Motor dysfunction influence on executive functioning in manifest and premanifest Huntington's disease

Motor disturbances can be present in both manifest and premanifest Huntington's disease (HD). We aimed to investigate the role of motor functioning on executive functioning to better understand the progression of cognitive dysfunction in HD. Forty patients with manifest HD, 21 patients with premanifest HD, and a group of 28 controls were tested twice with a 1‐year interval. For the Symbol Digit Modalities Test and the Figure Fluency Test, extra conditions were designed to measure motor involvement. Subtraction of this motor score from the original test score resulted in isolation of the cognitive component. Groups were compared on motor, cognitive, and original test scores using multilevel regression analysis. Manifest patients had lower baseline scores of 0.53 standard deviations (SD) on the original Symbol Digit Modalities Test (P = 0.03) and 0.71 SD on the motor isolation part (P = 0.006), and they showed a deterioration of 0.47 SD over 1 year of follow‐up on the original Symbol Digit Modalities Test (P = 0.001) compared with controls. Premanifest patients had lower baseline scores of 0.67 SD on the Symbol Digit Modalities motor part (P = 0.008) and deterioration of 0.48 SD on the original (P = 0.001) and cognitive isolation (P = 0.02) parts. Secondary analyses revealed that the premanifest deterioration resulted from the close‐to‐predicted‐onset group. Motor disturbances have a negative influence on performance on the Symbol Digit Modalities Test. Isolation of the cognitive component of this test revealed cognitive deterioration in the premanifest group only, caused by deteriorating scores for patients who were close to their predicted clinical disease onset. The Figure Fluency Test did not prove sensitive to cognitive change. © 2014 International Parkinson and Movement Disorder Society     

Smoking and cognitive function in Parkinson's disease.

The risk of dementia among Parkinson's disease (PD) patients is greatly elevated compared to controls, yet little is known about determinants of cognitive function among PD patients. We assessed the relation between cigarette smoking prior to disease onset and later cognitive function among PD patients (n = 286) and age- and sex-matched controls (n = 1144) participating in the Nurses' Health Study and Health Professionals Follow-up Study. Both groups completed telephone-administered assessments of cognitive function. We used linear regression to calculate mean differences in cognitive test scores across smoking categories, adjusted for age, education, sex, age at onset of PD, and years since diagnosis. PD patients scored significantly worse on all tests than their matched controls. In analyses only among PD cases, but not among controls, current smokers at PD onset scored worse than never smokers on the Telephone Interview for Cognitive Status (difference = -0.82, 95% CI: -1.33, -0.30, P = 0.002) as well as on a global score combining results of all tests (difference = -0.36, 95% CI: -0.72, 0.01, P = 0.06). This difference was equivalent to the difference in global score observed among controls approximately 10 years apart in age. Analyses of pack-years of smoking prior to disease onset gave similar results. These findings, nested in prospective cohort studies, suggest that cigarette smoking prior to disease onset is associated with worse cognitive function in PD.     

Task-Related Reorganization of Cognitive Network in Parkinson's Disease Using Electrophysiology

Background

Cognitive deficits in Parkinson's disease (PD) patients are well described, however, their underlying neural mechanisms as assessed by electrophysiology are not clear.

Objectives

To reveal specific neural network alterations during the performance of cognitive tasks in PD patients using electroencephalography (EEG).

Methods

Ninety participants, 60 PD patients and 30 controls underwent EEG recording while performing a GO/NOGO task. Source localization of 16 regions of interest known to play a pivotal role in GO/NOGO task was performed to assess power density and connectivity within this cognitive network. The connectivity matrices were evaluated using a graph-theory approach that included measures of cluster-coefficient, degree, and global-efficiency. A mixed-model analysis, corrected for age and levodopa equivalent daily dose was performed to examine neural changes between PD patients and controls.

Results

PD patients performed worse in the GO/NOGO task (P < 0.001). The power density was higher in δ and θ bands, but lower in α and β bands in PD patients compared to controls (interaction group × band: P < 0.001), indicating a general slowness within the network. Patients had more connections within the network (P < 0.034) than controls and these were used for graph-theory analysis. Differences between groups in graph-theory measures were found only in cluster-coefficient, which was higher in PD compared to controls (interaction group × band: P < 0.001).

Conclusions

Cognitive deficits in PD are underlined by alterations at the brain network level, including higher δ and θ activity, lower α and β activity, increased connectivity, and segregated network organization. These findings may have important implications on future adaptive deep brain stimulation. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Cardiac stress test is normal in pre‐motor Parkinson's disease

Cardiac sympathetic denervation is an early nonmotor feature of Parkinson's disease (PD). The aim of the current study was to trace evidence for cardiac dysfunction abnormalities in the premotor phase of PD. We retrospectively reviewed treadmill ergometric tests of a large cohort (n = 16,841) between 2000 and 2012, that attended the Executive Screening Survey (ESS) at Sheba Medical Center. Heart rate and blood pressure profiles as well as exercise capacity were compared between subjects who later developed PD and age‐ and sex‐matched subjects (ratio 1:2) who did not. We identified 28 subjects (24 males) who developed PD at follow‐up. The PD group was older than the group of subjects who did not develop PD on first ergometric test (64.82 ± 8.82 vs. 48.91 ± 10.60 years, P < 0.001). The time between the first ergometric test and motor symptoms onset was 4.64 ± 2.86 years. Patients who later developed PD had lower maximal heart rate (P < 0.001) and lower heart rate reserve than healthy controls (P < 0.001); however, compared with age‐ and sex‐matched subjects, subjects who developed PD had similar exercise capacity and heart rate profile during rest, exercise, and recovery, even 1 year before diagnosis. In this study, we did not detect significant signs of sympathetic dysfunction during the premotor phase of PD. © 2014 International Parkinson and Movement Disorder Society     

Development of a prediction formula of Parkinson disease severity by optical coherence tomography

The aims of this study were to assess the peripapillary retinal nerve fiber layer (RNFL) thickness in patients with Parkinson's disease (PD), to determine its correlation with disease severity, and to define a simple biomarker for predicting clinical severity. One hundred two eyes from 52 patients affected by PD were compared with 97 eyes from 50 age‐comparable controls. In all patients, peripapillary RNFL thickness was measured by optical coherence tomography (OCT). We used the Unified Parkinson's Disease Rating Scale (UPDRS) total score and measured responses in the on medication state. Eyes from patients with PD had a statistically significant decrease in average peripapillary RNFL thickness compared with control eyes (P < 0.001). This reduction was observed in every quadrant (inferior, superior, nasal [P < 0.001], and temporal [P = 0.017]) in patients with PD. Furthermore, a strong inverse correlation was found between the PD severity measured according to the UPDRS score and the average peripapillary RNFL thickness (r = ?0.615; P < 0.001) and PD duration (r = ?0.303; P = 0.002). From these results, we defined a regression equation that predicts the UPDRS score from the above‐mentioned variables: UPDRS = 81.6 + 29.6 * log PD duration (years) ? 0.6 * RFNL thickness (μm). We observed that, as the evolution and severity of PD progress, the peripapillary RNFL layer thickness, as evaluated by OCT, gradually diminishes. These results suggest that the average peripapillary RNFL thickness measured by OCT might be useful as a biomarker to detect the early onset and progression of PD. © 2013 International Parkinson and Movement Disorder Society     

Age-induced cognitive disturbances in Parkinson's disease

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.     

Cognitive impairment and white matter damage in hypertension: a pilot study

Objectives – Hypertension has been associated with impaired cognition. Diffusion tensor imaging (DTI) and magnetic resonance spectroscopy were applied to assess white matter abnormalities in treated vs untreated hypertension and if these correlated with neuropsychological performance. Methods – Subjects were 40 patients with medically treated hypertension (mean age 69.3 years), 10 patients with untreated hypertension (mean age 57.6 years) and 30 normotensive controls (mean age 68.2 years). Hypertension was defined as a previous diagnosis and taking hypertensive medication, or a resting blood pressure of >140/90 mmHg on the day of assessment. Results – Patients with treated hypertension performed worse on immediate (P = 0.037) as well as delayed memory tasks (P = 0.024) compared with normotensive controls. Cognitive performance was worse in untreated compared with treated hypertension on executive functions (P = 0.041) and psychomotor speed (P = 0.003). There was no significant correlation between cognition and any of the imaging parameters in treated hypertension. However, in untreated hypertension the results revealed a positive correlation between an executive functioning and attention composite score and DTI mean diffusivity values (P = 0.016) and between psychomotor speed and spectroscopy NAA/tCr levels (P = 0.015). Conclusions – These results suggest there is cognitive impairment in hypertension. Treated hypertension was associated with deficits in memory while untreated hypertension revealed a more ‘subcortical’ pattern of cognitive impairment.     

A pilot study of psychometric properties of the Beijing version of Montreal Cognitive Assessment in patients with idiopathic Parkinson’s disease in China

Cognitive dysfunction is one of the most critical clinical manifestations of Parkinson’s disease (PD), and its accurate and efficient diagnosis is crucial for treatment. We evaluated the psychometric properties of the Beijing version of the Montreal Cognitive Assessment (BJ–MoCA) in 123 Chinese patients with idiopathic PD. The internal consistency and convergent validity of the BJ-MoCA were examined and psychometric characteristics of BJ–MoCA scores were analyzed in PD patients with ‘‘normal’’ Mini-Mental State Examination (MMSE) scores. More than half (56.9%) of the patients with normal MMSE scores showed cognitive impairment in multiple cognitive domains, including visuospatial and executive functions, naming, attention, language, delayed recall, and orientation. The impaired delayed recall was less likely to occur in newly diagnosed patients, and the orientation ability in patients with early onset was rarely affected. The multivariate regression analysis revealed that the age of symptom onset and disease severity were independent predictors of cognitive impairment. Thus, the current findings demonstrate that the BJ–MoCA is a reliable tool for screening cognitive dysfunction in Chinese patients with idiopathic PD. It is more sensitive than the MMSE for screening early cognitive decline in non-memory dysfunction.     

ORIGINAL ARTICLE: Investigation of responders and non‐responders to long‐term donepezil treatment

Background: Donepezil is effective in maintaining the cognitive function of patients with mild to moderate Alzheimer's disease (AD). However, not all patients respond to donepezil. In the present study, we examined the clinical features of responders and non‐responders to long‐term donepezil treatment. Methods: The present retrospective study was performed on 95 AD outpatients who had been taking donepezil for ≥2 years. All subjects underwent periodic examinations of cognitive function, namely Mini‐Mental State Examination (MMSE) and Rorschach Cognitive Index (RCI), as well as clinical evaluations using the Clinical Dementia Rating (CDR) scale. Patients were divided into three groups as follows: (i) the ‘maintained’ group (MG), in which the global CDR score was maintained over the ≥2 years of treatment; (ii) the ‘declined’ group (DeG), in which the global CDR score increased one rank over the treatment period; and (iii) the ‘obvious and rapid decline’ group (ORDeG), in which the global CDR score increased two ranks early during the treatment period. Clinical features, treatment outcome, the time lag between a caregiver's recognition of the onset of dementia and the start of treatment, behavioral and psychological symptoms of dementia (BPSD), and cognitive functions were compared between the three groups. Results: Patients in the ORDeG (i.e. non‐responders) were significantly younger and had a longer time lag between the onset of dementia and the start of treatment than patients in the MG (P < 0.05). Of note, patients in the ORDeG had a longer period of executive dysfunction before treatment started than patients in the MG (P < 0.001). Evaluation of cognitive function revealed that mean changes from baseline on the MMSE and RCI were significantly lower for patients in the ORDeG compared with the MG at 8 and 4 months, respectively (P < 0.001 and P < 0.05, respectively). Conclusion: Donezepil non‐responders are likely to be younger and to have a longer time lag between the onset of dementia and the start of treatment, in particular a longer duration of executive dysfunction. Furthermore, the non‐responders do not demonstrate maintenance of cognitive functions in the short term. Thus, the early diagnosis of dementia and prompt initiation of donepezil treatment is indicated for a good outcome. To this end, it is important to educate people to recognize a deterioration of executive function in daily living.     

Addenbrooke's Cognitive Examination validation in Parkinson's disease

Background: There is a clear need for brief, sensitive and specific cognitive screening instruments in Parkinson’s disease (PD). Objectives: To study Addenbrooke’s Cognitive Examination (ACE) validity for cognitive assessment of PD patient’s using the Mattis Dementia Rating Scale (MDRS) as reference method. A specific scale for cognitive evaluation in PD, in this instance the Scales for Outcomes of Parkinson’s disease – Cognition (SCOPA‐COG), as well as a general use scale the Mini‐mental state examination (MMSE) were also studied for further correlation. Methods: Forty‐four PD patients were studied, of these 27 were males (61%), with a mean (SD) age of 69.5 (11.8) years, mean (SD) disease duration of 7.6 (6.4) years (range 1–25), mean (SD) total Unified Parkinson’s Disease Rating Scale (UPDRS) score 37 (24) points, UPDRS III 16.5 (11.3) points. MDRS, ACE and SCOPA‐COG scales were administered in random order. All patients remained in on‐state during the study. Results: Addenbrooke’s Cognitive Examination correlated with SCOPA‐COG (r = 0.93, P < 0.0001), and MDRS (r = 0.91 P < 0.0001) and also with MMSE (r = 0.84, P < 0.001). Area under the receiver‐operating curve, taking MDRS as the reference test, was 0.97 [95% confidence interval (CI): 0.92–1.00] for ACE, 0.92 (95% CI: 0.83–1.00) for SCOPA‐COG and 0.91 (95% CI: 0.83–1.00) for MMSE. Best cut‐off value for ACE was 83 points [Sensitivity (Se) = 92%; Specificity (Sp) = 91%; Kappa concordance (K) = 0.79], 20 points for the SCOPA‐COG (Se = 92%; Sp = 87%; K = 0.74) and 26 points for MMSE (Se = 61%; Sp = 100%; K = 0.69). Conclusion: Addenbrooke’s Cognitive Examination appears to be a valid tool for dementia evaluation in PD, with a cut‐off point which should probably be set at 83 points, displaying good correlation with both the scale specifically designed for cognitive deficits in PD namely SCOPA‐COG, as well as with less specific tests such as MMSE.     

Morphometry of the human substantia nigra in ageing and Parkinson’s disease

To investigate the relation between the loss of substantia nigra (SN) neurons in normal ageing and Parkinson’s disease (PD), we measured the total number and the cell body volume of pigmented (neuromelanin) neurons in the SN. We examined young (n = 7, mean age: 19.9), middle-aged (n = 9, mean age: 50.1), and older controls from the Baltimore Longitudinal Study of Aging (n = 7, mean age: 87.6), as well as PD cases (n = 8, mean age: 74.8). On random-systematically selected paraffin Nissl-stained sections, we used the Optical Fractionator to estimate the total number of neurons on one side of the SN. Using the Nucleator probe, we measured the volume of these neurons. In young and older controls, we also estimated the total number and volume of tyrosine hydroxylase (TH) positive (+) nigral neurons. We observed a significant loss of pigmented (-28.3%, P < 0.01) and TH (+) (−36.2%, P < 0.001) neurons in older controls compared with younger subjects. Analysis of the size distribution of pigmented and TH (+) neurons showed a significant hypertrophy in older controls compared to young controls (P < 0.01). In contrast, in PD we observed a significant atrophy of pigmented neurons compared to all control groups (P < 0.01). These data suggest that neuronal hypertrophy represents a compensatory mechanism within individual SN neurons that allows for normal motor function despite the loss of neurons in normal ageing. Presumably, this compensatory mechanism breaks down or is overwhelmed by the pathological events of PD leading to the onset of the characteristic motor disturbances.     

Impaired finger dexterity in patients with parkinson's disease correlates with discriminative cutaneous sensory dysfunction

To study the influence of discriminative cutaneous sensory dysfunction on impaired finger dexterity in Parkinson's disease (PD), we evaluated 48 right‐handed PD patients during a practically defined off‐medication period and 24 healthy age‐matched controls. With visual deprivation, a finger tapping task (FTT) was performed to assess the speed of simple repetitive finger movements and a coin rotation task (CRT) was used to assess finger dexterity. The tasks were performed with the right hand. We measured the somesthetic temporal discrimination threshold (sTDT) in the right index finger. The mean ± SD FTT score of the patient group was lower than that of the control group (24.0 ± 8.0 vs. 29.8 ± 7.8; P < 0.01). The patient group performed worse on the CRT than the control group (8.5 ± 3.5 vs. 12.6 ± 1.7; P < 0.001). The mean sTDT value of the patient group was longer than that of the control group (124.0 ± 44.8 vs. 78.1 ± 26.2 ms; P < 0.001). The CRT scores correlated with the sTDT values (Pearson's correlation coefficient = ?0.43; P < 0.01), but not with the Unified Parkinson's Disease Rating Scale (UPDRS) finger bradykinesia scores or FTT scores. Multiple regression analysis showed that the sTDT values (parameter estimate = ?0.03, SE = 0.01; P < 0.01), but not patient age, UPDRS finger bradykinesia score, or FTT score, affected the CRT score. Slowness of simple repetitive finger movements did not have a strong impact on the impaired manual dexterity of PD. Discriminative sensory dysfunction and consequent abnormal sensorimotor integration seem to be involved in the impaired finger dexterity of PD. © 2010 Movement Disorder Society.     

Rate of cognitive decline in premotor Parkinson's disease: A prospective study (NEDICES)

Previous research has documented cognitive impairment in the early stages of Parkinson's disease (PD). It is not known when this decline starts or if decline progresses at an accelerated rate during the premotor period of the disorder. In this population‐based prospective study of older people (≥65 years) from the Neurological Disorders in Central Spain (NEDICES) cohort, we compared the rates of cognitive decline in 3 groups: (1) non‐PD elderly controls; (2) prevalent PD patients (those diagnosed with the disease at baseline, 1994–95); and (3) premotor PD subjects (those diagnosed with the disease at follow up, 1997–98, but not at baseline). A 37‐item version of the Mini–Mental State Examination (37‐MMSE) was administered in the 2 visits of the study. From 2487 participants (age, 72.8 ± 6.0 years), including 2429 controls, we recruited 21 premotor PD cases, and 37 prevalent PD cases. At baseline, the mean 37‐MMSE score was 28.5 ± 4.7 in prevalent cases, 28.1 ± 4.6 in premotor cases, and 29.9 ± 5.0 in controls (P = .046). During the 3‐year follow‐up period, there was a significant score decline of 2.4 ± 4.6 points in prevalent cases versus 0.2 ± 4.1 points in premotor cases and 0.3 ± 4.0 points in controls (Kruskal–Wallis test, P = .03). In the NEDICES cohort, cognitive test scores of prevalent PD cases declined at a rate above and beyond that observed in premotor PD cases and in controls. The rate of cognitive decline in premotor PD and controls was similar. Our data suggest that a decline in global cognitive function does not occur in premotor PD. © 2012 Movement Disorder Society     

Cognitive executive impairment and dopaminergic deficits in de novo Parkinson's disease

Cognitive impairment in Parkinson's disease (PD) is common and does directly impact patients' everyday functioning. However, the underlying mechanisms of early cognitive decline are not known. This study explored the association between striatal dopaminergic deficits and cognitive impairment within a large cohort of early, drug‐naïve PD patients and tested the hypothesis that executive dysfunction in PD is associated with striatal dopaminergic depletion. A cross‐sectional multicenter cohort of 339 PD patients and 158 healthy controls from the Parkinson's Progression Markers Initiative study was analyzed. Each individual underwent cerebral single‐photon emission CT (SPECT) and a standardized neuropsychological assessment with tests of memory as well as visuospatial and executive function. SPECT imaging was performed with [¹²³I]FP‐CIT, and specific binding ratios in left and right putamen and caudate nucleus were calculated. The association between specific binding ratios, cognitive domain scores, and age was analyzed using Pearson's correlations, partial correlation, and conditional process analysis. A small, but significant, positive association between total striatal dopamine transporter binding and the attention/executive domain was found (r = 0.141; P = 0.009) in PD, but this was not significant after adjusting for age. However, in a moderated mediation model, we found that cognitive executive differences between controls and patients with PD were mediated by an age‐moderated striatal dopaminergic deficit. Our findings support the hypothesis that nigrostriatal dopaminergic deficit is associated with executive impairment, but not to memory or visuospatial impairment, in early PD. © 2014 International Parkinson and Movement Disorder Society     

Striatal dopamine transporter imaging correlates with depressive symptoms and tower of London task performance in Parkinson's disease

We studied whether the ¹²³I‐FP‐CIT uptake in the striatum correlates with depressive symptoms and cognitive performance in patients with Parkinson's disease (PD). Twenty patients with PD without major depression and/or dementia (mean age 61.7 ± 12.7 years) underwent the ¹²³I‐FP‐CIT SPECT. Depressive symptoms and cognitive performance were assessed in the ON state. The ratios of striatal to occipital binding for the entire striatum, putamina, and putamen to the caudate (put/caud) index were calculated in the basal ganglia. The association between neuropsychiatric measures and dopamine transporter (DAT) availability was calculated; multiple regression analysis was used to assess association with age and disease duration. We found significant correlations between Montgomery and Asberg Depression Rating Scale (MARDS) and Tower of London (TOL) task scores and ¹²³I‐FP‐CIT uptake in various striatal ROIs. Multiple regression analysis confirmed the significant relationship between TOL performance and put/caud ratio (P = 0.001) and to age (P = 0.001), and between MADRS and left striatal (P = 0.005) and putaminal DAT availability (P = 0.003). Our pilot study results demonstrate that imaging with ¹²³I‐FP‐CIT SPECT appears to be sensitive for detecting dopaminergic deficit associated with mild depressive symptoms and specific cognitive dysfunction in patients with PD, yet without a current depressive episode and/or dementia. © 2008 Movement Disorder Society     

Is there an association between subjective and objective measures of cognitive function in patients with affective disorders?

Background: Patients with affective disorders experience cognitive dysfunction in addition to their affective symptoms. The relationship between subjectively experienced and objectively measured cognitive function is controversial with several studies reporting no correlation between subjective and objective deficits. Aims: To investigate whether there is a correlation between subjectively reported and objectively measured cognitive function in patients with affective disorders, and whether subjective complaints predict objectively measured dysfunction. Methods: The study included 45 participants; 15 with bipolar disorder (BD), 15 with unipolar disorder (UD) and 15 healthy individuals. Participants’ subjectively experienced cognitive function and objective cognitive function were assessed with the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) and the Screen for Cognitive Impairment in Psychiatry (SCIP), respectively. Patients were rated for affective symptoms with Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS). Results: Patients demonstrated subjective and objective cognitive dysfunction relative to controls (P-values ≤ 0.01) but there were no differences between patient groups (P > 0.1). We found no correlation between subjectively experienced and objectively measured cognitive dysfunction in BD (P = 0.7), and a non-significant trend towards a correlation in UD (P = 0.06), which disappeared when controlling for gender (P = 0.1). Conclusion: Our results suggest that it is not necessarily patients who have cognitive complaints that are most impaired. If confirmed in a larger sample, our findings suggest that neuropsychological assessment is warranted to elucidate the potential role of cognitive dysfunction in patients’ everyday lives and to inform treatment strategies targeting these difficulties.     

Association studies of the adenosine A2a receptor (1976T > C) genetic polymorphism in Parkinson’s disease and schizophrenia

Summary. Given the implications with respect to the pathogenesis of dopaminergic dysfunction in schizophrenia and Parkinson’s disease (PD), as well as the reciprocal antagonistic interactions between adenosine A2a receptor (A2aAR) and the dopamine D2 receptors, A2aAR may be a candidate gene conferring susceptibility to PD or schizophrenia. In this study, we tested the hypothesis that the A2aAR 1976T > C genetic variant confers susceptibility to or is related to the onset age of schizophrenia or PD using a sample population consisting of 94 PD and 227 schizophrenic patients. We also tested whether the A2aAR 1976T > C relates to antipsychotic-induced tardive dyskinesia in the schizophrenic population. The results demonstrated that in comparing PD patients and controls the distribution of the A2aAR 1976T > C genotypes (P = 0.788) and alleles (P = 0.702) did not vary significantly. Furthermore, the PD onset age was not significantly different amongst the three A2aAR 1976T > C genotypic groups. In comparing schizophrenic patients and controls, the distribution of the A2aAR genotypes (P = 0.330) and alleles (P = 0.632) also did not differ significantly. The onset age of schizophrenia and tardive dyskinesia (evaluated with Abnormal Involuntary Movements Scale) were similar within the three A2aAR genotypic groups. Our findings suggest that it is unlikely that the A2aAR 1976T > C polymorphism plays a major role in the pathogenesis of PD, schizophrenia, or antipsychotic-induced tardive dyskinesia in the Chinese population.     

Cognitive impairment after three decades of multiple sclerosis

Background: Population‐based studies of cognitive impairment in patients with multiple sclerosis (MS) with long disease duration are limited. The aim of this study was to evaluate long‐term outcome and the predictors of cognitive impairment in a cohort of patients with MS. Methods: Patients living in Oslo, Norway, with definite MS and onset in 1940–1980 alive on 1 May 2006 were included. Disability was assessed by Expanded Disability Status Scale (EDSS). Cognitive functioning was assessed in terms of psychomotor speed, attention, learning/memory and executive functions. Results: A total of 123 patients was included. EDSS was ≤3.0 in 26% and ≥6.0 in 60% after mean disease duration of 34.5 years. Cognitive impairment was found in 48% of the patients eligible for neuropsychological evaluation (n = 84). Typical pattern was moderate impairment within areas of information processing, attention and memory. In the univariate analysis, younger onset age was significantly associated with cognitive impairment (P = 0.014). Younger onset age (P = 0.017) and disease course (secondary progressive vs. relapsing‐remitting MS, P = 0.049) were significantly associated with cognitive impairment in the multivariate analysis. Conclusions: After three decades of disease, half of the MS patients experienced reduced cognitive functioning; however, nearly one‐third of the patients were only mildly disabled based on the EDSS. Younger onset age was associated with higher prevalence of cognitive impairment. A thorough evaluation of cognitive function in addition to EDSS is essential for evaluating long‐term impairment in patients with MS.     

[11C]d-threo-methylphenidate PET in patients with Parkinson’s disease and essential tremor

Summary. Twenty Parkinson’s disease (PD) patients, 6 patients with essential tremor and 10 healthy controls were studied with the dopamine transporter ligand [¹¹C]d-threo-methylphenidate ([¹¹C]dMP) and positron emission tomography (PET) to assess dopamine terminal loss in relation to disease duration and motor disability. Dopamine transporter availability was expressed as [¹¹C]dMP binding potential (BP_dMP) in percentage of the mean of healthy controls. In PD patients (age at onset 57.7 ± 8.9 yrs; disease duration 5.2 ± 3.3 yrs; UPDRS motor score 24.2 ± 9.8; Hoehn & Yahr 2.1 ± 0.8; mean ± SD) BP_dMP was reduced to 30% (range: 11–55%) in the putamen and 52% (range: 14–96%) in the caudate nucleus. BP_dMP in the putamen closely correlated with the UPDRS motor score (r = −0.79, p < 0.001), and disease duration (r = −0.76, p < 0.001) but not with age at onset. The correlation with the UPDRS score depended on akinesia and rigidity, while the tremor scores were related neither to putamen nor caudate BP_dMP. Interestingly, when plotted over disease duration, PD patients with severe asymmetry of symptoms showed significantly lower BP_dMP in the contralateral putamen (exponential fit: 34% at onset) than the other PD patients (41% at onset), indicating a different symptomatic threshold of these subgroups and an even closer correlation with the hypothetical “true” disease duration. The exponential fit across all patients indicated a mean symptomatic threshold of 37% contra- and 62% ipsilateral, corresponding with an observed mean BP_dMP of 51% (average contra- and ipsilateral) in those patients with disease duration less than one year. No differences in BP_dMP were observed between patients with essential tremor and healthy controls. [¹¹C]dMP appears to be a useful and sensitive marker of dopaminergic dysfunction in PD and can be used to assess and monitor disease severity. Both authors contributed equally     

Health‐related quality of life in early Parkinson's disease: The impact of nonmotor symptoms

Nonmotor symptoms (NMS) are common in patients with established Parkinson's disease (PD) and have a major impact upon quality of life. We investigated the significance of NMS in relation to health‐related quality of life (HRQoL) in patients with newly diagnosed PD. Patients and healthy controls were recruited as part of the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation in Parkinson's Disease Study. Prevalence of NMS was determined with the Non‐Motor Symptom Questionnaire. HRQoL was recorded with the 39‐item Parkinson's Disease Quality of Life Questionnaire (PDQ‐39). Further assessments included measures of motor disability, depression, sleep, and cognition. One hundred and fifty‐eight patients with newly diagnosed PD and 99 controls participated in this cross‐sectional study. Patients reported greater numbers of NMS than controls (mean 8.3 ± 4.3 versus 2.8 ± 2.5 symptoms; P < 0.001). Patients reported lowest HRQoL in the domains assessing bodily discomfort, mobility, and activities of daily living. Motor and nonmotor symptoms impacted negatively upon HRQoL scores. Patients with the postural instability and gait difficulty motor subtype reported worse HRQoL, compared with those with tremor‐dominant disease. Depression (P < 0.001), incomplete bowel emptying (P < 0.001), anxiety (P < 0.001), impaired concentration (P < 0.001), memory complaints (P < 0.001), and insomnia (P = 0.001) had the greatest negative impact upon HRQoL. NMS are common in patients with early PD and represent a significant cause of poorer health‐related quality of life. Cognitive, neuropsychiatric, and sleep disturbances are particularly associated with reduced well‐being. Screening and management of these symptoms should be prioritized at the time of diagnosis. © 2013 International Parkinson and Movement Disorder Society