S. van Rooden

Cognitive impairment in Parkinson's disease

Background: Cognitive impairment plays a role in Parkinson’s disease (PD) and has important consequences for patient management. However, many aspects of cognitive impairment in PD remain unclear because of the use of different and often invalid measurement instruments. In this study, a reliable and valid instrument, the SCales for Outcomes in PArkinson’s disease-COGnition (SCOPA-COG), was used. Aim: To evaluate cognitive functioning in a large cohort of patients with Parkinson’s disease and to assess the relations with demographic, disease related and clinical variables. Methods: A cohort of 400 patients with PD was evaluated for cognition, motor and non-motor domains, as well as for demographic and disease related characteristics. Results were compared with 150 controls matched for overall age, sex and education distribution. Results: Patients with PD scored significantly lower on all cognitive subdomains compared with controls, with the largest differences for executive functioning and memory. After correction for age and years of education, 22% of patients had impaired cognition, as measured by the total SCOPA-COG score, compared with controls. Across all patients, more severe cognitive impairment was associated with significantly more impairment in motor, autonomic, depressive and psychotic domains. Patients with the postural instability gait difficulty (PIGD) dominant phenotype showed more cognitive impairment compared with patients with the tremor dominant phenotype. Contrary to tremor scores, PIGD scores significantly worsened with increasing disease severity. Conclusions: Cognition is an important domain of the clinical spectrum of PD and poorer cognitive performance is associated with greater impairment in motor and non-motor domains in PD. The difference in cognitive scores between PIGD dominant patients and tremor dominant patients likely reflects more advanced disease.

Patient-reported autonomic symptoms in Parkinson disease

Objective: There is a wide range of autonomic symptoms (AS) in Parkinson disease (PD), but the full spectrum has never been evaluated with a validated instrument and in comparison with control subjects. In this study a reliable and valid instrument, the SCOPA–AUT, was used to evaluate the occurrence of AS in a large cohort of patients with PD and control subjects and to assess the relations with demographic, disease-related, and clinical variables. Methods: A cohort of 420 patients with PD was evaluated for the occurrence of AS, motor and nonmotor symptoms, as well as for demographic and disease-related characteristics. Results were compared with those of 150 control subjects. Associations between AS and demographic and clinical characteristics were also studied. Results: For all autonomic domains, patients with PD reported more symptoms compared to control subjects, with the greatest differences in the gastrointestinal and urinary domain. Higher age, greater disease severity, and higher doses of dopaminergic medication were related to more autonomic problems. Autonomic symptom severity was associated with more motor dysfunction, depressive symptoms, cognitive dysfunction, psychiatric complications, nighttime sleep disturbances, and excessive daytime sleepiness (all p values < 0.01). Conclusions: Autonomic symptoms (AS) are an important feature of Parkinson disease (PD) and increase with age, disease severity, and medication use. The prominent presence of AS warrants increased clinical awareness and highlights the need for efficacious therapies for the wide spectrum of problems related to this domain of PD.

A comprehensive model of health-related quality of life in Parkinson’s disease

BackgroundInsight in how impairments and disabilities related to Parkinson’s disease (PD) influence health-related quality of life (HRQoL) is required to review adequacy of current management strategies.MethodsThe Scales for Outcomes in Parkinson’s disease (SCOPA) evaluation was used to assess impairments and disabilities. HRQoL was assessed with the EuroQol-5D Visual Analogue Scale. 378 patients with PD who participated in the SCOPA/PROPARK cohort were assessed while on their usual treatment. Multiple linear regression analysis and structural equation modelling were used to construct a model of factors that influence HRQoL.ResultsA model with good fit was constructed that identified various impairments and disabilities as important contributors to HRQoL in PD. Of the disabilities, psychosocial well-being had a larger impact on HRQoL than physical functioning. Of the impairments, depression had the largest contribution to HRQoL, followed by axial motor symptoms, gastrointestinal symptoms, and urinary symptoms. In addition, pain, psychiatric and motor complications, and daytime sleepiness had small but significant influences on HRQoL.ConclusionMultiple factors, including disabilities, nonmotor symptoms and axial motor symptoms, affect HRQoL in patients with PD. In patients who are on symptomatic treatment aiming to alleviate mainly motor symptoms, there is a large impact on HRQoL of nonmotor and nondopaminergic symptoms. Research is warranted to develop and evaluate management strategies for the aspects that currently impact on HRQoL as psychosocial well-being, depressive symptoms, axial motor symptoms, gastrointestinal symptoms, and urinary symptoms. These findings call for a multidisciplinary approach in the care of these features.

Origin and reduction of motion and f0 artifacts in high resolution T2*-weighted magnetic resonance imaging: application in Alzheimer's disease patients.

The altered iron concentration in many neurodegenerative diseases such as Alzheimers disease (AD) has led to the development of MRI sequences that are sensitive to the accompanying changes in the transverse relaxation rate. Heavily T(2)*-weighted imaging sequences at high magnetic field strength (7T and above), in particular, show potential for detecting small changes in iron concentration. However, these sequences require a long echo time in combination with a long scanning time for high resolution and are therefore prone to image artifacts caused by physiological fluctuations, patient motion or system instabilities. Many groups have found that the high image quality that was obtained using high resolution T(2)*-weighted sequences at 7T in healthy volunteers, could not be obtained in AD patients. In this study the source of the image artifacts was investigated in phantom and in healthy volunteer experiments by incorporating movement parameters and resonance frequency (f0) variations which were measured in AD patients. It was found that image degradation caused by typical f0 variations was a factor-of-four times larger than artifacts caused by movement characteristic of AD patients in the scanner. In addition to respiratory induced f0 variations, large jumps in the f0 were observed in AD patients. By implementing a navigator echo technique to correct for f0 variations, the image quality of high resolution T(2)*-weighted images increased considerably. This technique was successfully applied in five AD patients and in five subjective memory complainers. Visual scoring showed improvements in image quality in 9 out of 10 subjects. Ghosting levels were reduced by 24+/-13%.

Is olfactory impairment in Parkinson disease related to phenotypic or genotypic characteristics

Objective: To evaluate the relation between olfactory impairment (OI) and other impairment domains in Parkinson disease (PD) and the characteristics of OI in patients with certain genotypic characteristics. Methods: In 295 nondemented patients with PD and 150 controls with a similar overall age and sex distribution, olfactory function was evaluated with the identification (ID) and discrimination (DIS) tests of the Sniffin’ Sticks. In patients, demographic and clinical characteristics were evaluated, and genetic analyses were performed. Results: Of all patients, 61% had an impaired ID and 43% had an impaired DIS. No significant correlations >0.4 were found between olfactory scores and other demographic or clinical variables. Age and sex accounted for the 22% explained variance of the ID score regression model, whereas age, sex, and disease duration accounted for the 15% explained variance of the DIS score regression model. Parkin and DJ-1 mutation carriers (homozygous or heterozygous compound, n = 6) had normal ID scores. APOE ε2 or APOE ε4 carriers had no significantly different olfactory scores than noncarriers. The allele distribution of the alpha-synuclein (SNCA)-REP1 polymorphism in groups with an impaired or normal ID or DIS was comparable. Conclusions: Olfactory impairment (OI) in Parkinson disease (PD) may be unrelated to other impairment domains of the disease, which may indicate that olfaction is an independent feature of PD. Parkin and DJ-1 mutation carriers had normal identification scores but the number of mutation carriers is too small to draw conclusions. The APOE genotype (APOE ε2 or APOE ε4 alleles) and SNCA-REP1 polymorphism do not seem to influence olfaction in PD. GLOSSARY: AAO = age at onset; BDI = Beck Depression Inventory; DIS = discrimination test of the Sniffin’ Sticks; EOPD = early-onset PD; H&Y = Hoehn & Yahr; ID = identification test of the Sniffin’ Sticks; LDE = levodopa equivalent; LUMC = Leiden University Medical Center; MMSE = Mini-Mental State Examination; OI = olfactory impairment; PD = Parkinson disease; PIGD = postural instability gait difficulty; PROPARK = PROfiling PARKinson’s disease; SCOPA = SCales for Outcomes in PArkinson’s disease; SNPs = single nucleotide polymorphisms; UPSIT = University of Pennsylvania Smell IdentificationTest; VUMC = VU University Medical Center.

Patterns of motor and non-motor features in Parkinson’s disease

Objective: To evaluate the presence and nature of patterns of coherency among the motor and non-motor domains in Parkinson’s disease (PD) and to examine which clinical parameters are related to the potential patterns. Methods: A cohort of 397 patients with PD were randomly divided into two samples. Exploratory factor analysis (EFA) was performed on the motor and non-motor symptoms in PD in the first sample. Findings of the EFA were used to construct a model which was tested in the second sample by confirmatory factor analysis. Multiple regression analyses on the resulting factors were performed to evaluate the influence of clinical parameters on these factors. Results: Four factors were identified. The first and strongest factor (cognitive impairment, autonomic dysfunction, psychotic symptoms, depression, daytime sleepiness and axial symptoms) reflected advancing disease. Another factor largely reflected motor complications of therapy and was related to dopaminergic medication. The other two factors reflected sleep/depression and tremor/bradykinesia/rigidity, and were only marginally related to disease severity or medication. Conclusions: The motor and non-motor features in PD can be characterised by four distinct patterns of coherency, which provide insight into the contributions of the primary disease process and antiparkinsonian medication to the broad clinical spectrum of PD. One factor, consisting of predominantly non-motor symptoms together with axial features, clearly reflected disease severity and may provide a new basis for monitoring disease progression in PD.

Handedness associated to side of onset of Parkinson's disease?

1353-8020/

SPES/SCOPA and MDS-UPDRS: Formulas for converting scores of two motor scales in Parkinson’s disease

– see front matter 2008 Elsevier Ltd. doi:10.1016/j.parkreldis.2008.11.002 With great interest we read the article ‘‘Handedness as a predictor of side of onset of Parkinson’s disease’’ by Yust-Katz et al. [1], which was published online in this journal on March 15, 2008. The authors assessed the relation between side of onset and handedness in 307 Parkinson’s disease (PD) patients, where handedness was determined by the hand used for writing. Although more patients in this study experienced their first symptoms on the dominant side, the association between handedness and side of onset was not significant. We also studied this relation in the SCOPA-PROPARK cohort (www.scopa-propark.eu). The hypothesis was that handedness has a protective effect on the progression of PD symptoms, resulting in asymmetry in the side of PD onset. This assumption was based on studies in rodents, in which it was demonstrated that enhanced physical activity of the extremities slowed the progression of PD [2]. Compared to the non-dominant side, the dominant side in humans exhibits more physical activity, since it is used more often and performs more complicated tasks, which, in line with the earlier findings, could act as a protective factor. We took two aspects into account. First, we considered handedness as a continuous rather than a dichotomous variable, with gradients in being more or less left or right handed [3]. In this respect, it could be hypothesized that only extreme right or left handedness would have a protective effect on the motor symptoms of PD. Second, since the effect of neuroplasticity may be expected to be larger in younger patients [4], a relation between handedness and side of first PD symptoms could be demonstrated more clearly in patients with a young onset. Data of the side of onset of PD symptoms, derived from a chart review, were collected in 290 patients with PD. The modified Annett Handedness Inventory was used to evaluate handedness, with the items adjusted to address hand preference in the period before the onset of PD [3]. The total score of this scale ranges