By contrast, several other factors associated with incident AD had effects that were separate from any of the three common causes of dementia. These include cognitive activity, neuroticism (especially the facets of anxiety and vulnerability to stress), and loneliness. Thus, these factors alter the likelihood that AD pathology will lead to clinical disease. The biologic mechanisms underlying the association of these traits with clinical disease are unknown. However, identifying these pathways is important as an understanding of pathways would provide new targets for therapeutic interventions. A variety of efforts are ongoing in the Memory and Aging Project aimed at identifying additional therapeutic targets including epigenome-wide DNA methylation and histone acetylation studies, RNA expression studies, and proteomics.
