Prevalence, correlates and course of behavioural and psychological symptoms of dementia in the population.

BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) are major contributors to the burden of dementia. AIMS: To describe the prevalence, correlates and course of BPSD in the population of England and Wales. METHOD: The prevalence of 12 symptoms was estimated in 587 participants with dementia and 2050 participants without dementia as part of a population-based longitudinal study of ageing. The effect of risk factors and the factor structure were estimated using 1782 interviews provided by participants with dementia throughout the study. RESULTS: Each symptom apart from sleeping problems was more common in the population with dementia. The co-occurrence of the symptoms was explained by a four-factor solution, corresponding to psychosis/apathy, depression/anxiety, irritability/persecution and wandering/sleep problems. Psychosis occurred more frequently with declining cognition. Anxiety and depression were more common in younger individuals and in those with poor self-reported health. Persistence varied between symptoms. CONCLUSIONS: Behavioural and psychological symptoms of dementia affect nearly all people with dementia. Symptoms co-occur, and the symptoms that affected individuals experience are related to their socio-demographic and clinical characteristics.

Population-based neuropathological studies of dementia: design, methods and areas of investigation--a systematic review.

BACKGROUND: Prospective population-based neuropathological studies have a special place in dementia research which is under emphasised. METHODS: A systematic review of the methods of population-based neuropathological studies of dementia was carried out. These studies were assessed in relation to their representativeness of underlying populations and the clinical, neuropsychological and neuropathological approaches adopted. RESULTS: Six studies were found to be true population-based neuropathological studies of dementia in the older people: the Hisayama study (Japan); Vantaa 85+ study (Finland); CC75C study (Cambridge, UK); CFAS (multicentre, UK); Cache County study (Utah, USA); HAAS (Hawaï, USA). These differ in the core characteristics of their populations. The studies used standardised neuropathological methods which facilitate analyses on: clinicopathological associations and confirmation of diagnosis, assessing the validity of hierarchical models of neuropathological lesion burden; investigating the associations between neuropathological burden and risk factors including genetic factors. Examples of findings are given although there is too little overlap in the areas investigated amongst these studies to form the basis of a systematic review of the results. CONCLUSION: Clinicopathological studies based on true population samples can provide unique insights in dementia. Individually they are limited in power and scope; together they represent a powerful source to translate findings from laboratory to populations.

Alpha-synucleinopathy and neuropsychological symptoms in a population-based cohort of the elderly.

INTRODUCTION: Studies with strong selection biases propose that alpha-synucleinopathy (AS) spreads upwards and downwards in the neuraxis from the medulla, that amygdala-dominant AS is strongly associated with Alzheimer's disease (AD), and that a more severe involvement of the cerebral cortex is correlated with increasing risk of dementia. This study examines the association of AS patterns and observed neuropsychological symptoms in brains of a population-representative donor cohort. METHODS: Brains donated in 2 out of 6 cognitive function and ageing study cohorts (Cambridgeshire and Nottingham) were examined. Over 80% were >80 years old at death. The respondents were evaluated prospectively in life for cognitive decline and dementia. Immunocytochemistry for tau and alpha-synuclein (using LB509 by Zymed Laboratories) was carried out in 208 brains to establish Braak stage and the pattern and severity of AS following the dementia with Lewy bodies (DLB) consensus recommendations. Dementia, specific neuropsychological measures as measured using the Cambridge cognitive examination, the presence of hallucinations and Parkinson's disease were investigated. RESULTS: Four patterns of AS were observed: no AS pathology (n = 92), AS pathology following the DLB consensus guidelines (n = 33, of which five were 'neocortical'), amygdala-predominant AS (n = 18), and other AS patterns (n = 33). Each group was subdivided according to high/low neurofibrillary tangles (NFT) Braak stage. Results showed no association between dementia and these patterns of AS, adjusting for the presence of NFT or not. The risk of visual hallucinations shows a weak association with AS in the substantia nigra (odds ratio (OR) = 3.2; 95% confidence interval (CI) 0.5 to 15.5; P = 0.09) and amygdala (OR = 3.0; 95% CI 0.7 to 12.3; P = 0.07). The analysis is similar for auditory hallucinations in subcortical regions. CONCLUSIONS: Among the whole population of older people, AS does not increase the risks for dementia, irrespective of Braak stage of NFT pathology. There was no evidence that the pattern of AS pathology in cortical areas was relevant to the risk of hallucination. In general, the hypothesis that AS as measured using these methods per se is a key determinant of cognitive clinical phenotypes is not supported.

Genome-wide association study of neocortical Lewy-related pathology.

OBJECTIVE: Dementia with Lewy bodies is an α-synucleinopathy characterized by neocortical Lewy-related pathology (LRP). We carried out a genome-wide association study (GWAS) on neocortical LRP in a population-based sample of subjects aged 85 or over. METHODS: LRP was analyzed in 304 subjects in the Vantaa 85+ sample from Southern Finland. The GWAS included 41 cases with midbrain, hippocampal, and neocortical LRP and 177 controls without midbrain and hippocampal LRP. The Medical Research Council Cognitive Function and Ageing Study (CFAS) material was used for replication (51 cases and 131 controls). RESULTS: By analyzing 327,010 markers the top signal was obtained at the HLA-DPA1/DPB1 locus (P = 1.29 × 10(-7)); five other loci on chromosomes 15q14, 2p21, 2q31, 18p11, and 5q23 were associated with neocortical LRP at P < 10(-5). Two loci were marked by multiple markers, 2p21 (P = 3.9 × 10(-6), upstream of the SPTBN1 gene), and HLA-DPA1/DPB1; these were tested in the CFAS material. Single marker (P = 0.0035) and haplotype (P = 0.04) associations on 2p21 were replicated in CFAS, whereas HLA-DPA1/DPB1 association was not. Bioinformatic analyses suggest functional effects for the HLA-DPA1/DPB1 markers as well as the 15q14 marker rs8037309. INTERPRETATION: We identified suggestive novel risk factors for neocortical LRP. SPTBN1 is the candidate on 2p21, it encodes beta-spectrin, an α-synuclein binding protein and a component of Lewy bodies. The HLA-DPA1/DPB1 association suggests a role for antigen presentation or alternatively, cis-regulatory effects, one of the regulated neighboring genes identified here (vacuolar protein sorting 52) plays a role in vesicular trafficking and has been shown to interact with α-synuclein in a yeast model.

A systematic review of prevalence studies of dementia in Parkinson's disease.

Substantial variation in the prevalence of dementia in Parkinson's disease (PDD) has been reported. The aim of this study was to review systematically and critically previous studies of the prevalence of PDD using PubMed to search the literature. Studies focusing on PD and PDD, as well as those examining on the epidemiology of dementia subtypes, were included. Predefined inclusion and exclusion criteria were used and the quality of the studies included was rated. Articles were included if: (1) the proportion of PDD among patients with either PD or dementia was reported in an original study; (2) patients had been subjected to prospective clinical examination; and (3) strategies to include all subjects with either PD or dementia within the community or hospital clinics within a geographical area were employed. Twelve studies of the prevalence of PD or PDD (1,767 patients included) and 24 prevalence studies of dementia subtypes (4,711 patients included) met the inclusion criteria. In the PD/PDD studies, the proportion (mean and 95% confidence interval) with PDD in PD was 24.5% (17.4-31.5). There were significant methodological variations between studies and in the four studies that matched the quality criteria most closely, the rate of PDD was 31.1% (20.1-42.1). The prevalence of PDD was estimated as 0.5% in subjects 65 years or older. The percentage of PDD among those with dementia was 3.6% (3.1-4.1), with an estimated prevalence of PDD of 0.2% in subjects aged 65 years or older. Despite methodological variation, this systematic review suggests that 24 to 31% of PD patients have dementia, and that 3 to 4% of the dementia in the population would be due to PDD. The estimated prevalence of PDD in the general population aged 65 years and over is 0.2 to 0.5%.

A systematic review of prevalence and incidence studies of dementia with Lewy bodies.

BACKGROUND: Substantial variation in the prevalence of Dementia with Lewy Bodies (DLB) has been reported with estimates ranging from 0 to 26.3% of all dementia cases, potentially making it the second most common dementia subtype. OBJECTIVES: The aim of this study was to review systematically and critically for the first time previous studies of the clinical prevalence and incidence of DLB in the population. METHODS: A systematic literature search was performed using PubMed. Selected articles had to describe an original study that provided a prevalence and/or incidence number for the whole population for DLB as defined by pre-set clinical criteria and findings. RESULTS: Six studies reporting the prevalence of DLB and one study reporting the incidence of DLB met the inclusion criteria. Prevalence estimates, depending on case criteria, range from 0 to 5% with regard to the general population, and from 0 to 30.5% of all dementia cases. The only estimate for DLB incidence is 0.1% a year for the general population and 3.2% a year for all new dementia cases. The number of available studies was too small to hypothesise on the potential effect of age, sex and genetic background on the results. CONCLUSIONS: Although the literature on the prevalence and incidence of DLB is limited, there is a general consensus that DLB must be considered in the range of neurodegenerative conditions in the elderly. The move towards use of consensus criteria facilitates comparison and is welcome. Their application in a more routine way towards rigorously defined and selected study populations will lead to more comparable and generalisable studies in the future.