Depressive Symptoms and Tau Accumulation in the Inferior Temporal Lobe and Entorhinal Cortex in Cognitively Normal Older Adults: A Pilot Study

Article type: Research Article

Authors: Gatchel, Jennifer R.^{a; b; *} | Donovan, Nancy J.^{a; c; d; e} | Locascio, Joseph J.^f | Schultz, Aaron P.^f | Becker, J. Alex^g | Chhatwal, Jasmeer^f | Papp, Kathryn V.^{c; e} | Amariglio, Rebecca E.^{c; e} | Rentz, Dorene M.^{c; e; f} | Blacker, Deborah^{a; h} | Sperling, Reisa A.^{c; e; f} | Johnson, Keith A.^{c; e; f; g} | Marshall, Gad A.^{c; e; f}

Affiliations: [a] Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [b] Division of Geriatric Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA, USA | [c] Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA | [d] Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA | [e] Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA | [f] Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [g] Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [h] Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

Correspondence: [*] Correspondence to: Jennifer R. Gatchel, MD, PhD, Instructor in Psychiatry, Harvard Medical School, Assistant Psychiatrist, Massachusetts General Hospital and McLean Hospital; 149 13th Street, Room 2671, Charlestown, MA 02219, USA. Tel.: +1 617 643 8435; Fax: +1 617 726 5760; E-mail: jgatchel@partners.org.

Abstract: Background:Depressive symptoms are common in older adults and associated with increased morbidity and cognitive decline. These symptoms occur during preclinical and prodromal stages of Alzheimer’s disease (AD), but their relationship to tau, one of the main AD proteinopathies, is poorly understood. Objective:The objective of this study was to investigate the cross-sectional association between depressive symptoms and cerebral tau [18F T807 (also known as 18F-AV-1451) tau positron emission tomography (PET) imaging] in cognitively normal (CN) older adults. Methods:We measured depressive symptoms using the Geriatric Depression Scale (GDS), and in vivo cerebral tau using T807 PET in 111 CN older adults. We employed general linear regression models to evaluate the relationship of GDS score regressed on entorhinal cortex (EC) or inferior temporal (IT) tau in separate backward elimination models. Other predictors included age, sex, and in secondary analyses, amyloid (Pittsburgh Compound B PET). Results:Higher GDS was significantly associated with greater IT tau (partial r = 0.188, p = 0.050) and marginally associated with greater EC tau (partial r = 0.183, p = 0.055). In additional analyses including both linear and quadratic age terms, we found a significant U-shaped relation of GDS to age (p = 0.001). Conclusions:Results suggest that IT and EC tau are modestly associated with depressive symptoms in CN older adults. Findings suggest a link between depressive symptoms and tau-mediated neurodegeneration in a region vulnerable in AD. Future longitudinal studies examining the association of more severe depressive symptoms and cerebral tau accumulation are needed to substantiate this finding and to guide prevention and treatment in AD.

Keywords: Alzheimer’s disease, amyloid, cognitively normal, depression, depressive symptoms, positron emission tomography, tau

DOI: 10.3233/JAD-170001

Journal: Journal of Alzheimer's Disease, vol. 59, no. 3, pp. 975-985, 2017