Motor complications in Parkinson disease: a prospective follow-up study

Currently, Parkinson disease (PD) can be symptomatically controlled with standard treatments; however, after a few years this response typically declines. The authors carried out a prospective practice-based study to evaluate the evolution and motor complications during the first 5 years in 59 de novo PD patients. They observed a significant improvement in UPDRS scores during the first year, then the UPDRS mean score declined progressively, especially after the third year (UPDRS score at baseline, 27 points; year 1, 19 points; year 2, 20.3 points; year 3, 22.6 points; year 4, 24.9 points; year 5, 29.5 points). Motor fluctuations, dyskinesias, and freezing also increased after year 3 from 10%, 16%, and 8% respectively to 35%, 32%, and 27% at year 5. At 5 years, 50% of patients (30 of 59) still had UPDRS scores better or equal to baseline, and 44% (26 of 59) had no motor complications. This latter group represented 38% of those subjects initially treated with levodopa and 52% initially treated with other agents.     

Prevalence of neuroleptic-induced movement disorders: an 8-year follow-up study in chronic schizophrenia inpatients

Background: Atypical antipsychotic drug use by schizophrenia patients in Estonia increased from 32% in 2004 to 61% in 2009.

Aims: To assess the prevalence of neuroleptic-induced movement disorders in the Estonian institutionalized population of schizophrenia patients twice over a period of eight years, before and after introduction of atypical antipsychotic drugs using DSM-IV criteria.

Methods: DSM-IV criteria and specific rating scales were used to evaluate the prevalence of neuroleptic-induced movement disorders among 72 patients who participated in the study in 2009 compared to 99 patients who participated in 2001.

Results: Despite increased use of atypical antipsychotics in the study population (up to 30% from 20%), the proportion of movement disorder-free population remained the same over 8 years – 38.9% in 2001 versus 38.4% in 2009. There were significant intra-individual fluctuations. Use of a typical antipsychotic resulted in an almost seven times higher risk of tardive dyskinesia after 8 years. Doses of antipsychotic drugs had no effect on the severity of neuroleptic-induced movement disorders.

Conclusions: Unfortunately, in 18% of patients the switch of medication from typical to atypical did not change the overall prevalence of neuroleptic-induced movement disorders in the group. The long-term benefit of atypical antipsychotics requires further research in patients who are treated with antipsychotics for years.     

Parkinson’s disease and dementia

Neurological Sciences - Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, affecting about 1% of the population over the age of 60. In addition to motor...     

Biomarkers: Parkinson disease with dementia and dementia with Lewy bodies

Dementia is a common feature in Parkinson disease (PD), the time of onset determining how patients are classified. Those patients where dementia develops prior to parkinsonism or during the first year of disease are designated as having dementia with Lewy bodies (DLB). In those where dementia develops over a year after the onset of motor signs, the condition is known as Parkinson's disease with dementia (PDD).While this seems at first sight to be a definitive way to distinguish these conditions, reality is rather different. The overlap between them is considerable, and there is much uncertainty associated with patients who have both motor symptoms and early cognitive impairment. The diagnosis is still based on medical history and clinical evaluation. It is not even certain that they can be accurately distinguished at autopsy. For this reason, the data concerning these entities have been reviewed, to examine various markers employed or measured in clinical, neuropathological, neuroimaging, and biochemical investigations. The concept of PDD and DLB being separate conditions is comparatively new, and the most promising tools with which to separate them at present are cerebrospinal fluid (CSF) markers and positron emission tomography (PET) scanning that indicate increased amyloid-β burden in DLB compared to PDD. However as yet there are no markers that unequivocally distinguish between PDD and DLB.     

The incidence and risk factors of falls in Parkinson disease: prospective study

Background and purposeAlthough Parkinson disease (PD) patients suffer falls more frequently than other old people, only a few studies have focused on identifying the specific risk factors for falls in PD patients. The aim of this study was to assess the incidence and risk factors of falls in a prospective study in comparison to a control group.Material and methodsOne hundred patients with PD were recruited to the study along with 55 gender- and age-matched healthy controls. Both groups were examined twice; the second examination took place one year after the first one. Examination of the PD group included: medical history including falls, neurological examination, assessment of the severity of parkinsonism [Unified Parkinson's Disease Rating Scale (UPDRS), Schwab and England scale (S&E), Hoehn and Yahr scale (H&Y), Mini-Mental State Examination (MMSE)], Hamilton scale and quality of life scales (SF-36, EQ-5D) and Freezing of Gait Questionnaire (FOG-Q). In both groups falls were recorded over the 12 months. Frequent fallers are defined as having more than 3 falls a year.ResultsOver the year falls occurred in 54% of PD patients and 18% of controls. In a prospective study 28% of PD patients fell more frequently than in retrospective analysis. Frequent fallers were found in 20% of patients and in 7% of controls. Fallers showed higher scores in UPDRS, H&Y, S&E, MMSE, and Hamilton scale than non-fallers. Independent risk factors for falls were: age, previously reported falls and higher score in the FOG-Q.ConclusionsFalls in PD patients occurred three times more frequently than in controls. Independent risk factors for falls were: high score in FOG-Q, older age and presence of falls in medical history.     

Cardiovascular autonomic neuropathy and falls in Parkinson disease: a prospective cohort study

Journal of Neurology - Falls represent one of the main complications of Parkinson’s disease (PD), significantly lowering quality of life. Cardiovascular autonomic neuropathy (cAN) is one of...     

Alzheimer disease and the dementia of Parkinson disease: comparative investigations

Intellectual abnormalities are common in Parkinson disease (PD), occurring in a majority of patients and exhibiting a spectrum of severity from mild to severe. Alzheimer disease (AD) has been posited as the cause of dementia in PD. Comparative neuropsychological studies, however, show differences in memory, language, and frontal lobe functions between AD and PD patients even when the two groups have comparably severe dementia syndromes. The AD-type neuropathology occurs in 10-60% of PD patients, and dementia is usually overt when AD pathology is identified at autopsy. The AD changes are less frequent than intellectual deterioration in PD, and dementia has been observed in PD patients without AD pathology. Therefore, concurrent AD cannot be the cause of all cases of dementia in PD. Cholinergic deficits occur in some PD patients, but cholinergic deficits have been described in patients without dementia and dementia has been documented in patients without cholinergic system abnormalities. Dopaminergic disturbances contribute to the dementia of PD. Differences in neuropeptide concentrations, electrophysiologic responses, and cerebral metabolism also support pathophysiologic distinctions between AD and the dementia of PD. Genetic investigations suggest a role for heredity in AD, whereas PD appears to be an acquired, nongenetic disorder. These studies indicate that despite areas of overlap in clinical symptoms and neuropathology, AD and the dementia of PD are largely distinct.     

Structural brain changes in Parkinson disease with dementia: a voxel-based morphometry study

BACKGROUND: Parkinson disease with dementia (PDD) results from neuropathological changes in cortical and subcortical brain regions. Voxel-based morphometric analysis of magnetic resonance images can contribute to in vivo identification of the cerebral regions predominantly involved in PDD. OBJECTIVE: To identify structural cerebral regions most closely related to the presence of PDD. DESIGN: Magnetic resonance images were obtained from 16 patients who had PDD, 13 patients with PD without dementia, and 13 age-matched healthy control subjects. Gray matter volumes were compared using optimized voxel-based morphometric analyses. RESULTS: Compared with healthy controls, patients with PDD showed gray matter volume decreases in several of the following regions: bilateral putamen, accumbens nuclei, left side of the thalamus, bilateral hippocampus, parahippocampal region, and anterior cingulate gyrus. Patients with PD also showed gray matter reductions compared with healthy controls in the right side of the hippocampus, left anterior cingulate gyrus, and left superior temporal gyrus. CONCLUSIONS: The hippocampus, thalamus, and anterior cingulate are the regions most affected in PDD. Our results agree with recent neuropathological findings suggesting the involvement of the limbic and cortical areas in PD.     

Parkinson's disease and risk of hip fracture: an 8-year follow-up study in Taiwan

BackgroundPatients with Parkinson’s disease (PD) are subject to posture instability and falling. However, PD was not included as one of the risk factors in commonly used fracture risk calculation tools and the fracture rate in patients with PD was rarely reported. The aim of this study was to evaluate the risk of hip fracture in patients with PD.MethodsData were collected from the National Health Insurance Research Database of Taiwan. The study group included 394 patients with PD diagnosed in 1999–2000. The comparison cohort was comprised of 3940 age- and sex-matched patients from the same enrollment period. All patients were tracked from their index visits for eight years.ResultsHip fracture developed in 10.4% of patients with PD and 4.1% of patients in the comparison cohort during the follow-up period. Log-rank test analysis showed a significantly higher rate of hip fracture in PD. The Cox proportional regression model showed an adjusted hazard ratio of 2.71 (95% confidence interval = 1.92–3.83, P < 0.001) for patients with PD.ConclusionThe hip fracture rate was as high as 10.4% in PD patients during 8 years follow-up period. While assessing the risk of hip fracture, PD should be taken into consideration. For those very high risk patients (elderly women with PD, osteoporosis, diabetes and diabetic neuropathy), many efforts should be made to prevent fracture.     

Apolipoprotein E and dementia in Parkinson disease: a meta-analysis

OBJECTIVE: To understand the relationship of apolipoprotein E (APOE) polymorphism to dementia in Parkinson disease (PD) because the APOE epsilon4 allele is linked to Alzheimer disease. DATA SOURCE: We reviewed MEDLINE, BIOSIS Previews, and ISI Web of Science from January 1, 1966, to May 7, 2004, supplemented by citation analysis from retrieved articles. STUDY SELECTION: Case-control studies using clinical or pathologic criteria for PD and dementia, and with complete APOE genotype frequencies data. DATA EXTRACTION: We compared estimated prevalence odds ratios for dementia in PD in relation to each allele. We also looked for evidence of heterogeneity and publication bias and performed a stratified analysis on several study characteristics. DATA SYNTHESIS: Data analyses suggest publication bias and heterogeneity of source data for the epsilon4 allele (homogeneity P = .2; Begg and Mazumdar, P = .06; and Egger et al, P = .1). The estimated odds ratios for development of dementia in PD are 1.6 for epsilon4 (95% confidence interval, 1.0-2.5); 1.3 for epsilon2 (95% confidence interval, 0.73-2.4); and 0.54 for epsilon3 (95% confidence interval, 0.18-1.6). The odds ratio estimates for epsilon4 were higher for studies published in 1996 or later (2.3 vs 1.0) and for studies conducted outside North American sites (2.4 vs 1.2). CONCLUSIONS: The APOE epsilon4 allele appears to be associated with a higher prevalence of dementia in PD. Publication bias and heterogeneous source data may, however, confound this conclusion. Confirmatory studies that use standardized and validated diagnostic criteria for dementia in PD are needed.     

Incidence of dementia in Parkinson disease]

The aim of our study was to assess the frequency of dementia in a highly selected (according to diagnostic criteria of Parkinson's disease and other causes of dementia) group of patients. MATERIAL AND METHODS: 46 patients (F 18, M 28), mean age--63.9 (39-80) years, with good response to L-Dopa. Besides the neurological examination, all patients underwent CT and psychological tests (Wechsler-Bellevue, Mini Mental and Hamilton test--to exclude severe depression as cognitive problem cause). In the group with dementia thyroxine and cholesterol tests and EEG were performed. RESULTS: Within the whole group the features of dementia (the index of deterioration in Wechsler test > 25% and/or 23 or less points in Mini-Mental) were recognized in 11 (23.9%) patients. In comparison to the rest of the patients, in the group with dementia the mean age was 8.1 years higher, mean age at onset of the disease was 6.4 years higher, mean time of the disease 1.5 years longer and the severity of the disease measured in Hoehn-Yahr rating scale was 0.76 points higher (2.20 vs 2.96). In the whole group severe depression (> 18 points in Hamilton test) was revealed in 6%, whereas moderate (8-17 points) occurred in 71%. CONCLUSIONS: Older age, later onset of symptoms and more advanced disease are the risk factors of dementia. Other causes--like dementia of Alzheimer's type may be suspected or two distinctive forms of Parkinson's Disease with and without dementia exist.     

Early self-experienced neuropsychological deficits and subsequent schizophrenic diseases: an 8-year average follow-up prospective study

The aim of the present study was to investigate the potential predictive value of early self-experienced neuropsychological deficits for the subsequent development of schizophrenia. A total of 96 patients with DSM-III-R diagnoses of personality disorders (formerly called ‘neurotic disorders’) who had been examined for the presence of such subjective experiences of deficits with standardized instruments were re-examined for the possible development of schizophrenic symptoms. After an average follow-up period of about 8 years, more than 50% of the patients had developed schizophrenia according to DSM-III-R criteria. In 77% of cases the outcome ‘schizophrenia vs. no schizophrenia’ was correctly predicted by the earlier presence or absence of self-experienced disturbances of thought, speech, memory, perception and action. These findings suggest that certain self-experienced neuropsychological deficits are able to indicate susceptibility to psychosis.