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Open Access Research article

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

Julia Zaccai1*, Paul Ince2 and Carol Brayne3

Author Affiliations

1 Department of Public Health and Primary Care, University of Cambridge, Robinson Way, Cambridge CB2 2SR, UK

2 Academic Unit of Neuropathology, University of Sheffield, 'E' Floor, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UK

3 Department of Public Health and Primary Care, University of Cambridge, Robinson Way, Cambridge CB2 2SR, UK

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BMC Neurology 2006, 6:2  doi:10.1186/1471-2377-6-2

Published: 9 January 2006



Prospective population-based neuropathological studies have a special place in dementia research which is under emphasised.


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.


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.


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.