Association Between Elevated Depressive Symptoms and Cognitive Function Moderated by APOE4 Status: Framingham Offspring Study

Article type: Research Article

Authors: Piers, Ryan J.^a | Liu, Yulin^{b; c} | Ang, Ting F.A.^{b; d; e} | Tao, Qiushan^f | Au, Rhoda^{b; c; d; e; g; h; 1} | Qiu, Wei Qiao^{f; h; i; 1; *}

Affiliations: [a] Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA | [b] The Framingham Heart Study, Boston University School of Medicine, Boston, MA, USA | [c] Department of Neurology, Boston University School of Medicine, Boston, MA, USA | [d] Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, USA | [e] Slone Epidemiology Center, Boston University School of Medicine, Boston, MA, USA | [f] Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA | [g] Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA | [h] Alzheimer’s Disease Center, Boston University School of Medicine, Boston, MA, USA | [i] Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA

Correspondence: [*] Correspondence to: Wei Qiao Qiu, MD, PhD, Professor, Boston University School of Medicine, 72 East Concord Street, R-623, Boston, MA 02118, USA. Tel.: +1 617 358 1886; Fax: +1 617 638 5254; E-mail: wqiu67@bu.edu.

Note: [1] These authors contributed equally as senior authors.

Abstract: Background:Depression and Apolipoprotein E4 (APOE4) are associated with decreased cognitive function and differences in brain structure. Objective:This study investigated whether APOE4 status moderates the association between elevated depressive symptoms, cognitive function, and brain structure. Methods:Stroke- and dementia-free participants (n = 1,968) underwent neuropsychological evaluation, brain MRI, and depression screening. Linear and logistic regression was used to examine all associations. Secondary analyses were performed using interaction terms to assess effect modification by APOE4 status. Results:Elevated depressive symptoms were associated with lower cognitive performance in several domains. In stratified analyses, elevated depressive symptoms were associated with poorer visual short- and long-term memory performance for APOE4 + participants. Elevated depressive symptoms were not associated with any brain structure in this study sample. Conclusion:Elevated depressive symptoms impact cognitive function in non-demented individuals. Having the APOE4 allele may exacerbate the deleterious effects of elevated depressive symptoms on visual memory performance. Screening for elevated depressive symptoms in both research studies and clinical practice may be warranted to avoid false positive identification of neurodegeneration, particularly among those who are APOE4 + .

Keywords: APOE4 , cognition, depression, framingham offspring study, magnetic resonance imaging

DOI: 10.3233/JAD-200998

Journal: Journal of Alzheimer's Disease, vol. 80, no. 3, pp. 1269-1279, 2021