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Neuropsychological Performance in Lateralized Parkinsonism
Abstract
Seven dextral patients with Parkinson's disease (PD) who had predominant right-sided motor signs were compared on neuropsychological tests with eight dextral patients with PD who had predominant left-sided signs. Objective criteria for group designation were developed from clinical ratings. The patient subgroups were matched on age, education, estimated premorbid IQ, severity of motor signs, and medication usage. Patients with signs lateralized to the right were more impaired on tests of dominant hemisphere function (serial digit learning, confrontation naming, and verbal associative fluency), but no differences were found on tests of nondominant hemisphere function (form sequence learning, line orientation, facial recognition), indicating some correlation of neuropsychological performance with lateralization of predominant motor signs. Findings demonstrate that the cognitive deficits (particularly visuospatial) previously reported in the literature are not seen consistently in all subjects with PD.
... Dopamine neuromodulation is intrinsic to processes of movement and motor learning, cognition, reward processing, food intake, nociception, and endocrine and autonomic regulation. Studies on the lateralization of cognitive functions in patients with PD yielded conflicting results: some reported that neuropsychological deficits are consistent with the lateralization of motor symptoms [4][5][6][7][8][9][10], whilst others failed to find a correlation [11][12][13][14][15]. A limitation of several of these studies is that they prevalently investigated global lateralized brain functions in patients with variable disease severity. ...
... Our data on cognition confirm a number of earlier studies reporting no association between laterality of motor impairment and executive functions [12,13,15] and challenge other studies suggesting that patients with left hemisphere involvement have a reduced performance in verbal fluency [7,9,10], digit span [7], and Wisconsin Card Sorting Test [8,10]. The strict inclusion criteria of this protocol probably accounts for the observed normal cognitive features. ...
... Our data on cognition confirm a number of earlier studies reporting no association between laterality of motor impairment and executive functions [12,13,15] and challenge other studies suggesting that patients with left hemisphere involvement have a reduced performance in verbal fluency [7,9,10], digit span [7], and Wisconsin Card Sorting Test [8,10]. The strict inclusion criteria of this protocol probably accounts for the observed normal cognitive features. ...
Dopamine neurotransmission plays a key role in several brain activities, including motor, cognitive, and behavioral functions. Parkinson's disease (PD) typically begins with asymmetrical motor features related to asymmetrical dopamine denervation. This study was designed to examine whether distinct cognitive, behavioral, and personality features are related to this asymmetry.
Fifty-six patients with mild PD and lateralized motor features were grouped according to dominant side of motor features and evaluated using a neuropsychological assessment focused on attention and executive functions, impulse control disorders, and personality inventory.
There were no differences in neuropsychological functions between patients with right and left lateralized PD, but differences occurred in personality features. Patients with motor impairment predominant on the left-hand side had prevalence of hypomania and conversion profile.
This study suggests that side dominance of dopaminergic denervation may be related to personality features in patients with PD that could influence behavioral aspects.
... PD has been viewed by many experts as a lateralised disorder with each hemisphere having designated motor and cognitive responsibilities. Thus, the side of symptom onset may carry differential effects on cognitive, visuospatial and perceptuo-motor functions [4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Although some studies did not demonstrate a hemispheric difference on cognitive functioning [8,11] the majority of studies revealed some association with cognitive functions, especially those known to be located in a specific hemisphere [4,6,9,10,13,14]. ...
... Thus, the side of symptom onset may carry differential effects on cognitive, visuospatial and perceptuo-motor functions [4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Although some studies did not demonstrate a hemispheric difference on cognitive functioning [8,11] the majority of studies revealed some association with cognitive functions, especially those known to be located in a specific hemisphere [4,6,9,10,13,14]. ...
Researchers have consistently observed in right-handed individuals across normal and disease states that the 'dominant' left hemisphere has greater ipsilateral control of the left side than the right hemisphere has over the right. We sought to determine whether this ipsilateral influence of the dominant hemisphere reported in Parkinson's disease extends to treatments such as deep brain stimulation (DBS) and whether it affects outcome. We hypothesised that among Parkinson right-handers, unilateral left DBS would provide greater ipsilateral motor improvement compared with the ipsilateral motor improvement experienced on the right side.
A total of 73 Parkinson patients who underwent unilateral DBS of the subthalamic nucleus (STN) or globus palidus internus (GPi) participated. Left and right 'composite scores', were computed by separately adding all items on the left and right side from the motor section of the Unified Parkinson Disease Rating Scale. The change in the pre- and 4-month post-implantation score was the primary outcome measure. The mean motor scores improved by 4.96 ± 11.79 points (p < 0.001) post-surgery on the ipsilateral side of the DBS implantation. Regression analyses revealed that the side (left vs. right) and target (STN vs. GPi) did not significantly contribute in the effect of ipsilateral motor improvement (p = 0.3557).
While DBS on the 'dominant' left side failed to exert a greater ipsilateral influence compared with DBS on the non-dominant right side, significant ipsilateral motor improvements were observed after unilateral stimulation regardless of site of implantation and laterality.
... This possibility has been addressed in previous studies, but results have been mixed. A number of studies fully or partially support the expected pattern of lateralized cognitive deficits: PD participants with worse left-sided motor dysfunction perform more poorly on visuospatial (right hemisphere) tasks and those with worse right-sided motor dysfunction perform more poorly on verbally mediated (left-hemisphere) tasks (Amick, Grace, & Chou, 2006; Blonder, Gur, Gur, Saykin, & Hurtig, 1989; Huber, Miller, Bohaska, Christy, & Bornstein, 1992; Spicer, Roberts, & LeWitt, 1988; Starkstein, Leiguarda, Gershanik, & Berthier, 1987; Taylor, Saint-Cyr, & Lang, 1986). Others found widespread cognitive deficits in participants with worse left-sided dysfunction while participants with worse rightsided dysfunction were relatively cognitively spared (Direnfeld et al., 1984; Tomer, Levin, & Weiner, 1993). ...
... Other studies have demonstrated worse performance by RPD groups on a variety of cognitive tasks and specifically those that rely on verbal abilities (e.g. Blonder et al., 1989; Spicer et al., 1988; Williams et al., 2007). These points reduce the likelihood of widespread impairment in individuals with predominantly left-body motor dysfunction. ...
Studies suggest motor deficit asymmetry may help predict the pattern of cognitive impairment in individuals with Parkinson disease (PD). We tested this hypothesis using a highly validated and sensitive spatial memory task, spatial delayed response (SDR), and clinical and neuroimaging measures of PD asymmetry. We predicted SDR performance would be more impaired by PD-related changes in the right side of the brain than in the left. PD (n=35) and control (n=28) participants performed the SDR task. PD participants either had worse motor deficits on the right (RPD) or left (LPD) side of the body. Some participants also had magnetic resonance imaging for measurement of their substantia nigra (SN) volumes. The LPD group performed worse on the SDR task than the RPD and control groups. Right SN volume accounted for a unique and significant portion of the variance in SDR error, with smaller volume predicting poorer performance. In conclusion, left motor dysfunction and smaller right SN volume are associated with poorer spatial memory.
... As far as neuropsychological functions are concerned, reduced cognitive performances in patients with predominantly right-sided motor symptoms (RPD) have been previously documented in comparison to patients with predominantly left-sided motor symptoms (LPD) (Agosta et al., 2020;Huber et al., 1992;Katzen et al., 2006). These deficits concern global cognitive efficiency (Agosta et al., 2020), long-term verbal memory (Amick et al., 2006;Cubo et al., 2010;Foster et al., 2010;Huber et al., 1992;Starkstein et al., 1987;Starkstein and Leiguarda, 1993), language (Blonder et al., 1989;Mohr et al., 1992;Spicer et al., 1988;Starkstein et al., 1987) and for some specific authors, executive functions (Huber et al., 1992;Voruz et al., 2020;Voruz et al., 2022). Some have even suggested that RPD patients may be more vulnerable to the onset of dementia associated with PD in the long term (Harris et al., 2013). ...
Introduction
The longitudinal trajectories of cognitive-neuropsychiatric symptoms from the early stages of Parkinson's disease, as a function of motor symptom asymmetry at the onset of the disease, remain to be fully explored. Moreover, the relationship to biomarkers warrants further investigation.
Method
ology: Non-motor and biospecimen data from 413 patients with Parkinson's disease, dissociating predominantly left-sided motor symptoms patients (n = 179) and predominantly right-sided motor symptoms patients (n = 234), and matched healthy controls (n = 196), were extracted from the Parkinson's Progression Marker Initiative database during a 3-Year follow-up. Non-parametric and conservative correction for multivariate comparison were carried out on neuropsychiatric and biomarker data.
Results
A decline for global cognitive efficiency scores in predominantly right-sided motor symptoms patients was observed, whereas depressive and anxiety symptoms were greater overtime for predominantly left-sided motor symptoms patients. Biomarkers analysis revealed that predominantly right-sided patients expressed decreased levels of total-tau and phospho-tau over time, while left-sided patients didn't differ from healthy controls.
Conclusion
From the early course of the disease, the existence of different clinical phenotypes is proposed, associated to emerging evidences of distinct pathological pathways and a left-hemispheric vulnerability for cognitive decline.
... No associations with laterality of initial symptoms were evident in group 1, however, and performance on the selective reminding test was unrelated to right (v left) sided presentation in group 2. Simultaneous assessment of motor and cognitive deficits have shown various associations between motor symptom laterality and cognitive impairment. Spicer et al 18 found that patients with unilateral right sided motor signs had greater impairment on serial digit learning, confrontation naming, and verbal associative fluency than patients with left sided disease. Blonder et al 19 reported an association between right sided symptoms and verbal deficits and between left sided symptoms and visuospatial impairment. ...
Introduction
Neuroendocrine tumours(NETs) are an uncommon group of heterogenous neoplasms that originate from neuroendocrine cells. Patients with NETs frequently experience diarrhoea that can impact their quality of life. Approximately 20% develop carcinoid syndorme characterised by dry flushing and diarrhoea but causes other than functional syndromes may not be considered. Pancreatic enzyme insufficiency(PEI), bile acid diarrhoea(BAD) and small intestinal bacterial overgrowth(SIBO) are potential causes. There is limited data on prevalence of these conditions in NETs. The main aim of this study is to evaluate the prevalence of PEI, BAD and SIBO in a heterogeneous population of NET patients and secondarily to assess the impact of these conditions on quality of life.
Methods
This was a retrospective, single centre observational study in a dedicated NET. 257 patients were included in this study. PEI was defined as low faecal elastase or treatment with pancreatic enzyme replacement therapy. BAD was defined as an abnormal SeHCAT scan or treatment with bile acid sequestrants. SIBO was defined as a positive hydrogen breath test or empirical antibiotics. The EORTC QLQ-GI.NET21 and a modified Gastrointestinal Symptom Rating Scale(GSRS) questionnaires were completed as part of normal clinical practice. Total scores of the questionnaires of those with and without a diarrhoeal condition were compared.
Results
The majority of patients had a midgut primary (n=202;78.6%), were Grade 1 (n=182;70.8%) and had metastatic disease(n=211;82.1%). Most were on somatostatin analogues(SSAs) (n=186;72.4%) and had surgery(n=175;68.1%). PEI was diagnosed in 153(59.5%) patients with a significant association with the use of SSAs (p<0.001). BAD was diagnosed in 52(20.2%) patients with a significant association with bowel resection (p<0.001). SIBO was diagnosed in 42(16.3%) patients. 163(63.8%) patients had at least one of PEI, BAD or SIBO. of these, 107(65.9%) had a single diagnosis, 29(17.7%) had two diagnoses and 27(16.5%) had three. The median total EORTC QLQ-GINET21 and GSRS scores were significantly higher in those with PEI, BAD or SIBO (p<0.001).
Conclusions
We provide the first systematic study to assess the common causes of diarrhoea in a NET population. PEI, BAD and SIBO are common causes of diarrhoea in patients with NETs. A third of those diagnosed had more than one condition suggesting that if symptoms do not improve with treatment, alongside dose titration an additional cause may need investigation. Ultimately through a stepwise approach to the diagnosis of diarrhoea, symptoms and quality of life of patients may be improved.
... The frequency of non-motor symptom increases along with the duration of the disease (29) and some non-motor symptoms that may be related to asymmetry may not yet appear. We also found no difference between LPD and RPD in the cognitive function, which supports previous studies (30,31). Considering that our sample size is relatively small, more research is needed. ...
Background and Purpose: The unilateral onset and persistent asymmetry of motor symptoms are important characteristics of Parkinson's disease (PD). By using scales and wearable sensors, this study explored whether motor symptom laterality could affect non-motor symptom and gait performance.
Methods: A total of 130 right-handed patients with PD were enrolled in our study and were divided into two groups according to the side of predominant motor symptom presentation by using the Unified Parkinson's Disease Rating Scale part III. We measured the non-motor symptoms with the Non-motor symptoms Scale, sleep quality with the Parkinson's Disease Sleep Scale and Pittsburgh sleep quality index, cognitive function with the Mini-mental State Examination and Montreal Cognitive Assessment, quality of life with the Parkinson's Disease Questionnaire-39, and the severity of anxiety and depression with the Hamilton Anxiety Scale and Hamilton Depression Scale, respectively. All participants underwent the instrumented stand and walk test, and gait data were collected using a set of JiBuEn gait analysis system.
Results: We observed that left-dominant symptom PD patients (LPD) were associated with a greater impairment of sleep quality than right-dominant symptom PD patients (RPD). We found no difference between LPD and RPD in terms of gait performance. However, compared with the severe asymmetry RPD patients (RPD-S), severe asymmetry LPD patients (LPD-S) showed a shorter stride length and decreased range of motion of hip joints.
Conclusions: In this study, LPD was associated with a more severe sleep-related dysfunction than RPD. In addition, LPD-S exhibited more gait impairments than RPD-S. Considering that motor symptom laterality may affect the non-motor symptom and gait performance, it should be taken into account when evaluating and treating PD patients.
... On the other hand there are also studies that did not find differences between hemiparkinsonian groups in visual mem-ory, visuoconstruction, and other visuospatial areas (Agniel et al., 1991;Finali et al., 1995;Goldenberg, 1989;Hietanen & Teräväinen, 1989;Huber et al., 1989;Natsopoulos et al., 1993;Raskin et al., 1992;Riklan et al., 1990;Spicer et al., 1988). The few studies which also incorporated a control group mostly revealed inferior performance of the Parkinson groups compared to healthy controls. ...
Parkinsons disease is characterized by tremor, rigidity, and bradykinesia. The study of patients with predominant symp- toms on one side of the body (hemiparkinsonism) is clinically relevant for different disciplines. The predominantely affect- ed side of the dopamine system in patients with Parkinsons disease might have differential effects on certain functions. The functional architecture of the basal ganglia suggests their involvement in visuocognitive processes. Earlier studies have yielded mixed results. Only few studies examined differences in visuocognitive functions in hemiparkinsonism compared to a control group. The aim of our study was to examine such functions and their interrelations in hemiparkinsonism in comparison to a control group in detail. We compared 22 Par- kinson patients with predominantely right sided symptoms (Parkinson right), 22 Parkinson patients with predominantely left sided symptoms (Parkinson left) and 22 healthy controls on several visuocognitive measures. We found no significant differences between the three groups in visuoconstruction, visual memory, mental rotation, and movement imagery. Significant differences were found in a self-rating instrument of visual imagery. The control group generally has a clearer visual imagination than the Parkinson left group. On sub- scale level the control group has a clearer geometric-sche- matic imagery than the Parkinson right and the Parkinson left group. The control group further has a clearer phantasy imagery than the Parkinson left group. In the Parkinson right group there is a significant association of self-rated visual imagery and visual memory. In the Parkinson left group there are significant correlations between geometric-schematic im - agery on one side and visual memory and mental rotation on the other side. In the control group there are significant as - sociations between mental rotation and figural memory and between visuoconstruction and visual reproduction. These correlational patterns suggest that there are different under- lying mechanisms in the three groups that are relevant for performance in visuocognitive tasks. Our results suggest no differential role of the basal ganglia in objective neuropsy- chological measures of visual cognition. The self-rated visu- al imagery ability seems to be mainly mediated by the right basal ganglia because especially the Parkinson left group is impaired in this area. The definition of laterality of motor symptoms should be standardized.
... Laterality of motor symptoms during early stages of the disease have related to asymmetric dopamine depletion in the substantia nigra (Kempster et al., 1989), asymmetric dysfunction of cortico-striatal circuitry (Middleton & Strick, 2000a), and might be associated with specific cognitive deficits (Middleton & Strick, 2000b). Patients with right-sided symptoms (left brain) perform poorly on verbal tasks while patients with left-sided symptoms (right brain) show reduced performance on visuospatial tasks (Bentin et al., 1981;Blonder, Gur, Gur, Saykin, & Hurtig, 1989;Cooper et al., 2009;Spicer, Roberts, & LeWitt, 1988). ...
Objective:
A 71-year-old (MN) with an 11-year history of left onset tremor diagnosed as Parkinson's disease (PD) completed longitudinal brain magnetic resonance imaging (MRI) and neuropsychological testing. MRI scans showed an asymmetric caudate nucleus (right < left volume). We describe this asymmetry at baseline and the progression over time relative to other subcortical gray, frontal white matter, and cortical gray matter regions of interest. Isolated structural changes are compared to MN's cognitive profiles.
Method:
MN completed yearly MRIs and neuropsychological assessments. For comparison, left onset PD (n = 15) and non-PD (n = 43) peers completed the same baseline protocol. All MRI scans were processed with FreeSurfer and the FMRIB Software Library to analyze gray matter structures and frontal fractional anisotropy (FA) metrics. Processing speed, working memory, language, verbal memory, abstract reasoning, visuospatial, and motor functions were examined using reliable change methods.
Results:
At baseline, MN had striatal volume and frontal lobe thickness asymmetry relative to peers with mild prefrontal white matter FA asymmetry. Over time only MN's right caudate nucleus showed accelerated atrophy. Cognitively, MN had slowed psychomotor speed and visuospatial-linked deficits with mild visuospatial working memory declines longitudinally.
Conclusions:
This is a unique report using normative neuroimaging and neuropsychology to describe an individual diagnosed with PD who had striking striatal asymmetry followed secondarily by cortical thickness asymmetry and possible frontal white matter asymmetry. His decline and variability in visual working memory could be linked to ongoing atrophy of his right caudate nucleus.
... On the other hand there are also studies that did not find differences between hemiparkinsonian groups in visual mem-ory, visuoconstruction, and other visuospatial areas (Agniel et al., 1991;Finali et al., 1995;Goldenberg, 1989;Hietanen & Teräväinen, 1989;Huber et al., 1989;Natsopoulos et al., 1993;Raskin et al., 1992;Riklan et al., 1990;Spicer et al., 1988). The few studies which also incorporated a control group mostly revealed inferior performance of the Parkinson groups compared to healthy controls. ...
... Other studies have shown a relationship between lateralization of PD symptoms and hemisphere specific cognitive dysfunction. Several studies reported that predominant right-sided parkinsonian symptoms (reflecting left-hemisphere dysfunction) correlate with impaired performance on verbal fluency and verbal memory, (Huber, Freidenberg, Shuttleworth, Paulson, & Clapp, 1989;Spicer, Roberts, & LeWitt, 1988;Starkstein et al., 1987;Taylor, Saint-Cyr, & Lang, 1986). Left-sided symptoms have been associated with visuospatial impairments (Direnfeld et al., 1984;Finali, Piccirilli, & Rizzuto, 1994) and mild left hemispatial neglect (Starkstein et al., 1987). ...
The current study examined cognitive effects of unilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) patients. Neuropsychological evaluations were conducted at baseline and follow-up. Data was collected from 28 unilateral STN DBS patients (15 English- and 13 Spanish-speaking), and 15 English-speaking matched PD control patients. English-speaking DBS patients demonstrated significant declines in verbal fluency and attention/executive function, whereas PD control patients did not experience significant cognitive decline. Cognitive performance did not differ based on side of DBS. Spanish-speaking DBS patients experienced significant declines in verbal fluency, confrontational naming and visuospatial abilities. Among Spanish-speaking DBS patients, older age and later age of disease onset predicted verbal fluency decline, even after controlling for education.
... We also recorded the clinical phenotype and the antiparkinsonian treatment. The most affected side was defined by the patient's reported initial side of symptoms onset and confirmed if the sum of the UPDRS motor items for this side of the body was at least twice that of the other side (Spicer, Roberts, & LeWitt, 1988 ). All patients were additionally referred for psychiatric evaluation by a psychiatrist who was unaware of the neurological data. ...
This study was designed to evaluate the association of different apathy conceptual domains with central fatigue perception in Parkinson's disease (PD), taking into consideration other nonmotor symptoms. To this end, 90 consecutive PD patients (66.7% men, mean age 61.44 ± 13.2 years) underwent a comprehensive neurological and psychiatric examination, including the Structured Clinical Interview for DSM–IV, Parkinson Fatigue Scale, Lille Apathy Rating Scale, Hamilton Depression Scale, and State–Trait Anxiety Inventory. A linear regression model was applied to analyze the relationship between apathy and its different conceptual domains with fatigue severity. Thirty-seven (41.1%) patients presented fatigue. Its presence was associated with higher apathy total scores and with 2 of the 4 apathy conceptual domains (less intellectual curiosity and action initiation) with no associations in the emotion and self-awareness apathy domains. Patients with fatigue scored higher in depression (p < .001), anxiety trait (p < .001), and anxiety state (p = .006). Regression analysis identified that Lille Apathy Rating Scale total score (p = .008), intellectual curiosity and action initiation apathy subscores (p = .001 and p = .003) were associated with fatigue severity in patients with right predominant motor symptoms. Sex, age, disease duration, clinical stage, motor complications, prior psychiatric disorders, and treatment were not significantly associated with presence of fatigue. The findings suggest that some apathy-related domains are more frequent in fatigued PD and may be related with fatigue severity.
... Huber, Miller, Bohaska, Christy, and Bornstein (1992) reported that PD participants with more severe right-side symptoms performed significantly more poorly than left-sided PD participants on tests of intelligence, verbal (but not visual) memory, and concentration. Spicer, Roberts, and LeWitt (1988) reported significantly poorer performance by right-sided PD than left-sided PD on serial digit learning, visual naming, and word fluency tasks. ...
Asymmetric motor severity is common in Parkinson's Disease (PD) and provides a method for examining the neurobiologic mechanisms underlying cognitive and linguistic deficits associated with the disorder. In the present research, PD participants (N=31) were assessed in terms of the asymmetry of their motor symptoms. Interviews with the participants were analyzed with the Linguistic Inquiry and Word Count (LIWC) program. Three measures of linguistic complexity - the proportion of verbs, proportion of function words, and sentence length - were found to be affected by symptom asymmetry. Greater left-side motor severity (and hence greater right-hemisphere dysfunction) was associated with the production of significantly fewer verbs, function words, and shorter sentences. Hence, the production of linguistic complexity in a natural language context was associated with relatively greater right hemisphere involvement. The potential neurobiological mechanisms underlying this effect are discussed.
... No associations with laterality of initial symptoms were evident in group 1, however, and performance on the selective reminding test was unrelated to right (v left) sided presentation in group 2. Simultaneous assessment of motor and cognitive deficits have shown various associations between motor symptom laterality and cognitive impairment. Spicer et al 18 found that patients with unilateral right sided motor signs had greater impairment on serial digit learning, confrontation naming, and verbal associative fluency than patients with left sided disease. Blonder et al 19 reported an association between right sided symptoms and verbal deficits and between left sided symptoms and visuospatial impairment. ...
Neuropsychological data collected from two groups of patients with idiopathic Parkinson's disease (n = 50, 159) were analysed to investigate the association between presenting motor symptoms determined from retrospective chart review and the risk of cognitive impairment. Presenting motor symptoms were abstracted from the medical records and coded by type, location, and laterality. Longitudinal data on changes in the maximum speed of voluntary arm movements were available for a subsample of patients. Bilateral (v unilateral) presentation was associated with an increased risk of cognitive impairment an average of nine years after onset of disease as measured by memory tests and the mini-mental state examination. A higher rate of decline of arm movement speed was also predictive of greater memory dysfunction. The type, side (left v right), and location (lower v upper extremity) of the presenting symptoms were not, however, consistently associated with the risk of cognitive impairment later in the course of the disease.
... of the disease (Gabrieli, Singh et al., 1996; Lewis, Slabosz et al., 2005), perhaps due to altered basal ganglia output or changes in mesocortical dopaminergic pathways (Carbon and Marie, 2003). The degree of impairment in spatial working memory may depend in part on which hemisphere of the brain is more affected by PD, since worse left-sided motor dysfunction in PD is associated with worse spatial (right hemisphere) tasks and worse right-sided motor dysfunction is associated with more impairment on verbally mediated (left-hemisphere) tasks (Taylor, Saint-Cyr et al., 1986; Starkstein, Leiguarda et al., 1987; Spicer, Roberts et al., 1988; Blonder, Gur et al., 1989; Huber, Miller et al., 1992; Amick, Grace et al., 2006). ...
Bilateral subthalamic nucleus deep brain stimulation (STN DBS) can reduce working memory while improving motor function in Parkinson disease (PD), but findings are variable. One possible explanation for this variability is that the effects of bilateral STN DBS on working memory function depend in part on functional or disease asymmetry. The goal of this study was to determine the relative contributions of unilateral DBS to the effects seen with bilateral DBS. Motor (Unified Parkinson Disease Rating Scale Part III, UPDRS) and working memory function (Spatial Delayed Response, SDR) were measured in 49 PD patients with bilateral STN DBS while stimulators were Both-off, Left-on, Right-on and Both-on in a randomized, double-blind manner. Patients were off PD medications overnight. Effects of unilateral DBS were compared to effects of bilateral STN DBS. Mean UPDRS and SDR responses to Left-on vs. Right-on conditions did not differ (p>.20). However, improvement in contralateral UPDRS was greater and SDR performance was more impaired by unilateral DBS in the more affected side of the brain than in the less affected side of the brain (p=.008). The effect of unilateral DBS on the more affected side on contralateral UPDRS and SDR responses was equivalent to that of bilateral DBS. These results suggest that motor and working memory function respond to unilateral STN DBS differentially depending on the asymmetry of motor symptoms.
Patients with predominantly unilateral parkinsonian signs may provide a unique opportunity to evaluate the cerebral representation of cognitive functions characteristically affected in idiopathic Parkinson’s disease. Twenty hemiparkinsonian patients (ten left and ten right) and 10 healthy controls, matched for age and education, were studied with neuropsychological tests and positron emission tomography. Both right and left hemiparkinsonians evidenced impairments in visuospatial and verbal episodic memory function, but had no deficits in executive abilities, compared to controls. None of the neuropsychological test scores distinguished right from left hemiparkinsonians. Glucose metabolic profiles were identical for the three groups in all cortical areas assessed; in the subcortex however, lenticular hypermetabolism contralateral to the predominant side of motor involvement was evident in the left hemiparkinsonian group. Correlational analysis revealed that higher glucose metabolic rates in the basal ganglia of these hemiparkinsonians were associated with lower visuospatial test scores. In frontal and parietal cortex, decreasing glucose metabolism was positively associated with neurobehavioral function; in temporal cortex, measures of attention and memory decreased with increasing glucose metabolic rates.
O presente capítulo aborda os métodos avaliativos mais comumente utilizados, bem como a reabilitação dos desajustes laríngeos presentes na disfonia.
Introduction:
Symptom laterality is one of the main characteristics of Parkinson disease (PD) and reported to be associated with motor and nonmotor symptom severity and prognosis. This study aimed to evaluate the changes of laterality after deep brain stimulation (DBS) and the association between dopamine transporter SPECT using I FP-CIT (DAT SPECT) and symptom laterality in PD before and after DBS.
Methods:
Nineteen patients with PD who received bilateral subthalamic nucleus DBS were enrolled. The clinical scores including Unified Parkinson Disease Rating Scale (UPDRS) and Hoehn and Yahr were evaluated at baseline, 6 months, and 1 year after DBS. Also, the patients underwent DAT SPECT before and 6 months and 1 year after DBS. Symptom and DAT laterality indices were determined based on the UPDRS part 3 and DAT SPECT, respectively. The association between DAT and symptom laterality was assessed at baseline and 6 months and 1 year after DBS.
Results:
At baseline, 11, 6, and 2 among 19 patients had left-side-dominant, right-side-dominant, and symmetric motor symptom, respectively. Among 19 patients, there were 10 patients who showed changed symptom laterality within 1 year after DBS. The agreement between symptom laterality and DAT laterality was good to excellent at baseline and 6 months and 1 year after DBS (weighted κ = 0.742, 0.736, and 0.813). Furthermore, symptom and DAT laterality indices showed significant correlation at baseline (r = 0.542, P = 0.02), 6 months (r = 0.579, P = 0.01), and 1 year after DBS (r = 0.689, P = 0.02). Symptom laterality could be determined by DAT laterality index with areas under curve of 0.833 (P = 0.045), 0.982 (P < 0.001), and 1.000 (P < 0.001) at baseline and 6 and 12 months after DBS, respectively.
Conclusions:
The symptom laterality could be altered after DBS and was well correlated with laterality evaluated by DAT SPECT. An objective evaluation of laterality using DAT SPECT would be helpful for the management of patients with PD especially for adjusting the DBS programming for fine balancing of the asymmetric symptom after DBS. The large-scale study is warranted for validation of this result.
Escrever sobre reabilitação enquanto campo de prática clínica e sua integração com a pesquisa é uma tarefa mais complexa do que pode parecer. O livro que ora apresentamos nasceu de uma iniciativa dos organizadores, a partir da busca por um enfoque da reabilitação clínica e da integração com a pesquisa realizada no PPG Ciências da Reabilitação da Universidade Federal de Ciências da Saúde de Porto Alegre. A tarefa, que parecia simples, de coadunar colegas especialistas em diferentes áreas da reabilitação para escreverem sobre tema de sua produção teórica e científica mostrou-se um trabalho extenso. O trabalho compreendeu vastas revisões dos especialistas em cada um dos temas. O cuidado dos autores dos capítulos apresentados neste livro é típico de pesquisadores, cientistas de um campo com aplicações clínicas de amplo espectro e que têm visualização clara sob a matéria. Nos dezesseis capítulos são exploradas temáticas presentes nas três linhas de pesquisa do programa: reabilitação musculoesquelética, reabilitação cardiorrespiratória e reabilitação neurológica. No primeiro capítulo, as autoras Michele Rocha e Maria Cristina Cardoso apresentam os métodos de avaliação dos distúrbios da deglutição e exploram a prática clínica aliada à pesquisa, através da comparação dos diferentes processos de avaliação das disfagias que, quando presentes, podem desencadear quadros clínicos de desidratação, desnutrição e distúrbios pulmonares aspirativos. No mesmo caminho, no segundo capítulo, Camila Lucia Etges, Lisiane de Rosa Barbosa e Maria Cristina Cardoso tratam do diagnóstico de distúrbios de deglutição em pediatria no ambiente hospitalar, apresentando uma atualização dos dados para o diagnóstico de distúrbios de deglutição em pediatria, tema constantemente carente de informações empíricas e ensaios clínicos. No terceiro capítulo, Camila Maria de Paula da Silva, Cecília Cristine Pohren Dhein, Eveline de Lima Nunes, Patrícia Keitel da Silva, Samara Regina Fávero e Maria Cristina Cardoso apresentam a aplicabilidade clínica da auscultação cervical, indicando uma atualização quanto ao uso da auscultação cervical nas avaliações de beira de leito nos distúrbios da deglutição, cujo perfil é subjetivo, mas com possibilidades objetivas. No quarto capítulo, Bruno Barcellos Hervé, Janice Luisa Lukrafka Tartari, Mariane Borba Monteiro, Fernanda Machado Balzan, Wagner da Silva Naue, Paulo Roberto Stefani Sanches, Danton Pereira da Silva Junior e André Frotta Müller discutem dados sobre a exploração da avaliação da assincronia paciente-ventilador na Doença Pulmonar Obstrutiva Crônica (DPOC) em ventilação não invasiva (VNI), visto que a assincronia é uma das complicações decorrentes da interação entre o paciente e o ventilador. No quinto capítulo, Isadora de Oliveira Lemos, Gabriela da Cunha Pereira e Mauriceia Cassol discorrem sobre a avaliação e a reabilitação frente aos quadros clínicos de distúrbio voz, que são tão frequentes quanto debilitantes. No sexto capítulo, Giesse Albeche Duarte e Maria Cristina Cardoso propõem ações fonoaudiológicas nas fissuras labiopalatinas, que são exploradas através de uma visão geral das possibilidades clínicas junto a uma das malformações mais frequentes que acometem o ser humano e que comprometem o indivíduo como um todo. No sétimo capítulo, as autoras Chenia Caldeira Martinez e Mauriceia Cassol apresentam evidências científicas sobre ansiedade e depressão relacionadas aos distúrbios vocais em pacientes com problemas de saúde mental (ansiedade e depressão), comuns em nossa sociedade. Na sequência, as autoras do oitavo capítulo, Thayse Steffen Pereira, Fabiana de Oliveira e Maria Cristina Cardoso, abordam a saúde bucal a partir da interferência dos hábitos orais viciosos continuados e de difícil eliminação. No nono capítulo, Sabrina Braga dos Santos e Mauriceia Cassol exploram o uso de uma técnica específica para distúrbios de voz, junto a uma população crescente na nossa sociedade, a de idosos. No décimo capítulo, as principais intervenções em escrita e leitura na perspectiva da saúde coletiva e da atenção primária focando a prevenção e a promoção de saúde são abordadas por Caroline Tozzi Reppold, Léia Gonçalves Gurgel e Flavia Amaral Machado. Os modelos das intervenções neuropsicológicas no processo de aprendizagem de crianças em idade escolar são o foco do décimo primeiro capítulo. Caroline Tozzi Reppold, Flavia Amaral Machado e Léia Gonçalves Gurgel, novamente, fazem uma análise voltada para o aprimoramento e para a reabilitação da aprendizagem em âmbito escolar, além de discutirem a importância das funções executivas nesse processo.
A elaboração de instrumentos de avaliação do desenvolvimento motor em crianças com paralisia cerebral é o tema do décimo segundo capítulo. Esse é um campo dominado por escalas que concedem pouca ou nenhuma atenção às habilidades motoras finas. Priscilla Pereira Antunes, Daniela Centenaro Levandowski, Fabiana Rita Camara Machado e Alcyr Alves de Oliveira Jr. exploram outras escalas motoras e sua utilização na avaliação de pacientes com paralisia cerebral. No décimo terceiro capítulo, são apresentados os avanços e a aplicação da tecnologia computacional interativa de videogames para o tratamento de habilidades motoras através de jogos interativos na reabilitação de crianças com paralisia cerebral. Os autores Fabiana Rita Camara Machado, Daniela Centenaro Levandowski e Alcyr Alves de Oliveira Jr. revisam o tema considerando a facilidade de acesso aos equipamentos e aos jogos, aliada ao baixo custo, o que torna possível uso desses aparatos como ferramentas domésticas para o treinamento motor de crianças com paralisia cerebral. A qualidade de vida dos cuidadores de crianças com paralisia cerebral é o foco do décimo quarto capítulo, já que o nível de sobrecarga encontrada nas famílias desses pacientes é considerável. Os autores Jandara de Moura Souza, Daniela Centenaro Levandowski e Alcyr Alves de Oliveira Jr. tratam do desenvolvimento neuromotor dessas crianças durante o processo de reabilitação. Um dos pontos importantes da temática é a expectativa parental sobre o filho recém-chegado e a sobrecarrega advinda quando a criança não atende às expectativas. No décimo quinto capítulo, Juliana de Lima Cordeiro e Alcyr Alves de Oliveira Jr. apresentam um breve levantamento bibliográfico sobre a doença de Parkinson, enfocando nas características motoras e em suas influências no comprometimento cognitivo. Concluem que o rendimento das funções cognitivas na
doença de Parkinson pode ser um fator tão importante quanto os visíveis prejuízos motores. Por fim, no décimo sexto capítulo, Marlon Francys Vidmar, Verônica Bidinotto Brito, Gilnei Lopes Pimentel, Carlos Rafael de Almeida, Luis Henrique Telles da Rosa e Marcelo Faria Silva tratam da suplementação com ômega-3 em processos inflamatórios e do estresse oxidativo em processos pós-lesões do joelho. Abordam as possíveis alterações no metabolismo celular produzido pelo estresse oxidativo que podem conduzir ao agravamento de lesões de joelho e a um maior dano nas estruturas articulares. Assim, nesses dezesseis capítulos, os autores apresentam brevemente uma série de produtos, frutos de pesquisas conduzidas por profissionais e acadêmicos atuantes no PPG em Ciências da Reabilitação e em outros programas parceiros.
Verhaltensstörungen, Depressionen, isolierte kognitive Störungen, pharmakotoxische Psychosen und schließlich dementive Veränderungen werden in zunehmendem Maße bei Parkinson-Patienten beobachtet und mÜssen bei der Behandlung berÜcksichtigt werden. Zur Zeit James Parkinsons stand die Beurteilung der motorischen StÖrung vÖllig im Vordergrund. HÖhere psychische Funktionen — mit Ausnahme von Depressionen, seltenen sensorischen Mißempfindungen und im Finalstadium auftretende delirante Zustandsbilder — wurden im wesentlichen bis zur EinfÜhrung der modernen Anti-Parkinson-Therapie selten und nur am Rande beschrieben. In den letzten hundert Jahren hat sich die durchschnittliche Lebenserwartung in den Industriestaaten nahezu verdoppelt, und es kam zu einer explosionsartigen Zuwachsrate der Hochbetagten von mehreren 100 bis über 1000% (Rückert 1984).
Until recently, the “conventional wisdom” within the field of neuropsychology was that depression had little or no impact upon neuropsychological test performance. In many of the currently influential neuropsychology textbooks, depression is either not dealt with (e.g., Golden, 1981) or is dismissed as an insignificant variable. For example, Reitan and Wolfson (1985) state that “a severe and clinically significant degree of depression... usually seem[s] to be irrelevant to interpretation of neuropsychological test findings.” There has been a growing body of research in recent years, however, that clearly challenges this long-held belief. Studies with ability tests and neuropsychological measures with psychiatric populations have been accumulating and growing interest in this area has recently spawned a flurry of research showing that depression can have a significant impact upon neuropsychological test performance.
In the first part of this study, a simple dichotic word listening task was administered to 275 normal control subjects. Normative data demonstrated that age and gender both had significant effects on dichotic listening performance (i.e., females outperformed males, and younger adults did better than older adults). In the second part of this study, clinical observations on three patient populations (status-post closed-head injury, cerebral malaria survivors, and Parkinson Disease) demonstrated significantly poorer dichotic listening performance relative to controls. Overall, the results suggest that, when normative observations are systematically collected, dichotic listening tasks may become useful adjuncts to traditional neuropsychological assessments. Dichotic listening may be particularly useful in demonstrating cerebral dysfunction in a wider variety of neurologically impaired patients than has commonly been assumed.
Some research has supported differences in mood functioning in patients with Parkinson's disease (PD) whose motor symptoms begin at the left or right hemibody. Also, a relationship between disease duration and mood disturbances has been reported, but only for PD patients with right hemibody onset. There have been no investigations reported examining the potential interactions between side of onset of motor symptoms, mood, and disease duration on cognitive functioning. Hence, the purpose of this investigation was to determine whether the interaction between mood and disease duration differentially affects cognitive functioning in patients with PD whose motor symptoms begin at the left and right hemibody. A total of 33 PD patients with left hemibody onset and 29 PD patients with right hemibody onset were given a battery of tests to evaluate mood functioning and general cognitive functioning. As predicted, the results indicated that the interaction of disease duration and mood significantly predicted cognitive functioning for PD patients with right hemibody onset of symptoms but not for PD patients with left hemibody onset of symptoms. Interestingly, an unexpected finding was a significant positive relationship between disease duration and energy level for patients with left hemibody onset but not for patients with right hemibody onset. These results indicate that mood problems and disease duration interact to significantly affect cognitive functioning but only for those PD patients who experience a right hemibody onset of symptoms.
We studied the relationship between two screening cognitive measures and off motor Unified Parkinson's Disease Rating Scale (UPDRS) scores in 108 Parkinson's disease patients. Multiple regressions were conducted to examine the UPDRS subscores' unique contributions to cognitive function. When including bradykinesia, rigidity, and postural/gait instability subscores, only bradykinesia predicted Mini Mental Status Examination (MMSE), normalized beta = -0.57, t(104) = -3.31, P < 0.01, and Dementia Rating Scale-2 (DRS-2), normalized beta = -0.45, t(104) = -2.55, P < 0.05. Tremor was not included in the regression analyses because it did not correlate with cognitive function. When including axial and appendicular subscores, only the axial subscore predicted MMSE, normalized beta = -0.39, t(105) = -3.19, P < 0.01, and DRS-2 scores, normalized beta = -0.40, t(106) = -3.28, P < 0.01. When including left-sided and right-sided subscores, only the right-sided symptoms predicted DRS-2 scores, normalized beta = -0.28, t(105) = -2.45, P < 0.05, and showed a trend toward predicting MMSE scores, normalized beta = -0.22, t(105) = -1.95, P = 0.054. We therefore found that right-sided symptoms (for laterality), axial symptoms (for region), and bradykinesia (for type of symptoms) were the best predictors of cognitive function.
At disease onset, patients with Parkinson's disease (PD) typically report one side of the body to be more affected than the other. Previous studies have reported that this motor symptom asymmetry is associated with asymmetric dopaminergic degeneration in the brain. Research on the cognitive repercussions of this asymmetric degeneration has yielded inconsistent results. Here, we review studies that reported on the cognitive performance of patients with left-sided (LPD) or right-sided (RPD) motor symptom predominance. We present evidence that patients with RPD typically experience problems with language-related tasks and verbal memory, whereas patients with LPD more often perform worse on tasks of spatial attention, visuospatial orienting and memory and mental imagery. In general, no differences were found between both groups on tasks measuring attention and executive function. The association between motor asymmetry and cognitive performance indicates that PD does not lead to one typical cognitive profile. The effect of symptom laterality on the cognitive complaints should be considered in the assessment and treatment of each individual patient.
Depression and anxiety have both been associated with relative left frontal hypoactivation and the motor symptoms of Parkinson's disease typically begin in a lateral or asymmetrical fashion. Hence, PD patients with right hemibody onset may experience heightened depression and anxiety. However, research is mixed regarding whether right or left hemibody onset PD is associated with elevated levels of depression and anxiety. This literature, though, has not considered the potential moderating variable of disease duration. We hypothesized that disease duration would be positively correlated with measures of depression and anxiety in right but not left hemibody onset PD patients. The results indicated that scores on the Geriatric Depression Scale, Beck Depression Inventory-II, and the State Trait Anxiety Scale - State correlated positively with disease duration, but only in the right hemibody onset group of PD patients. Thus, right hemibody onset PD is associated with more severe depressive and anxiety symptoms, but only when disease duration is considered.
This investigation sought to study immediate and delayed verbal and visuospatial recall in Parkinson disease (PD) patients with left hemibody (LHO) and right hemibody (RHO) onset of motor symptoms and to examine the role of mental processing speed in recall of this information.
Research is mixed regarding material specific memory impairments in LHO and RHO PD. However, earlier research has not used a factorial approach in investigating material specific memory in LHO and RHO PD. We hypothesized that LHO PD patients would exhibit an increase in performance following the delayed verbal free recall trial and either decline or stability in performance on the delayed visuospatial free recall trial. The opposite pattern was hypothesized for RHO PD patients.
The Hopkins Verbal Learning Test-revised (HVLT-R) and the Brief Visuospatial Memory Test-revised (BVMT-R) were administered to a sample of 28 LHO PD patients and 36 RHO PD patients. The Stroop Color-word Test was administered as a measure of mental processing speed.
The results indicated that the RHO group experienced a significant decline in performance on verbal free recall from the immediate to the delayed trials and a significant improvement in performance from the immediate to the delayed visuospatial free recall trials. Additionally, a significant negative correlation was found between mental processing speed and changes in recall from the immediate to the delayed conditions for the RHO group.
These results indicate that the RHO PD group experienced a significant decline in verbal free recall and a significant improvement in visuospatial free recall from the immediate to the delayed trials and that the LHO PD patients experienced no significant changes. Further, mental processing speed appears to influence the recall of information from the immediate to the delayed conditions.
In patients with Parkinson's disease (PD), asymmetric motor signs provide an interesting model to evaluate whether asymmetric nigrostriatal degeneration can affect neuropsychological function and other nonmotor symptoms (NMS). This study was designed to evaluate the predominant laterality of motor symptoms and its relationship with cognition and other NMS in idiopathic PD.
Nationwide, longitudinal, and multicenter study (ELEP Registry) using outpatients with PD. Left PD (LPD) and right PD (RPD) was defined based on the motor signs on the SCOPA-motor scale. To include the clinical spectrum of asymmetric PD patients, we considered two groups of patients with mild-moderate and extreme asymmetry. Predominant LPD or RPD with mild-moderate versus extreme asymmetry were compared using the following scales: cognition, psychosis (Parkinson Psychosis Rating Scale), anxiety/depression, sleep (and autonomic dysfunction at baseline and 1 year later. Nonparametric tests were used for comparison.
One hundred forty-nine PD patients (74 RPD and 75 LPD) with mild-moderate asymmetry and 90 (47 RPD and 43 LPD) with extreme asymmetry and a mean age of 64.5 (10.4) years were included. Extreme RPD had higher Parkinson Psychosis Rating Scale scores over time (P = 0.005) compared with LPD, but no significant differences were observed between LPD and RPD in terms of other NMS.
These findings suggest that damage to left-hemisphere plays a disproportionately greater role in PD-related psychosis over time. In contrast, motor laterality does not consistently affect other NMS, suggesting that NMS are related to a more widespread brain disorder.
Visual-spatial disembedding requires a person to visually scan the stimulus and allocate spatial selective attention to the locations of relevant stimuli. Parkinson's disease (PD) is often associated with visual-spatial deficits, but the influence of PD on disembedding is not entirely known. The goal of this study is to learn whether participants with PD have defective visuospatial disembedding and whether this defect responds to dopaminergic treatment. We also wanted to examine the relationship of disembedding with other cognitive processes and the different parkinsonian clinical symptoms. Participants were PD patients and matched controls. PD participants were tested "on" and "off" medications on the Hidden Patterns Test (HPT) and tests of frontal-executive functions. PD patients had difficulties in visual-spatial disembedding that were not related to medication status, illness duration or severity, or symptom presentation, but were related to other tasks requiring visual scanning in response to alterations in spatial allocation of attention. Lack of improvement with dopaminergic treatment suggests deficits in other neurotransmitter-neuromodulatory systems or degenerative processes in the frontal-striatal networks, cortex, or basal ganglia.
This cross-sectional study investigates the relationship between severity of right- and left-sided motor symptoms and deficits in global cognitive function as well as individual cognitive domains in 117 Parkinson disease patients. Items of the Unified Parkinson Disease Rating Scale Part III were divided into right- and left-sided total scores. Composite scores in verbal fluency, verbal memory, executive function, and visuoperceptual skills were obtained from a full neuropsychological battery. We observed a significant association between right-sided motor impairment and verbal memory, visuoperceptual skills, and verbal fluency, but not executive function. The relationship between right symptoms and verbal fluency was fully mediated by cognitive status, while the relationship between right symptoms and verbal memory as well as visuoperceptual skills was not. Left-sided motor symptoms were not significantly related to any composite cognitive domain. When patients were divided into groups based on the side of predominant symptoms, no group differences were found in performance on the specific cognitive domains. This suggests that the degree of right-sided symptoms is more correlated to specific cognitive domains than is group classification of laterality.
Comprehensive examinations of neurobehavioral function were performed in two groups of workers with chronic exposure to industrial manganese, and two control groups. Group 1 included 17 exposed workers without parkinsonism while Group 2 consisted of four exposed workers with parkinsonian syndrome resulting from chronic manganese poisoning. Group 3 was composed of eight idiopathic parkinsonian patients while Group 4 included 19 control subjects. Age, sex, and educational level of these four groups were matched. The neuropsychological battery consisted of tests of orientation, intelligence, learning and memory, language and communication, visuospatial and visual perception, visual attention, manual dexterity, and information processing speed. There was no evidence of neurobehavioral impairment in the non-parkinsonian workers whereas impaired general intelligence, visuoperceptive impairment and defective manual dexterity, as well as slowdown in response speed were manifested in the parkinsonian workers.
Cognitive and cerebral blood flow (CBF) lateral asymmetries have been quantified in 23 right handed patients with lateralised idiopathic Parkinson's disease. Thirteen patients who had predominant right-sided symptoms (RPD) were compared with ten who had predominant left-sided symptoms (LPD). The patient subgroups were matched for age, education, duration of illness, disease severity and medication. Normalised asymmetries scores were calculated from the data obtained with a test battery and SPECT. No correlation was found between laterality of motor Parkinsonian symptoms and cognitive or haemodynamic asymmetry scores.
The neuropsychological effects of Parkinson's disease have gained wide recognition in recent literature. Effects have been documented in almost all areas of cognitive functioning, including general intellectual functioning, visual-spatial functioning, executive functions, attention and memory functions, language functions, and affective processes. Visual-spatial functions, memory functions, and executive functions have received particular interest. This review of the literature is an attempt to tie together the large number of studies in these cognitive areas and to present a suggestion for a comprehensive neuropsychological battery tailored to the patient with Parkinson's disease. Throughout the review, factors relevant to Parkinson's disease, e.g., dementia, motor symptoms, and hemiparkinsonism, are considered.
A wide variety of conditions seen in medical practice can produce memory impairment (amnesia). Normal aging, depression, and anxiety are commonly associated with memory difficulties, as are many neurologic conditions. Systemic illnesses can impair memory by injuring vulnerable limbic regions sensitive to hypoxia or hypoglycemia. Commonly used over-the-counter and prescription medications can likewise cause amnesia. These conditions disrupt memory in characteristic ways. Recent studies suggest that immediate, recent, and remote memory functions have different neuroanatomic substrates, as do the processes of registration, retention, and retrieval. New classifications have emerged to explain the evidence for multiple memory subsystems. The neuropharmacology of memory now includes several peptides in addition to cholinergic and noradrenergic pathways. Critical limbic regions have been discovered that mediate memory consolidation, and neuronal mechanisms such as long-term potentiation are being implicated in the unique capacity of these areas to permit new learning to take place.
Visuospatial functioning in patients with Parkinson's disease was investigated using neuropsychological measures of basic visual perception, complex perceptual discrimination, and spatial orientation. Three subgroups of patients were described: (a) those with broadly impaired visuospatial abilities, (b) those with generally intact abilities, and (c) those whose performance on a task of spatial orientation was lower than their performance on a task of complex perceptual discrimination. These subgroup differences were also concordant with three other variables: age, duration of disease, and degree of dementia. It is suggested that decreases in spatial orientation functioning in Parkinson's disease may reflect the speed of progression of this disease.
Parkinson's disease (PD) patients who have left or right predominance of motor symptoms may exhibit cognitive differences. Previous research found greater neuropsychological impairment in patients with both right and left motor predominance, and some found no differences. Variability in overall severity of disease among the patients studied makes evaluation of these reports difficult. We examined the possibility that neuropsychological differences may occur in different stages of disease by comparing patients with mild unilateral disease (Exp. 1) and advanced disease (Exp. 2). Results indicated that while overall cognitive impairment increased with advancing disease, the pattern of neuropsychological impairments were not different with respect to laterality of motor symptoms in either experiment.
A predominant symptom of Parkinson's disease is akinesia and bradykinesia, slowing in the initiation and execution of voluntary movement. There has long been speculation as to whether cognitive processes undergo similar processes, but findings may be confounded by the frequent co-occurrence of dementia and/or depression. Mental rotation provides an internal or cognitive analogue of real movement, and enables us to determine the speed of such mental processes independent of any concurrent motor slowing in response initiation and execution. Medicated patients with Parkinson's disease who were free of dementia and depression were found to be able to mentally rotate alphanumeric or figural stimuli, with and without advance information as to the view (front or back) of a stick figure shortly to be shown, as rapidly as normal healthy controls. We conclude that cognitive processes involved in mental rotation are not necessarily slowed in Parkinson's disease.
Studies attempting to relate cognitive impairment to asymmetry of motor symptoms in Parkinson's disease (PD) have found contradictory results. We examined 88 patients with unilateral onset of idiopathic PD who underwent a comprehensive neuropsychological assessment, including language, visuospatial abilities, abstraction and reasoning, attention and mental tracking, set shifting, and memory. Patients whose motor signs began on the left side of the body consistently performed more poorly on the battery of cognitive measures than did patients with right-side onset. Significant differences were found on immediate and delayed verbal recall, word retrieval, semantic verbal fluency, visuospatial analysis, abstract reasoning, attention span, and mental tracking. These differences could not be attributed to differences in the overall severity of motor symptoms at the time of cognitive assessment, or the current pattern of motor asymmetry. This finding suggests that damage to right-hemisphere dopamine systems plays a disproportionately greater role in PD-related cognitive decline than a presumably comparable left-hemisphere dopamine depletion.
Twenty-one normal subjects, 32 bilateral parkinsonian patients (BPs) and 29 hemiparkinsonian patients (HP) were submitted to separate or sequentially associated motor tasks that included simple reaction times (RT), choice RTs, directional RTs, and movement RTs. The results showed that simple RTs, directional RTs, and movement times (MT) were slower in BPs as compared to normal subjects; for choice RTs there was no difference. Response patterns were similar in normal controls and BPs. In both groups RTs became more prolonged as sequentially programmed operations increased. If movement occurred at the end of the sequence, they prolonged the RTs of the preceding operations, but MTs per se did not vary. In HPs the same results were observed on the "bad" hand side versus normal controls and versus the healthy side, but a significant statistical level was reached mainly when the "bad" hand was the right one.
Parkinsonians with predominantly unilateral signs provide an interesting experimental means to evaluate if asymmetric nigro-striatal degeneration may affect neuropsychological functions. The aim of our study was to establish if the side of onset of idiopathic Parkinson's disease, right (PDR) or left (PDL), determines a selective pattern of cognitive performances. Furthermore, we verified if PDR and PDL groups show a different frequency of dementia. PDR and PDL patients with at least seven years of disease duration, matched for age, schooling, severity of extrapyramidal symptomatology and index of lateralization, were evaluated by using an extensive neuropsychological battery aimed at assessing hemispheric cognitive asymmetries. Current side of greater motor impairment was the same as the one affected at the onset of the disease.
Only subtle differences in the profile of neuropsychological dysfunction emerged from the comparison of PDR and PDL subjects. Moreover, the number of parkinsonians showing dementia syndrome was the same in both groups. Our results suggest that the side of onset of motor impairment does not significantly influence the cognitive performances in PD. Subcortical anatomic and/or functional asymmetries seem to play a less important role in the intellectual functions than in motor activities.
Earlier approaches to pallidotomy for refractory Parkinson's disease had significant complication rates. More recent approaches show fewer complications, but the effect of pallidotomy on cognition is unclear. The current study was conducted to examine the neuropsychological effects of unilateral pallidotomy.
Neuropsychological testing was performed on patients with medically refractory, predominantly unilateral Parkinson's disease at baseline and after unilateral ventral pallidotomy (n=28) or after an equivalent period without surgery in control patients (n=10).
Pallidotomy patients showed no significant changes from baseline to retesting relative to the control group for any measure. Across all of the tests administered, only five of the surgery patients showed a significant decline, and of these five none declined on more than one test. Depression did not relate to preoperative or postoperative cognition. The pallidotomy group showed a significant improvement in motor functioning and activities of daily living whereas the control group did not. These measures were not associated with the neuropsychological test scores at baseline or retest.
Stereotactic unilateral ventral pallidotomy does not seem to produce dramatic cognitive declines in most patients.
The evidence for a receptive prosodic loss in Parkinson's disease (PD) has remained inconclusive since the first reports in the early 1980s (Scott, Caird and Williams, 1984). The present study examined three aspects of comprehension in 11 PD patients and a group of age matched controls. Experiment 1 found no evidence of deficits in phonological discrimination or lexical access in the PD patients. Experiment 2 found that one patient (EA) was significantly impaired on a test of lexical stress discrimination. Experiment 3 examined the discrimination, comprehension and identification of utterance prosody. This experiment found that overall the PD patients were significantly impaired at the identification of utterance prosody. Patient TB was significantly worse than controls on the identification and comprehension of utterance prosody. The study has shown that PD patients can exhibit impairments in the comprehension of prosody and lexical stress. The evidence suggests that only some patients are impaired and the pattern of deficits can differ significantly.
The contribution of striatal (caudate nucleus-putamen) dopaminergic deficiency to the severity of motor signs is well established in Parkinson's disease (PD), while its role in the occurrence of cognitive and mood changes remains unresolved. We therefore measured in 27 non-demented PD patients and 10 age-matched controls striatal uptake of [18F]-6-fluoro-L-Dopa (F-Dopa) with PET, and mood (Beck depression), memory (Grober-Buschke), frontal executive functions (verbal fluency and Wisconsin card sorting), and attentional processing of sensory stimuli (N2-P3 auditory event-related potentials--ERPs). Locomotor disability of patients was assessed by Hoehn and Yahr score and Unified Parkinson's Disease Rating Scale (UPDRS). ANOVA showed that memory, but neither frontal lobe functions nor ERPs, was significantly altered in PD patients, whereas indices of depression were found only in advanced PD. The F-Dopa rate constant Ki was significantly reduced in the striatum, more in putamen than caudate nucleus, and inversely correlated with disease duration. A significant inverse correlation was found between both putamen and caudate nucleus Ki and Hoehn and Yahr score, and between putamen--but not caudate nucleus Ki --and UPDRS motor score. Principal components analysis (PCA) of PD patients Ki values and mood, cognitive and ERP parameters gave a three-factor solution. Variables contributing to factor 1 were memory score and N2-P3 ERP latencies, those to factor 2 were striatal Ki values, and those to factor 3 frontal executive performances. Depression did not segregate with any variable. Our findings suggest that unlike locomotor disability, cognitive abilities and mood state of non-demented PD patients are for the most part unrelated to striatal dopaminergic depletion and may result from dysfunction of extra-striatal dopaminergic or from non-dopaminergic systems.
20) became non-depressed, while five patients (22%) among 23 initially non-depressed became depressed. With long-term levodopa therapy, the UPDRS-motor score significantly improved (35+/-15. 7-18+/-7.6), but the BDI score was unchanged (18+/-9.3-19+/-9.2). The initial BDI score was significantly and inversely correlated to the parkinsonian motor symptoms, but their percentage changes were not correlated to each other. These results provide strong support to previous observations that levodopa therapy does not alter parkinsonian depression as well as providing additional evidence to support the role of non-dopaminergic mechanisms in parkinsonian depression.
This paper reviews seven studies evaluating the impact of lesion laterality on the neuropsychological sequelae of posterior pallidotomy for treatment of Parkinson's disease. Left lesions of the internal globus pallidus (GPi) were associated with subtle deficits on measures sensitive to frontal lobe function. The findings of a randomized clinical trial including a patient control group indicated that many of these deficits were transient, resolving by 6 months following surgery. Right GPi lesions were not consistently associated with neuropsychological deficit, except in one study that included a significant proportion of demented patients. It is hypothesized that when neuropsychological decline is present following surgery, this reflects impingement of posterior GPi lesions into proximal regions such as anterior GPi or the external pallidum that participate in cognitive basal ganglia-thalamocortical circuits. The findings from neuroimaging will be important for elucidating the relationship between lesion locus and neuropsychological sequelae.
Non-demented patients with Parkinson's disease (PD), especially if they are high functioning and early in the course of their disease, usually exhibit mild deficits in anterograde recall memory for verbal and non-verbal material, visuospatial reasoning, visuomotor construction, temporal ordering and sequencing. Impairments in problem solving and verbal fluency tests may also occur. PD patients with predominantly right-sided symptoms usually exhibit more severe difficulties with verbal than with non-verbal tasks. We report a case of a highly educated right-handed man with very mild right-sided hemiparkinsonism who never received anti-Parkinsonian or other psychoactive medication. Our patient showed anterograde and retrograde amnesia for faces and spatial locations and difficulties on complex visuospatial tasks that required manual responses, but normal to above average performance on all other cognitive tests. The specific pattern of cognitive loss early in PD may depend on which spatial, facial or verbal pre-frontal striatal circuits are deprived of their dopaminergic inputs.
The question of whether Parkinson's disease (PD) patients who have left (LPD) or right (RPD) motor predominance also exhibit cognitive differences is controversial. We examined this issue using a neuropsychological battery designed to provide a balanced sampling of both right- and left-hemispheric functions. RPD patients were impaired relative to LPD patients on verbally mediated tasks (left hemisphere function), but there was no group difference for visuospatial tasks (right-hemispheric function). In addition, there was a significant correlation between the extent of right side motor predominance and performance on verbal tasks, but there was no relationship between left side motor symptoms and performance on visuospatial tasks. The controversy related to cognitive differences in hemiparkinsonism may be due to the balance of the assessment procedure, the severity of motor asymmetry, or both.
The basal ganglia have been proposed as one of the neural correlates of timekeeping functions. Both encoding and memory retrieval components for time perception are impaired in Parkinson's disease (PD). The aim of our study was to investigate in hemi-Parkinsonian patients the existence of a specific alteration in memory for time depending on the affected side, to better understand the contribution of the left or right basal ganglia circuits in different components of time perception. Right and left hemi-PD patients performed a time reproduction task in which they were required to reproduce in the same session short (5 s) and long (15 s) time intervals, in off- and on-therapy condition. While the right hemi-PD patients overestimated the shorter interval, only the left hemi-PD group showed the memory migration effect, overestimating the shorter and underestimating the longer time intervals. These results argue for a critical involvement of the right basal ganglia in memory retrieval for time intervals, in the range of seconds.
It is well known that many patients with Parkinson's disease experience neuropsychological decline. However, the nature and extent of mental status change varies widely, with some patients showing mild or no cognitive impairments and others exhibiting frank dementia. Research has shown that several clinical disease parameters may differentially correlate with patterns of neuropsychological dysfunction. The present study examined side and type of motor symptom at disease onset and their relationship to cognition in idiopathic Parkinson's disease (PD). We identified 58 patients who initially presented with one of the following symptom profiles: right-side tremor onset (RSO-T; n = 15), right-side bradykinesia/rigidity onset (n = 12), left-side tremor onset (n = 19), and left-side bradykinesia/rigidity onset (n = 12). There were no differences between groups in disease duration, overall mental status, education, or depression severity. We administered a battery of neuropsychological measures to the four PD subgroups and a group of matched control subjects (n = 40). MANCOVAs controlling for age revealed patients with RSO-T performed significantly better than the other three PD subgroups across the entire neuropsychological battery. Further, the RSO-T subgroup performed comparably to controls. In contrast, the other three PD subgroups showed widespread cognitive deficits. These findings suggest an intricate relationship between motor symptom and side of disease onset and it is the combination of these factors that may influence the disease course and extent of cognitive deterioration. Furthermore, patients who develop tremor on the right side of their body represent a distinct subgroup of PD patients who exhibit relative sparing of cognitive function.
The performances of 500 normal subjects on serial digit learning (8 or 9 digits over 12 trials) were obtained and normative standards in relation to age, educational level, and sex were established. The performances of 112 hospital control patients on digit span were also obtained to develop parallel empirical standards. The performances of 100 patients with hemispheric brain disease on these two tasks were then compared. Classificatory agreement (pass or fail) between the two tests was moderately high (69%), but serial digit learning was the more sensitive index of the presence of brain disease. The advantages of including digit learning in the mental status examination are discussed.
Patients with Parkinson's disease and patients with dementia showed greater deterioration on functions attributed to the right cerebral hemisphere, than on functions attributed to the left. Relative to matched controls, Parkinson patients were significantly impaired on right hemisphere tests, but did not differ on left hemisphere tests. Demented patients were significantly deficient on all tests, but right decline was greater than left. Ninety-six patients were tested: 32 diagnosed as senile or presenile dementia, 32 Parkinson patients, and 32 non-neurological patients matched for age, sex and education. Functional performance was assessed by a battery of validated tests for left and right hemisphere cognitive functions. Patients were defined with two scores based on the results of the test: Cognitive Laterally Quotient (CLQ) reflecting the averaged performance on the left hemisphere tests, subtracted from the average performance on right hemisphere tests, and Cognitive Performance Quotient (CPQ), reflecting the total level of performance of both hemispheres. These measures defined a characteristic cognitive profile for each group.