D. Muslimovic

Cognitive profile of patients with newly diagnosed Parkinson disease.

Objective: To determine the frequency and pattern of cognitive dysfunction in patients with newly diagnosed Parkinson disease (PD) and to identify its demographic and clinical correlates. Methods: A cohort of 115 consecutive patients with newly diagnosed PD and 70 healthy controls underwent a comprehensive neuropsychological assessment including tests of psychomotor speed, attention, language, memory, executive and visuospatial functions, as well as measures of affective status. Patients also received quantitative ratings of motor symptom severity and functional status. Neuropsychological performance of PD patients was compared with that of healthy controls and with available normative data. Independent demographic and clinical predictors of cognitive impairment were identified with multiple logistic regression analysis. Results: Relative to controls, PD patients performed significantly worse on most cognitive measures. However, further analysis revealed that group differences in cognitive performance could mainly be explained by measures of immediate memory and executive function. Comparison with normative data showed that impairments were most frequent on measures of executive function, memory and psychomotor speed. In all, 24% of PD patients (4% of controls) displayed defective performance on at least three neuropsychological tests and were classified as cognitively impaired. Late onset of disease was an independent predictor of cognitive dysfunction in PD. Conclusion: Cognitive impairments are common even in newly diagnosed Parkinson disease patients, with deficits being most prominent in the domains of memory and executive functions. Older age at disease onset is likely to be an important determinant of cognitive dysfunction in Parkinson disease.

Determinants of disability and quality of life in mild to moderate Parkinson disease

Objective: To identify factors that independently contribute to disability and quality of life (QoL) in patients with mild to moderate Parkinson disease (PD). Methods: A group of 190 patients with PD recruited from outpatient clinics and the Dutch Parkinson’s Disease Association participated in this cross-sectional study. Data on demographic and clinical factors, motor symptoms, cognitive functions, affective symptoms, comorbidity, and social support were collected during neurologic and neuropsychological examinations. Disability was rated using the Schwab and England Activities of Daily Living Scale (SE-ADL), the AMC Linear Disability Score (ALDS), and the Functional Independence Measure (FIM). QoL was assessed with the Parkinson’s Disease Quality of Life questionnaire (PDQL) and the Medical Outcome Study Short Form (SF-36). Multiple linear regression analyses were conducted to identify determinants of disability and poor QoL. Results: Axial impairment (postural instability and gait difficulty) explained the largest proportion of variance in disability. Bradykinesia and comorbidity contributed to disability, but to a lesser extent. Self-reported mood symptoms and axial impairment were the two factors most closely associated with poorer QoL, but comorbidity and bradykinesia additionally contributed to the explanatory power. Semantic fluency and psychomotor skills were the only cognitive variables related to some aspects of functional outcome. Conclusion: Axial impairment is strongly associated with disability in patients with mild to moderate Parkinson disease (PD). Self-report indices of mood status and axial impairment are identified as the main determinants of poor quality of life (QoL). The results of this study may help to identify patients with PD at risk for functional dependence and reduced QoL.

Evolution of mild cognitive impairment in Parkinson disease

Objective: We examined the development of Parkinson disease (PD)–mild cognitive impairment (MCI) in patients with newly diagnosed PD over 5 years using recently proposed consensus criteria, and we assessed the reliability of the criteria. Methods: Patients with PD (n = 123) underwent extensive neuropsychological testing at baseline and after 3 (n = 93) and 5 years (n = 59). Two neuropsychologists independently applied the PD-MCI criteria to examine the interrater and intrarater reliability. Results: At baseline, 35% of patients had PD-MCI. Three years later, 53% of the patients had PD-MCI. At 5-year follow-up, 20 patients who had PD-MCI at an earlier assessment had converted to PD dementia and 50% of the remaining patients without dementia had MCI. The interrater reliability (kappa) was 0.91. The intrarater reliabilities were 0.85 and 0.96. Conclusion: Approximately one-third of patients with newly diagnosed PD fulfill the consensus criteria for PD-MCI; after 5 years, this proportion is approximately 50% of patients without dementia. The criteria have good interrater and intrarater reliability.

Cognitive decline in Parkinson's disease: a prospective longitudinal study

This controlled prospective study examined the evolution and predictors of cognitive decline in Parkinsons disease (PD). Consecutive patients diagnosed at baseline with PD (n = 89), established PD (EPD) patients (n = 52) with a mean disease duration of 6.5 years, and healthy control subjects (n = 64) underwent extensive neuropsychological assessment twice, approximately 3 years apart. A standardized regression-based method, normative data, and multivariate normative comparisons were used to assess the cognitive course of PD. Cognitive performance of newly diagnosed patients decreased significantly over time, particularly on measures of psychomotor speed and attention and to a lesser extent on tests of memory, visuospatial skills, and executive functions. About 50% of the patients showed cognitive decline and 9% developed dementia. Similar results were observed in EPD patients. None of the baseline features predicted cognitive change in newly diagnosed patients, whereas age at disease onset and axial impairment (postural and gait disorders) contributed to decline in established patients. We conclude that within few years after diagnosis, PD patients show faster rate of cognitive decline than matched healthy subjects, particularly in domains of attention and psychomotor speed. Selection bias probably led to underestimation of the true extent of cognitive decline in established patients.

Course of cognitive decline in Parkinson's disease: A meta-analysis

A meta-analysis was conducted on 25 longitudinal studies involving 901 initially non-demented Parkinsons disease (PD) patients to examine the magnitude of decline across multiple cognitive domains associated with disease progression. Pooled effect sizes reflecting the standardized difference between baseline and follow-up neuropsychological performance were calculated for 8 cognitive domains using a random-effects model. Relatively small effect sizes were found across all cognitive domains (d = .00 - .40). During a mean follow-up interval of 29 months, significant declines were detected in global cognitive ability (d = .40), visuoconstructive skills (d = .32), and memory (d = .29). Age showed a significant relation with decline in global cognitive ability and memory. Lower educational level was associated with greater decline in all cognitive domains. Studies with longer follow-up intervals yielded larger effect sizes for global cognitive ability. In non-demented PD patients, changes in cognitive functions over time appear to be modest. Educational level, age, and length of the follow-up interval are likely to affect the magnitude of decline in several domains. Methodological flaws, such as selection bias and uncontrolled practice effects, may have caused underestimation of the true extent of decline.

Progression and prognostic factors of motor impairment, disability and quality of life in newly diagnosed Parkinson's disease.

To determine progression and prognostic factors of progression rate of motor impairment, disability, and quality of life (QoL) in patients with newly diagnosed Parkinsons disease.

Catechol-O-methyltransferase val158met and cognitive function in Parkinson's disease.

Cognitive dysfunction is one of the most incapacitating non‐motor symptoms of Parkinsons disease (PD). Some cognitive deficits are thought to be related to abnormal dopamine homeostasis. The latter is influenced by catechol‐O‐methyltransferase (COMT), an enzyme that degrades dopamine. Previous research suggests a relationship between the COMT val158met functional polymorphism (SNP) and measures of executive function. We evaluated this hypothesis in a cohort of PD patients with an extensive neuropsychological test battery. Cognitive assessment and COMT genotyping were performed in 153 early PD patients from outpatient clinics general hospitals in the Netherlands. Our results do not support a direct effect of COMT val158met genotype on performance on neuropsychological measures of attention and executive function, but they suggest that genotype may interact with dopaminergic medication use to influence cognitive ability.

Cognitive change in newly-diagnosed patients with Parkinson's disease: a 5-year follow-up study

Cognitive change is frequently observed in patients with Parkinsons disease (PD). However, the exact profile and extent of cognitive impairments remain unclear due to the clinical heterogeneity of PD and methodological issues in many previous studies. In this study, we aimed to examine the severity, frequency, and profile of cognitive changes in newly diagnosed PD patients over 5 years. At baseline and after 3 and 5 years, a hospital-based sample of PD patients (n = 59) and healthy controls (n = 40) were given neuropsychological tests covering six cognitive domains. Patients showed greater decline over time than healthy controls on all cognitive domains, except for attention. The profile of decline showed that psychomotor speed and memory were most affected. At the individual level 53% of the patients showed more cognitive decline than controls. Age at onset and memory impairment at baseline predicted cognitive decline. Cognitive functions in PD patients show greater decline in most domains than in healthy elderly over the course of 5 years. Due to selection bias as a result of attrition, the actual degree of decline may be greater than reported here.

Normative comparisons for large neuropsychological test batteries: User-friendly and sensitive solutions to minimize familywise false positives.

ABSTRACT Introduction. In neuropsychological research and clinical practice, a large battery of tests is often administered to determine whether an individual deviates from the norm. We formulate three criteria for such large battery normative comparisons. First, familywise false-positive error rate (i.e., the complement of specificity) should be controlled at, or below, a prespecified level. Second, sensitivity to detect genuine deviations from the norm should be high. Third, the comparisons should be easy enough for routine application, not only in research, but also in clinical practice. Here we show that these criteria are satisfied for current procedures used to assess an overall deviation from the norm—that is, a deviation given all test results. However, we also show that these criteria are not satisfied for current procedures used to assess test-specific deviations, which are required, for example, to investigate dissociations in a test profile. We therefore propose several new procedures to assess such test-specific deviations. These new procedures are expected to satisfy all three criteria. Method. In Monte Carlo simulations and in an applied example pertaining to Parkinson disease, we compare current procedures to assess test-specific deviations (uncorrected and Bonferroni normative comparisons) to new procedures (Holm, one-step resampling, and step-down resampling normative comparisons). Results. The new procedures are shown to: (a) control familywise false-positive error rate, whereas uncorrected comparisons do not; (b) have higher sensitivity than Bonferroni corrected comparisons, where especially step-down resampling is favorable in this respect; (c) be user-friendly as they are implemented in a user-friendly normative comparisons website, and as the required normative data are provided by a database. Conclusion. These new normative comparisons procedures, especially step-down resampling, are valuable additional tools to assess test-specific deviations from the norm in large test batteries.