Affiliations: [a] Department of Psychiatry, The University of Texas Health Science Center, San Antonio, TX, USA | [b] Department of Medicine, The University of Texas Health Science Center, San Antonio, TX, USA | [c] Department of Family and Community Medicine, The University of Texas Health Science Center, San Antonio, TX, USA | [d] South Texas Veterans' Health System Audie L. Murphy Division, GRECC, San Antonio, TX, USA | [e] Department of Neurology, KU Alzheimer and Memory Program, University of Kansas Medical Center, Kansas City, KS, USA
Correspondence:
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Correspondence to: Donald R. Royall, M.D., Departments of Psychiatry, Medicine, and Family and Community Medicine, the University of Texas Health Science Center, San Antonio, TX, USA. Tel.: +1 210 567 1255; Fax: +1 210 567 1269; E-mail: royall@uthscsa.edu.
Abstract: Depressive symptoms are associated with an increased risk of Alzheimer's disease (AD) but the mechanism(s) involved has not been well established. In a convenience sample of participants in the University of Kansas' Brain Aging Project, we use structural equation modeling (SEM) to explicitly distinguish depressive symptom-related variance in cognitive task performance (i.e., DEPCOG) from that which is unrelated to a depressive symptoms. DEPCOG is strongly associated with the cognitive correlates of functional status (δ), which we previously associated with elements of the Default Mode Network (DMN). Both δ and DEPCOG map to a posterior cingulate seeded network that has recently been associated with amyloid-β deposition and includes elements of the DMN. Both contribute significantly to clinical dementia status and dementia severity, as measured by the Clinical Dementia Rating Scale Sum of Boxes. These findings suggest that the cognitive correlates of depressive symptoms, even in the absence of a major depressive episode, may contribute to dementia in their own right, and could be responsible for some cases of incident clinical “AD”. This conclusion suggests new opportunities for the latter's diagnosis, prevention, and treatment.
Keywords: Aging, cognition, dementia, depression, g, functional status
