ArticlesPathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales
Introduction
Epidemiological, clinical, and neuropathological studies of dementia in elderly people have proliferated in the past three decades. Most have used a model of dementia based on neuropathological definitions of Alzheimer's disease,1, 2 vascular dementia, 3 dementia with Lewy bodies, 4 and other less frequent ‘causes’ of dementia. The disease entities that have emerged from these studies are defined within consensus guidelines for the burden of pathology required to achieve a particular degree of certainty of diagnosis. This situation can lead to circularity in the design of studies: for example, for studies of Alzheimer's disease, only patients with abundant neuritic plaques may be selected. This process then reinforces the concept of Alzheimer's disease as an amyloidosis and contributes to theories of causation such as the amyloid cascade hypothesis.5
Despite all this work, there are important unanswered questions about the pathology of dementia. What is the relative prevalence of these different types of pathology in community populations? How do they interact as substrates for dementia? How are the processes that lead to dementia distinct from normal effects of ageing? Most clinicopathological studies in more developed countries suggest that Alzheimer's disease is the commonest cause of dementia, with vascular disease the second most common cause. Other studies have suggested that dementia with Lewy bodies is more frequent than vascular dementia. 6, 7 Yet another has suggested that vascular disease predominates over all other causes in the oldest age-group.8
Community-based studies have been few but instructive. For example, the ɛ4 allele of the apolipoprotein E gene is associated with increased Alzheimer-type pathology in both demented and nondemented individuals.9 In another study, only 60% of individuals with sufficient Alzheimer-type pathology to warrant a neuropathological diagnosis of Alzheimer's disease1 were demented.10 The severity of Alzheimer-type pathology associated with dementia was inversely correlated with the presence of cerebral ischaemic lesions-in demented individuals with ischaemic lesions the burden of neocortical neurofibrillary tangles was an eighth of that in patients without ischaemic lesions.10 Such studies suggest that the relation between lesion burden and cognitive status, and the interactions between lesions, may differ in the wider community from those in selected secondary referral cohorts of demented people.
The Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) 11 is a large multicentre, community-based, prospective study of prevalent and incident dementia, which has a strategy of necropsy. A large sample of brains from elderly people is available, with a strategy to enrich the number of demented individuals. The non-demented cohort was based on a random sample of the rest of the general population. We report standardised neuropathological findings in the first 209 individuals coming to necropsy, representing those accumulated up to July, 1998.
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Respondents
The study and the methods for necropsy approach were approved in each centre by the local research ethics committee, and more recently by the Multicentre Research Ethics Committee.
MRC CFAS has been fully described elsewhere.11 At each of five centres in England and Wales (Cambridgeshire, Gwynedd, Newcastle upon Tyne, Nottingham, and Oxford), random samples of about 2500 people aged 64 years and over (with an 82% response rate), agreed to a structured initial interview, which included the
Results
Age at death in this sample ranged from 70 years to 103 years. There were more women than men in the sample (table 1). The median age at death was 86 for women and 85 years for men. The median time from last interview until death was 1·2 years (range 3 days to 4·2 years; 81% within the 2 years before death). The proportion with dementia diagnosis before death was similar in all the centres (overall, 48%). Dementia was more common in women than in men, and in both sexes it was more common at
Discussion
Although there have been many epidemiological studies based on clinical methods of detection of dementia that have reported on prevalence and incidence, there have been no large community-based neuropathological studies of the relation between dementia and ageing. We present data from the first 209 individuals who came to necropsy in this large multicentre study. The striking findings are the high frequency of the neuropathological features usually associated with dementia in this older
References (28)
Amyloid, the presenilins and Alzheimer's disease
Trends Neurol Sci
(1997)- et al.
Senile dementia of Lewy body type: a clinically and neuropathologically distinct form of Lewy body dementia in the elderly
J Neurol Sci
(1990) - et al.
Observations on the brains of demented old people
J Neurol Sci
(1970) The diagnosis of Alzheimer's disease
Arch Neurol
(1985)- et al.
The consortium to establish a registry of Alzheimer's disease (CERAD) part II: standardization of the neuropathologic assessment of Alzheimer's disease
Neurology
(1991) - et al.
Vascular dementia: diagnostic criteria for research studies–report of the NINDS-AIREN International Workshop
Neurology
(1993) - et al.
Consensus guidelines for the clinical and pathological diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB International Workshop
Neurology
(1996) - et al.
A neuropathogical subset of Alzheimer's disease with concomitant Lewy body disease and spongiform change
Acta Neuropathol
(1989) - et al.
A population based study of dementia in 85-year-olds
N Engl J Med
(1993) - et al.
Apolipoprotein E, dementia, and cortical deposition of beta amyloid protein
N Engl J Med
(1995)
Brain infarction and the clinical expression of Alzheimer's disease: the nun study
JAMA
Cognitive function and dementia in six areas of England and Wales: the distribution of MMSE and prevalence of GMS organicity level in the MRC CFA study
Psychol Med
Mini-mental state: a practical method for grading the cognitive state of patients for the clinician
J Psychiatr Res
Computerised psychiatric diagnostic system and case nomenclature for elderly subjects: GMS and AGECAT
Psychol Med
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