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Long-term therapy of Parkinson's disease with L‑DOPA is associated with a high risk of developing motor fluctuations and dyskinesia. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can improve these motor complications. Although the positive effect on motor symptoms has been proven, postoperative cognitive decline has been documented. To tackle the impact of DBS on cognition, 18 DBS patients were compared to 25 best medically treated Parkinson's patients, 24 patients with mild cognitive impairment (MCI) and 12 healthy controls using the Neuropsychological Test Battery Vienna short version (NTBV-short) for cognitive outcome 12 months after the first examination. Reliable change index methodology was used. Roughly 10% of DBS patients showed cognitive decline mainly affecting the domains attention and executive functioning (phonemic fluency). Further research is needed to identify the mechanisms that lead to improvement or deterioration of cognitive functions in individual cases.

In Parkinson's disease (PD) the prevalence of apraxia increases with disease severity implying that patients in early stages may already have subclinical deficits. The aim of this exploratory fMRI study was to investigate if subclinical aberrations of the praxis network are already present in patients with early PD. In previous functional imaging literature only data on basal motor functions in PD exists. Thirteen patients with mild parkinsonian symptoms and without clinically diagnosed apraxia and 14 healthy controls entered this study. During fMRI participants performed a pantomime task in which they imitated the use of visually presented objects. Patients were measured ON and OFF dopaminergic therapy to evaluate a potential medication effect on praxis abilities and related brain functions. Although none of the patients was apraxic according to De Renzi ideomotor scores (range 62-72), patients OFF showed significantly lower praxis scores than controls. Patients exhibited significant hyperactivation in left fronto-parietal core areas of the praxis network. Frontal activations were clearly dominant in patients and were correlated with lower individual praxis scores. We conclude that early PD patients already show characteristic signs of praxis network dysfunctions and rely on specific hyperactivations to avoid clinically evident apraxic symptoms. Subclinical apraxic deficits were shown to correlate with an activation shift from left parietal to left frontal areas implying a prospective individual imaging marker for incipient apraxia.

Background and Purpose: Impaired dexterity (fine hand movements) is often present in Parkinson's disease (PD), even at early to moderate disease stages. It has a detrimental impact on activities of daily living (ADL) such as buttoning, contributing to reduced quality of life. Limb-kinetic apraxia, a loss of the ability to make precise, independent but coordinated finger and hand movements, may contribute to impaired dexterity even more than bradykinesia per se. However, the impact of limb-kinetic apraxia on ADL remains controversial. Our aim was to identify the strongest predictor of buttoning and unbuttoning in PD. It was hypothesized that coin rotation (a surrogate of limb-kinetic apraxia) represents the most important determinant., Methods: Sixty-four right-handed, early to moderate PD patients were recruited from three movement disorder centers (Hoehn andYahr stages 1-3). Buttoning, unbuttoning and coin rotation (right and left hand) represented the target tasks. Motor impairment was assessed according to the Unified Parkinson's Disease Rating Scale., Results: Multiple linear regression analysis showed that coin rotation with the right hand was the only significant predictor of buttoning (P < 0.001) and unbuttoning (P = 0.002). Notably, measures of bradykinesia or overall motor impairment did not represent significant predictors., Conclusions: Constituting the novel key finding, limb-kinetic apraxia seems to be particularly relevant for ADL requiring dexterity skills in PD, even at early to moderate disease stages. Our results prompt research into the pathophysiological background and therapeutic options to treat limb-kinetic apraxia. The simple coin rotation test provides valuable information about ADL-related dexterity skills., (© 2016 EAN.)

Background: Impairments in facial emotion recognition (FER) have been detected in patients with Parkinson disease (PD). Presently, we aim at assessing differences in emotion recognition performance in PD patient groups with and without mild forms of cognitive impairment (MCI) compared to healthy controls., Methods: Performance on a concise emotion recognition test battery (VERT-K) of three groups of 97 PD patients was compared with an age-equivalent sample of 168 healthy controls. Patients were categorized into groups according to two well-established classifications of MCI according to Petersen's (cognitively intact vs. amnestic MCI, aMCI, vs. non-amnestic MCI, non-aMCI) and Litvan's (cognitively intact vs. single-domain MCI, sMCI, vs. multi-domain MCI, mMCI) criteria. Patients and controls underwent individual assessments using a comprehensive neuropsychological test battery examining attention, executive functioning, language, and memory (Neuropsychological Test Battery Vienna, NTBV), the Beck Depression Inventory, and a measure of premorbid IQ (WST)., Results: Cognitively intact PD patients and patients with MCI in PD (PD-MCI) showed significantly worse emotion recognition performance when compared to healthy controls. Between-groups effect sizes were substantial, showing non-trivial effects in all comparisons (Cohen's ds from 0.31 to 1.22). Moreover, emotion recognition performance was higher in women, positively associated with premorbid IQ and negatively associated with age. Depressive symptoms were not related to FER., Conclusions: The present investigation yields further evidence for impaired FER in PD. Interestingly, our data suggest FER deficits even in cognitively intact PD patients indicating FER dysfunction prior to the development of overt cognitive dysfunction. Age showed a negative association whereas IQ showed a positive association with FER.

Background: Freezing of gait (FOG) is a common and debilitating phenomenon in Parkinson's disease (PD). Wearable accelerometers might help to assess FOG in the research setting. Here, we evaluate whether accelerometry can detect FOG while executing rapid full turns and while walking with rapid short steps (the two most common provoking circumstances for FOG)., Methods: We included 23 PD patients, who all had objective FOG. Participants performed several walking tasks, including walking rapidly with short steps and rapid full turns in both directions with a triaxial linear waist-mounted accelerometer. Two independent experts identified FOG episodes using off-line video-analysis (gold standard). A validated algorithm [ratio between pathological freezing (3-8 Hz)-and normal locomotor frequencies (0.5-3 Hz)] was applied on the accelerometer data to detect FOG episodes., Results: Clinically, FOG was most often observed during full rapid turns (81% of all episodes), followed by walking with short rapid steps (12% of all episodes). During full rapid turns, accelerometry yielded a sensitivity of 78% and specificity of 59%. A sensitivity of 64% and specificity of 69% was observed during walking rapidly with small steps. Combining all tasks rendered a sensitivity of 75% and specificity of 76%., Conclusion: Our results suggest that FOG can be detected from a single lumbar accelerometer during several walking tasks, including full rapid turns and walking with short steps rapidly, with reasonable sensitivity and specificity. This approach holds promise for possible implementation as complementary objective outcome in a research setting, but more work remains needed to improve the sensitivity and specificity., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Impaired awareness of memory deficits has been recognized as a common phenomenon in Alzheimer's disease (AD) and research is now increasingly focusing on awareness in groups at risk for future dementia. This study aimed to determine whether levels of awareness differ among healthy elderly people and patients with subjective cognitive decline (SCD), amnestic and non-amnestic subtypes of mild cognitive impairment (aMCI, naMCI), Alzheimer's disease (AD) and Parkinson's disease (PD), to explore correlates of awareness and to establish frequencies of memory over- and underestimation within each diagnostic group., Methods: 756 consecutive outpatients of a memory clinic and 211 healthy controls underwent thorough neuropsychological testing. Impairment of awareness was measured as the difference between subjective memory appraisals (16-item questionnaire on current memory-related problems in everyday life) and objective memory performance (15-item delayed recall task). Subgroups of over- and underestimators were classified using percentile ranks of controls., Results: At group level, awareness significantly decreased along the naMCI→aMCI→AD continuum, with naMCI patients showing a tendency towards overestimation of memory dysfunction. PD patients showed accurate self-appraisals as long as memory function was largely unaffected. However, there was a considerable between-group overlap in awareness scores. Furthermore, different correlates of awareness were observed depending on the diagnostic group. In general, unawareness seems to be associated with decreased cognitive performance in various domains (especially memory), higher age and lower levels of depression and self-reported functional impairment., Conclusion: Impaired awareness is an important symptom in aMCI. Yet, given the considerable variability in awareness scores, longitudinal studies are required to evaluate their predictive power.

Introduction: The patho-physiological basis for finger dexterity deficits in Parkinson's disease (PD) is controversial. Previously, bradykinesia was regarded as the major mechanism. However, recent research suggested limb-kinetic apraxia as an important component of impaired fine motor skills in PD. In contrast to bradykinesia, limb-kinetic apraxia only marginally responds to dopaminergic treatment. Here we investigate the novel hypothesis that the dexterity deficits are related to an intrinsic dysfunction of primary somatosensory cortex (S1), which is not reversible by dopaminergic medication., Methods: Applying a standard and approved dexterity task (coin rotation), brain activation networks were investigated using functional magnetic resonance imaging in PD patients both ON and OFF medication and matched healthy controls., Results: PD patients both ON and OFF medication showed impaired S1 activation relative to controls (p < 0.05; region of interest based analysis). The impaired S1 activation remained unchanged by dopaminergic medication. Despite the considerable clinical deficit, no other brain area showed impaired activation. In contrast, structures of the basal ganglia--motor cortex loop responded to dopaminergic medication. Behaviorally, dexterity performance both ON and OFF was significantly (p < 0.05) reduced relative to controls., Conclusions: Our results provide first evidence that dexterity deficits in PD are related to an S1 dysfunction which is insensitive to dopaminergic treatment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Several recently proposed criteria for assessing cognitive disorder require measuring the cognitive domain of visuo-constructional function. The aims of the present study were to develop a new test (Vienna Visuo-constructional Test-VVT) measuring visuo-constructional functions and to determine the reliability and validity of the VVT in patients with mild cognitive impairment (MCI), Parkinson's disease (PD), and Alzheimer's disease (AD). We further examined age and sex effects and the psychometric quality of the VVT., Methods: The study included 76 healthy controls and 103 patients who were referred to the Department of Neurology, Medical University of Vienna for neurocognitive assessment. An administering and scoring system for the VVT was developed., Results: Internal consistency (Cronbach's alpha) was found to range from 0.82 for the healthy control group to 0.93 for the total patient group. There was no sex effect, but age had a negative effect on VVT performance. The VVT successfully differentiated healthy controls from MCI patients, AD patients, and PD patients, respectively., Conclusion: The VVT shows satisfactory validity and reliability and can be administered easily in clinical practice. It constitutes a new measure that can successfully be used to identify visuo-constructional problems in patients with cognitive dysfunction.

Background and Purpose: The goal of this study was to establish the prevalence of subjective memory complaints (SMCs) and depressive symptoms (DS)s and their relation to cognitive functioning in patients with Parkinson's disease (PD)., Methods: In all, 248 controls and 104 PD patients were included in the study. The PD group was subdivided into three PD subtypes with mild cognitive impairment (MCI) according to the Petersen criteria and three PD subtypes with MCI according to the Litvan criteria., Results: Substantial SMCs were reported by 7.7% of controls and 16.3% of the PD patients (P < 0.001). A clinically relevant degree of DSs was evident in 16.6% of controls compared with 40.4% in the PD group (P < 0.001). An analysis of variance revealed a statistically significant difference for SMCs across all Petersen groups as well across all Litvan groups. Two-factor analyses of variance with the factors cognitive status (MCI subtype) and depressive state (depressed versus not depressed) and SMCs as dependent variable revealed significant results., Conclusions: Approximately 15% of PD patients seeking help in a movement disorder clinic report significant SMCs, with an increasing degree from cognitively healthy PD to PD-MCI. Significant DSs increase SMCs across all cognitive status groups., (© 2014 The Author(s) European Journal of Neurology © 2014 EAN.)

Recently a new autosomal dominant Parkinson's disease mutation (p.Asp620Asn) in the VPS35 gene was discovered. The clinical features of 14 PD patients with this mutation from three Austrian families were evaluated. Age at disease-onset appears lower and depression was more common in Austrian patients compared to sporadic PD patients. However, we were unable to identify a specific clinical maker of VPS35 patients, who otherwise resemble sporadic PD patients.

Background: Antonovsky's salutogenic model of the "Sense of Coherence" (SOC) is an important resource in dealing with chronic diseases. The aim of this study was to investigate SOC as a psychological factor and its correlation with illness, subjective well-being, and health-related quality of life (QoL) in patients with Parkinson disease (PD) compared to patients with other chronic diseases., Methods: Fifty-one patients suffering from PD and 59 participants with other chronic non-neurological diseases took part in this study. The PD patients were assessed through medical routine examinations and all participants were asked to complete several questionnaires for psychological assessment. In order to compare controls with the PD group, t-tests, U-tests, and multivariate analysis were conducted. Multiple regression analysis was calculated to identify predictor variables., Results: Patients with PD were characterized by lower SOC and higher scores concerning depression compared to the control group (CG). Furthermore, the PD group showed fewer active coping strategies and lower scores concerning well-being. There were correlations between depression, coping, well-being and QoL, and SOC. The SOC had a particular predictive value with regards to the outcome "quality of life" and coping strategies., Conclusions: There are a number of differences regarding psychological characteristics of coping mechanisms in neurological and non-neurological patients. The SOC correlated with several psychological factors; however, there was no correlation with medical data. The SOC predicts scores pertaining coping mechanism and health-related QoL.

To identify rare causal variants in late-onset Parkinson disease (PD), we investigated an Austrian family with 16 affected individuals by exome sequencing. We found a missense mutation, c.1858G>A (p.Asp620Asn), in the VPS35 gene in all seven affected family members who are alive. By screening additional PD cases, we saw the same variant cosegregating with the disease in an autosomal-dominant mode with high but incomplete penetrance in two further families with five and ten affected members, respectively. The mean age of onset in the affected individuals was 53 years. Genotyping showed that the shared haplotype extends across 65 kilobases around VPS35. Screening the entire VPS35 coding sequence in an additional 860 cases and 1014 controls revealed six further nonsynonymous missense variants. Three were only present in cases, two were only present in controls, and one was present in cases and controls. The familial mutation p.Asp620Asn and a further variant, c.1570C>T (p.Arg524Trp), detected in a sporadic PD case were predicted to be damaging by sequence-based and molecular-dynamics analyses. VPS35 is a component of the retromer complex and mediates retrograde transport between endosomes and the trans-Golgi network, and it has recently been found to be involved in Alzheimer disease., (Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

The transcription factors PITX3 and Engrailed 1 (EN1), among others, have been shown to play a crucial role in the maturation and survival of midbrain dopaminergic neurons. The degeneration of those neurons is the pathological hallmark in Parkinson's disease (PD). In a hypothesis-driven candidate gene approach, it has been recently shown that polymorphisms in the genes coding for PITX3 and EN1 are associated with sporadic PD. In a study on 365 patients with PD and 418 controls, we genotyped nine single nucleotide polymorphisms spanning the entire genomic region of PITX3 and EN1. Furthermore, we analyzed whether the genotype of these SNPs associate with the age of onset in PD. We found a strong association between the PITX3 promoter rs3758549 polymorphism and PD (p=0.0001), as well as an association between EN1 rs1438852 and PD (p=0.046). In particular, our highly significant findings regarding the association of rs3758549 reproduce the results of the initial report on transcription factor gene variants, providing further evidence for PITX3 and EN1 polymorphisms as potential genetic risk factors for sporadic PD., (Copyright © 2009 Elsevier Inc. All rights reserved.)

Impairment of hand dexterity in Parkinson's disease (PD) is usually attributed to bradykinesia. Recently, behavioral studies illustrated that decreased dexterity might also be due to limb-kinetic apraxia (LkA), as demonstrated by impaired performance in a coin rotation task. Here, we provide a first investigation on whether functional magnetic resonance imaging (fMRI) may reveal specific brain activation patterns for PD patients with impaired performance in a coin rotation task. We compared coin rotation as an apraxia task to simple finger tapping as a bradykinesia task in ten PD patients OFF medication and matched healthy controls. In addition to a tendency for general overactivation, PD patients showed a perirolandic dissociation with precentral overactivation and postcentral underactivation. This finding significantly separated PD patients from healthy controls., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Several randomized placebo-controlled trials have consistently shown antidyskinetic effects of amantadine in levodopa treated patients with advanced Parkinson's disease (PD). However, all of these were of short duration and there have been claims that the effect of amantadine on levodopa induced dyskinesias (LID's) wear off after about 9 months of treatment. This randomized placebo-controlled parallel-group study was performed to assess the long-term antidyskinetic effect of amantadine in 32 PD patients, who after having been on stable amantadine therapy for LID over at least one year- were switched in a double blind manner to amantadine or placebo and followed for 3 weeks. Dyskinesia duration and intensity were assessed by UPDRS IV items 32 and 33 as well as by patient's diaries. The primary outcome was the score change of UPDRS IV items 32 + 33 between baseline and 3 weeks after treatment as well as the between treatment group comparison of the score change of UPDRS IV items 32 + 33. There was a significant increase of UPDRS IV items 32 + 33 in patients treated with placebo from 3.06 (95% CI, 2.1-4.03) at baseline to 4.28 (95% CI, 3.1-5.4) at three-week follow-up (P = 0.02) compared with no significant change between baseline 3.2 (95% CI, 2.1-4.4) to follow-up 3.6 (95% CI, 2.3-4.8) in patients staying on amantadine. These findings argue for long-term antidyskinetic efficacy of amantadine in PD patients with LID's., ((c) 2010 Movement Disorder Society.)

Purpose: To create a population-specific symmetric phase model and to evaluate the susceptibility-weighted imaging (SWI) phase in terms of phase shift using different segmentation methods (manual and automatic) and phase shift symmetry, which is expected as a marker for lateralized Parkinson's disease (PD) symptoms., Materials and Methods: SWI and T(1)-weighted data from 25 PD patients and five healthy controls were acquired on a 3T MRI system. A population-specific, symmetric phase model was developed. Regions of interest (ROIs) were defined manually on the phase model, manually on each individual data set, and automatically using model-based segmentation (MBS). Manually- and MBS-defined ROIs were compared using kappa values, and left-right phase symmetry was evaluated using correlation analysis., Results: Independent of the analysis method, a phase increase from the anterior to the posterior putamen, and the average phase value relationship substantia nigra > globus pallidus > red nucleus was found. Phase symmetry analysis shows a difference between lateralized and symmetric PD., Conclusion: The symmetric phase model helps to analyze phase data with similar accuracy, but a greatly reduced tracing effort compared to individual tracing and also allows evaluating left-right phase symmetries., ((c) 2009 Wiley-Liss, Inc.)

A clinical overlap between Parkinson's disease (PD) and essential tremor (ET) has prompted a discussion whether these conditions share common genetic susceptibility factors. Recently, the first genome-wide association study in ET revealed a significant association with a variant in the LINGO1 gene. LINGO1 has also been demonstrated to play a role in the survival of dopaminergic neurons in an animal model of PD, and therefore constitutes a potential candidate gene for PD. In this study, SNPs rs9652490, rs11856808, and rs7177008 of LINGO1 were genotyped in a total of 694 Austrian subjects (349 PD, 345 controls). No association could be found between genotype or allele counts and PD. Neither did a subgroup analysis in tremor-dominant patients with PD reveal a significant association. This study on LINGO1-variants in PD argues against a major role of LINGO1 gene variations for PD., ((c) 2009 Movement Disorder Society.)

The GIGYF2 (Grb10-Interacting GYF Protein-2) gene has recently been proposed to be the responsible gene for the PARK11 locus. Ten different putative pathogenic variants were identified in cohorts of Parkinson's disease (PD) patients from Italy and France. Among these variants Asn56Ser and Asn457Thr were found repeatedly. In the present study we screened 669 PD patients (predominantly of central European origin) and 1051 control individuals for the presence of these two variants. Asn56Ser was found in one patient with a positive family history of the disease and in one control individual. The affected sister of the patient did not carry this variant. Asn457Thr was found in one patient, who was exceptional for his Egyptian origin and in three control individuals. This variant was not found in 50 control individuals from Egypt. We conclude that neither of these two variants plays a major role in the pathogenesis of PD in our study population.

Purpose of the Study: In this study the relevance of sense of coherence (SOC) for coping with an illness was examined in subjects with Parkinson's disease. According to Antonovsky's model (1997) the sense of coherence is an important resource when it comes to dealing with stressors. To take into consideration the integrated view of Parkinson patients, severity of the illness (UPDRS) was determined by the neurologist and tendency toward depression was recorded., Method: 51 patients with PD (mean age: 67.7; 43.1% female; 56.9% male) and 59 volunteers without any neurological illness (mean age: 65.7; 54.2% female; 45.8% male) took part in this study. The sample was recruited from the Neurological Department of the Medical University of Vienna. This quasi-experimental sample was assessed with standardized self-assessment questionnaires: FKV-LIS-SE, SOC-Scale and GDS. Correlations, t-tests, U-tests, multivariate analyses of variance and linear regressions were used for calculation., Results: Persons with PD were characterized by lower SOC (p<.01) and higher scores on depression (p<.01), compared to persons of the control group. Parkinson patients tend to use depressive and minimizing coping strategies (p<.01). In addition the study indicates an influence of SOC and tendency toward depression on coping (R(2)=0.43). Sense of coherence and coping strategies are independent of severity of illness, but there is a significant association between the duration of illness and active-problem focused coping., Conclusion: In general, sense of coherence correlates only with psychological variables, and not with physical variables. Results indicate the importance of SOC on effective coping. Therefore strengthening of SOC is important, especially in context with chronic neurological illness. Individual orientated analysis of resources should be implemented in every counselling interview, so that possibilities for activities of daily living and leisure can be developed.

To investigate the frequency of mutations in the Leucine-Rich Repeat Kinase 2 gene (LRRK2) in a sample of Austrian Parkinson's disease (PD) patients, we sequenced the complete coding region in 16 patients with autosomal dominant PD. Furthermore, we sequenced exons 31, 35, and 41 additionally in 146 patients with idiopathic PD and 30 patients with dementia with Lewy bodies. Furthermore, all 192 patients were screened for 21 putative LRRK2 mutations. While the most common mutation G2019S and the risk variant G2385R were not found in our samples, we detected a novel missense mutation (S973N) in a patient with familial, late-onset and dopa-responsive PD., (Copyright (c) 2007 Movement Disorder Society.)

Objectives: Sleep disorders and depression are frequent in patients with Parkinson's disease (PD). However, the exact prevalence and the causality are still unknown., Patients and Methods: We interviewed 56 consecutive PD patients and 59 age-matched healthy controls concerning sleep disorders and depression. Sleep Disorders Questionnaire (SDQ) and Zung Depression Scale (ZDS) were used as standardized valid and reliable psychometric tests., Results: Patients with PD had significantly higher values in the clinical-diagnostic scale narcolepsy (P=0.01), correlating with the L-dopa dose (P=0.007). Concerning sleep apnea (P=0.49), psychiatric sleep disorder (P=1.00) and periodic limb movement disorder (P=0.12), no significant difference could be identified. PD patients showed significantly higher depression scores than healthy control subjects (P=0.01), increasing with the duration of PD (P=0.04)., Conclusion: The significant higher narcolepsy score in PD patients must be seen due to dopaminergic medication and PD-specific neurodegeneration and immobility rather than due to narcolepsy. This leads to the conclusion that extreme caution is advised when carrying out the SDQ and interpreting the results in various persons and patient groups with motor problems. The strong association of depression, disease severity and sleep disorders in PD patients underlines the importance of identifying and treating both conditions in these patients.

Parkinson's disease is not only a disorder affecting locomotion, but often also causes speech problems. Functional impairment of articulation, phonation, prosody and also respiration may occur. Speech disorder is frequent in Parkinson's disease and often has an impact on the quality of life. Speech therapy is by no means offered as a matter of course to these patients. This article outlines the different approaches of speech therapy regarding respiration, loudness, articulation, prosody, and intonation. Speech therapy seems to be useful in patients with Parkinson's disease only if there is no cognitive impairment; success also depends on motivation and eventual frequent repetition of therapy series.

Modern rehabilitation is becoming more and more "social integration" instead of "going back to work". Therefore rehabilitation is also a matter in chronic disease and in old people. Parkinson patients are somewhat disabled in nearly every aspect of their life, although the extent is related to the stage of the disease. Moreover, symptoms do not respond equally to drug treatment, balance (with succeeding falls) and swallowing being special problems for anti-parkinsonian drug treatment, but also vegetative symptoms, dysarthria, motor skills etc. Apart from medication patients get relief also from adjuvant therapy like physiotherapy, occupational therapy, and speech therapy, which all can lead to improvement of quality of life. Rehabilitation needs team effort. Patient and family supporting groups (like Parkinson Disease Society and others) are an important factor for all needs of neurological rehabilitation.

We studied the initiation of saccades to visual-guided random time and remembered targets in a group of nine Parkinsonian patients with severe motor fluctuations and in 9 age matched control subjects. In contrast to a marked skeletomotor improvement during the "on" condition, saccadic latencies for both visual-guided random saccades and remembered saccades were increased in the patients during the "on" condition compared to the "off" condition. This result of dissociation between skeletomotor and oculomotor function indicates that common concepts of saccadic initiation in parkinsonian patients do not hold true in patients with severe fluctuations since dopaminergic stimulation seems to increase saccadic latencies in these patients.

Aim of this study was the characterization of the circadian melatonin profile in de novo Parkinson patients (N = 9, age 60.0 +/- 3.2 years, mean +/- SEM) and the comparison of these profiles with those of controls and Parkinson patients treated with l-dopa/decarboxylase inhibitor (l-dopa/DCI). We collected 14 venous blood samples during a period of 24 hours and measured the serum melatonin levels by a radioimmuno assay. De novo Parkinson patients displayed the nocturnal melatonin peak (acrophase) at the same time as controls and significantly later than l-dopa/DCI treated patients (1:54 +/- 15.6 min [average clock time +/- SEM in minutes] vs. 1:45 +/- 15.6 min vs. 0:13 +/- 40.8 min). The amount of secreted melatonin did not differ among the three groups. Stage and duration of Parkinson's disease did not correlate with the amount of secreted melatonin. Patients of the tremor subgroup, however, secreted more melatonin than patients presenting only with rigidity and akinesia. The phase advance in Parkinson patients treated with l-dopa/DCI is possibly due to a central nervous dopaminergic effect elicited by l-dopa administration and not inherent to Parkinson's disease per se.

Physical activity during lifetime was investigated among 32 Parkinson patients (age 65.6 +/- 8.1 yrs, mean +/- SD) retrospectively by means of a structured interview. Data were compared with 31 healthy controls (age 61.7 +/- 5.8 yrs). An objective score was obtained by presenting a list of all kinds of sports, subjective estimation of physical activity was done by visual analogous scales. Until the occurrence of the first symptoms (mean = 58.5 yrs) the patients did not differ from controls. During the course of disease a striking reduction in physical activity but no complete abandonment of sports was found. Swimming, hiking and gymnastics were the favoured sports in both groups. Learning of new sports seemed to be impossible for the patients.

Although several studies on the efficacy and the toxicity of exogenous melatonin in Parkinson patients have been carried out, there are no data available on melatonin secretion in these patients. We therefore performed a controlled trial in 9 Parkinson patients (aged 62.1 +/- 8.7 years, x +/- SD) and in 14 control persons (58.0 +/- 10.4 years). Parkinson patients were treated with l-dopa (300-1000 mg per day) in combination with a peripheral decarboxylase inhibitor (benserazide, carbidopa). 14 venous blood samples were taken from each person during a period of 24 hours in order to investigate the circadian secretion pattern of melatonin. Serum melatonin levels were estimated by radioimmuno assay. We found that the circadian secretion patterns of l-dopa-treated Parkinson patients and age-matched controls were very similar except for a phase advance of the nocturnal melatonin elevation in the parkinsonian group.

Neuropsychological, neuropathological and neurochemical findings show different types of dementias. Few of them have been able to confirm a division into "subcortical" and "cortical" dementia, so this concept has to be questioned. The present clinical study compared type and severity of dementia in 12 Parkinson-patients (PD) and 12 Alzheimer-patients (AD). The age-adjusted normal value differed a significantly from both patient groups. No significant difference in pattern of neuropsychological deficits between PD- and AD-patients was apparent. However, after similar duration of illness, dementia was more severe in AD- than in PD-patients.

Compared with a group of age matched controls, patients with Parkinson's disease scored significantly lower in testing for ideomotor apraxia. Imitation of movement sequences was affected more severely than performance of single movements. The degree of impairment was not related to severity of motor disability, but correlated strongly with the results of tests that measured visuospatial and visuoperceptive abilities. It is suggested that defective encoding and central processing of visuospatial information impairs memory for movement which is necessary for correct imitation of movements. Enhanced vulnerability to interference between successively presented items may cause further deterioration of performance in the copying of movement sequences.