A combined analysis of the Rush Memory and Aging Project and the Religious Orders Study results showed that only 41% of the variance in cognitive decline can be explained by the commonly examined pathologies (AD, vascular lesions, dementia with Lewy bodies), suggesting that further causes – such as TDP-43 aggregation, HS or inflammation – should be considered in neuropathological evaluation to obtain representative explanations for cognitive alterations in aging [94]. The gene discussed is TARDBP; the disease is Alzheimer disease.