Original Article

Molecular Psychiatry (2016) 21, 910–915; doi:10.1038/mp.2015.129; published online 1 September 2015

Midlife adiposity predicts earlier onset of Alzheimer’s dementia, neuropathology and presymptomatic cerebral amyloid accumulation

Y-F Chuang1,2,3,11, Y An4,11, M Bilgel4,5, D F Wong6,7, J C Troncoso8, R J O'Brien9, J C Breitner10, L Ferruci4, S M Resnick4 and M Thambisetty1

  1. 1Clinical and Translational Neuroscience Unit, Laboratory of Behavioral Neuroscience, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, MD, USA
  2. 2Institute of Public Health, National Yang-Ming University, Taipei, Taiwan
  3. 3Department of Psychiatry, Far Eastern Memorial Hospital, New Taipei City, Taiwan
  4. 4Intramural Research Program, National Institute on Aging, Baltimore, MD, USA
  5. 5Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
  6. 6Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
  7. 7Department of Psychiatry and Behavioral Science and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
  8. 8Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
  9. 9Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
  10. 10Centre for Studies on Prevention of Alzheimer's Disease, Douglas Mental Health University Institute Research Centre, Montreal, QC, Canada

Correspondence: Dr M Thambisetty, Clinical and Translational Neuroscience Unit, Laboratory of Behavioral Neuroscience, National Institute on Aging (NIA), National Institutes of Health (NIH), Room 4B-311, 251 Bayview Boulevard, Baltimore, MD 21224, USA. E-mail: thambisettym@mail.nih.gov

11The first two authors contributed equally to this work.

Received 13 March 2015; Revised 14 July 2015; Accepted 22 July 2015
Advance online publication 1 September 2015

Top

Abstract

Understanding how midlife risk factors influence age at onset (AAO) of Alzheimer’s disease (AD) may provide clues to delay disease expression. Although midlife adiposity predicts increased incidence of AD, it is unclear whether it affects AAO and severity of Alzheimer’s neuropathology. Using a prospective population-based cohort, Baltimore Longitudinal Study of Aging (BLSA), this study aims to examine the relationships between midlife body mass index (BMI) and (1) AAO of AD (2) severity of Alzheimer’s neuropathology and (3) fibrillar brain amyloid deposition during aging. We analyzed data on 1394 cognitively normal individuals at baseline (8643 visits; average follow-up interval 13.9 years), among whom 142 participants developed incident AD. In two subsamples of BLSA, 191 participants underwent autopsy and neuropathological assessment, and 75 non-demented individuals underwent brain amyloid imaging. Midlife adiposity was derived from BMI data at 50 years of age. We find that each unit increase in midlife BMI predicts earlier onset of AD by 6.7 months (P=0.013). Higher midlife BMI was associated with greater Braak neurofibrillary but not CERAD (Consortium to Establish a Registry for Alzheimer's Disease) neuritic plaque scores at autopsy overall. Associations between midlife BMI and brain amyloid burden approached statistical significance. Thus, higher midlife BMI was also associated with greater fibrillar amyloid measured by global mean cortical distribution volume ratio (P=0.075) and within the precuneus (left, P=0.061; right, P=0.079). In conclusion, midlife overweight predicts earlier onset of AD and greater burden of Alzheimer’s neuropathology. A healthy BMI at midlife may delay the onset of AD.