Residence near power lines and mortality from neurodegenerative diseases: longitudinal study of the Swiss population

The relation between residential magnetic field exposure from power lines and mortality from neurodegenerative conditions was analyzed among 4.7 million persons of the Swiss National Cohort (linking mortality and census data), covering the period 2000-2005. Cox proportional hazard models were used to analyze the relation of living in the proximity of 220-380 kV power lines and the risk of death from neurodegenerative diseases, with adjustment for a range of potential confounders. Overall, the adjusted hazard ratio for Alzheimer's disease in persons living within 50 m of a 220-380 kV power line was 1.24 (95% confidence interval (CI): 0.80, 1.92) compared with persons who lived at a distance of 600 m or more. There was a dose-response relation with respect to years of residence in the immediate vicinity of power lines and Alzheimer's disease: Persons living at least 5 years within 50 m had an adjusted hazard ratio of 1.51 (95% CI: 0.91, 2.51), increasing to 1.78 (95% CI: 1.07, 2.96) with at least 10 years and to 2.00 (95% CI: 1.21, 3.33) with at least 15 years. The pattern was similar for senile dementia. There was little evidence for an increased risk of amyotrophic lateral sclerosis, Parkinson's disease, or multiple sclerosis.

The moderating role of personal mastery on the relationship between caregiving status and multiple dimensions of fatigue

OBJECTIVE: A substantial proportion of chronically-stressed spousal dementia caregivers report fatigue. The objective of this study was to examine whether personal mastery moderates the relationship between caregiving status (caregiver/non-caregiver) and multiple dimensions of fatigue. METHODS: Seventy-three elderly Alzheimer's caregivers and 41 elderly non-caregivers completed the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) and questionnaires assessing mastery. RESULTS: Regression analyses indicated that global fatigue was significantly higher for caregivers (M = 38.0 +/- 21.0) compared to non-caregivers (M = 18.2 +/- 10.4). However, personal mastery moderated the relation between caregiving status and global fatigue (t = -2.03, df = 107, p = 0.045), such that for those with low mastery, caregivers' fatigue scores were 18.1 points higher than non-caregivers, and for those with high mastery, this difference was only 7.5 points. For specific dimensions of fatigue, mastery moderated the relations between caregiving status and both emotional (t = -2.01, df = 107, p = 0.047) and physical (t = -2.51, df = 107, p = 0.014) fatigue. Specifically, association between caregiving status and emotional fatigue was greater when mastery was low than when mastery was high. Caregiving status was significantly associated with physical fatigue when mastery was low, but not when mastery was high. Significant main effects were found between mastery and general fatigue and vigor. CONCLUSION: Given the proportion of fatigued caregivers and the impact fatigue has on health; these findings provide important information regarding mastery's relationship with fatigue and may inform interventions aiming to alleviate fatigue in caregivers. Copyright (c) 2009 John Wiley ; Sons, Ltd.

Event-related potential and EEG measures in Parkinson's disease without and with dementia

Nondemented Parkinson’s disease (PD) patients showed increased amplitude of event-related potential component P3. We recorded 18-channel spontaneous eyes-closed resting EEG and auditory oddball event-related potentials in 29 PD patients and 11 age-matched controls. Combining Mini-Mental State Examination score and oddball P3 counting performance, 15 patients were intellectually normal, 7 moderately, and 7 severely demented. P3 and N1 amplitude and latency, mean amplitude of 1,024 ms post-stimulus (separate after rare and after frequent stimuli), and resting EEG total power for 40 s were computed, and linearly regressed for age, sex, and L-dopa dosage. In nondemented PD patients, increased P3 amplitude was confirmed, but N1 amplitude and mean amplitude after rare and frequent stimuli were also increased as well as – most important – resting EEG total power. With increasing dementia, amplitude and power decreased, and P3 latency increased. Task demands cannot explain increased P3 amplitude, since similarly increased EEG total power was found during no-task resting. Prospective studies must determine whether P3 amplitude and EEG power in nondemented PD patients can serve as predictors of dementia.

Ecological validity of virtual reality daily living activities screening for early dementia: longitudinal study

Background: Dementia is a multifaceted disorder that impairs cognitive functions, such as memory, language, and executive functions necessary to plan, organize, and prioritize tasks required for goal-directed behaviors. In most cases, individuals with dementia experience difficulties interacting with physical and social environments. The purpose of this study was to establish ecological validity and initial construct validity of a fire evacuation Virtual Reality Day-Out Task (VR-DOT) environment based on performance profiles as a screening tool for early dementia. Objective: The objectives were (1) to examine the relationships among the performances of 3 groups of participants in the VR-DOT and traditional neuropsychological tests employed to assess executive functions, and (2) to compare the performance of participants with mild Alzheimer’s-type dementia (AD) to those with amnestic single-domain mild cognitive impairment (MCI) and healthy controls in the VR-DOT and traditional neuropsychological tests used to assess executive functions. We hypothesized that the 2 cognitively impaired groups would have distinct performance profiles and show significantly impaired independent functioning in ADL compared to the healthy controls. Methods: The study population included 3 groups: 72 healthy control elderly participants, 65 amnestic MCI participants, and 68 mild AD participants. A natural user interface framework based on a fire evacuation VR-DOT environment was used for assessing physical and cognitive abilities of seniors over 3 years. VR-DOT focuses on the subtle errors and patterns in performing everyday activities and has the advantage of not depending on a subjective rating of an individual person. We further assessed functional capacity by both neuropsychological tests (including measures of attention, memory, working memory, executive functions, language, and depression). We also evaluated performance in finger tapping, grip strength, stride length, gait speed, and chair stands separately and while performing VR-DOTs in order to correlate performance in these measures with VR-DOTs because performance while navigating a virtual environment is a valid and reliable indicator of cognitive decline in elderly persons. Results: The mild AD group was more impaired than the amnestic MCI group, and both were more impaired than healthy controls. The novel VR-DOT functional index correlated strongly with standard cognitive and functional measurements, such as mini-mental state examination (MMSE; rho=0.26, P=.01) and Bristol Activities of Daily Living (ADL) scale scores (rho=0.32, P=.001). Conclusions: Functional impairment is a defining characteristic of predementia and is partly dependent on the degree of cognitive impairment. The novel virtual reality measures of functional ability seem more sensitive to functional impairment than qualitative measures in predementia, thus accurately differentiating from healthy controls. We conclude that VR-DOT is an effective tool for discriminating predementia and mild AD from controls by detecting differences in terms of errors, omissions, and perseverations while measuring ADL functional ability.

Complex visual hallucinations and attentional performance in eye disease and dementia: a test of the Perception and Attention Deficit model

OBJECTIVE This study aimed to test the prediction from the Perception and Attention Deficit model of complex visual hallucinations (CVH) that impairments in visual attention and perception are key risk factors for complex hallucinations in eye disease and dementia. METHODS Two studies ran concurrently to investigate the relationship between CVH and impairments in perception (picture naming using the Graded Naming Test) and attention (Stroop task plus a novel Imagery task). The studies were in two populations-older patients with dementia (n = 28) and older people with eye disease (n = 50) with a shared control group (n = 37). The same methodology was used in both studies, and the North East Visual Hallucinations Inventory was used to identify CVH. RESULTS A reliable relationship was found for older patients with dementia between impaired perceptual and attentional performance and CVH. A reliable relationship was not found in the population of people with eye disease. CONCLUSIONS The results add to previous research that object perception and attentional deficits are associated with CVH in dementia, but that risk factors for CVH in eye disease are inconsistent, suggesting that dynamic rather than static impairments in attentional processes may be key in this population.

Visual exploration in Parkinson's disease and Parkinson's disease dementia

Parkinson's disease, typically thought of as a movement disorder, is increasingly recognized as causing cognitive impairment and dementia. Eye movement abnormalities are also described, including impairment of rapid eye movements (saccades) and the fixations interspersed between them. Such movements are under the influence of cortical and subcortical networks commonly targeted by the neurodegeneration seen in Parkinson's disease and, as such, may provide a marker for cognitive decline. This study examined the error rates and visual exploration strategies of subjects with Parkinson's disease, with and without cognitive impairment, whilst performing a battery of visuo-cognitive tasks. Error rates were significantly higher in those Parkinson's disease groups with either mild cognitive impairment (P = 0.001) or dementia (P < 0.001), than in cognitively normal subjects with Parkinson's disease. When compared with cognitively normal subjects with Parkinson's disease, exploration strategy, as measured by a number of eye tracking variables, was least efficient in the dementia group but was also affected in those subjects with Parkinson's disease with mild cognitive impairment. When compared with control subjects and cognitively normal subjects with Parkinson's disease, saccade amplitudes were significantly reduced in the groups with mild cognitive impairment or dementia. Fixation duration was longer in all Parkinson's disease groups compared with healthy control subjects but was longest for cognitively impaired Parkinson's disease groups. The strongest predictor of average fixation duration was disease severity. Analysing only data from the most complex task, with the highest error rates, both cognitive impairment and disease severity contributed to a predictive model for fixation duration [F(2,76) = 12.52, P ≤ 0.001], but medication dose did not (r = 0.18, n = 78, P = 0.098, not significant). This study highlights the potential use of exploration strategy measures as a marker of cognitive decline in Parkinson's disease and reveals the efficiency by which fixations and saccades are deployed in the build-up to a cognitive response, rather than merely focusing on the outcome itself. The prolongation of fixation duration, present to a small but significant degree even in cognitively normal subjects with Parkinson's disease, suggests a disease-specific impact on the networks directing visual exploration, although the study also highlights the multi-factorial nature of changes in exploration and the significant impact of cognitive decline on efficiency of visual search.

Cholinesterase inhibitors in advanced dementia with Lewy bodies: increase or stop?

INTRODUCTION There is little data on stopping cholinesterase inhibitors in Dementia with Lewy bodies (DLB). Equally, it is not known if increasing the dose of cholinesterase inhibitors may help neuropsychiatric symptoms in advanced DLB. METHOD We conducted an open label trial with donepezil involving 16 patients with LBD when the dose was reduced and treatment stopped over 4 weeks. Another 7 patients were given a trial of an increased dose of donepezil (15 mg) to resolve rehyphen;emergent neuropsychiatric symptoms. RESULTS The slow discontinuation protocol was well tolerated in advanced DLB. Five of the seven patients given a trial of a higher dose of donepezil were rated as clinically improved after 12 weeks treatment. CONCLUSION Cholinesterase inhibitors can be discontinued slowly in advanced DLB. Increasing the dose of donepezil may be of benefit to some patients with DLB who experience a recurrence in their neuropsychiatric symptoms.

Characteristics of visual hallucinations in Parkinson disease dementia and dementia with Lewy bodies

OBJECTIVE Parkinson disease dementia (PDD) and dementia with Lewy bodies (DLB) have overlapping clinical and pathologic features. Recurrent visual hallucinations (RVH) are common in both disorders. The authors have compared details of hallucination characteristics and associated neuropsychiatric features in DLB and PDD. METHODS This is a descriptive, cross-sectional study using the Institute of Psychiatry Visual Hallucinations Interview (IP-VHI) to explore self-reported frequency, duration, and phenomenology of RVH in PDD and DLB. The caregivers' ratings of hallucinations and other neuropsychiatric features were elicited with the Neuropsychiatric Inventory (NPI). RESULTS Fifty-six patients (35 PDD; 21 DLB) with RVH were assessed. Hallucination characteristics were similar in both disorders. Simple hallucinations were rare. Most patients experienced complex hallucinations daily, normally lasting minutes. They commonly saw people or animals and the experiences were usually perceived as unpleasant. NPI anxiety scores were higher in PDD. Neuropsychiatric symptoms coexisting with hallucinations were apathy, sleep disturbance, and anxiety. CONCLUSIONS Patients with mild to moderate dementia can provide detailed information about their hallucinations. Characteristics of RVH were similar in PDD and DLB, and phenomenology suggests the involvement of dorsal and ventral visual pathways in their generation. The coexistence of RVH with anxiety, apathy, and sleep disturbance is likely to impair patients' quality of life and may have treatment implications.

Change in perfusion, hallucinations and fluctuations in consciousness in dementia with Lewy bodies.

Fluctuations in consciousness and visual hallucinations are common neuropsychiatric features of dementia with Lewy bodies and Parkinson's disease dementia. To investigate potential neural correlates, we compared how changes in brain perfusion over a 1-year period were related to changes in the severity of these key clinical features. We recruited 29 subjects with either Parkinson's disease with dementia (15 subjects) or dementia with Lewy bodies (14 subjects). Cerebral perfusion was measured using HMPAO SPECT at baseline, and repeated 1 year later. The presence of hallucinations (Neuropsychiatric Inventory), severity of fluctuations in consciousness (fluctuation assessment scale) and cognitive ability (CAMCOG) were assessed at both time points. After controlling for changes in cognitive ability and effect of cholinesterase medication, we found a significant correlation between an increase in perfusion in midline posterior cingulate and decrease in hallucination severity. There was also a significant correlation between increased fluctuations of consciousness and increased thalamic and decreased inferior occipital perfusion. We have identified important neural correlates of key clinical features in Lewy body dementia and postulate that the associations can be understood through the influence of the cholinergic system on attention.

Role of cholinesterase inhibitors in Parkinson's disease and dementia with Lewy bodies

This article reviews the cholinergic changes in Parkinson's disease and dementia (PDD) and dementia with Lewy bodies (DLB), their potential clinical implications, and the available evidence for cholinesterase inhibitors in the treatment of PDD and DLB. Marked neuronal loss of cholinergic nuclei, reduced cholinergic markers in the neocortex, hippocampus, and selected thalamic nuclei, and receptor changes have been reported. One large and 2 small placebo-controlled trials and nearly 20 open-label studies suggest that cholinesterase inhibitors have a positive effect on cognition, psychiatric symptoms, and global function in patients with DLB and PDD. The treatment is well tolerated in most patients without any apparent worsening of extrapyramidal motor features. Given the high risk of severe sensitivity reactions and increased risk of cerebrovascular incidents during treatment with neuroleptics, more clinical trials of cholinesterase inhibitors are encouraged to establish their precise role in DLB and PDD.

Dementia with Lewy bodies and Parkinson's disease

Lewy bodies (LB) in the central nervous system are associated with several different clinical syndromes including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Long term follow up of PD patients finds up to 78% eventually develop dementia, most of these patients exhibiting fluctuating cognition and visual hallucinations similar to DLB and with extensive cortical LB at autopsy. alpha-Synuclein positive, neuritic pathology, in the putamen of DLB and Parkinson's disease dementia (PDD), may contribute to postural-instability gait difficulty, parkinsonism, diminished levodopa responsiveness and increased neuroleptic sensitivity. Cognitive and neuropsychiatric symptoms improve with cholinesterase inhibitor treatment in both patient groups. DLB and PDD should be seen as different points on a spectrum of LB disease. Distinguishing them as separate disorders may be useful in clinical practice, but may be of limited value in terms of investigating and treating the underlying neurobiology.