Amyloid-beta burden predicts prospective decline in body mass index in clinically normal adults

Jennifer S Rabin; Zahra Shirzadi; Walter Swardfager; Bradley J MacIntosh; Aaron Schultz; Hyun-Sik Yang; Rachel F Buckley; Jennifer R Gatchel; Dylan Kirn; Jeremy J Pruzin; Trey Hedden; Nir Lipsman; Dorene M Rentz; Sandra E Black; Keith A Johnson; Reisa A Sperling; Jasmeer P Chhatwal; Harvard Aging Brain Study; Alzheimer's Disease Neuroimaging Initiative

doi:10.1016/j.neurobiolaging.2020.03.002

Amyloid-beta burden predicts prospective decline in body mass index in clinically normal adults

Neurobiol Aging. 2020 Sep:93:124-130. doi: 10.1016/j.neurobiolaging.2020.03.002. Epub 2020 Mar 7.

Authors

Jennifer S Rabin¹, Zahra Shirzadi², Walter Swardfager³, Bradley J MacIntosh², Aaron Schultz⁴, Hyun-Sik Yang⁵, Rachel F Buckley⁶, Jennifer R Gatchel⁷, Dylan Kirn⁸, Jeremy J Pruzin⁵, Trey Hedden⁹, Nir Lipsman¹⁰, Dorene M Rentz⁵, Sandra E Black¹¹, Keith A Johnson¹², Reisa A Sperling¹³, Jasmeer P Chhatwal¹⁴; Harvard Aging Brain Study; Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Harquail Centre for Neuromodulation, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Medicine, Division of Neurology, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
² Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
³ Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.
⁴ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁵ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital; Boston, MA, USA.
⁶ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital; Boston, MA, USA; Florey Institutes of Neuroscience and Mental Health, Melbourne and Melbourne School of Psychological Science, University of Melbourne, Melbourne, Australia.
⁷ Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁸ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁹ Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Icahn School of Medicine, Mount Sinai, New York, NY, USA.
¹⁰ Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Harquail Centre for Neuromodulation, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Medicine, Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada.
¹¹ Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Medicine, Division of Neurology, University of Toronto, Toronto, Ontario, Canada.
¹² Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital; Boston, MA, USA; Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, MA, USA.
¹³ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital; Boston, MA, USA.
¹⁴ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital; Boston, MA, USA. Electronic address: [email protected].

PMID: 32249013
PMCID: PMC7429980
DOI: 10.1016/j.neurobiolaging.2020.03.002

Abstract

In the present study, we tested the hypothesis that higher amyloid-beta (Aβ) burden at baseline is associated with greater longitudinal decline in body mass index (BMI) in clinically normal adults. Participants from the Harvard Aging Brain Study (n = 312) and the Alzheimer's Disease Neuroimaging Initiative (n = 336) underwent Aβ positron emission tomography at baseline. BMI was assessed longitudinally over a median of >4 years. Linear mixed models showed that higher baseline Aβ burden was significantly associated with greater decline in BMI in both the Harvard Aging Brain Study (t = -1.93; p = 0.05) and Alzheimer's Disease Neuroimaging Initiative cohorts (t = -2.54; p = 0.01), after adjusting for covariates, including cognitive performance and depressive symptoms. In addition, the association of Aβ burden with longitudinal decline in BMI persisted in both cohorts after excluding participants with diabetes/endocrine disturbances and participants classified as underweight or obese (BMI <18.5 or >30). These findings suggest that decline in BMI in clinically normal adults may be an early manifestation related to cerebral amyloidosis that precedes objective cognitive impairment. Therefore, unintentional BMI decline in otherwise healthy individuals might alert clinicians to increased risk of Alzheimer's disease.

Keywords: ADNI; Amyloid-beta; Body mass index; HABS; Longitudinal; Preclinical Alzheimer's disease; Weight loss.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / diagnosis*
Amyloid beta-Peptides / metabolism*
Body Mass Index*
Brain / metabolism*
Cohort Studies
Female
Healthy Volunteers*
Humans
Longitudinal Studies
Male
Positron-Emission Tomography
Risk

Substances

Amyloid beta-Peptides

Abstract

Publication types

MeSH terms

Substances

Grants and funding