Recent neuropathologic autopsy studies found that 15 to 25% of elderly demented patients have Lewy bodies (LB) in their brainstem and cortex, and in hospital series this may constitute the most common pathologic subgroup after pure Alzheimer's disease (AD). The Consortium on Dementia with Lewy bodies met to establish consensus guidelines for the clinical diagnosis of dementia with Lewy bodies (DLB) and to establish a common framework for the assessment and characterization of pathologic lesions at autopsy. The importance of accurate antemortem diagnosis of DLB includes a characteristic and often rapidly progressive clinical syndrome, a need for particular caution with neuroleptic medication, and the possibility that DLB patients may be particularly responsive to cholinesterase inhibitors. We identified progressive disabling mental impairment progressing to dementia as the central feature of DLB. Attentional impairments and disproportionate problem solving and visuospatial difficulties are often early and prominent. Fluctuation in cognitive function, persistent well-formed visual hallucinations, and spontaneous motor features of parkinsonism are core features with diagnostic significance in discriminating DLB from AD and other dementias. Appropriate clinical methods for eliciting these key symptoms are described. Brainstem or cortical LB are the only features considered essential for a pathologic diagnosis of DLB, although Lewy-related neurites, Alzheimer pathology, and spongiform change may also be seen. We identified optimal staining methods for each of these and devised a protocol for the evaluation of cortical LB frequency based on a brain sampling procedure consistent with CERAD. This allows cases to be classified into brainstem predominant, limbic (transitional), and neocortical subtypes, using a simple scoring system based on the relative distribution of semiquantitative LB counts. Alzheimer pathology is also frequently present in DLB, usually as diffuse or neuritic plaques, neocortical neurofibrillary tangles being much less common. The precise nosological relationship between DLB and AD remains uncertain, as does that between DLB and patients with Parkinson's disease who subsequently develop neuropsychiatric features. Finally, we recommend procedures for the selective sampling and storage of frozen tissue for a variety of neurochemical assays, which together with developments in molecular genetics, should assist future refinements of diagnosis and classification.

Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB) Report of the consortium on DLB international workshop

ContextAtypical antipsychotic medications are widely used to treat delusions,
aggression, and agitation in people with Alzheimer disease and other dementia;
however, concerns have arisen about the increased risk for cerebrovascular
adverse events, rapid cognitive decline, and mortality with their use.ObjectiveTo assess the evidence for increased mortality from atypical antipsychotic
drug treatment for people with dementia.Data SourcesMEDLINE (1966 to April 2005), the Cochrane Controlled Trials Register
(2005, Issue 1), meetings presentations (1997-2004), and information from
the sponsors were searched using the terms for atypical antipsychotic drugs
(aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone), dementia, Alzheimer disease, and clinical trial.Study SelectionPublished and unpublished randomized placebo-controlled, parallel-group
clinical trials of atypical antipsychotic drugs marketed in the United States
to treat patients with Alzheimer disease or dementia were selected by consensus
of the authors.Data ExtractionTrials, baseline characteristics, outcomes, all-cause dropouts, and
deaths were extracted by one reviewer; treatment exposure was obtained or
estimated. Data were checked by a second reviewer.Data SynthesisFifteen trials (9 unpublished), generally 10 to 12 weeks in duration,
including 16 contrasts of atypical antipsychotic drugs with placebo met criteria
(aripiprazole [n = 3], olanzapine [n = 5], quetiapine
[n = 3], risperidone [n = 5]). A total of 3353 patients
were randomized to study drug and 1757 were randomized to placebo. Outcomes
were assessed using standard methods (with random- or fixed-effects models)
to calculate odds ratios (ORs) and risk differences based on patients randomized
and relative risks based on total exposure to treatment. There were no differences
in dropouts. Death occurred more often among patients randomized to drugs
(118 [3.5%] vs 40 [2.3%]. The OR by meta-analysis was 1.54; 95% confidence
interval [CI], 1.06-2.23; P = .02; and
risk difference was 0.01; 95% CI, 0.004-0.02; P = .01).
Sensitivity analyses did not show evidence for differential risks for individual
drugs, severity, sample selection, or diagnosis.ConclusionsAtypical antipsychotic drugs may be associated with a small increased
risk for death compared with placebo. This risk should be considered within
the context of medical need for the drugs, efficacy evidence, medical comorbidity,
and the efficacy and safety of alternatives. Individual patient analyses modeling
survival and causes of death are needed.

/pdf/risk-of-death-with-atypical-antipsychotic-drug-treatment-for-ov5oaoqaaa.pdf

Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials.

Purpose: To identify current evidence of factors influencing dementia-related caregiver burden (CB), describe patient and caregiver characteristics associated with CB, and describe evidence-based interventions designed to lessen the burden of caregiving.

Data sources: Comprehensive literature review of Cumulative Index of Nursing and Allied Health Literature, MEDLINE, and Psych Info was performed for the years 1996–2006 of peer-reviewed journals using keywords CB and dementia.

Conclusion: Dementia caregiving has been associated with negative effects on caregiver health and early nursing home placement for dementia patients. Many factors influence the impact of the caregiving experience such as gender, relationship to the patient, culture, and personal characteristics. Although various interventions have been developed with the goal of alleviating CB, evidence suggests that individually developed multicomponent interventions including a diversity of services will decrease burden, improve quality of life, and enable caregivers to provide at-home care for longer periods prior to institutionalization.

Implications for practice: The ability to properly assess the dementia patient–caregiver dyad related to CB is critical to decreasing its negative physical and psychological health outcomes. Appropriately tailored interventions can improve the health and well-being of both caregiver and patient.

Caregiver burden among dementia patient caregivers: a review of the literature.

Hallucinations, mainly of a visual nature, are considered to affect about one-quarter of patients with Parkinson's disease. They are commonly viewed as a side-effect of antiparkinsonian treatment, but other factors may be involved. The aim of this study was to determine the phenomenology, prevalence and risk factors of hallucinations in Parkinson's disease. Two-hundred and sixteen consecutive patients fulfilling clinical criteria for Parkinson's disease were studied. Demographic and clinical variables were recorded, including motor and cognitive status, depressive symptoms and sleep-wake disturbances. Patients with and without hallucinations were compared using non-parametric tests, and logistic regression was applied to significant data. Hallucinations had been present during the previous 3 months in 39.8% of the patients, and fell into three categories: minor forms, consisting of a sensation of a presence (person), a sideways passage (commonly of an animal) or illusions were present in 25.5% of the patients (an isolated occurrence in 14.3%), formed visual hallucinations were present in 22.2% (isolated in 9.3%) and auditory hallucinations were present in 9.7% (isolated in 2.3%). Patients with minor hallucinations had a higher depression score than non-hallucinators but did not differ in other respects. Logistic regression analysis identified three factors independently predictive of formed visual hallucinations: severe cognitive disorders, daytime somnolence and a long duration of Parkinson's disease. These findings indicate that, when minor hallucinations are included, the total prevalence is much higher than previously reported. A simple side-effect of dopaminergic treatment is not sufficient to explain the occurrence of all visual hallucinations. The main risk factor in treated patients is cognitive impairment, although sleep-wake cycle disturbances, and possibly other factors related to the duration of the disease, act as cofactors.

/pdf/hallucinations-in-parkinson-s-disease-prevalence-3d2uc6a357.pdf

Hallucinations in Parkinson's disease: prevalence, phenomenology and risk factors.

Objective: Atypical antipsychotic medications are widely used to treat delusions, aggression, and agitation in people with Alzheimer disease (AD) and other dementia. Several clinical trials have not shown efficacy, and there have been concerns about adverse events. The objective of this study was to assess the evidence for efficacy and adverse events of atypicals for people with dementia Methods: MEDLINE, the Cochrane Register of Controlled Trials, meetings, presentations, and information obtained from sponsors were used in this study. Published and unpublished randomized, placebo-controlled, double-blind, parallel-group trials in patients with AD or dementia of atypical antipsychotics marketed in the United States were studied. Clinical and trials characteristics, outcomes, and adverse events were extracted. Data were checked by a second reviewer. Fifteen trials including 16 contrasts of atypical antipsychotics with placebo met selection criteria: aripiprazole (k3), olanzapine (k5), quetiapine (k3), and risperidone (k5). A total of 3,353 patients were randomized to drug and 1,757 to placebo. Standard meta-analysis methods were used to summarize outcomes. Results: Quality of the reporting of trials varied. Efficacy on rating scales was observed by meta-analysis for aripiprazole and risperidone, but not for olanzapine. Response rates were frequently not reported. There were smaller effects for less severe dementia, outpatients, and patients selected for psychosis. Approximately one-third dropped out without overall differences between drug and placebo. Adverse events were mainly somnolence and urinary tract infection or incontinence across drugs, and extrapyramidal symptoms or abnormal gait with risperidone or olanzapine. Cognitive test scores worsened with drugs. There was no evidence for increased injury, falls, or syncope. There was a significant risk for cerebrovascular events, especially with risperidone; increased risk for death overall was reported elsewhere. Conclusions: Small statistical effect sizes on symptom rating scales support the evidence for the efficacy of aripiprazole and risperidone. Incomplete reporting restricts estimates of response rates and clinical significance. Dropouts and adverse events further limit effectiveness. Atypicals should be considered within the context of medical need and the efficacy and safety of alternatives. Individual patient meta-analyses are needed to better assess clinical significance and effectiveness. (Am J Geriatr Psychiatry 2006; 14:191–210)

Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials.

Objective. This article examines the relationships between behaviour, psychological functioning, the caring environment and subsequent institutionalization in patients with dementia living at home with a carer.



Design. Longitudinal study of behaviour in dementia, with a nested case-control study to investigate predictors of institutionalization.



Setting. Subjects with dementia, known to service, living at home with a carer. All lived in Oxfordshire, UK.



Participants. 100 people with dementia (Alzheimer's disease and/or vascular dementia) who were living at home with a carer at the start of the study.



Measures. At 4-monthly intervals, the carers were interviewed and the subjects with dementia were assessed cognitively. Subjects' behaviour and psychological functioning were assessed using the Present Behavioural Examination.



Results. The characteristics which best predicted institutionalization 1 year later were: excessive night-time activity; immobility or difficulty in walking; incontinence; being away from a carer for more than 16 hours a week; and being cared for by a female. Aggressive behaviour was not associated with an increased chance of entry into an institution 1 year later, although it was more prevalent 4 months before entering an institution.



Conclusions. Both behaviour and psychological functioning and the caring environment can help in predicting which patients with dementia currently living at home will enter an institution 1 year later. These predictors are not the same as those which are the immediate cause of institutionalization. Copyright© 1998 John Wiley & Sons, Ltd.

Predictors of institutionalization for people with dementia living at home with a carer

Objective: To investigate the contribution of neuroleptic drugs to cognitive decline in dementia. Design: Two year prospective, longitudinal study consisting of interviews every four months, with necropsy follow up. Setting: Community settings in Oxfordshire. Subjects: 71 subjects with dementia, initially living at home with informant. Main outcome measures: Cognitive function (score from expanded minimental state examination); behavioural problems (physical aggression, hallucinations, persecutory ideas, and disturbance of diurnal rhythm); and postmortem neuropathological assessment (cortical Lewy body pathology). Results: The mean (SE) decline in cognitive score in the 16 patients who took neuroleptics was twice that in the patients who did not (20.7 (2.9) v 9.3 (1.3), P=0.002). An increased rate of decline was also associated with aggression, disturbed diurnal rhythm, and persecutory ideas. However, only use of neuroleptics and severity of persecutory ideas were independently associated with more rapid cognitive decline when all other variables were adjusted for. The start of neuroleptic treatment coincided with more rapid cognitive decline: median rate of decline was 5 (interquartile range 8.5) points per year before treatment and 11 (12) points per year after treatment (P=0.02). Cortical Lewy body pathology did not account for association between neuroleptic use and more rapid decline. Conclusions: Neuroleptic drugs that are sometimes used to treat behavioural complications of dementia may worsen already poor cognitive function. Randomised controlled trials are needed to confirm a causal relation. Key messages Neuroleptic drugs are used to treat behavioural problems in patients with dementia, but they may cause more rapid decline in cognitive function In our longitudinal study of patients with dementia we found that the rate of cognitive decline in patients taking neuroleptics was twice that in those not taking neuroleptics Furthermore, the start of neuroleptic treatment was associated with an increase in the rate of cognitive decline Cortical Lewy body pathology at necropsy did not account for the association between neuroleptic use and more rapid decline Although our study does not prove a causal relation, we suggest that there should be regular review of the need for patients to continue taking neuroleptic drugs

/pdf/do-neuroleptic-drugs-hasten-cognitive-decline-in-dementia-1v3d2d4v5t.pdf

Do neuroleptic drugs hasten cognitive decline in dementia? Prospective study with necropsy follow up.

The occurrence of episodes of getting lost was examined in 104 subjects with dementia who were assessed every 4 months over 5 years. All subjects were initially living at home with a caregiver who could give good information. Forty-three subjects needed to be brought back home at least once. Five subjects repeatedly got lost. Forty-six subjects were kept behind locked doors at some point. Subjects who got lost were more likely to become permanently resident in institutions (odds ratio = 7.3; 95% confidence interval: 3.0 to 17.8). Patients who performed better on a behavioral test of topographical memory were less likely to get lost over the subsequent 5 years (negative predictive value: 90%). The risk of patients with dementia getting lost is substantial and requires frequent intervention by caregivers. This risk is a major reason for institutionalization. A simple test may help in assessing the risk of getting lost in patients with dementia.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S1041610298005365

Getting lost in dementia: a longitudinal study of a behavioral symptom.

Objective
This article analyses changes in aggressive behaviour throughout the course of dementia.

Design
Prospective, 10 year, longitudinal study of aggressive behaviour in dementia, with autopsy follow-up.

Setting
Subjects with dementia, living at home with a carer, Oxfordshire, UK.

Participants
Ninety-nine people with dementia (Alzheimer's disease and/or vascular dementia) who were living at home with a carer.

Measures
At 4-monthly intervals, the carers were interviewed about the subjects and the subjects were assessed cognitively. Subjects' behaviour was assessed using the Present Behavioural Examination. This is an investigator-based, semi-structured interview consisting of eight main sections monitoring behavioural and psychological change. Eight different aspects of aggressive behaviour were assessed in detail and comparison made with other relevant factors.

Results
Verbal aggression is the most common and longest lasting form of aggressive behaviour. Aggressive resistance and physical aggression are most likely to persist until death. Intimate care is the main factor precipitating aggressive behaviour. There are no correlations between any type of aggressive behaviour and age, gender or time since onset of dementia.

Conclusions
Aggressive behaviour creates problems for carers. In general, the physical types of aggressive behaviour are most prevalent in people with more severe dementia. Copyright © 1999 John Wiley & Sons, Ltd.

Natural history of aggressive behaviour in dementia.

Objective. This article analyses behaviour changes in dementia at the point of entry to a longitudinal study.



Design. Prospective, longitudinal study of behaviour in dementia, with autopsy follow-up.



Setting. Subjects with dementia, living at home with a carer. All lived in Oxfordshire, UK.



Participants. Ninety-seven people with dementia (Alzheimer's disease and/or vascular dementia) who were living at home with a carer.



Measures. At 4-monthly intervals, the carers were interviewed and the subjects with dementia were assessed cognitively. Subjects' behaviour was assessed using the Present Behavioural Examination. This is an investigator-based, semi-structured interview consisting of eight main sections covering many different aspects of behaviour. The 121 main questions, with 66 further ‘nested’ questions, have been shown to have high reliability.



Results. This article analyses the types of behaviour change reported by carers at the point of entry to this long-term study. Few correlations were found between behaviour and age, gender and time since onset of dementia. Some types of behaviour were significantly more prevalent in those with greater cognitive impairment.



Conclusions. Many of these changes create problems for carers, for example increased aggressive behaviour, wandering, wakefulness at night, incontinence and persecutory ideas. In general, they are more prevalent in people with more severe dementia. © 1997 John Wiley & Sons, Ltd.

Kathy Gedling

Papers

Predictors of institutionalization for people with dementia living at home with a carer

Do neuroleptic drugs hasten cognitive decline in dementia? Prospective study with necropsy follow up.

Getting lost in dementia: a longitudinal study of a behavioral symptom.

Natural history of aggressive behaviour in dementia.

Behaviour changes in dementia. 1: Point of entry data of a prospective study.