Almost everyone who dies in old age has some pathology in their brain at death, but does not necessarily die with dementia. Cognitive reserve factors such as education are thought to protect (“neuroprotection”) or provide resilience (“compensation”) against dementia-related pathology. We investigated the neuroprotection and compensation hypotheses in a large population-based cohort study (Epidemiological Clinicopathological Studies in Europe; EClipSE).
EClipSE has harmonised longitudinal clinical data and neuropathology from three longstanding population-based studies that included post-mortem brain donation. These three studies started between 1985 and 1991. Number of years of education during earlier life was recorded at baseline in each study. Incident dementia was detected through follow-up interviews, complemented by retrospective informant interviews, death certificate data and linked health / social records (dependent on study) after death. Dementia-related neuropathologies were assessed in each study in a comparable manner based on the CERAD protocol. Eight hundred and seventy-two brain donors were included of whom 56% were demented at death.
Longer years in education were associated with decreased dementia risk and greater brain weight but had no relationship with the burden of neurodegenerative or vascular pathologies. The associations between neuropathological variables and clinical dementia differed according to the “dose” of education such that more education reduced dementia risk largely independently of severity of pathology.
In conclusion, more education in early life did not protect individuals from developing neurodegenerative and vascular neuropathology by the time they died but it did appear to mitigate the impact of pathology on the clinical expression of dementia before death.
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