Bart Post

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.

Prognostic factors for the progression of Parkinson's disease: a systematic review.

The purpose of this systematic review is to summarize studies that describe the course of Parkinsons disease (PD) and to identify factors that predict change in motor impairment, disability, and quality of life. A literature search was conducted in MEDLINE, EMBASE, CINAHL, and Web of Science limited to the English, French, German, Spanish, and Dutch language. Reports were selected if the study involved subjects with PD, the outcome measures described impairment, disability, or quality of life and follow‐up was at least 6 months. All included studies were scored for methodological quality. Data were extracted and summarized in a best evidence synthesis. We screened 1,535 titles and abstracts, of which 27 fulfilled our inclusion criteria. A meta‐analysis to quantitatively aggregate progression scores of motor impairment and disability was not possible because of the wide variety of outcome measures used and the heterogeneous study populations. Limited evidence is found for lower UPDRS‐ME at baseline, dementia and SE < 70% as prognostic factors for future motor impairment. There is strong evidence for higher age at onset and higher PIGD‐score; and limited evidence for higher bradykinesia‐score, non‐tremor dominant subtype, symmetrical disease at baseline, and depression as prognostic factors for progression of disability. Prognostic factors were identified for impairment and disability. The literature on prognosis in PD is not fulfilling the high methodological standards applied nowadays. There is a need for prospective cohorts of PD patients assembled at a common early point in the disease with long time follow‐up.

Genome-wide association study confirms extant PD risk loci among the Dutch.

In view of the population-specific heterogeneity in reported genetic risk factors for Parkinsons disease (PD), we conducted a genome-wide association study (GWAS) in a large sample of PD cases and controls from the Netherlands. After quality control (QC), a total of 514 799 SNPs genotyped in 772 PD cases and 2024 controls were included in our analyses. Direct replication of SNPs within SNCA and BST1 confirmed these two genes to be associated with PD in the Netherlands (SNCA, rs2736990: P=1.63 × 10−5, OR=1.325 and BST1, rs12502586: P=1.63 × 10−3, OR=1.337). Within SNCA, two independent signals in two different linkage disequilibrium (LD) blocks in the 3′ and 5′ ends of the gene were detected. Besides, post-hoc analysis confirmed GAK/DGKQ, HLA and MAPT as PD risk loci among the Dutch (GAK/DGKQ, rs2242235: P=1.22 × 10−4, OR=1.51; HLA, rs4248166: P=4.39 × 10−5, OR=1.36; and MAPT, rs3785880: P=1.9 × 10−3, OR=1.19).

Prognostic Tests in Term Neonates With Hypoxic-Ischemic Encephalopathy: A Systematic Review

BACKGROUND AND OBJECTIVE: Hypoxic-ischemic encephalopathy (HIE) after perinatal asphyxia in term neonates causes long-term neurologic sequelae or death. A reliable evidence-based prognosis is essential. The study goal was to investigate the prognostic value of currently used clinical tests in neonatal patients with perinatal asphyxia and HIE. METHODS: Searches were made on MEDLINE, Embase, Central, and CINAHL for studies occurring between January 1980 and November 2011. Studies were included if they (1) evaluated outcome in term infants with perinatal asphyxia and HIE, (2) evaluated prognostic tests, and (3) reported outcome at a minimal follow-up age of 18 months. Study selection, assessment of methodologic quality, and data extraction were performed by 3 independent reviewers. Pooled sensitivities and specificities of investigated tests were calculated when possible. RESULTS: Of the 259 relevant studies, 29 were included describing 13 prognostic tests conducted 1631 times in 1306 term neonates. A considerable heterogeneity was noted in test performance, cut-off values, and outcome measures. The most promising tests were amplitude-integrated electroencephalography (sensitivity 0.93, [95% confidence interval 0.78–0.98]; specificity 0.90 [0.60–0.98]), EEG (sensitivity 0.92 [0.66–0.99]; specificity 0.83 [0.64–0.93]), and visual evoked potentials (sensitivity 0.90 [0.74–0.97]; specificity 0.92 [0.68–0.98]). In imaging, diffusion weighted MRI performed best on specificity (0.89 [0.62–0.98]) and T1/T2-weighted MRI performed best on sensitivity (0.98 [0.80–1.00]). Magnetic resonance spectroscopy demonstrated a sensitivity of 0.75 (0.26–0.96) with poor specificity (0.58 [0.23–0.87]). CONCLUSIONS: This evidence suggests an important role for amplitude-integrated electroencephalography, EEG, visual evoked potentials, and diffusion weighted and conventional MRI. Given the heterogeneity in the tests’ performance and outcomes studied, well-designed large prospective studies are needed.

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.

Unified Parkinson's disease rating scale motor examination: are ratings of nurses, residents in neurology, and movement disorders specialists interchangeable?

The Unified Parkinsons Disease Rating Scale (UPDRS) is widely used for the clinical evaluation of Parkinsons disease (PD). We assessed the rater variability of the UPDRS Motor examination (UPDRS‐ME) of nurse practitioners, residents in neurology, and a movement disorders specialist (MDS) compared to a senior MDS. We assessed the videotaped UPDRS‐ME of 50 PD patients. Inter‐rater and intra‐rater variability were estimated using weighted kappa (κw) and intraclass correlation coefficients (ICC). Additionally, inter‐rater agreement was quantified by calculation of the mean difference between 2 raters and its 95% limits of agreement. Intra‐rater agreement was also estimated by calculation of a 95% repeatability limits. The κw and ICC statistics indicated good to very good inter‐rater and intra‐rater reliability for the majority of individual UPDRS items and the sum score of the UPDRS‐ME in all raters. However, for inter‐rater agreement, it appeared that both nurses, residents, and the MDS consistently assigned higher scores than the senior MDS. Mean differences ranged between 1.7 and 5.4 (all differences P < 0.05), with rather wide 95% limits of agreement. The intra‐rater 95% repeatability limits were rather wide. We found considerable rater difference for the whole range of UPDRS‐ME scores between a senior MDS and nurse practitioners, residents in neurology, and the MDS. This finding suggests that the amount by which raters may disagree should be quantified before starting longitudinal studies of disease progression or clinical trials. Finally, evaluation of rater agreement should always include the assessment of the extent of bias between different raters.

Dystonia rating scales: Critique and recommendations

Many rating scales have been applied to the evaluation of dystonia, but only few have been assessed for clinimetric properties. The Movement Disorders Society commissioned this task force to critique existing dystonia rating scales and place them in the clinical and clinimetric context. A systematic literature review was conducted to identify rating scales that have either been validated or used in dystonia. Thirty‐six potential scales were identified. Eight were excluded because they did not meet review criteria, leaving 28 scales that were critiqued and rated by the task force. Seven scales were found to meet criteria to be “recommended”: the Blepharospasm Disability Index is recommended for rating blepharospasm; the Cervical Dystonia Impact Scale and the Toronto Western Spasmodic Torticollis Rating Scale for rating cervical dystonia; the Craniocervical Dystonia Questionnaire for blepharospasm and cervical dystonia; the Voice Handicap Index (VHI) and the Vocal Performance Questionnaire (VPQ) for laryngeal dystonia; and the Fahn‐Marsden Dystonia Rating Scale for rating generalized dystonia. Two “recommended” scales (VHI and VPQ) are generic scales validated on few patients with laryngeal dystonia, whereas the others are disease‐specific scales. Twelve scales met criteria for “suggested” and 7 scales met criteria for “listed.” All the scales are individually reviewed in the online information. The task force recommends 5 specific dystonia scales and suggests to further validate 2 recommended generic voice‐disorder scales in dystonia. Existing scales for oromandibular, arm, and task‐specific dystonia should be refined and fully assessed. Scales should be developed for body regions for which no scales are available, such as lower limbs and trunk.

Clinical heterogeneity in newly diagnosed Parkinson's disease.

ObjectiveTo determine clinical heterogeneity in newly diagnosed Parkinson’s disease using cluster analysis and to describe the subgroups in terms of impairment, disability, perceived quality of life, and use of dopaminergic therapy.MethodsWe conducted a k-means cluster analysis in a prospective hospital based cohort of 133 patients with newly diagnosed Parkinson’s disease. Variables selected for the cluster analysis were age of disease onset, age at the moment of examination, rate of disease progression, levodopa responsive PD symptoms and levodopa non-responsive PD symptoms, cognition (mini-mental state examination) and emotional functioning (hospital anxiety depression scale). In addition, the homogeneous subgroups identified were clinically validated using descriptive statistics.ResultsCluster analysis with a two-cluster solution identified a younger and older age group. The three-cluster solution identified an intermediate group with respect to age. In both cluster solutions the older the onset group, the higher the progression rate and the level of motor impairments. The intermediate older onset group in the three cluster solution was characterized by more anxiety and depressive symptoms. Increasing age at disease onset was significantly associated with higher Hoehn and Yahr stages, level of disability and lower perceived quality of life.ConclusionsWe hypothesize there are three distinct subgroups in patients with newly diagnosed PD: a younger onset group, an intermediate older onset group with more anxiety and depressive symptoms and an oldest onset group with more motor impairment and higher rate of progression.

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.