems, patients with the same combination of memory impairment developed more neuronal inclusions in the dentate gyrus, cornu ammonis regions 1, 2 and 4, and the subiculum compared to patients with normal cognition. Using patients with normal cognition (n = 18), frontal-subcortical dysfunction (n = 12) and memory impairment + frontal-subcortical dysfunction (n = 18), we further investigated whether neuronal or glial cytoplasmic inclusions in the prefrontal, temporal and cingulate cortices or the underlying white matter might affect cognitive impairment in patients with multiple system atrophy. We also examined topographic correlates of frontal-subcortical dysfunction with other clinical symptoms. Although no differences in neuronal or glial cytoplasmic inclusions were identified between the groups in the regions examined, frontal release signs were found more commonly when patients developed frontal-subcortical dysfunction, indicating the involvement of the frontal-subcortical circuit in the pathogenesis of frontal-subcortical dysfunction. Here, investigating cognitive impairment in the largest number of pathologically proven multiple system atrophy cases described to date, we provide evidence that neuronal cytoplasmic inclusion burden in the hippocampus and parahippocampus is associated with the occurrence of memory impairment in multiple system atrophy. Further investigation is necessary to identify the underlying pathological basis of frontal-subcortical dysfunction in multiple system atrophy.
... C'est notamment l'interface entre le striatum et le système régulateur des neurones dopaminergiques du mésencéphale qui, organisée en « spirales ascendantes », permet aux différentes parties du striatum de faire circuler l'information quelle que soit sa nature ( Figure 6). Enfin, la maladie de Parkinson entraîne un déficit dans la gestion spontanée des stratégies d'encodage et de rappel des informations en mémoire (Green et al., 2002). Fournir aux patients des éléments utiles à l'élaboration de ces stratégies de façon explicite (sous forme d'indices) revient à rendre comparables leurs performances à celles de sujets témoins (Brown & Marsden, 1988;Defebvre & Vérin, 2015). ...
... Les patients ont besoin de plus de temps pour réfléchir et tout mécanisme se réalise suite à un effort volontaire(Defebvre & Vérin, 2015). Les capacités de résistance à l'interférence avec un maintien efficace du plan d'action et l'inhibition des informations non pertinentes sont aussi impactées par la maladie avec une sensibilité plus grande à l'interférence(Green et al., 2002). Les capacités d'attention soutenue semblent conservées. ...
La maladie de Parkinson est une affection neurodégénérative principalement associée à la dégénérescence progressive des neurones dopaminergiques du mésencéphale provoquant un dysfonctionnement des noyaux gris centraux. En parallèle de symptômes moteurs bien connus, cette affection entraîne également l’émergence de déficits émotionnels impactant en outre l’expression et la reconnaissance des émotions. Ici, se pose la question d’un déficit de reconnaissance des émotions faciales chez les patients parkinsoniens lié au moins en partie aux troubles moteurs. En effet, selon les théories de simulation des émotions, copier les émotions de l’autre nous permettrait de mieux les reconnaître. Ce serait le rôle du mimétisme facial. Automatique et inconscient, ce phénomène est caractérisé par des réactions musculaires congruentes à l’émotion exprimée par autrui. Dans ce contexte, une perturbation des capacités motrices pourrait conduire à une altération des capacités de reconnaissance des émotions. Or, l’un des symptômes moteurs les plus fréquents dans la maladie de Parkinson, l’amimie faciale, consiste en une perte de la mobilité des muscles du visage. Ainsi, nous avons examiné l’efficience du mimétisme facial dans la maladie de Parkinson, son influence sur la qualité du processus de reconnaissance des émotions, ainsi que l’effet du traitement dopaminergique antiparkinsonien sur ces processus. Pour cela, nous avons développé un paradigme permettant l’évaluation simultanée des capacités de reconnaissance et de mimétisme (corrugator supercilii, zygomaticus major et orbicularis oculi) d’émotions exprimées sur des visages dynamiques (joie, colère, neutre). Cette expérience a été proposée à un groupe de patients parkinsoniens comparé à un groupe de sujets sains témoins. Nos résultats supportent l’hypothèse selon laquelle le déficit de reconnaissance des émotions chez le patient parkinsonien pourrait résulter d’un système « bruité » au sein duquel le mimétisme facial participerait. Cependant, l’altération du mimétisme facial dans la maladie de Parkinson et son influence sur la reconnaissance des émotions dépendraient des muscles impliqués dans l’expression à reconnaître. En effet, ce serait davantage le relâchement du corrugateur plutôt que les contractions du zygomatique ou de l’orbiculaire de l’œil qui nous aiderait à bien reconnaître les expressions de joie. D’un autre côté, rien ne nous permet ici de confirmer l’influence du mimétisme facial sur la reconnaissance des expressions de colère. Enfin, nous avons proposé cette expérience à des patients en condition de traitement habituel et après une interruption temporaire de traitement. Les résultats préliminaires de cette étude apportent des éléments en faveur d’un effet bénéfique du traitement dopaminergique tant sur la reconnaissance des émotions que sur les capacités de mimétisme. L’hypothèse d’un effet bénéfique dit « périphérique » sur la reconnaissance des émotions par restauration du mimétisme facial reste à tester à ce jour. Nous discutons l’ensemble de ces résultats selon les conceptions récentes sur le rôle des noyaux gris centraux et sous l’angle de l’hypothèse de feedback facial.
... Many studies have demonstrated that MCI is present in patients with PD at various stages of their illness (Green et al. 2002;Emre 2003;Janvin et al. 2003Janvin et al. , 2006Foltynie et al. 2004;Muslimovic et al. 2005). Deficits in executive function tasks requiring the integrity of the frontostriatal pathway, episodic memory impairment, as well as visuospatial and visuoperceptual dysfunctions have often been reported in PD (Helkala et al. 1988;Levin et al. 1991;Green et al. 2002;Emre 2003;Janvin et al. 2003;Foltynie et al. 2004;Muslimovic et al. 2005). ...
... Many studies have demonstrated that MCI is present in patients with PD at various stages of their illness (Green et al. 2002;Emre 2003;Janvin et al. 2003Janvin et al. , 2006Foltynie et al. 2004;Muslimovic et al. 2005). Deficits in executive function tasks requiring the integrity of the frontostriatal pathway, episodic memory impairment, as well as visuospatial and visuoperceptual dysfunctions have often been reported in PD (Helkala et al. 1988;Levin et al. 1991;Green et al. 2002;Emre 2003;Janvin et al. 2003;Foltynie et al. 2004;Muslimovic et al. 2005). ...
Central cholinergic dysfunction has been reported in patients with Parkinson& s disease (PD) and hallucinations by evaluating short latency afferent inhibition (SAI), a transcranial magnetic stimulation protocol which gives the possibility to test an inhibitory cholinergic circuit in the human brain. REM sleep behavior disorder (RBD) was also found to be associated with cognitive impairment in PD patients. The objective of the study was to assess the cholinergic function, as measured by SAI, in PD patients with RBD (PD-RBD) and PD patients without RBD (PD-nRBD). We applied the SAI technique in 10 PD-RBD patients, in 13 PD-nRBD patients and in 15 age-matched normal controls. All PD patients and control subjects also underwent a comprehensive battery of neu-ropsychological tests. Mean SAI was significantly reduced in PD-RBD patients when compared with PD-nRBD patients and controls. Neuropsychological examination showed mild cognitive impairment in 9 out of the 10 PD-RBD patients, and in 5 out of the 13 PD-nRBD. SAI values correlated positively with neuropsychological tests measuring episodic verbal memory, executive functions, visuoconstructional and visuoperceptual abilities. Similar to that previously reported in the idiopathic form of RBD, SAI abnormalities suggest a cholinergic dysfunction in PD patients who develop cognitive impairment, and present findings indicate that RBD is an important determinant of MCI in PD.
... 60 The most affected cognitive domains in PD are executive function, visuospatial processes, and attention. 61 Full-blown dementia suggests a more widespread and dense PD pathology, which not only represents a marker to a less robust motor response to DBS but most of all, a risk for further worsening of cognitive status in the short and long-term follow-up after DBS surgery. 51,62 Additionally, patients with mild cognitive impairment preoperatively appear to be at the highest risk for cognitive deterioration after surgery and should be evaluated individually with caution. ...
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.
... Asimismo, se ha reportado en pacientes con EP la degeneración de neuronas colinérgicas del núcleo basalis de Meynert (Ch4) que proyectan a la corteza frontal, el hipocampo y el accumbens, siendo ésta alteración más severa en la DEP (Gaspar & Gray, 1984). En contraste con lo anterior, las alteraciones cognitivas de pacientes con EP no demenciados se han relacionado principalmente con la disfunción de los circuitos frontoestriatales (Dubois & Pillon, 1997) asociada a la deficiencia dopaminérgica (Halliday et al., 2014), ya que los circuitos que establecen la corteza prefrontal dorsolateral y orbital con el núcleo caudado son de especial relevancia para el funcionamiento cognitivo (Green et al., 2002). Aunado a lo anterior, la denervación colinérgica a nivel neocortical también se ha asociado a los déficits cognitivos presentes en la EP sin demencia (Bohnen et al., 2006;Bohnen et al., 2012). ...
La enfermedad de Parkinson (EP) incluye diversos síntomas motores y no motores.Se ha demostrado la eficacia de la estimulación cerebral profunda(DBS)sobre los síntomas motores, pero el efecto sobre los no motores ha sido materia de controversia.La EP de inicio temprano (EPIT) es una variante EP que inicia antes de los 50 años. Las características neuropsicológicas de la EPIT han sido poco estudiadas y el efecto de la DBS sobre éstas es desconocido. Objetivo: Describir las características neuropsicológicas, la frecuencia de deterioro cognitivo leve (DCL)y demencia (DEP)en la EPIT. Determinar si la DBS tiene algún efecto sobre el estado de ánimo y la cognición de estos pacientes. Material y Métodos: Se evaluó a81 pacientes con EPIT y se describió su rendimiento en tareas de atención, memoria, funciones visuoespaciales, funciones ejecutivas y lenguaje;se determinó la frecuencia de DCL y DEP; se calculó la frecuencia de pacientes con síntomas depresivos.Un grupo de 15 pacientes sometidos a DBS fueron reevaluados un año posterior al procedimiento. Se determinó si existió un cambio significativo en alguna de las variables neuropsicológicas tras el procedimiento.Resultados: Ningún paciente presentó DEP,el 31% cumplió criterios para DCL. Los dominios más afectados fueron el visuoespacial, mnésico y la flexibilidad cognitiva. Más del 50% de la muestra presentó sintomatología depresiva.No existieron diferencias significativas entre el grupo pre y postquirúrgico en ninguna medida neuropsicológica;el porcentaje de pacientes con mayor capacidad en AVD incrementó posterior a la cirugía. Existió una tendencia a la mejoría en los niveles de ansiedad en el estado postquirúrgico. Conclusiones: el DCL es común en la EPIT pero no se asoció a los factores de riesgo reportados en pacientes con un inicio tardío. La DBS en pacientes con EPIT no tuvo efecto consistente sobre variables cognitivas y psiquiátricas, no obstante el análisis individual muestra gran variabilidad.
... (Albin-Delong classic model). In addition, Nambu et al. (2002) described the "hyper-direct" pathway, a fast pathway forming a loop from the cortex that has a glutamatergic excitatory connection to the GPi via the STN and stimulates the GPi which then inhibits the thalamus and neocortex (Nambu et al., 2002). The main pathological hallmark of PD is the neurodegeneration of SNc dopaminergic neurons (Yelnik, 2002). ...
Deep brain stimulation (DBS) is among the most successful paradigms in both translational and reverse translational neuroscience. DBS has developed into a standard treatment for movement disorders such as Parkinson’s disease (PD) in recent decades, however, specific mechanisms behind DBS’s efficacy and side effects remain unrevealed. Several hypotheses have been proposed, including neuronal firing rate and pattern theories that emphasize the impact of DBS on local circuitry but detail distant electrophysiological readouts to a lesser extent. Furthermore, ample preclinical and clinical evidence indicates that DBS influences neurotransmitter dynamics in PD, particularly the effects of subthalamic nucleus (STN) DBS on striatal dopaminergic and glutamatergic systems; pallidum DBS on striatal dopaminergic and GABAergic systems; pedunculopontine nucleus DBS on cholinergic systems; and STN-DBS on locus coeruleus (LC) noradrenergic system. DBS has additionally been associated with mood-related side effects within brainstem serotoninergic systems in response to STN-DBS. Still, addressing the mechanisms of DBS on neurotransmitters’ dynamics is commonly overlooked due to its practical difficulties in monitoring real-time changes in remote areas. Given that electrical stimulation alters neurotransmitter release in local and remote regions, it eventually exhibits changes in specific neuronal functions. Consequently, such changes lead to further modulation, synthesis, and release of neurotransmitters. This narrative review discusses the main neurotransmitter dynamics in PD and their role in mediating DBS effects from preclinical and clinical data.
... The finding implies that the uncinate fasciculus might be more susceptible to neurodegeneration in PD. Consistently, the dysfunction of executive control was found to be the characteristic cognitive deficit in PD (Green et al., 2002), which was presumably related to the altered integrity of the uncinate fasciculus that interacted with the control systems in the prefrontal areas (Di Tella et al., 2020). ...
Multiple system atrophy (MSA) and Parkinson’s disease (PD) belong to alpha-synucleinopathy, but they have very different clinical courses and prognoses. An imaging biomarker that can differentiate between the two diseases early in the disease course is desirable for appropriate treatment. Neuroimaging-based brain age paradigm provides an individualized marker to differentiate aberrant brain aging patterns in neurodegenerative diseases. In this study, patients with MSA (N = 23), PD (N = 33), and healthy controls (N = 34; HC) were recruited. A deep learning approach was used to estimate brain-predicted age difference (PAD) of gray matter (GM) and white matter (WM) based on image features extracted from T1-weighted and diffusion-weighted magnetic resonance images, respectively. Spatial normative models of image features were utilized to quantify neuroanatomical impairments in patients, which were then used to estimate the contributions of image features to brain age measures. For PAD of GM (GM-PAD), patients with MSA had significantly older brain age (9.33 years) than those with PD (0.75 years; P = 0.002) and HC (-1.47 years; P
... For none of the cognitive tests was the interaction Time × Age significant. However, as age at diagnosis has been shown to predict progression of cognitive decline in previous studies (Green et al. 2002;Santangelo et al. 2015), we present estimates of decline slopes for two age groups as supplemental material: young patients (below the median of age at first diagnosis in our sample: 65.6 years) and older patients (above the median value). With the exception of Stroop-Interference, all cognitive performances showed a steeper decline for the old-age onset group (Supplementary Table 3). ...
Cognitive impairment and dementia are common non-motor symptoms in Parkinson’s disease (PD). To elucidate the potentially typical progression of cognitive decline in PD and its variation, we retrospectively surveyed neuropsychological data obtained at the Parkinson-Klinik Ortenau, Germany in the years 1996–2015. Many of the patients in the surveyed period were repeatedly admitted to our clinic and we were thus able to compile neuropsychological re-test data for 252 patients obtained at varying time intervals. Neuropsychological testing was conducted with the NAI (Nürnberger Alters-Inventar). This battery provides sub-tests that examine cognitive processing speed, executive function, working memory, and verbal/visual memory functions. The re-test time span varied across patients from below 1 year up to about 12 years. Most patients were seen twice, but some patients were tested up to eight times. The steepest rates of cognitive decline were observed for the NAI sub-tests Trail-Making, Maze Test, and Stroop-Word Reading/Color Naming. Intermediate rates of decline were found for Digit Span, Word List—Immediate Recall, and Picture Test. Stroop Test—Interference, Word List—Delayed Recognition, and Figure Test exhibited the slowest decline rates. We did not observe a significant effect of age at diagnosis or gender on the rate of decline. In sum, this study retrospectively evaluated cognitive decline in a sample of patients with PD. Our data suggest a broad cognitive decline that particularly affects the cognitive capacities for processing speed, executive functions, and immediate memory functions.
... The authors concluded that a decrease in MMSE scores between the disease stages 3 to 6 raises the risk of developing dementia during PD progression (Ross et al., 1996;Braak et al., 2005). However, in some patients, cognitive decline develops in the absence of substantial PD-related cortical pathology and, on the contrary, in other patients, extensive cortical neuropathology does not unavoidably lead to cognitive decline and dementia (Green et al., 2002;Braak et al., 2005;Leverenz et al., 2009). Further studies have given more insight into the mechanisms and morphological correlations of cognitive impairment progression to dementia (Aybek et al., 2009;Foster et al., 2013;Aarsland et al., 2017;Lanskey et al., 2018). ...
Parkinson’s disease (PD) is a neurodegenerative condition characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) in the midbrain resulting in progressive impairment in cognitive and motor abilities. The physiological and molecular mechanisms triggering dopaminergic neuronal loss are not entirely defined. PD occurrence is associated with various genetic and environmental factors causing inflammation and mitochondrial dysfunction in the brain, leading to oxidative stress, proteinopathy, and reduced viability of dopaminergic neurons. Oxidative stress affects the conformation and function of ions, proteins, and lipids, provoking mitochondrial DNA (mtDNA) mutation and dysfunction. The disruption of protein homeostasis induces the aggregation of alpha-synuclein (α-SYN) and parkin and a deficit in proteasome degradation. Also, oxidative stress affects dopamine release by activating ATP-sensitive potassium channels. The cholinergic system is essential in modulating the striatal cells regulating cognitive and motor functions. Several muscarinic acetylcholine receptors (mAChR) and nicotinic acetylcholine receptors (nAChRs) are expressed in the striatum. The nAChRs signaling reduces neuroinflammation and facilitates neuronal survival, neurotransmitter release, and synaptic plasticity. Since there is a deficit in the nAChRs in PD, inhibiting nAChRs loss in the striatum may help prevent dopaminergic neurons loss in the striatum and its pathological consequences. The nAChRs can also stimulate other brain cells supporting cognitive and motor functions. This review discusses the cholinergic system as a therapeutic target of cotinine to prevent cognitive symptoms and transition to dementia in PD.
... Apart from the mobility distortions, patients experience cognitive symptoms associated with different skills and functions that increment the risk of social isolation and the consequent burden to caregivers. The cognitive decline includes diverse damages in executive functions, including attention, short-term memory loss, planning, or reasoning (Green et al., 2002). ...
Parkinson's disease and Alzheimer's disease are progressive nervous system disorders that affect physical and cognitive capacities of individuals, including memory loss, motion impairment, or problem-solving dysfunctions. Leisure activities are associated with reducing the risk of dementia and are preventive policies for delaying the cognitive impairment in later stages of those neurodegenerative diseases. Electronic games related to cognitive abilities are an easy and inexpensive alternative for stimulating brain activity in this kind of patients. The previous research demonstrated the acceptance of these activities in the environment of Connected TV when playing at home and in daily care centers. Interaction in Connected TV applications has its own particularities that influence the design of the interface, including the viewing distance, the type of interaction through a remote control or other techniques, the size of the screen, or the collectiveness of consumption. Iterative testing with patients of these groups revealed how the physical characteristics and cognitive impairment of these concrete end-users affect the human–computer interaction, offering guidelines and recommendations in good practices for the Smart TV interface design. On the other hand, data analytics extracted from the interaction and evolution of the game offer important information enabling the creation of estimation prediction models about the cognitive state of the patient.
... (Kempster et al. 2010), so the relative infrequency of hallucinations may have favoured misdiagnosis of LBD cases as MSA-P. Dementia is a common clinical manifestation in idiopathic PD with a cumulative incidence approaching 80% (Green et al., 2002;Aarsland and Kurz, 2010). In the present study, 46% of patients with LBD developed dementia during the disease course. ...
Clinical diagnosis of multiple system atrophy is challenging and many patients with Lewy body disease (i.e. Parkinson's disease or dementia with Lewy bodies) or progressive supranuclear palsy are misdiagnosed as having multiple system atrophy in life. The clinical records of 203 patients with a clinical diagnosis of multiple system atrophy were reviewed to identify diagnostic pitfalls. We also examined 12 features supporting a diagnosis of multiple system atrophy (red flag features: orofacial dystonia, disproportionate antecollis, camptocormia and/or Pisa syndrome, contractures of hands or feet, inspiratory sighs, severe dysphonia, severe dysarthria, snoring, cold hands and feet, pathological laughter and crying, jerky myoclonic postural/action tremor and polyminimyoclonus) and seven disability milestones (frequent falls, use of urinary catheters, wheelchair dependent, unintelligible speech, cognitive impairment, severe dysphagia, residential care). Of 203 cases, 160 (78.8%) were correctly diagnosed in life and had pathologically confirmed multiple system atrophy. The remaining 21.2% (43/203) had alternative pathological diagnoses including Lewy body disease (12.8%; n = 26), progressive supranuclear palsy (6.4%; n = 13), cerebrovascular diseases (1%; n = 2), amyotrophic lateral sclerosis (0.5%; n = 1) and cerebellar degeneration (0.5%; n = 1). More patients with multiple system atrophy developed ataxia, stridor, dysphagia and falls than patients with Lewy body disease; resting tremor, pill-rolling tremor and hallucinations were more frequent in Lewy body disease. Although patients with multiple system atrophy and progressive supranuclear palsy shared several symptoms and signs, ataxia and stridor were more common in multiple system atrophy. Multiple logistic regression analysis revealed increased likelihood of multiple system atrophy versus Lewy body disease and progressive supranuclear palsy if a patient developed orthostatic hypotension or urinary incontinence with the requirement for urinary catheters [multiple system atrophy versus Lewy body disease: odds ratio (OR): 2.0, 95% confidence interval (CI): 1.1-3.7, P = 0.021; multiple system atrophy versus progressive supranuclear palsy: OR: 11.2, 95% CI: 3.2-39.2, P < 0.01]. Furthermore, autonomic dysfunction within the first 3 years from onset can differentiate multiple system atrophy from progressive supranuclear palsy (multiple system atrophy versus progressive supranuclear palsy: OR: 3.4, 95% CI: 1.2-9.7, P = 0.023). Multiple system atrophy patients with predominant parkinsonian signs had a higher number of red flag features than patients with Lewy body disease (OR: 8.8, 95% CI: 3.2-24.2, P < 0.01) and progressive supranuclear palsy (OR: 4.8, 95% CI: 1.7-13.6, P < 0.01). The number of red flag features in multiple system atrophy with predominant cerebellar signs was also higher than in Lewy body disease (OR: 7.0, 95% CI: 2.5-19.5, P < 0.01) and progressive supranuclear palsy (OR: 3.1, 95% CI: 1.1-8.9, P = 0.032). Patients with multiple system atrophy had shorter latency to reach use of urinary catheter and longer latency to residential care than progressive supranuclear palsy patients, whereas patients with Lewy body disease took longer to reach multiple milestones than patients with multiple system atrophy. The present study has highlighted features which should improve the ante-mortem diagnostic accuracy of multiple system atrophy.
... Cognitive impairment is common in PD patients, and includes deficits in working memory, visuospatial processing, language fluency and verbal learning (Bradley et al., 1989;Cooper et al., 1991;Goldman and Postuma, 2014;Tröster et al., 1995). It is mostly associated with frontal lobe dysfunction from either cortical atrophy (Auning et al., 2014;Green et al., 2002;Pereira et al., 2014;Rektorova et al., 2014) or Lewy body pathology (Kehagia et al., 2012). Dysfunctions in various neurotransmitter systems, including DA, serotonin, noradrenaline and acetylcholine, are thought to contribute to the cognitive decline associated with PD (O'Callaghan and , although the primary biochemical deficit is thought to be cholinergic (Hall et al., 2014). ...
Parkinson's disease (PD) is characterised by degeneration of dopaminergic neurons of the nigrostriatal pathway, which leads to the cardinal motor symptoms of the disease - tremor, rigidity and postural instability. A number of non-motor symptoms are also associated with PD, including cognitive impairment, mood disturbances and dysfunction of gastrointestinal and autonomic systems. Current therapies provide symptomatic relief but do not halt the disease process, so there is an urgent need for preventative strategies. Lifestyle interventions such as aerobic exercise have shown potential to lower the risk of developing PD and to alleviate both motor and non-motor symptoms. However, there is a lack of large-scale randomised clinical trials that have employed exercise in PD patients. This review will focus on the evidence from studies on rodent models of PD, for employing exercise as an intervention for both motor and non-motor symptoms.
... Our study showed a disparity between male and female patients in two domains of cognition. Male patients surpassed female patients on BNT, a measure less commonly used to assess frontal lobe dysfunction [28], while female patients were superior on verbal retrieval test, reflecting the impairment of hippocampus [29]. Since no significant differences were observed in these two measures between male and female controls, it is reasonable to infer that gender-based differences existed in PD patients. ...
Background
Cognitive impairment is one of the non-motor symptoms in Parkinson’s disease (PD). In the present study, we aim to examine the cognitive function of non-demented Parkinson’s disease patients and compare the results between male and female patients as well as control groups in search of any gender effect. Methods
Sixty PD Patients (30 males and 30 females) from the Movement Disorders Clinic at Huashan Hospital Affiliated to Fudan University were recruited to participate in the study. One hundred age and gender matched control subjects without neurological or psychiatric disorders were voluntarily recruited. The participants were administered measures of cognition in five domains including memory, language, spatial processing abilities, attention and executive function. ResultsPD patients attained significantly lower scores in the visual spatial function, language and attention/executive function compared with the control group. Anti-parkinsonian treated patients performed worse in Rey-copy score, Clock Drawing Test (CDT) and Verbal Fluency-City than untreated ones. In regard to gender differences, though no general cognitive differences were found in Mini-mental State Examination (MMSE), men surpassed women on Boston naming test (BNT) while women were superior on Auditory Verbal Learning Test-long (AVLT) delayed cued recall test. Conclusions
Cognitive impairments were common in PD patients even in the absence of dementia. PD patients with anti-parkinsonian medication had worse cognitive impairment than untreated patients. Genders may have different manifestations of cognitive impairment in PD patients.
... Green et al. found poorer performance and increased bradykinesia with older age and longer disease duration. [9] Executive dysfunction also influences the instrumental activities of daily living in PD. [10] Few studies on cognitive impairments in PD patients from India are available, with studies on comparative assessment of cognitive impairment in young-and late-onset PD being sparse. Early recognition of cognitive impairment is of paramount importance since it is a disabling nonmotor symptom. ...
Background
Cognitive impairment is increasingly being recognized as a major cause of morbidity and increased dependence over the caregivers in Parkinson's disease (PD) patients.
Objective
The present study aimed to compare the cognition testing in young- and late-onset PD patient.
Methods
Sixty PD patients (20 young onset and 40 late onset) fulfilling UKPDS Brain Bank diagnostic criteria were enrolled in the study. Patients were assessed clinically and using scales for cognition testing such as Scales for Outcomes in PDCognition (SCOPA-COG), Unified Parkinson's Disease Rating scale (motor part), and Hoehn and Yahr staging.
Results
Young-onset group comprised 20 (33.3%) and late-onset group comprised 40 (66.7%) patients. Most of the young- and late-onset patients, 15 (75%) and 21 (52.5%), had SCOPA-COG score in the range of 30–39, respectively. On comparison between young- and late-onset groups, SCOPA-COG score's mean ± standard deviation (SD) for young and late onset was 32.60 ± 2.52 and 30.30 ± 3.65, respectively, with statistical significance (P = 0.01). SCOPA-COG score's mean ± SD for mild, moderate, and severely impaired PD patients was 31.48 ± 3.19, 30.60 ± 3.24, and 23.50 ± 3.53, respectively, which on group comparisons (ANOVA) were statistically significant (P = 0.004). However, the SCOPA-COG score was statistically insignificant with respect to disease duration.
Conclusion
There was statistically significant difference in SCOPA-COG score between young- and late-onset PD patients and in patients with more severe motor impairment.
... Cognitive decline in PD includes deterioration in diverse functions and skills. To date, there is considerable evidence of damage in executive functions such as working memory, attention, reasoning, and planning even in early nondemented PD patients [8]. Perceptual visuospatial and verbal processes have been shown consistently to be impaired in PD [9] and decline in memory have also been documented [10]. ...
Different types of dementia associated to later stages of Parkinson's or Alzheimer's diseases may include memory loss and difficulties with thinking, problem-solving or language. People affected by such diseases may also experience changes in their mood, expressiveness or behaviour which can provoke a communication impact in their lives and problems for socializing. Preventive policies, such as a balanced diet, daily exercise, frequent intellectual activity and interaction with others are protective factors that could help to reduce (or at least to delay) the effect of this cognitive impairment. Cognitive electronic games are an effective methodology to develop cognitive training and to stimulate the brain activity in this kind of patients. The user's interaction information allows analyzing the cognitive training and drawing conclusions about their evolution in controlled environments supervised by a professional. Preliminary tests revealed that users are familiarized with the use of televisions facing other devices such as tablets or smartphones. For that purpose, a Smart TV application containing different kinds of cognitive games, such as Bingo, Trivial or Memory was developed, taking benefits of the Connected TV environment. The Smart TV device for cognitive games received a good acceptance while tested among caregivers, patients and professionals, as demonstrated after testing the cognitive games individually and also collectively in daily care centers. Those tests revealed that the use of this device was a good chance to improve socialization with collaborative gaming, as this activity obliged them to communicate with other people and interact with their surrounding environment.
... Previous studies examined executive function in PD using standard assessments, such as the Stroop test, the Wisconsin card sorting test, the Frontal Assessment Battery, and others. [11][12][13][14] However, these assessments may be insensitive to executive deficits experienced in daily life. 15 However, the Behavioral Assessment of the Dysexecutive Syndrome (BADS), which includes six subtests to assess executive function required in daily life (Table 1), is designed to examine subtle impairment in executive function. ...
Background
Effects of dopaminergic medication on executive function in patients with Parkinson’s disease (PD) are inconsistent.
Objective
We examined the effect of dopaminergic medication on executive function in 24 drug-naïve PD patients (de novo group) and in 21 PD patients on chronic dopaminergic medication (chronic medication group).
Methods
PD patients without dementia were included in this study. For the de novo group patients, dopaminergic medication was initiated, and the dose was increased to improve motor symptoms. For the chronic medication group patients, dopaminergic medication was adjusted to relieve clinical problems. All participants were tested prior to and at 4–7 months after the drug initiation/adjustment. Executive function was assessed by using the Behavioral Assessment of the Dysexecutive Syndrome (BADS). Motor function was assessed by using the Unified Parkinson’s Disease Rating Scale (UPDRS; part III). Improvement in executive function was compared with a simultaneous change in levodopa equivalent doses (LED) of dopaminergic medication and with improvement in motor functions.
Results
The mean standardized BADS scores showed no significant improvement in both the groups. In the de novo group, percent improvement in the standardized BADS scores showed a significant positive correlation with the LED, but not with percent improvement in UPDRS part III. In the chronic medication group, percent improvement in the standardized BADS scores was negatively correlated with change in the LED, but not with percent improvement in UPDRS part III. Multiple regression analysis using improvement in the standardized BADS score as a dependent variable and patient’s background factors (ie, age, education, disease duration, and motor and executive assessments at baseline) as independent variable showed that improvement in the executive assessment is significantly correlated with the LED only in the de novo group.
Conclusion
Effects of dopaminergic drug adjustment on executive function differ according to the patient’s clinical stage and depend on LED in de novo stage.
... The negative association of total MoCA scores not only with motor symptoms (MDS-UPDRS-II) but also imbalance is intriguing. In the past, cognitive functions (performance on frontal-executive tasks or global cognitive functions assessed by total MMSE or MoCA scores) were reported to be correlated with symptoms assessed by MDS-UPDRS total scores or sub-scores (i.e., bradykinesia or postural instability) ( [33][34][35][36]). These past studies, however, were based mainly on simple correlation analyses using cross-sectional data with limited variables of interest. ...
Background
It is challenging for current statistical models to predict clinical progression of Parkinson’s disease (PD) because of the involvement of multi-domains and longitudinal data. Methods
Past univariate longitudinal or multivariate analyses from cross-sectional trials have limited power to predict individual outcomes or a single moment. The multivariate generalized linear mixed-effect model (GLMM) under the Bayesian framework was proposed to study multi-domain longitudinal outcomes obtained at baseline, 18-, and 36-month. The outcomes included motor, non-motor, and postural instability scores from the MDS-UPDRS, and demographic and standardized clinical data were utilized as covariates. The dynamic prediction was performed for both internal and external subjects using the samples from the posterior distributions of the parameter estimates and random effects, and also the predictive accuracy was evaluated based on the root of mean square error (RMSE), absolute bias (AB) and the area under the receiver operating characteristic (ROC) curve. ResultsFirst, our prediction model identified clinical data that were differentially associated with motor, non-motor, and postural stability scores. Second, the predictive accuracy of our model for the training data was assessed, and improved prediction was gained in particularly for non-motor (RMSE and AB: 2.89 and 2.20) compared to univariate analysis (RMSE and AB: 3.04 and 2.35). Third, the individual-level predictions of longitudinal trajectories for the testing data were performed, with ~80% observed values falling within the 95% credible intervals. Conclusions
Multivariate general mixed models hold promise to predict clinical progression of individual outcomes in PD. Trial registrationThe data was obtained from Dr. Xuemei Huang’s NIH grant R01 NS060722, part of NINDS PD Biomarker Program (PDBP). All data was entered within 24 h of collection to the Data Management Repository (DMR), which is publically available (https://pdbp.ninds.nih.gov/data-management).
... This in turn might explain the negative impact of PCBs on word fluency. One common finding in patients with Parkinson's disease suffering from DA depletion is an impairment of verbal fluency (Emre et al., 2014;Green et al., 2002;Lanni et al., 2014;Polito et al., 2012;Zec et al., 1999) that can be traced back to DA depletion in the striatum and dorsolateral prefrontal cortex (Picco et al., 2015;Polito et al., 2012) and be ameliorated by dopaminergic medication (Herrera et al., 2012;Lange et al., 1995). Thus, it is reasonable to assume verbal fluency to depend on fronto-striatal structures and dopaminergic transmission. ...
In the context of a health surveillance program for former PCB-exposed workers of a transformer and capacitor recycling company in Germany, their family members, employees of surrounding companies and area residents a broad range of cognitive functions covering attention, executive processing, reasoning, memory and motor performance was examined. The study aimed at identifying potential adverse effects of PCB load on cognitive functions. Detailed analysis of PCB burden of the participants revealed rather high correlations of lower and higher chlorinated as well as dioxin-like PCBs. Nearly one half of the participants exhibited increased burden in all three PCB classes whereas only 33 out of 237 participants did not show any increased PCB burden. Thus, data analysis followed a two-fold strategy: (1) Based on studies providing data on PCB exposure of the German general population the PCB burden of every participant was classified as normal (percentile rank PR <95) or increased (PR ≥95). Increased burden with respect to lower (LPCBs) and higher chlorinated (HPCBs) as well as dioxin-like (dlPCBs) PCBs was assumed if a participant showed at least one congener surpassing the PR95 criterion for the respective congener class and (2) Overall plasma PCB level per congener class was used as measure of PCB load. In a multivariate approach using structural equation modelling and multiple regression analysis we found a significant impact of PCBs on word fluency and sensorimotor processing irrespective of the measure of PCB burden (PR95 criterion or overall plasma level). However, no effect of PCB burden on memory, attention, and cognitive flexibility could be demonstrated. Particularly, an increase of LPCBs was associated with an overall reduction of verbal fluency of letter and semantic word generation as well as word production based on a single or two alternating criteria. In addition, participants with increased burden of LPCBs exhibited a time-on-task effect in terms of a stronger decline of performance with increasing duration of the verbal fluency task. Moreover, we found adverse effects of HPCBs on Aiming and of dlPCBs on Line Tracking. Results are discussed in terms of (1) a decrease of cerebral dopamine (DA) with non-coplanar PCBs resulting in an impact on fronto-striatal cerebral structures subserving verbal fluency and motor processing, (2) a PCB-induced reduction of norepinephrine leading to the time-on-task effect with verbal fluency, and (3) adverse effects of PCBs on dopaminergic receptors in the cerebellum resulting in impaired fine motor function.
... Истощение стриарного дофамина считается одной из причин КР при БП [27]. Прямые дофаминергические связи между вентральной покрышечной областью и префронтальной корой также могут оказывать влияние на изменение когнитивной сферы [28,29]. ...
Aim:
To study the relationship between early cognitive impairment symptoms and cerebral glucose metabolism in different brain regions (according to the positron emission tomography (PET) data) in Parkinson's disease (PD) in order to increase the diagnostic and treatment efficacy.
Material and methods:
Two groups of patients with PD (stage I-III), including 11 patients without cognitive disorders and 13 with mild cognitive impairment (MCI), were examined. The control group included 10 age-matched people with normal cognition. To evaluate cognitive state, the Mini mental state examination (MMSE), the Frontal assessment battery (FAB) and the 'clock drawing test' were used. The regional cerebral glucose metabolism rate (CMRglu) was assessed using PET with 18F-fluorodeoxyglucose (FDG).
Results and conclusion:
In PD patients, CMRglu were decreased in the frontal (Brodmann areas (BA) 9, 10, 11, 46, 47), occipital (BA 19) and parietal (BA 39), temporal (BA 20, 37), and cingulate cortex (BA 32) compared to the control group. Cerebral glucose metabolism was decreased in the frontal (BA 8, 9, 10, 45, 46, 47), parietal (BA 7, 39, 40) and cingulate cortex (BA 23, 24, 31, 32) in the group of PD patients with MCI compared to PD patients with normal cognition. Hypometabolism in BA 7, 8, 23, 24, 31, 40 was revealed only in comparison of PD and PD-MCI groups, and did not appear in case of comparison of cognitively normal PD patients with the control group. It is possible to suggest that the mentioned above brain areas were associated with cognitive impairment. The revealed glucose hypometabolism pattern possibly has the diagnostic value for the early and preclinical diagnosis of MCI in PD and control of treatment efficacy.
... PVF is usually impaired very early in the disease (i.e., frontotemporal dementia (FTD), Parkinson's (PD) or Huntington's disease (HD)) afflicting frontal-temporal and striatal circuits. (Green et al., 2002;Henry, Crawford, & Phillips, 2005;Jacobs et al., 1995). ...
Patients with subjective cognitive decline (SCD) are at higher risk for conversion to dementia due to Alzheimer’s disease (AD). Semantic verbal fluency (SVF) seems to be impaired in the early stages of AD. The goal of the present study was to identify the discriminative potential of verbal fluency (VF) in patients with SCD to show if very early signs of cognitive decline may be detected in SCD. We examined 93 normal controls (NC) and 61 participants with SCD. Each participant was administered a comprehensive neuropsychological battery. All participants underwent tests of VF: phonemic verbal fluency (PVF), letters K and P and SVF (animals and vegetables categories). In addition to the total score, two 30-second intervals, and clustering and switching indices in SVF were evaluated. SCD generated fewer words in the total score and 30- to 60-second interval in vegetables category and they performed more switches in animals category. There was no significant difference between the SCD and the NC groups in all other VF measures. Quantitative measures of SVF (a decreased number of vegetables) as well as qualitative measures were detected in SCD group and could be considered as an early neuropsychological marker of subtle cognitive impairment.
... It is unclear why a similar increase in alpha-band LFP power was not observed in animal B. It is possible that the relative percentage of neurons with alpha-band oscillatory firing in animal B is so low that the contribution to the recorded LFP is negligible, or neurons with oscillatory firing were not synchronized with each other. Given that cortical alpha oscillations have been associated with attention and memory load (Jensen et al. 2002;Stoffers et al. 2007), it is possible that the abnormal oscillatory activity in this frequency band we observed is related to such cognitive processes, which are known to be impaired in PD (Grossman et al. 1992;Green et al. 2002). Such a relationship remains to be tested experimentally. ...
A number of studies suggest that Parkinson's disease (PD) is associated with alterations of neuronal activity patterns in the basal-ganglia-thalamocortical circuit. There are limited electrophysiological data, however, describing how premotor cortex, which is involved in movement and decision making, is likely impacted in PD. In this study, spontaneous local field potential (LFP) and single unit neuronal activity were recorded in the dorsal premotor area of non-human primates in both the naïve and parkinsonian state using the MPTP model of parkinsonism. In both animals we observed a shift of power in LFP power spectral densities (1-350Hz) from higher to lower frequency bands; Parkinsonism resulted in increased power in frequencies below 8Hz and decreased power at frequencies above 30Hz. A comparable but not identical trend was observed in the power spectral analysis of single unit spike trains: alpha power increased in both animals and gamma power decreased in one; power in other frequency bands remaining unchanged. Although not consistent across animals we also observed changes in discharge rates and bursting activity. Overall, the LFP and single unit analysis suggest that abnormalities in premotor neural activity are a feature of parkinsonism, though specific details of those abnormalities may differ between subjects. This study further supports the concept that PD is a network disorder that induces abnormal spontaneous neural activities across the basal-ganglia-thalamocortical circuit including the premotor cortex, and provides foundational knowledge for future studies regarding the relationship between changes in neuronal activity in this region and the development of motor deficits in PD.
... Cognitive decline in PD includes impairments in diverse functions and skills. To date, there is considerable evidence of impairments in executive functions such as working memory (WM), attention, reasoning, and planning even in early, nondemented PD patients [29][30][31][32]. Additionally, more basic perceptual visuospatial and verbal processes have been shown consistently to be impaired in PD [32][33][34][35]. ...
Cognitive deficits are prevalent among patients with Parkinson’s disease (PD), in both early and late stages of the disease. These deficits are associated with lower quality of life, loss of independence, and institutionalization. To date, there is no effective pharmacological treatment for the range of cognitive impairments presented in PD. Cognitive training (CT) has been explored as an alternative approach to remediating cognition in PD. In this review we present a detailed summary of 13 studies of CT that have been conducted between 2000 and 2014 and a critical examination of the evidence for the effectiveness and applicability of CT in PD. Although the evidence shows that CT leads to short-term, moderate improvements in some cognitive functions, methodological inconsistencies weaken these results. We discuss several key limitations of the literature to date, propose methods of addressing these questions, and outline the future directions that studies of CT in PD should pursue. Studies need to provide more detail about the cognitive profile of participants, include larger sample sizes, be hypothesis driven, and be clearer about the training interventions and the outcome measures.
... % of PD patients [2][3][4]. Further, a prospective longitudinal study reported that 36 % of PD patients had mild cognitive impairment and an additional 48 % met the diagnostic criteria for PDD within 15 years [5]. It has been suggested that PDD patients have increased health care burden, declined quality of life and increased mortality, which highlight the importance of PDD prediction [6]. ...
Brain gray matter volume (GMV) reduction has been reported in Parkinson's disease (PD) with mild cognitive impairment (PD-MCI) and in PD patients with dementia (PDD) with cumulative evidence using voxel-based morphometry (VBM). However, the findings of these studies have not been entirely concordant. Whole-brain VBM studies comparing PD-MCI with PD patients without cognitive impairment (PD-NCI) and comparing PDD with PD patients without dementia (PDND) were systematically searched in PubMed and EMBASE databases from January 1995 to December 2015. Coordinates with significant differences were extracted from each cluster. Meta-analysis was performed using AES-SDM to quantitatively evaluate the GMV changes. Five studies comparing 92 PD-MCI with 192 PD-NCI patients were included in the PD-MCI vs. PD-NCI meta-analysis. Ten studies with 168 PDD and 233 PDND patients were included in the PDD vs. PDND meta-analysis. Compared with PD-NCI, GMV reductions were observed in left superior temporal lobe, left insula and left superior frontal lobe in PD-MCI patients. Significant GMV reduction were found in bilateral superior temporal lobe extending to hippocampus, and left superior frontal lobe in PDD patients comparing with PDND. Meta-regression of PDD studies showed that disease duration was negatively correlated with GMV in the left superior frontal lobe. GMV reductions in the frontal-limbic-temporal regions were main features of cognitive decline in PD. Unilateral-to-bilateral development of GMV reduction in the frontal-limbic-temporal regions is a possible indicator for PD-MCI to PDD progression, whereas significant hippocampal GMV reduction may not be a marker for early cognitive decline in PD.
... alteración en la secuenciación, trastornos en la formación de conceptos, dificultad en la inhibición de estímulos periféricos, tendencia a las alteraciones en el mantenimiento de la atención. Todo ello desencadena una conducta caracterizada por la lentificación de las tareas cognitivas, tanto en su aspecto de análisis aferente como en la ejecución, con un notable aumento en el tiempo de procesamiento de la información 31 . ...
... Estas investigaciones han sugerido que los déficits cognoscitivos en la EP no reflejan problemas en el funcionamiento de los ganglios basales sino una desconexión a los lóbulos frontales. Se ha sugerido que las desconexiones fronto-talámicas explican la pérdida de espontaneidad e imaginación y la falta de iniciativa que presentan los pacientes con EP 32 . En un cuestionario de funciones cotidianas los pacientes con EP fueron clasificados diferentes a los normales en conductas relacionadas a la iniciativa, Independientemente de la problemática de evaluación, en la EP aparece con frecuencia una semiología marcada de alteración frontal: alteración en la secuenciación, trastornos en la formación de conceptos, dificultad en la inhibición de estímulos periféricos, tendencia a las alteraciones atencionales concretas y dificultad en el mantenimiento atencional. ...
... Several studies have shown that patients with Parkinson's disease (PD), besides having motor dysfunctions, may also display mild cognitive deficits in the early stage of disease which increase with disease progression (Green et al., 2002;Janvin et al., 2003;Muslimovic et al., 2005). In particular, clinical and experimental findings consistently demonstrated that, in respect to healthy subjects, PD patients exhibit poorer performance on tests tapping selected components of executive functions, such as shifting and planning (Cools, 2006;Cools and D'Esposito, 2011;MacDonald and Monchi, 2011), working memory (Cools, 2006;Cools and D'Esposito, 2011), and free recall mechanisms in the content of episodic memory (Costa et al., 2014a). ...
Brain-derived neurotrophic factor (BDNF) is a trophic factor regulating cell survival and synaptic plasticity. Recent findings indicate that BDNF could be a potential regulatory factor for cognitive functioning in normal and/or neuropathological conditions. With regard to neurological disorders, recent data suggest that individuals with Parkinson's disease (PD) may be affected by cognitive deficits and that they have altered BDNF production. Therefore, the hypothesis can be advanced that BDNF levels are associated with the cognitive state of these patients. With this in mind, the present study was aimed at exploring the relationship between BDNF serum levels and cognitive functioning in PD patients with mild cognitive impairment (MCI). Thirteen PD patients with MCI were included in the study. They were administered an extensive neuropsychological test battery that investigated executive, episodic memory, attention, visual-spatial and language domains. A single score was obtained for each cognitive domain by averaging z-scores on tests belonging to that specific domain. BDNF serum levels were measured by enzyme-linked immunoassay (ELISA). Pearson's correlation analyses were performed between BDNF serum levels and cognitive performance. Results showed a significant positive correlation between BDNF serum levels and both attention (p < 0.05) and executive (p < 0.05) domains. Moreover, in the executive domain we found a significant correlation between BDNF levels and scores on tests assessing working memory and self-monitoring/inhibition. These preliminary data suggest that BDNF serum levels are associated with cognitive state in PD patients with MCI. Given the role of BDNF in regulating synaptic plasticity, the present findings give further support to the hypothesis that this trophic factor may be a potential biomarker for evaluating cognitive changes in PD and other neurological syndromes associated with cognitive decline.
... Studie prováděné na zdravých jedincích totiž ukazují, že zejména těmito kognitivními funkcemi jsou signifi kantně ovlivněny identifikace a diskriminace pachů, ale ne detekční prahy [128]. Pa cienti s ACH i PCH často vykazují poruchu exekutivních funkcí [129,130] i sémantické paměti [131,132]. Není doposud jasné, nakolik s poklesem kognitivních funkcí souvisí hodnocení jednotlivých percepčních charakteristik (např. ...
Changes in olfactory perception, which can be tested with psychophysical tests, have been noted in many neurodegenerative diseases. Olfactory testing is of greatest significance in Alzheimer’s and Parkinson’s disease, in which olfactory decline precedes other clinical symptoms. It can indicate the presence of a neurological disorder, aid in differential diagnosis, or help estimate the future development of the disease. This review presents olfactory dysfunction profiles in selected neurodegenerative diseases with an emphasis on Alzheimer’s and Parkinson’s disease, assessment of quantitative and qualitative olfactory dysfunction, focusing on the widely used psychophysical tests which can be employed in routine olfactory testing in everyday clinical practice, and the contribution of olfactory testing to the diagnosis of the selected neurodegenerative diseases. In Alzheimer’s disease, identification is more severely affected than detection thresholds, whereas in Parkinson’s disease, the decline is more homogeneous across the various olfactory measures and the increase in detection thresholds is more prominent.
... The interpretative manual recommends a cut-off score of less than 123 for diagnosis of dementia; however, lower cutoffs (i.e., 116-123 points) have been recommended for use in individuals with PD to correct for the negative impact of motor impairment on test performance. [6][7][8] Patients completed the DRS-2 during both pre-and 6-month postoperative neuropsychological evaluations. Patients were grouped into one of five categories based on preoperative DRS-2 performance. ...
Presence of dementia is a contraindication for DBS treatment of Parkinson's disease. Recent evidence suggests that borderline cognitive function, as measured with a common screening measure, the Mattis Dementia Rating Scale, has a negative impact on quality of life (QoL) after DBS of the STN.
We attempted to replicate and extend this finding in a larger group of patients with a wider range of preoperative global cognitive performance.
Our data indicate that performance on the screening measure is not associated with QoL or medical outcomes, even with scores well below the cutoff for identifying dementia.
This cognitive screening measure lacks sufficient sensitivity to warrant its use in predicting which patients will show QoL benefit from DBS. © 2015 International Parkinson and Movement Disorder Society.
© 2015 International Parkinson and Movement Disorder Society.
... Some studies have shown that in healthy adults, low educational status (LES) impairs visuospatial perception, [23][24][25] praxis, 26-28 dual-task performance, 29 memory, 27 and executive function. 4 LES also contributes to neuropsychiatric complications in individuals with Alzheimer disease 23 and Parkinson disease (PD), [30][31][32][33] and might amplify depressive symptoms. 17 According to Kummer et al, 34 the toll that depression takes on patients with PD is worse among those with LES. ...
... El concepto clásico de demencia subcortical en la EP implica la afectación predominante de las funciones ejecutivas, atención y visuopercepción [28], dominios considerados como no amnésicos. No obstante, en estos pacientes puede encontrarse además una afectación de la memoria [68] e incluso del lenguaje [69][70][71][72]. Respecto a la memoria, se destaca una alteración mayor de la codificación [68] que de la recuperación [73], lo que refleja una afectación del lóbulo temporal, como ocurre en la enfermedad de Alzheimer. ...
Cognitive impairment may appear at the earliest stages in Parkinson's disease (PD). To assess the prevalence of mild cognitive impairment (MCI) and its different subtypes, as transitional stage, is complicated by the lack of consensus diagnostic criteria.
To review MCI in PD (MCI-PD), diagnostic criteria and predictive factors of conversion to dementia.
Systematic review of articles published in Medline (PubMed) using the combination of keywords 'mild cognitive impairment' and 'Parkinson's disease'.
MCI-PD diagnostic criteria published by the Movement Disorders Society are an interesting tool for the diagnosis, in spite they are not validated. Its implementation has the following limitations: 1) the heterogeneity of cognitive deficits described in PD; 2) a variable evolution of cognitive symptoms in PD which difficult the identification of dementia predictors; 3) selection of the more appropriate neuropsychological tests and cut-off points; 4) patient characteristics, disease stage and type of antiparkinsonian treatment.
Neuropsychological subtypes, neuroimaging, biomarkers or limitation in some instrumental activities seem to be very sensitive for detecting patients with MCI-PD and increased risk of conversion to dementia.
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.
Parkinson's disease (PD) is a multisystem disorder considered the second most common neurodegenerative disease worldwide of which neuroprotective therapies are not yet available. PD is known mainly by its cardinal motor symptoms which are believed to be associated with dopamine deficiency in the nigrostriatal pathway as a result of DAergic neurons degeneration in the substantia nigra pars compacta of the midbrain. However, other brain structures degenerate (non-dopaminergic abnormalities) in PD resulting in other symptoms known as non-motor symptoms (NMS). NMS and non-DAergic abnormalities are sometimes present before diagnosis and almost inevitably emerge with the disease progression. Hence, they might play a tremendously important role in the management and sometimes even the diagnosis of PD. This chapter will provide an overview on the neuropathobiology of NMS in PD.
Background
Parkinson’s disease (PD) is a chronic neurodegenerative disorder complicated by cognitive dysfunctions which are associated with increased caregiver burden, pressure on community health facilities, and mortality in affected patients. Most of the data concerning cognitive dysfunctions in PD are from studies conducted in Europe and North America, but there is paucity of data from Sub-Saharan Africa.
Objective
The objective of this study is to determine the frequency, pattern and predictors of cognitive impairments amongst patients with Parkinson’s disease.
Materials and methods
This was a cross sectional case control study carried out at a tertiary health facility in South-south Nigeria. Participants with PD were consecutively recruited from the neurology outpatient clinics. Demographic and disease-specific data were obtained with the use of a pre-tested questionnaire. Cognitive performance of thirty patients with PD were compared with thirty demographically matched controls using the Community Screening Instrument for Dementia (CSID). CSID was already validated among Nigerians.
Results
The frequency of cognitive impairment using the CSID was 50% for PD patients (3.3% for controls). Poor cognitive performance was observed across several cognitive domains including language, executive dysfunction, psychomotor speed, and constructional apraxia among PD patients. The independent predictors of the overall cognitive impairment in patients with PD determined by logistic regression analysis include recall deficiency (p = 0.007), impairment with naming (p = 0.044), apraxia (p = 0.003), Hoen&Yahr staging (p = 0.046), UPDRS score (p = 0.015) and age at presentation (p = 0.014).
Conclusion
Cognitive impairments occur more frequently in patients with PD compared to controls. This study also demonstrated the predictive role of severity of disease based on Hoehn &Yahr staging and UPDRS score, and presence of recall deficiency, poor naming ability and apraxia.
Background and purpose:
The circuitry underlying heterogenous cognitive profiles in Parkinson's disease (PD) remains unclear. The purpose of this study is to investigate whether structural changes in frontostriatal and limbic pathways contribute to different cognitive trajectories in PD.
Methods:
We obtained clinical and multimodal MRI data from 120 control and 122 PD subjects without dementia or severe motor disability. T1/T2-weighted images estimated volume, and diffusion imaging evaluated fractional anisotropy (FA) of frontostriatal (striatum and frontostriatal white matter [FSWM]) and limbic (hippocampus and fornix) structures. Montreal Cognitive Assessment (MoCA) gauged total and domain-specific (attention/executive and memory) cognitive function. Linear mixed-effects models were used to compare MRI and cognitive progression over 4.5 years between controls and PD and evaluate associations between baseline MRI and cognitive changes in PD.
Results:
At baseline, control and PD groups were comparable, except PD participants had smaller striatal volume (p < 0.001). Longitudinally, PD showed faster decline in hippocampal volume, FSWM FA, and fornix FA (ps < .016), but not striatal volume (p = .218). Total and domain-specific MoCA scores declined faster in PD (ps < .030). In PD, lower baseline hippocampal volume (p = .005) and fornix FA (p = .032), but not striatal volume (p = .662) or FSWM FA (p = .143), were associated with faster total MoCA decline. Baseline frontostriatal metrics of striatal volume and FSWM FA were associated with faster attention/executive decline (p < .038), whereas lower baseline hippocampal volume was associated with faster memory decline (p = .005).
Conclusion:
In PD, frontostriatal structural metrics are associated with attention/executive tasks, whereas limbic changes correlated with faster global cognitive decline, particularly in memory tasks.
Epidemiology is the study of the distribution of disease in human populations, which is important in evaluating burden of illness, identifying modifiable risk factors, and planning for current and projected needs of the health care system. Parkinson's disease (PD) is the second most common serious neurodegenerative illness and is expected to further increase in prevalence. Cognitive changes are increasingly viewed as an integral non-motor feature in PD, emerging even in the prodromal phase of the disease. The prevalence of PD-MCI ranges from 20% to 40% depending on the population studied. The incidence of PD-dementia increases with duration of disease, with estimates growing from 3% to 30% of individuals followed for 5 years or less to over 80% after 20 years. There are several challenges in estimating the frequency of cognitive change, including only recently standardized diagnostic criteria, variation depending on exact neuropsychological evaluations performed, and differences in population sampling. Clinical features associated with cognitive decline include older age, increased disease duration and severity, early gait dysfunction, dysautonomia, hallucinations and other neuropsychiatric features, the presence of REM behavior disorder, and posterior predominant dysfunction on neuropsychological testing. There is increasing evidence that genetic risk factors, in particular GBA and MAPT mutations, contribute to cognitive change. Possible protective factors include higher cognitive reserve and regular exercise. Important sequelae of cognitive decline in PD include higher caregiver burden, decreased functional status, and increased risk of institutionalization and mortality. Many remaining uncertainties regarding the epidemiology of cognitive change in PD require future research, with improved biomarkers and more sensitive and convenient outcome measures.
Background:
Previous studies showed inconsistent results for the correlation between cognitive reserve (CR) and cognitive function in Parkinson's disease (PD). Additionally, conflicting results were obtained for the association between CR and risk of longitudinal cognitive decline, longitudinal progression to mild cognitive impairment (MCI), and longitudinal progression to dementia in PD patients.
Objectives:
Thus, a meta-analysis is essential to summary these inconsistent results.
Methods:
Articles published before November 2021 were searched in databases as follows: PubMed, Web of Science, Medline, EMBASE, and Google Scholar. We computed Fisher's z score and standard error (SE) of each transformation value of correlation coefficient for the correlation between educational level and cognitive function. Additionally, odds ratios (ORs) or hazard ratios (HRs) and their 95% confidence intervals (CIs) were computed as effect sizes for the correlation between educational level and risk of longitudinal progression to MCI.
Results:
The present study showed that higher educational levels were related to better general cognitive function, executive function, memory, and information processing speed in PD patients, whereas no significant association was showed between educational levels and visuospatial function, language in PD patients. Additionally, included studies reported a negative association between educational level and risk of longitudinal progression to MCI in PD patients.
Conclusions:
In conclusion, the study demonstrated that higher CR might be correlated with better cognitive function and lower risk of longitudinal progression to MCI in PD. In addition, large-scale prospective studies are necessary to explore the effect of CR on cognitive function in PD.
We explored with Diffusion Tensor Imaging (DTI) technique whether the ability to select words among competitive alternatives during word production is related to the integrity of the left Uncinate Fasciculus (UF) in Parkinson's disease (PD).
Nineteen PD patients (10 right-sided and 9 left-sided) and 17 matched healthy controls (HC) took part in the study. Participants were asked to derive nouns from verbs (reading from to read) or to generate verbs from nouns (to build from building). Noun and verb production, in this task, differ in the number of lexical entries among which the response is selected, as the noun must be selected from a larger number of alternatives compared to the verb, and thus is more demanding of processing resources. DTI evaluation was obtained for each subject. Fractional anisotropy (FA) and mean diffusivity (MD) maps were derived from DTI and median FA and MD values were computed within the left and right UF. Then, FA and MD of the left and right UF were correlated with noun and verb production.
Both the left and right UF-FA correlated with the global (noun + verb) production and noun production in the whole PD group. In right-sided PD, correlations were found with the contralateral UF-FA; in left-sided PD the correlations emerged with both the left and right UF-FA. The more difficult task, noun production, significantly correlated with the right UF-FA in left-sided PD.
The left UF is involved in word selection processes, and the right UF intervenes when the selection is particularly demanding of attentional resources.
This study aimed to analyze positron emission tomography with 18F-fluorodeoxyglucose data and event-related potentials in the Go/NoGo paradigm in patients with Parkinson's disease with and without cognitive impairment. In the group of cognitively impaired patients, glucose metabolism was decreased in the frontal, parietal, cingulate and posterior temporal cortex. Correlations were found between the cognitive scores and cerebral glucose metabolism in those areas. Event-related potentials analysis revealed a decrease in the amplitude of the late positive wave (P300 NoGo wave) in the group of cognitively impaired patients. The analysis revealed that decline in amplitude of P300 wave was accompanied by decreased glucose metabolism in several cortical areas associated with cognitive impairment in Parkinson's disease. Correlations of glucose metabolism in these areas with event-related potentials amplitude in the NoGo condition confirm the important role of executive functions disorders in the pathogenesis of cognitive impairment in Parkinson's disease.
Objectives
Patients with Parkinson’s disease (PD) exhibit impaired semantic and socioemotional processes, which are thought to be related to dysfunctions in the fronto-striatal circuit. However, little is known about how the memory enhancement by these processes was reduced in PD. The present study investigated this issue.
Methods
The retrieval performance of face memories encoded by semantic and socioemotional processes was compared between 24 PD patients and 24 age-matched healthy controls (HC). During encoding, participants were presented with unfamiliar faces and made judgment about them in three encoding conditions of semantic judgment (Semantics), attractiveness judgment (Attractiveness), and form judgment (Form). In Semantics, participants rated to what degree each face looked like an office worker, whereas in Attractiveness, participants rated how attractive each face was. The Form condition as a control required participants to judge the shape of each face. During retrieval after encoding, participants made old or new judgment for target and distracter faces.
Results
In HC, the retrieval of faces encoded by Semantics and Attractiveness was significantly more accurate than that encoded by Form, whereas this memory enhancement was not identified in PD. In addition, individual scores in frontal lobe function and long-term memory correlated with the retrieval performance of memories encoded in Semantics and Attractiveness but not Form.
Conclusions
These findings suggest that the processing of semantic and socioemotional signals conveyed from faces could be impaired in PD and that the impairment of these processes could decrease the enhancement of face memories by semantic and socioemotional elaborations.
Background:
To better understand the psychiatric disorders and cognition in Parkinson's disease (PD) and its impact on quality of life (QoL), patients need to be studied soon after diagnosis, before initiation of dopamine replacement therapy.
Aim:
This study aims to compare the nature and frequency of psychiatric morbidity, cognitive dysfunction, and quality of life in drug-naive patients with PD and healthy controls.
Materials and methods:
The cross-sectional, comparative study was conducted in tertiary care center. Fifty drug-naive PD patients and fifty healthy controls were included and assessed on Modified Hoehn and Yahr scale, PD Questionnaire 8, Kolkata cognitive screening battery, General Health Questionnaire-12, and Hamilton Anxiety and Depression Rating Scale (HAM-A and HAM-D).
Results:
The mean scores of HAM-A and HAM-D of patients with PD were significantly higher than that of the comparison group. The patients with PD had statistically significant impairment in verbal fluency, Mini-Mental State Examination, calculation, memory immediate recall, visuoconstructional ability, and memory (delayed recall and recognition) in comparison to patients without PD. No statistically significant difference was observed with respect to object naming between the two groups.
Conclusion:
QoL of a PD patient is adversely affected by both the motor and nonmotor symptoms of the disease such as depression, anxiety, apathy, sleep disturbances, and cognitive impairment. The link between nonmotor symptoms and reduced QoL has important implications for the management of PD because the nonmotor symptoms often appear before patients are given anti-parkinsonian therapy. Screening of nonmotor symptoms in early stage of disease will decrease the morbidity and mortality and improve the QoL.
Introduction
The development of assessment tools for individuals with dysarthria has been reported in many clinical and empirical studies.
Methodology
A literature review was based on online resources including Google Scholar, EBSCO, Medline, PubMed, and BIOMED Central articles and journals.
Results and Conclusion
In this paper, we summarized the commonly used formal and informal assessment tools and explained the assessment procedure when managing clients with dysarthria. We aimed to share the current practice of speech-language pathologists together with the allied health service providers in the management of patients with dysarthria.
Affective disorders, cognitive decline, and psychosis have long been recognized as common in Parkinson disease (PD), and other psychiatric disorders include impulse control disorders, anxiety symptoms, disorders of sleep and wakefulness, and apathy. Psychiatric aspects of PD are associated with numerous adverse outcomes, yet in spite of this and their frequent occurrence, there is incomplete understanding of epidemiology, presentation, risk factors, neural substrate, and management strategies. Psychiatric features are typically multimorbid, and there is great intra- and interindividual variability in presentation. The hallmark neuropathophysiological changes that occur in PD, plus the association between exposure to dopaminergic medications and certain psychiatric disorders, suggest a neurobiological basis for many psychiatric symptoms, although psychological factors are involved as well. There is evidence that psychiatric disorders in PD are still under-recognized and undertreated and although psychotropic medication use is common, controlled studies demonstrating efficacy and tolerability are largely lacking. Future research on neuropsychiatric complications in PD should be oriented toward determining modifiable correlates or risk factors and establishing efficacious and well-tolerated treatment strategies.
The chapter examines mental health in patients with myasthenia gravis (MG). Relatively few investigational studies have explored this area of patient care, with the most rigorous studies centered on cognitive manifestations. These studies reveal cognitive difficulties in a subset of patients, with a strong correspondence to mental fatigue. A small number of studies report elevated anxiety in MG but no major increase in depression, and no studies have clearly linked mental health with disease onset or progression. Ongoing disease severity is only modestly correlated with psychological distress and quality of life, though individuals with greater physical disability report more severe disruption in daily living activities. The chapter reviews four key predictors of psychological well-being in chronic disease (uncertainty, control, illness intrusiveness, social support) and pathways to optimize these factors in the clinical setting. Professionals involved in the care of MG play an important role in facilitating the mental health and quality of life of their patients. Incorporating mental health assessment and support into routine clinical practice empowers patients to achieve the best possible outcomes and life quality.
Impulse control disorders (ICDs), such as compulsive gambling, buying, sexual, and eating behaviors, are a serious and increasingly recognized complication in Parkinson's disease (PD), occurring in up to 20% of PD patients over the course of their illness. Related behaviors include punding (stereotyped, repetitive, purposeless behaviors), dopamine dysregulation syndrome (DDS) (compulsive medication overuse), and hobbyism (e.g., compulsive internet use, artistic endeavors, and writing). These disorders have a significant impact on quality of life and function, strain interpersonal relationships, and worsen caregiver burden, and are associated with significant psychiatric comorbidity. ICDs have been most closely related to the use of dopamine agonists (DAs), while DDS is primarily associated with shorter acting, higher potency dopamine replacement therapy (DRT), such as levodopa. However, in preliminary research ICDs have also been reported to occur with monoamine oxidase inhibitor-B and amantadine treatment, and after deep brain stimulation (DBS) surgery. Other risk factors for ICDs may include sex (e.g., male sex for compulsive sexual behavior, and female sex for compulsive buying behavior); younger age overall at PD onset; a pre-PD history of an ICD; personal or family history of substance abuse, bipolar disorder, or gambling problems; and impulsive personality traits. Dysregulation of the mesocorticolimbic dopamine system is thought to be the major neurobiological substrate for ICDs in PD, but there is preliminary evidence for alterations in opiate and serotonin systems too. The primary treatment of ICDs in PD is discontinuation of the offending treatment, but not all patients can tolerate this due to worsening motor symptoms or DA withdrawal syndrome. While psychiatric medications and psychosocial treatments are frequently used to treat ICDs in the general population, there is limited empirical evidence for their use in PD, so it is critical for patients to be monitored closely for ICDs from disease onset and routine throughout its course. In the future, it may be possible to use a precision medicine approach to decrease the incidence of ICDs in PD by avoiding DA use in patients determined to be at highest risk based on their clinical and neurobiological (e.g., motor presentation, behavioral measures of medication response, genetics, dopamine transporter neuroimaging) profile. Additionally, as empirically validated treatments for ICDs and similar disorders (e.g., substance use disorders) emerge, it will also be important to examine their efficacy and tolerability in individuals with comorbid PD.
Impulse control disorders (ICDs) typically involve pleasurable behaviors that are performed repetitively, excessively, and compulsively, and to an extent that interferes in major areas of life functioning. ICDs have been conceptualized as “behavioral” addictions [1,2], because of the extensive overlap between ICDs and disorders of addiction in terms of risk factors, clinical presentation, cognitive aspects, neurobiology, and treatment. There is increasing evidence and awareness that ICDs can occur as a behavioral complication of Parkinson's disease (PD), and the four major ICDs reported to occur in PD are compulsive gambling, buying, sexual, and eating behaviors. Of these disorders, only pathological gambling is included as an ICD in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) [3] (Table 13.1), but for convenience the term ICD has been broadly applied in PD to cover all four of the major ICDs that have been reported to occur. Related disorders include punding, hobbyism, and dopamine dysregulation syndrome (DDS), which are covered separately in this chapter.
Contrary findings notwithstanding, the prevailing notion is that recognition memory is little affected by Parkinson's disease (PD). Both a power analysis and a meta-analysis were conducted to help clarify the degree of recognition memory deficit associated with PD. The power analysis confirmed that, in general, memory studies of PD participants have been underpowered. This analysis indicated the need to pool study results in a subsequent meta-analysis, the main finding of which was that recognition memory deficits do occur with PD. The largest deficit occurs in PD participants with dementia. Nevertheless, deficits also occur in PD participants without dementia on medication, but nondopaminergic central nervous system abnormalities are more likely to underlie this deficit than PD medication itself. Future development of a theory of cognitive dysfunction in PD should take into account these recognition memory deficits, which may increase with disease progression.
This article provides a preliminary theoretical formulation of a threshold theory for acquired brain injury. The theory addresses the concept of brain reserve capacity as a major factor in explaining threshold differences in the onset of clinical symptoms or the expression of impaired test performance after acquired brain injury. The article provides the first critical review of the literature relevant to this theory.
Normative data stratified by three levels of age (16–59, 60–79, and 80–95 years) and three levels of education (0–8, 9–12, and 13–21 years) are presented for phonemic verbal fluency (FAS) and categorical verbal fluency (Animal Naming). The normative sample, aged 16 to 95 years, consisted of 1,300 cognitively intact individuals who resided in the community. Years of education ranged from 0 to 21. The total number of words in 1 minute for each of the letters F, A, and S was correlated r = .52 with the number of animal names generated in 1 minute. Regression analyses showed that FAS was more sensitive to the effects of education (18.6% of the variance) than age (11.0% of the variance). The opposite relationship occurred for Animal Naming, where age accounted for 23.4% of the variance and education accounted only for 13.6%. Gender accounted for less than 1% of variance for FAS and Animal Naming. The clinical utility of these norms is discussed.
We have used PET in conjunction with psychological activations to identify cortical areas involved in the intrinsic activation of word representations. In four normal subjects intrinsic generation of a word (verbal fluency) was associated with an increase in left dorsolateral prefrontal cortical activity (BA 46) and a bilateral decrease in activity in auditory and superior temporal cortices. Conversely, when subjects made lexical decisions about words that were heard, there was an increase in superior temporal activity with no change in area 46. We suggest that the superior temporal regions are the site of stored word representations and that inhibitory modulation of these areas by the left prefrontal cortex is the basis of intrinsic word generation.
One hundred and eight noninstitutionalized patients with Parkinson's disease were studied to find out whether the age of disease onset affects patients' cognitive, memory and psychomotor performance. "Early onset" patients (whose disease began before 60 years of age) showed a wide spectrum of impairments in neuropsychological performance compared with age-matched normal subjects. However, only one (2%) of these patients was demented according to DSM III criteria. Dementia was more frequent in patients with equivalent disease duration, but with late onset of disease (over 60 years); 13 of such patients (25%) were demented. The present study supports previous findings which show that dementia increases with advancing age in Parkinson's disease. It also suggests that cognitive changes are also found in patients with early onset of disease.
To compare the incidence of dementia in PD with that of a control group without PD, and to assess the relationship between dementia and other features of PD.
The authors recruited 83 patients with PD and 50 controls, all without dementia at initial assessment, and assessed them at regular intervals over a maximum period of 122 months. Dementia was diagnosed according to objective criteria, and included a judgment by researchers masked to subject group and to variables putatively associated with dementia.
Seventeen patients fulfilled dementia criteria; no controls did so. The cumulative proportion of PD patients becoming demented by 112 months was 0.38 (95% CI 0.20 to 0.55), or 42.6 cases per 1000 years of observation. Univariate analyses showed that incident dementia in patients with PD was associated with older age at entry into the study, greater severity of neurologic symptoms, longer duration of PD, greater disability, and male sex. The association of age at onset of PD with incident dementia was of only borderline significance. Multivariate analysis found that age at entry into the study and severity of motor symptoms were significant predictors of dementia but duration of PD and age at onset of PD were not.
Dementia in PD is likely to reflect interaction of the neuropathology of the basal ganglia and age-related pathology. The findings do not support the division of PD into early and late-onset cases.
Normative data stratified by three levels of age (16–59, 60–79, and 80–95 years) and three levels of education (0–8, 9–12,
and 13–21 years) are presented for phonemic verbal fluency (FAS) and categorical verbal fluency (Animal Naming). The normative
sample, aged 16 to 95 years, consisted of 1,300 cognitively intact individuals who resided in the community. Years of education
ranged from 0 to 21. The total number of words in 1 minute for each of the letters F, A, and S was correlated r = .52 with
the number of animal names generated in 1 minute. Regression analyses showed that FAS was more sensitive to the effects of
education (18.6% of the variance) than age (11.0% of the variance). The opposite relationship occurred for Animal Naming,
where age accounted for 23.4% of the variance and education accounted only for 13.6%. Gender accounted for less than 1% of
variance for FAS and Animal Naming. The clinical utility of these norms is discussed.
Provides a preliminary theoretical formulation of a threshold theory for acquired brain injury. The theory addresses the concept of brain reserve capacity as a major factor in explaining threshold differences in the onset of clinical symptoms or the expression of impaired test performance after acquired brain injury. The article provides the first critical review of the literature relevant to this theory. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Two studies examined the validity of the Dementia Rating Scale (DRS) as a measure of cognitive functioning among patients with Parkinson's disease (PD). The DRS accounted for more variation in the level of cognitive functioning of PD patients than either the Mini-Mental Status Examination or a battery of tests selected to assess specific cognitive deficits associated with PD. Further, DRS subtests displayed strong convergent and discriminant validity with a comprehensive Criterion Neuropsychology Battery. The DRS subtests appear to be valid measures of attention, perseveration, conceptualization, and memory among PD patients. However, the DRS-Construction subtest should be supplemented with additional visuoconstructional items to provide a thorough screen of cognitive functioning in PD. Although about three-quarters of nondemented PD patients did not appear to have any specific cognitive deficits on the DRS, the remaining patients were impaired on the Construction or Initiation/Perseveration subtests of the DRS. In summary, the DRS is a valid mental status screening test of cognitive functioning for individuals with PD.
To determine the neural circuitry engaged by performance of the Wisconsin Card Sorting Test (WCST), a neuropsychological test traditionally considered to be sensitive to prefrontal lesions, regional cerebral blood flow was measured with oxygen-15 water and positron emission tomography (PET) while young normal subjects performed the test as well as while they performed a specially designed sensorimotor control task. To consider which of the various cognitive operations and other experiential phenomena involved in the WCST PET scan are critical for the pattern of physiological activation and to focus on the working memory component of the test, repeat WCST scans were also performed on nine of the subjects after instruction on the test and practice to criteria. We confirmed that performance of the WCST engages the frontal cortex and also produces activation of a complex network of regions consistently including the inferior parietal lobule but also involving the visual association and inferior temporal cortices as well as portions of the cerebellum. The WCST activation in the dorsolateral prefrontal cortex (DLPFC) remained significant even after training and practice on the test, suggesting that working memory may be largely responsible for the physiological response in DLPFC during the WCST and, conversely, that the DLPFC plays a major role in modulating working memory.
The proportion of patients with idiopathic Parkinson's disease (PD) who are considered demented ranges from 10% to 15%. Because dementia may affect survival in PD, the incidence rate of dementia, rather than proportion, would be a more accurate measure of disease frequency. We previously estimated the proportion of patients with PD and dementia to be 10.9% from the records of a cohort with the idiopathic form of PD in a major medical center. We reviewed the clinical records of this cohort after 4 years and 9 months to estimate the incidence rate of dementia. We identified 65 new cases of dementia from the 249 patient-records available. Using the number of person-years of follow-up for each case as the denominator, we estimated the overall incidence rate to be 69 per 1,000 person-years of observation. The mean age of this cohort was 71.4 years. The cumulative incidence of dementia increased with age. By 85 years of age, over 65% of the surviving members of the cohort were demented. The age-specific incidence rates for dementia in this cohort of PD were significantly greater than for a similarly aged cohort of healthy elderly people. The age-specific standard morbidity ratios indicated that, compared with people of similar ages, patients with PD have the highest increase in risk for dementia between ages 65 and 75.
We investigated the influence of age on the occurrence of cognitive disturbances in Parkinson's disease (PD), by evaluating neuropsychological performances in early- and late-onset groups of patients (less than 45 and greater than 65 years, respectively), individually paired for all the variables of parkinsonism and compared with age-matched controls. Cognitive disorders were limited in the early-onset PD group compared with their age-matched controls. Conversely, we found global cognitive changes, including marked frontal lobe dysfunction, in the late-onset group. This specific cognitive impairment in older patients related to a significant interaction between the aging and disease processes. Late onset seemed to compound the subtle cognitive changes associated with the disease for which the early-onset group compensated. This compounding effect of aging may explain, at least partially, the high frequency of dementia in older PD patients.
In order to investigate the neuronal basis of cognitive disorders in Parkinson's disease, the neuropsychological performance of 120 patients with idiopathic Parkinson's disease was analysed in relation to motor symptoms as a function of their response to levodopa. Cognitive impairment was poorly correlated with akinesia and rigidity, symptoms which respond well to levodopa treatment, and was not correlated at all with that part of the patients' motor score that could be improved by the drug. In contrast, strong correlations were found between all neuropsychological test scores and axial symptoms such as gait disorder and dysarthria, which respond little if at all to levodopa treatment. The neuropsychological test scores were also strongly correlated with the motor score of patients estimated when clinical improvement was maximal under levodopa treatment. This score is assumed to represent residual non-dopaminergic motor dysfunctions. The correlations suggest that much of the cognitive impairment in Parkinson's disease results from the dysfunction of non-dopaminergic neuronal systems.
An abbreviated form of Moss et al.'s (1986) Recognition Span Test (RST) was administered to patients with mild or moderate dementia of the Alzheimer type (DAT) and to intact control (NC) subjects. Memory spans for verbal (i.e., words), spatial and configurational (i.e., faces) information were assessed. Delayed recall (15 s and 2 min) of the words used on the verbal recognition span was also determined. The results showed that both DAT patient groups were impaired on the three recognition tasks and that the spatial and verbal forms differentiated the mildly from the moderately demented patients. The mean overall recognition span scores (spatial + verbal + facial) differentiated between DAT patients and intact controls, with 37 of the 39 patients falling beyond the 95% confidence limits derived from the control subjects' scores. On verbal recall, both the mildly and moderately demented patients were severely impaired and evidenced a very rapid rate of forgetting between the 15-s and 2-min recall attempts. These findings suggest that the RST is not only highly sensitive to memory disorders in the early stages of DAT but also effective in discriminating among various stages of this disorder.
Information about the basal ganglia has accumulated at a prodigious pace over the past decade, necessitating major revisions in the authors' concepts of the structural and functional organization of these nuclei. Recent anatomical and physiological findings have further substantiated the concept of segregated basal ganglia-thalamocortical pathways, and reinforced the general principle that basal ganglia influences are transmitted only to restricted portions of the frontal lobe (even though the striatum receives projections from nearly the entire neocortex). Using the 'motor' circuit as a model, the authors have reexamined the available data on other portions of the basal ganglia-thalamocortical pathways and found that the evidence strongly suggests the existence of at least four additional circuits organized in parallel with the 'motor' circuit. In the discussion that follows, they review some of the anatomic and physiologic features of the 'motor circuit,' as well as the data that support the existence of the other proposed parallel circuits, which they have designated the 'oculomotor,' the 'dorsolateral prefrontal,' the 'lateral orbitofrontal,' and the 'anterior cingulate,' respectively. Each of these five basal ganglia-thalamocortical circuits appears to be centered upon a separate part of the frontal lobe. This list of basal ganglia-thalamocortical circuits is not intended to be exhaustive. In fact, if the conclusions suggested in this review are valid, future investigations might be expected to disclose not only further details (or the need for revisions) of these five circuits, but perhaps also the existence of additional parallel circuits whose identification is currently precluded by a paucity of data.
We attempted to characterize the changes in cognition associated with the earliest, or preclinical, stages of Alzheimer's disease (AD) by administering a comprehensive neuropsychological test battery to a group of initially nondemented older adults participating in a prospective epidemiologic study of dementia. Using Cox regression analyses, we examined the associations between baseline neuropsychological test scores and subsequent development of AD. Results confirmed preliminary findings that baseline scores on the Boston Naming Test, Immediate Recall on the Selective Reminding Test, and the Similarities subtest of the Wechsler Adult Intelligence Scale-Revised were significantly and independently associated with later diagnosis of AD. Analyses controlled for the effects of age, education, sex, and language of test administration. These results lend support to the notion of a preclinical phase of AD and indicate that this very early stage of AD is characterized by poor word-finding ability, abstract reasoning, and memory.
The study assessed cognitive decline in non-demented, non-depressed patients with well defined Parkinson's disease and determined the predictive value for cognitive decline of different motor symptoms. Motor disability was measured with the Unified Parkinson's disease rating scale, impairment in activities of daily living, levodopa test, and long term clinical follow up. Neuropsychological evaluations included modified mini mental state, fluency, Wechsler logical memory, Wisconsin card sorting test, and the Montgomery and Asberg depression rating scale. Fifty three patients fulfilling clinical criteria for idiopathic Parkinson's disease were studied. Cognitive performance on initial testing was significantly correlated with education and disease duration but not with age at disease onset. Cognitive performance on retesting after three years of follow up was significantly reduced. This reduction was significantly greater in the late onset group, in patients with isolated dystonic dyskinesiae, and in patients with a lower percentage of motor improvement on levodopa. Cognitive decline in idiopathic Parkinson's disease may depend on both the prevalence of non-dopaminergic lesions and the topography of dopaminergic denervation. Predictive factors for cognitive decline, especially in executive tasks, relate more to non-dopaminergic than to dopaminergic lesions.
Parkinson's disease patients (PD) do not differ from control subjects (CS) when they have to execute a problem solving task in which external cues for solving the problem are given. However, when PD have to solve a problem by means of an internally generated strategy, they show a serious decrease in performance. We hypothesised that this distinction may also apply to the way PD and CS organize recall. In order to test our hypothesis the California Verbal Learning Test (CVLT) was administered to 59 PD and 30 CS. The test consists of five learning trials using a 16-word target list, composed of four items from each of four semantic categories. The fact that the word list was built on this implicit organization was not divulged in advance. The sequence in which the words were read is fixed; each subsequent word belongs to a category being different from the category to which the preceding word belongs. The organization in recall according to the semantic categories is considered to be the result of an unprompted, internally generated strategy. Recall according to the sequence in which the words are read by the experimenter, is viewed as an externally offered strategy. The results prove to be in line with our hypothesis: unlike CS who appeared to rely mainly and increasingly on an internally generated semantic organization, PD showed evidence of gradually adhering more to the externally imposed serial sequence.
This article discusses the neuropsychological profile of Parkinson's disease from the perspective of cognitive theory, anatomical organization, and unit recording data. Despite the point of origin, methodologically controlled studies are converging to support the position that patients with this disorder suffer selective impairment in the acquisition of novel tasks which rely on internal (subjective) processing for the efficient establishment of new cognitive "habits." The roles of attention and learning as well as of unit activity within the relevant networks are considered. Also included are recent but important concepts from personality theory which potentially enhance understanding of the neuropsychology of Parkinson's disease.
This study investigated the psychometric properties of the Mattis Dementia Rating Scale (DRS), including its internal consistency, sensitivity to age and education effects, pattern of change scores, convergent validity and predictive utility. Age and education effects and stability were assessed in a sample of 280 cognitively normal persons over age 55. All other features were assessed in a sample of 274 persons with cognitive impairment, including 221 newly diagnosed dementia patients and 53 patients with mild cognitive impairment. Both samples were drawn from the Mayo Clinic Alzheimer's Disease Patient Registry. Within the normal sample, Pearson correlation coefficients for DRS Total score with age, education and intelligence were all significant, p < .0001; MAYO Full Scale IQ (FSIQ) shared approximately 20% variance with DRS Total score. Internal consistency was greater than .7 for Construction, Conceptualization, Memory, and Total score, greater than .65 for Attention and less than .5 for Initiation and Perseveration. DRS subscale scores for Memory, Attention, and Conceptualization were significantly correlated with appropriate indices from the WAIS-R or Wechsler Memory Scale-Revised, as assessed in the Mayo Older Americans Normative Studies, providing convergent validity for these DRS scales. Importantly, proportional hazards modeling revealed initial DRS Total score to be a significant predictor of longitudinal institutionalization and mortality outcomes.
It is controversial whether age of disease onset is related to cognitive decline in Parkinson's disease (PD). We administered 7 cognitive measures assessing visuospatial skills, memory, and executive functions to 222 patients with idiopathic PD and 108 normal control participants. Regression analyses demonstrated that older age of disease onset consistently predicted cognitive decline above and beyond normative aging and duration of illness. These findings suggest that older age of disease onset is a critical determinant of cognitive deterioration in PD.
Regression-based norms for the Trail Making Test, Boston Naming Test, and Wisconsin Card Sorting Test, which we published in 1991 and 1993, have been criticized by Fastenau (1998) as having overcorrected for demographic influences in a sample of 63 older adults. We present data from new, independent participant samples that are consistent with expectations from the regression-based norms. We propose that Fastenau's findings in this instance resulted from the nonrepresentative nature of his relatively small sample, rather than from statistical deficiencies of regression based norms. Our currently published norms on one of the four tests considered here, the Boston Naming Test, are based upon a participant sample that was small and had inadequate representation of young adults. We address this by providing updated norms based on a much larger and more representative sample (N = 531).
To determine whether the rate of decline in performance on a memory test is more rapid in AD patients with higher versus lower educational and occupational attainment.
Epidemiologic and imaging studies have suggested that, given comparable clinical severity of dementia, AD pathology is more advanced in patients with higher educational and occupational attainment. Because educational and occupational attainment should not influence the progression of AD pathology, and because severe AD pathology will eventually produce a mortality-causing condition, people with higher attainment might experience clinical AD for a shorter time and have a more rapid clinical progression.
A total of 177 AD patients were tested yearly for up to four study visits with the Selective Reminding Test (a memory test). Analysis of prospective change in the total recall score was performed by applying generalized estimating equations to regression analyses with repeated measures.
At the initial visit, scores were comparable in the high- and low-education and the high- and low-occupation groups. Overall, memory scores declined by approximately 1 point yearly (p<0.01). There was a more rapid decline in memory scores in patients with higher educational (p<0.057) and higher occupational attainment (p<0.02). The authors then stratified patients based on their initial memory scores. The more rapid decline in memory scores associated with higher educational and occupational attainment was noted only in the group with low initial scores (p<0.05 for both). The full group and stratified group analyses were also repeated controlling for other potentially relevant variables including age, gender, race, ethnicity, and the presence of extrapyramidal signs, stroke, or at least one apolipoprotein E-epsilon4 allele. The results remained unchanged.
Memory declined more rapidly in AD patients with higher educational and occupational attainment. This adds support to the idea that the discontinuity between the degree of AD pathology and the observed clinical severity of AD is mediated through some form of reserve.
Contrary findings notwithstanding, the prevailing notion is that recognition memory is little affected by Parkinson's disease (PD). Both a power analysis and a meta-analysis were conducted to help clarify the degree of recognition memory deficit associated with PD. The power analysis confirmed that, in general, memory studies of PD participants have been underpowered. This analysis indicated the need to pool study results in a subsequent meta-analysis, the main finding of which was that recognition memory deficits do occur with PD. The largest deficit occurs in PD participants with dementia. Nevertheless, deficits also occur in PD participants without dementia on medication, but nondopaminergic central nervous system abnormalities are more likely to underlie this deficit than PD medication itself. Future development of a theory of cognitive dysfunction in PD should take into account these recognition memory deficits, which may increase with disease progression.
To calculate the incidence of and determine possible risk factors for dementia in PD.
Dementia has important clinical consequences for patients with PD and their caregivers, but the incidence is unknown.
A population-based cohort of nondemented patients with PD (n = 171) from the county of Rogaland, Norway, was assessed at baseline and 4.2 years later with a comprehensive evaluation of motor, cognitive, and neuropsychiatric symptoms. The diagnosis of dementia was made according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised (DSM-III-R) criteria, based on interview of the patient and a caregiver, cognitive rating scales, and neuropsychologic tests. A representative sample of 3,062 nondemented elderly subjects without PD served as control group.
Forty-three patients with PD were demented at follow-up evaluation, equivalent to an incidence rate of 95.3 per 1,000 person-years (95% CI, 68.2 to 122.0). The risk for the development of dementia in patients with PD relative to the control subjects after adjusting for age, sex, and education was 5.9 (95% CI, 3.9 to 9.1). Predictive factors at baseline for dementia in PD in addition to age were Hoehn & Yahr score >2 (OR, 3.4; 95% CI, 1.3 to 8.6) and Mini-Mental State Examination score < 29 (OR, 3.3; 95% CI, 1.3 to 8.2).
Patients with PD have an almost sixfold increased risk for becoming demented compared with subjects without PD.
The aim of this paper is to update the over 20-year-old normative data for the Benton Controlled Word Association (COWA) Test. In a sample of 360 normal volunteers, the age ranged between 16-70 years, and the educational level ranged from 7-22 years. Care was taken to ensure that the population was heterogeneous, yet the two stratifications of gender, four age, and three educational groups led to 24 cells with 15 individuals in each. Test-retest reliability was established by testing 30% of the sample after a 6-month delay, which represents a typical follow up duration between testings in a clinical setting. The two forms of the COWA revealed significant test-retest reliability. Generally, our updated values fall above the original normative values, which were derived from a less well-educated and rural sample. No major gender or age trends were noted, but the COWA test performances were influenced by education, i.e., as the level of education increased, the performance on the COWA increased. The only gender differences that were found were for the women in the highest educational group ( > 16 years), who performed significantly better that men in the highest educational group. An error analysis of repetitions or perseverations is provided, with cut-off scores according to age levels. Finally, the updated COWA norms are compared to the original norms as well as to other measures of word fluency.
Parkinson’s disease. Neurobehavioral aspects
- Huber
- J L Cummings
Wisconsin Card Sorting Test Manual. Odessa FL: Psychological Assessment Resources
- R K Heaton
Multilingual Aphasia Examination 3rd ed. Iowa City: AJA Associates
- A Benton A Hamsher K Sivan
Sinemet CR for Parkinson’s disease
- M Abramowicz
Dementia rating scale. Odessa FL: Psychological Assessment Resources
- S Mattis