Odor identification and Alzheimer disease biomarkers in clinically normal elderly.
OBJECTIVE
Our objective was to investigate cross-sectional associations between odor identification ability and imaging biomarkers of neurodegeneration and amyloid deposition in clinically normal (CN) elderly individuals, specifically testing the hypothesis that there may be an interaction between amyloid deposition and neurodegeneration in predicting odor identification dysfunction.


METHODS
Data were collected on 215 CN participants from the Harvard Aging Brain Study. Measurements included the 40-item University of Pennsylvania Smell Identification Test and neuropsychological testing, hippocampal volume (HV) and entorhinal cortex (EC) thickness from MRI, and amyloid burden using Pittsburgh compound B (PiB) PET. A linear regression model with backward elimination (p < 0.05 retention) evaluated the cross-sectional association between the University of Pennsylvania Smell Identification Test and amyloid burden, HV, and EC thickness, assessing for effect modification by PiB status. Covariates included age, sex, premorbid intelligence, APOE ε4 carrier status, and Boston Naming Test.


RESULTS
In unadjusted univariate analyses, worse olfaction was associated with decreased HV (p < 0.001), thinner EC (p = 0.003), worse episodic memory (p = 0.03), and marginally associated with greater amyloid burden (binary PiB status, p = 0.06). In the multivariate model, thinner EC in PiB-positive individuals (interaction term) was associated with worse olfaction (p = 0.02).


CONCLUSIONS
In CN elderly, worse odor identification was associated with markers of neurodegeneration. Furthermore, individuals with elevated cortical amyloid and thinner EC exhibited worse odor identification, elucidating the potential contribution of olfactory testing to detect preclinical AD in CN individuals.
From Harvard Medical School (M.E.G., R.E.A., T.H., D.M.R., K.A.J., R.A.S., M.W.A., G.A.M.) and Harvard T.H. Chan School of Public Health (M.E.G.), Boston, MA; Athinoula A. Martinos Center for Biomedical Imaging (A.P.S., A.S.D., T.H., R.A.S., M.W.A.), Massachusetts General Hospital, Charlestown; Departments of Neurology (A.P.S., A.S.D., R.E.A., D.M.R., R.A.S., M.W.A., G.A.M.), Psychiatry (A.P.S., A.S.D.), and Radiology (T.H., K.A.J.), MassGeneral Institute of Neurodegenerative Disease (M.W.A.), Massachusetts General Hospital, Boston; and Center for Alzheimer Research and Treatment (R.E.A., D.M.R., K.A.J., R.A.S., G.A.M.) and Department of Neurology (R.E.A., D.M.R., K.A.J., R.A.S., G.A.M.), Brigham and Women's Hospital, Boston, MA.
Matthew E
ME
Growdon
From Harvard Medical School (M.E.G., R.E.A., T.H., D.M.R., K.A.J., R.A.S., M.W.A., G.A.M.) and Harvard T.H. Chan School of Public Health (M.E.G.), Boston, MA; Athinoula A. Martinos Center for Biomedical Imaging (A.P.S., A.S.D., T.H., R.A.S., M.W.A.), Massachusetts General Hospital, Charlestown; Departments of Neurology (A.P.S., A.S.D., R.E.A., D.M.R., R.A.S., M.W.A., G.A.M.), Psychiatry (A.P.S., A.S.D.), and Radiology (T.H., K.A.J.), MassGeneral Institute of Neurodegenerative Disease (M.W.A.), Massachusetts General Hospital, Boston; and Center for Alzheimer Research and Treatment (R.E.A., D.M.R., K.A.J., R.A.S., G.A.M.) and Department of Neurology (R.E.A., D.M.R., K.A.J., R.A.S., G.A.M.), Brigham and Women's Hospital, Boston, MA.
Aaron P
AP
Schultz
From Harvard Medical School (M.E.G., R.E.A., T.H., D.M.R., K.A.J., R.A.S., M.W.A., G.A.M.) and Harvard T.H. Chan School of Public Health (M.E.G.), Boston, MA; Athinoula A. Martinos Center for Biomedical Imaging (A.P.S., A.S.D., T.H., R.A.S., M.W.A.), Massachusetts General Hospital, Charlestown; Departments of Neurology (A.P.S., A.S.D., R.E.A., D.M.R., R.A.S., M.W.A., G.A.M.), Psychiatry (A.P.S., A.S.D.), and Radiology (T.H., K.A.J.), MassGeneral Institute of Neurodegenerative Disease (M.W.A.), Massachusetts General Hospital, Boston; and Center for Alzheimer Research and Treatment (R.E.A., D.M.R., K.A.J., R.A.S., G.A.M.) and Department of Neurology (R.E.A., D.M.R., K.A.J., R.A.S., G.A.M.), Brigham and Women's Hospital, Boston, MA.
Alexander S
AS
Dagley
From Harvard Medical School (M.E.G., R.E.A., T.H., D.M.R., K.A.J., R.A.S., M.W.A., G.A.M.) and Harvard T.H. Chan School of Public Health (M.E.G.), Boston, MA; Athinoula A. Martinos Center for Biomedical Imaging (A.P.S., A.S.D., T.H., R.A.S., M.W.A.), Massachusetts General Hospital, Charlestown; Departments of Neurology (A.P.S., A.S.D., R.E.A., D.M.R., R.A.S., M.W.A., G.A.M.), Psychiatry (A.P.S., A.S.D.), and Radiology (T.H., K.A.J.), MassGeneral Institute of Neurodegenerative Disease (M.W.A.), Massachusetts General Hospital, Boston; and Center for Alzheimer Research and Treatment (R.E.A., D.M.R., K.A.J., R.A.S., G.A.M.) and Department of Neurology (R.E.A., D.M.R., K.A.J., R.A.S., G.A.M.), Brigham and Women's Hospital, Boston, MA.
Rebecca E
RE
Amariglio
From Harvard Medical School (M.E.G., R.E.A., T.H., D.M.R., K.A.J., R.A.S., M.W.A., G.A.M.) and Harvard T.H. Chan School of Public Health (M.E.G.), Boston, MA; Athinoula A. Martinos Center for Biomedical Imaging (A.P.S., A.S.D., T.H., R.A.S., M.W.A.), Massachusetts General Hospital, Charlestown; Departments of Neurology (A.P.S., A.S.D., R.E.A., D.M.R., R.A.S., M.W.A., G.A.M.), Psychiatry (A.P.S., A.S.D.), and Radiology (T.H., K.A.J.), MassGeneral Institute of Neurodegenerative Disease (M.W.A.), Massachusetts General Hospital, Boston; and Center for Alzheimer Research and Treatment (R.E.A., D.M.R., K.A.J., R.A.S., G.A.M.) and Department of Neurology (R.E.A., D.M.R., K.A.J., R.A.S., G.A.M.), Brigham and Women's Hospital, Boston, MA.
Trey
T
Hedden
From Harvard Medical School (M.E.G., R.E.A., T.H., D.M.R., K.A.J., R.A.S., M.W.A., G.A.M.) and Harvard T.H. Chan School of Public Health (M.E.G.), Boston, MA; Athinoula A. Martinos Center for Biomedical Imaging (A.P.S., A.S.D., T.H., R.A.S., M.W.A.), Massachusetts General Hospital, Charlestown; Departments of Neurology (A.P.S., A.S.D., R.E.A., D.M.R., R.A.S., M.W.A., G.A.M.), Psychiatry (A.P.S., A.S.D.), and Radiology (T.H., K.A.J.), MassGeneral Institute of Neurodegenerative Disease (M.W.A.), Massachusetts General Hospital, Boston; and Center for Alzheimer Research and Treatment (R.E.A., D.M.R., K.A.J., R.A.S., G.A.M.) and Department of Neurology (R.E.A., D.M.R., K.A.J., R.A.S., G.A.M.), Brigham and Women's Hospital, Boston, MA.
Dorene M
DM
Rentz
From Harvard Medical School (M.E.G., R.E.A., T.H., D.M.R., K.A.J., R.A.S., M.W.A., G.A.M.) and Harvard T.H. Chan School of Public Health (M.E.G.), Boston, MA; Athinoula A. Martinos Center for Biomedical Imaging (A.P.S., A.S.D., T.H., R.A.S., M.W.A.), Massachusetts General Hospital, Charlestown; Departments of Neurology (A.P.S., A.S.D., R.E.A., D.M.R., R.A.S., M.W.A., G.A.M.), Psychiatry (A.P.S., A.S.D.), and Radiology (T.H., K.A.J.), MassGeneral Institute of Neurodegenerative Disease (M.W.A.), Massachusetts General Hospital, Boston; and Center for Alzheimer Research and Treatment (R.E.A., D.M.R., K.A.J., R.A.S., G.A.M.) and Department of Neurology (R.E.A., D.M.R., K.A.J., R.A.S., G.A.M.), Brigham and Women's Hospital, Boston, MA.
Keith A
KA
Johnson
From Harvard Medical School (M.E.G., R.E.A., T.H., D.M.R., K.A.J., R.A.S., M.W.A., G.A.M.) and Harvard T.H. Chan School of Public Health (M.E.G.), Boston, MA; Athinoula A. Martinos Center for Biomedical Imaging (A.P.S., A.S.D., T.H., R.A.S., M.W.A.), Massachusetts General Hospital, Charlestown; Departments of Neurology (A.P.S., A.S.D., R.E.A., D.M.R., R.A.S., M.W.A., G.A.M.), Psychiatry (A.P.S., A.S.D.), and Radiology (T.H., K.A.J.), MassGeneral Institute of Neurodegenerative Disease (M.W.A.), Massachusetts General Hospital, Boston; and Center for Alzheimer Research and Treatment (R.E.A., D.M.R., K.A.J., R.A.S., G.A.M.) and Department of Neurology (R.E.A., D.M.R., K.A.J., R.A.S., G.A.M.), Brigham and Women's Hospital, Boston, MA.
Reisa A
RA
Sperling
From Harvard Medical School (M.E.G., R.E.A., T.H., D.M.R., K.A.J., R.A.S., M.W.A., G.A.M.) and Harvard T.H. Chan School of Public Health (M.E.G.), Boston, MA; Athinoula A. Martinos Center for Biomedical Imaging (A.P.S., A.S.D., T.H., R.A.S., M.W.A.), Massachusetts General Hospital, Charlestown; Departments of Neurology (A.P.S., A.S.D., R.E.A., D.M.R., R.A.S., M.W.A., G.A.M.), Psychiatry (A.P.S., A.S.D.), and Radiology (T.H., K.A.J.), MassGeneral Institute of Neurodegenerative Disease (M.W.A.), Massachusetts General Hospital, Boston; and Center for Alzheimer Research and Treatment (R.E.A., D.M.R., K.A.J., R.A.S., G.A.M.) and Department of Neurology (R.E.A., D.M.R., K.A.J., R.A.S., G.A.M.), Brigham and Women's Hospital, Boston, MA.
Mark W
MW
Albers
From Harvard Medical School (M.E.G., R.E.A., T.H., D.M.R., K.A.J., R.A.S., M.W.A., G.A.M.) and Harvard T.H. Chan School of Public Health (M.E.G.), Boston, MA; Athinoula A. Martinos Center for Biomedical Imaging (A.P.S., A.S.D., T.H., R.A.S., M.W.A.), Massachusetts General Hospital, Charlestown; Departments of Neurology (A.P.S., A.S.D., R.E.A., D.M.R., R.A.S., M.W.A., G.A.M.), Psychiatry (A.P.S., A.S.D.), and Radiology (T.H., K.A.J.), MassGeneral Institute of Neurodegenerative Disease (M.W.A.), Massachusetts General Hospital, Boston; and Center for Alzheimer Research and Treatment (R.E.A., D.M.R., K.A.J., R.A.S., G.A.M.) and Department of Neurology (R.E.A., D.M.R., K.A.J., R.A.S., G.A.M.), Brigham and Women's Hospital, Boston, MA. gamarshall@partners.org.
Gad A
GA
Marshall
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D000544:Alzheimer Disease / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D015415:Biomarkers; D003430:Cross-Sectional Studies; D018728:Entorhinal Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D061212:Memory, Episodic; D000857:Olfaction Disorders / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D049268:Positron-Emission Tomography
D016229:Amyloid beta-Peptides; D015415:Biomarkers