Lower Late-Life Body-Mass Index is Associated with Higher Cortical Amyloid Burden in Clinically Normal Elderly

Article type: Research Article

Authors: Hsu, David C.^{a; d; f} | Mormino, Elizabeth C.^b | Schultz, Aaron P.^b | Amariglio, Rebecca E.^{b; d} | Donovan, Nancy J.^{a; d; e} | Rentz, Dorene M.^{b; d; e} | Johnson, Keith A.^{b; c; d} | Sperling, Reisa A.^{b; d} | Marshall, Gad A.^{b; d; *} | for the Harvard Aging Brain Study

Affiliations: [a] Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [b] Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [c] Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [d] Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA | [e] Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA | [f] Department of Psychiatry, Mercy Medical Group, Sacramento, CA, USA

Correspondence: [*] Correspondence to: Gad A. Marshall, MD, Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital, 221 Longwood Avenue, BL-104H, Boston, MA 02115, USA. Tel.: +1 617 732 8085; Fax: +1 617 264 5212; Email: [email protected].

Abstract: Background: Lower body-mass index (BMI) in late life has been associated with an increased risk of dementia, and weight loss has been associated with more rapid decline in Alzheimer’s disease (AD) dementia. Objective: To explore the association between BMI and cortical amyloid burden in clinically normal (CN) elderly at risk for AD dementia. Methods: Cross-sectional analyses were completed using baseline data from the Harvard Aging Brain Study, consisting of 280 community-dwelling CN older adults aged 62–90. Assessments included medical histories and physical exam, Pittsburgh compound B (PiB) positron emission tomography (PET) amyloid imaging, and apolipoprotein E ɛ4 (APOE4) genotyping. For the primary analysis, a general linear regression model was used to evaluate the association of BMI with PiB retention. Covariates included age, sex, years of education, and APOE4 carrier status. Secondary analyses were performed for BMI subdivisions (normal, overweight, obese), APOE4 carriers, and BMI×APOE4 interaction. Results: In the primary analysis, greater PiB retention was associated with lower BMI (β  =  –0.14, p = 0.02). In the secondary analyses, APOE4 carrier status (β= –0.27, p = 0.02) and normal BMI (β= –0.25, p = 0.01), as opposed to overweight or obese BMI, were associated with greater PiB retention. The BMI×APOE4 interaction was also significant (β= –0.14, p = 0.04). Conclusions: This finding offers new insight into the role of BMI at the preclinical stage of AD, wherein lower BMI late in life is associated with greater cortical amyloid burden. Future studies are needed to elucidate the mechanism behind this association, especially in those with lower BMI who are APOE4 carriers.

Keywords: Alzheimer’s disease, amyloid, apolipoprotein E, body mass index, clinically normal elderly, Pittsburgh compound B, positron emission tomography

DOI: 10.3233/JAD-150987

Journal: Journal of Alzheimer's Disease, vol. 53, no. 3, pp. 1097-1105, 2016