Midlife adiposity predicts earlier onset of Alzheimer's dementia, neuropathology and presymptomatic cerebral amyloid accumulation.
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.
Clinical and Translational Neuroscience Unit, Laboratory of Behavioral Neuroscience, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, MD, USA.|Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.|Department of Psychiatry, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
Y-F
YF
Chuang
Intramural Research Program, National Institute on Aging, Baltimore, MD, USA.
Y
Y
An
Intramural Research Program, National Institute on Aging, Baltimore, MD, USA.|Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
M
M
Bilgel
Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Psychiatry and Behavioral Science and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
D F
DF
Wong
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J C
JC
Troncoso
Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
R J
RJ
O'Brien
Centre for Studies on Prevention of Alzheimer's Disease, Douglas Mental Health University Institute Research Centre, Montreal, QC, Canada.
J C
JC
Breitner
Intramural Research Program, National Institute on Aging, Baltimore, MD, USA.
L
L
Ferruci
Intramural Research Program, National Institute on Aging, Baltimore, MD, USA.
S M
SM
Resnick
Clinical and Translational Neuroscience Unit, Laboratory of Behavioral Neuroscience, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, MD, USA.
M
M
Thambisetty
D050154:Adiposity / Q000502:physiology*; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D015992:Body Mass Index; D001921:Brain / Q000378:metabolism; D003704:Dementia / Q000473:pathology; D005260:Female; D005544:Forecasting / Q000379:methods; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology; D000069338:Neuropathology / Q000379:methods; D009765:Obesity / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods; D011446:Prospective Studies
D016229:Amyloid beta-Peptides