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Midlife adiposity predicts earlier onset of Alzheimer's dementia, neuropathology and presymptomatic cerebral amyloid accumulation.
Mol Psychiatry 2016; 21(7):910-5MP

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.

Authors+Show Affiliations

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.Intramural Research Program, National Institute on Aging, Baltimore, MD, USA.Intramural Research Program, National Institute on Aging, Baltimore, MD, USA. Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.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.Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.Centre for Studies on Prevention of Alzheimer's Disease, Douglas Mental Health University Institute Research Centre, Montreal, QC, Canada.Intramural Research Program, National Institute on Aging, Baltimore, MD, USA.Intramural Research Program, National Institute on Aging, Baltimore, MD, USA.Clinical and Translational Neuroscience Unit, Laboratory of Behavioral Neuroscience, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, MD, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

26324099

Citation

Chuang, Y-F, et al. "Midlife Adiposity Predicts Earlier Onset of Alzheimer's Dementia, Neuropathology and Presymptomatic Cerebral Amyloid Accumulation." Molecular Psychiatry, vol. 21, no. 7, 2016, pp. 910-5.
Chuang YF, An Y, Bilgel M, et al. Midlife adiposity predicts earlier onset of Alzheimer's dementia, neuropathology and presymptomatic cerebral amyloid accumulation. Mol Psychiatry. 2016;21(7):910-5.
Chuang, Y. F., An, Y., Bilgel, M., Wong, D. F., Troncoso, J. C., O'Brien, R. J., ... Thambisetty, M. (2016). Midlife adiposity predicts earlier onset of Alzheimer's dementia, neuropathology and presymptomatic cerebral amyloid accumulation. Molecular Psychiatry, 21(7), pp. 910-5. doi:10.1038/mp.2015.129.
Chuang YF, et al. Midlife Adiposity Predicts Earlier Onset of Alzheimer's Dementia, Neuropathology and Presymptomatic Cerebral Amyloid Accumulation. Mol Psychiatry. 2016;21(7):910-5. PubMed PMID: 26324099.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Midlife adiposity predicts earlier onset of Alzheimer's dementia, neuropathology and presymptomatic cerebral amyloid accumulation. AU - Chuang,Y-F, AU - An,Y, AU - Bilgel,M, AU - Wong,D F, AU - Troncoso,J C, AU - O'Brien,R J, AU - Breitner,J C, AU - Ferruci,L, AU - Resnick,S M, AU - Thambisetty,M, Y1 - 2015/09/01/ PY - 2015/03/13/received PY - 2015/07/14/revised PY - 2015/07/22/accepted PY - 2015/9/2/entrez PY - 2015/9/2/pubmed PY - 2017/9/26/medline SP - 910 EP - 5 JF - Molecular psychiatry JO - Mol. Psychiatry VL - 21 IS - 7 N2 - 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. SN - 1476-5578 UR - https://www.unboundmedicine.com/medline/citation/26324099/Midlife_adiposity_predicts_earlier_onset_of_Alzheimer's_dementia_neuropathology_and_presymptomatic_cerebral_amyloid_accumulation_ L2 - http://dx.doi.org/10.1038/mp.2015.129 DB - PRIME DP - Unbound Medicine ER -