Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS).

BACKGROUND: We have undertaken a large unselected, community-based neuropathology study in an elderly (70-103 years) UK population in relation to prospectively evaluated dementia status. The study tests the assumption that dementing disorders as defined by current diagnostic protocols underlie this syndrome in the community at large.
METHODS: Respondents in the Medical Research Council Cognitive Function and Ageing Study were approached for consent to examine the brain at necropsy. Dementia status was assigned by use of the automated geriatric examination for computer-assisted taxonomy algorithm. Neuropathological features were standardised by use of the protocol of the Consortium to Establish a Registry of Alzheimer's Disease, which assesses the severity and distribution of Alzheimer-type pathology, vascular lesions, and other potential causes of dementia. A statistical model of dementia risk related predominantly to Alzheimer-type and vascular pathology was developed by multivariate logistic regression.
FINDINGS: We report on the first 209 individuals who have come to necropsy. The median age at death was 85 years for men, and 86 years for women. Cerebrovascular (78%) and Alzheimer-type (70%) pathology were common. Dementia was present in 100 (48%), of whom 64% had features indicating probable or definite Alzheimer's disease. However, 33% of the 109 non-demented people had equivalent densities of neocortical neuritic plaques. Some degree of neocortical neurofibrillary pathology was found in 61% of demented and 34% of non-demented individuals. Vascular lesions were equally common in both groups, although the proportion with multiple vascular pathology was higher in the demented group (46% vs 33%).
INTERPRETATION: Alzheimer-type and vascular pathology were the major pathological correlates of cognitive decline in this elderly sample, as expected, but most patients had mixed disease. There were no clear thresholds of these features that predicted dementia status. The findings therefore challenge conventional dementia diagnostic criteria in this setting. Additional factors must determine whether moderate burdens of cerebral Alzheimer-type pathology and vascular lesions are associated with cognitive failure.