title: Amyloid and APOE ε4 interact to influence short-term decline in preclinical Alzheimer disease.
abstract: OBJECTIVE
  To examine whether β-amyloid (Aβ) and APOE ε4 status independently contribute or interact to influence longitudinal cognitive decline in clinically normal older individuals (CN).
  
  
  METHODS
  Data from 490 CNs were aggregated across 3 observational cohort studies (Harvard Aging Brain Study, Alzheimer's Disease Neuroimaging Initiative, and Australian Imaging Biomarkers and Lifestyle Study of Ageing; median age = 75.0 years, 255 female), and the contributions of APOE ε4 and Aβ on longitudinal change over a median of 1.49 years were examined. Cognitive decline was assessed with the Mini-Mental State Examination (MMSE) and Logical Memory (immediate and delayed recall scores).
  
  
  RESULTS
  High Aβ participants were more likely to be APOE ε4+ than low Aβ participants. CNs who were both high Aβ and APOE ε4+ showed greater decline in Logical Memory immediate recall (p < 0.087), Logical Memory delayed recall (p < 0.024), and MMSE (p < 0.034) compared to all other groups (low Aβ/APOE ε4-, low Aβ/APOE ε4+, and high Aβ/APOE ε4-). No other pairwise contrast was significant for any cognitive measure.
  
  
  CONCLUSIONS
  Clinically normal individuals who are APOE ε4+ and have high Aβ showed the highest cognitive decline. These results suggest that Aβ and APOE ε4 are not redundant contributors of decline in aging but rather interact to promote decline during the short follow-up period examined in this study. Longer follow-up periods will be essential to fully elucidate the influence of Alzheimer disease risk factors on cognitive decline in aging.
authors.affiliation: From the Departments of Neurology (E.C.M., A.P.S., D.M.R., K.A.J., R.A.S.), Radiology (T.H., A.P.S., K.A.J., R.A.S.), and Psychiatry (A.P.S., A.W.), and the Division of Nuclear Medicine and Molecular Imaging, Department of Radiology (K.A.J.), Massachusetts General Hospital, Harvard Medical School; the Department of Biostatistics (R.A.B.), Harvard School of Public Health, Boston; the Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (T.H.), Massachusetts General Hospital, Charleston; and the Center for Alzheimer Research and Treatment, Department of Neurology (A.W., W.H., D.M.R., K.A.J., R.A.S.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. bmormino@nmr.mgh.harvard.edu.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Mormino
authors.affiliation: From the Departments of Neurology (E.C.M., A.P.S., D.M.R., K.A.J., R.A.S.), Radiology (T.H., A.P.S., K.A.J., R.A.S.), and Psychiatry (A.P.S., A.W.), and the Division of Nuclear Medicine and Molecular Imaging, Department of Radiology (K.A.J.), Massachusetts General Hospital, Harvard Medical School; the Department of Biostatistics (R.A.B.), Harvard School of Public Health, Boston; the Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (T.H.), Massachusetts General Hospital, Charleston; and the Center for Alzheimer Research and Treatment, Department of Neurology (A.W., W.H., D.M.R., K.A.J., R.A.S.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Betensky
authors.affiliation: From the Departments of Neurology (E.C.M., A.P.S., D.M.R., K.A.J., R.A.S.), Radiology (T.H., A.P.S., K.A.J., R.A.S.), and Psychiatry (A.P.S., A.W.), and the Division of Nuclear Medicine and Molecular Imaging, Department of Radiology (K.A.J.), Massachusetts General Hospital, Harvard Medical School; the Department of Biostatistics (R.A.B.), Harvard School of Public Health, Boston; the Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (T.H.), Massachusetts General Hospital, Charleston; and the Center for Alzheimer Research and Treatment, Department of Neurology (A.W., W.H., D.M.R., K.A.J., R.A.S.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Trey
authors.initials: T
authors.lastname: Hedden
authors.affiliation: From the Departments of Neurology (E.C.M., A.P.S., D.M.R., K.A.J., R.A.S.), Radiology (T.H., A.P.S., K.A.J., R.A.S.), and Psychiatry (A.P.S., A.W.), and the Division of Nuclear Medicine and Molecular Imaging, Department of Radiology (K.A.J.), Massachusetts General Hospital, Harvard Medical School; the Department of Biostatistics (R.A.B.), Harvard School of Public Health, Boston; the Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (T.H.), Massachusetts General Hospital, Charleston; and the Center for Alzheimer Research and Treatment, Department of Neurology (A.W., W.H., D.M.R., K.A.J., R.A.S.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Schultz
authors.affiliation: From the Departments of Neurology (E.C.M., A.P.S., D.M.R., K.A.J., R.A.S.), Radiology (T.H., A.P.S., K.A.J., R.A.S.), and Psychiatry (A.P.S., A.W.), and the Division of Nuclear Medicine and Molecular Imaging, Department of Radiology (K.A.J.), Massachusetts General Hospital, Harvard Medical School; the Department of Biostatistics (R.A.B.), Harvard School of Public Health, Boston; the Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (T.H.), Massachusetts General Hospital, Charleston; and the Center for Alzheimer Research and Treatment, Department of Neurology (A.W., W.H., D.M.R., K.A.J., R.A.S.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Ward
authors.affiliation: From the Departments of Neurology (E.C.M., A.P.S., D.M.R., K.A.J., R.A.S.), Radiology (T.H., A.P.S., K.A.J., R.A.S.), and Psychiatry (A.P.S., A.W.), and the Division of Nuclear Medicine and Molecular Imaging, Department of Radiology (K.A.J.), Massachusetts General Hospital, Harvard Medical School; the Department of Biostatistics (R.A.B.), Harvard School of Public Health, Boston; the Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (T.H.), Massachusetts General Hospital, Charleston; and the Center for Alzheimer Research and Treatment, Department of Neurology (A.W., W.H., D.M.R., K.A.J., R.A.S.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Willem
authors.initials: W
authors.lastname: Huijbers
authors.affiliation: From the Departments of Neurology (E.C.M., A.P.S., D.M.R., K.A.J., R.A.S.), Radiology (T.H., A.P.S., K.A.J., R.A.S.), and Psychiatry (A.P.S., A.W.), and the Division of Nuclear Medicine and Molecular Imaging, Department of Radiology (K.A.J.), Massachusetts General Hospital, Harvard Medical School; the Department of Biostatistics (R.A.B.), Harvard School of Public Health, Boston; the Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (T.H.), Massachusetts General Hospital, Charleston; and the Center for Alzheimer Research and Treatment, Department of Neurology (A.W., W.H., D.M.R., K.A.J., R.A.S.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Dorene M
authors.initials: DM
authors.lastname: Rentz
authors.affiliation: From the Departments of Neurology (E.C.M., A.P.S., D.M.R., K.A.J., R.A.S.), Radiology (T.H., A.P.S., K.A.J., R.A.S.), and Psychiatry (A.P.S., A.W.), and the Division of Nuclear Medicine and Molecular Imaging, Department of Radiology (K.A.J.), Massachusetts General Hospital, Harvard Medical School; the Department of Biostatistics (R.A.B.), Harvard School of Public Health, Boston; the Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (T.H.), Massachusetts General Hospital, Charleston; and the Center for Alzheimer Research and Treatment, Department of Neurology (A.W., W.H., D.M.R., K.A.J., R.A.S.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Johnson
authors.affiliation: From the Departments of Neurology (E.C.M., A.P.S., D.M.R., K.A.J., R.A.S.), Radiology (T.H., A.P.S., K.A.J., R.A.S.), and Psychiatry (A.P.S., A.W.), and the Division of Nuclear Medicine and Molecular Imaging, Department of Radiology (K.A.J.), Massachusetts General Hospital, Harvard Medical School; the Department of Biostatistics (R.A.B.), Harvard School of Public Health, Boston; the Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (T.H.), Massachusetts General Hospital, Charleston; and the Center for Alzheimer Research and Treatment, Department of Neurology (A.W., W.H., D.M.R., K.A.J., R.A.S.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000523:psychology; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D003071:Cognition / Q000502:physiology*; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D009483:Neuropsychological Tests; D011877:Radionuclide Imaging; D012307:Risk Factors
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4
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