Association of Midlife Depressive Symptoms with Regional Amyloid-β and Tau in the Framingham Heart Study

Article type: Research Article

Authors: Gonzales, Mitzi M.^{a; b; *} | Samra, Jasmeet^{c; d} | O’Donnell, Adrienne^{c; d} | Mackin, R. Scott^{e; f} | Salinas, Joel^g | Jacob, Mini E.^a | Satizabal, Claudia L.^{a; c; h; i} | Aparicio, Hugo J.^{c; i} | Thibault, Emma G.^j | Sanchez, Justin S.^j | Finney, Rebecca^c | Rubinstein, Zoe B.^j | Mayblyum, Danielle V.^j | Killiany, Ron J.^{i; k} | Decarli, Charlie S.^{l; m} | Johnson, Keith A.^{j; n; o} | Beiser, Alexa S.^{c; d; i} | Seshadri, Sudha^{a; b; c; i}

Affiliations: [a] Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases, University of Texas Health Science Center, San Antonio, TX, USA | [b] Department of Neurology, University of Texas Health Science Center, San Antonio, TX, USA | [c] The Framingham Heart Study, Framingham, MA, USA | [d] Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA | [e] Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA | [f] Center for Imaging of Neurodegenerative Disease, Veteran Affairs Administration, San Francisco, CA, USA | [g] Department of Neurology, New York University Grossman School of Medicine, New York, NY, USA | [h] Department of Population Health Sciences, University of Texas Health Science Center, San Antonio, TX, USA | [i] Department of Neurology, Boston University School of Medicine, Boston, MA, USA | [j] Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA | [k] Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, USA | [l] Department of Neurology, University of California Davis, Davis, CA, USA | [m] Center for Neuroscience, University of California Davis, Davis, CA, USA | [n] Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA | [o] Department of Neurology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

Correspondence: [*] Correspondence to: Mitzi M. Gonzales, PhD, Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, Department of Neurology, University of Texas Health San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. Tel.: +1 210 450 9047; E-mail: [email protected].

Abstract: Background:Depressive symptoms predict increased risk for dementia decades before the emergence of cognitive symptoms. Studies in older adults provide preliminary evidence for an association between depressive symptoms and amyloid-β (Aβ) and tau accumulation. It is unknown if similar alterations are observed in midlife when preventive strategies may be most effective. Objective:The study aim was to evaluate the association between depressive symptoms and cerebral Aβ and tau in a predominately middle-aged cohort with examination of the apolipoprotein (APOE) ɛ4 allele as a moderator. Methods:Participants included 201 adults (mean age 53±8 years) who underwent 11C-Pittsburgh Compound B amyloid and 18F-Flortaucipir tau positron emission tomography (PET) imaging. Depressive symptoms were evaluated with the Center for Epidemiological Studies Depression Scale (CES-D) at the time of PET imaging, as well as eight years prior. Associations between depressive symptoms at both timepoints, as well as depression (CES-D≥16), with regional Aβ and tau PET retention were evaluated with linear regression adjusting for age and sex. Interactions with the APOE ɛ4 allele were explored. Results:Depressive symptoms and depression were not associated with PET outcomes in the overall sample. However, among APOE ɛ4 allele carriers, there was a significant cross-sectional association between depressive symptoms and increased tau PET uptake in the entorhinal cortex (β= 0.446, SE = 0.155, p = 0.006) and amygdala (β= 0.350, SE = 0.133, p = 0.012). Conclusion:Although longitudinal studies are necessary, the results suggest that APOE ɛ4 carriers with depressive symptoms may present with higher susceptibility to early tau accumulation in regions integral to affective regulation and memory consolidation.

Keywords: Amygdala, amyloid-β, APOE, depression, depressive symptoms, entorhinal, PET imaging, tau

DOI: 10.3233/JAD-210232

Journal: Journal of Alzheimer's Disease, vol. 82, no. 1, pp. 249-260, 2021