Postmortem indices linking risk factors to cognition: results from the Religious Order Study and the Memory and Aging...

We present data from the Religious Orders Study and the Memory and Aging Project linking risk factors to pathology and cognitive function. Both studies involve more than 1000 older persons who agreed to annual clinical evaluation and brain donation at death. Published findings from the studies to date suggest that the relationship between risk factors, pathology, and cognitive impairment is complex. In some cases, known neuropathologic indices mediate the association of risk factors to cognition. In other cases, risk factors modify the relation of pathology to cognition. Finally, some risk factors seem to be related to clinical Alzheimer disease and cognitive decline, even decline in episodic memory, in the absence of any association with amyloid plaques, neurofibrillary tangles, or other pathologic indices that can be identified and quantified at this time. The findings to date illustrate the kinds of insights that can be gained into mechanisms of disease through the incorporation of pathologic indices into well-designed, epidemiologic studies of aging and Alzheimer disease.