The Epidemiological Neuropathology of Dementia and the Implications for Drug Development

SUMMARY Identification of the determinants and risk factors for dementia, in addition to the underlying brain changes associated with disease, is fundamental to the development of dementia therapeutics. The gold standard to achieving this is through population-based (epidemiological) studies of the biology of aging, cognitive decline and dementia. In this paper, the main findings from epidemiological cohorts on dementia pathology are compared to case–control and convenience samples, and findings on the different neuropathological features of dementia, its risk factors and clinical course are summarized. The strengths and weakness of different research designs, the keys aspects of disease these have identified and the targets that have been subsequently developed will be discussed. It is highlighted that dementia within epidemiological frameworks is found to be a heterogeneous disease. For treatment to be effective it will therefore need to reflect not only population variation in patterns of pathology, but also intra-individual reactions to these treatments.