title: Hippocampal hypometabolism in older adults with memory complaints and increased amyloid burden.
abstract: OBJECTIVE
  To identify the functional and pathologic correlates underlying subjective memory complaints (SMCs) in cognitively normal older adults.
  
  
  METHODS
  Two hundred fifty-one older adults underwent resting-state fluorodeoxyglucose (FDG)-PET and Pittsburg compound B-PET β-amyloid (Aβ) imaging and filled out a questionnaire regarding SMCs. Participants were classified into 2 groups based on their Aβ burden. Age-adjusted voxel-wise correlations were used to examine SMCs, amyloid status (Aβ+vs Aβ-), and the interaction between SMCs and Aβ status as predictors of metabolism. Region-of-interest (ROI) analyses were performed to confirm the whole-brain analyses and to test for additional covariates.
  
  
  RESULTS
  Greater SMCs correlated with decreased FDG metabolism in the bilateral precuneus, bilateral inferior parietal lobes, right inferior temporal lobe, right medial frontal gyrus, and right orbitofrontal gyrus. A significant interaction effect between SMCs and amyloid burden was found such that Aβ+individuals with increased complaints had decreased FDG metabolism in the bilateral medial temporal lobes. ROI analyses confirmed the voxel-wise analyses result in that decreased precuneus metabolism was associated with greater SMCs regardless of Aβ status, age, or thickness, whereas the relationship between hippocampal metabolism and SMCs was a function of Aβ, even after adjustment for age, hippocampal volume, or depressive symptoms.
  
  
  CONCLUSIONS
  These data show the relevant role of posterior and anterior midline regions in SMCs in older individuals. Decreased hippocampal metabolism may be a specific marker of subclinical changes in cognition due to amyloid pathology. However, longitudinal studies are needed to determine whether our findings foreshadow clinical decline.
authors.affiliation: From the Department of Neurology (P.V., B.H., C.E.M., K.A.J., D.M.R., K.A.H., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (P.V., B.H., K.A.J., R.A.S.), Department of Psychiatry (P.V., B.H., K.A.J., R.A.S.), and Department of Radiology (B.H., K.A.J.), Division of Molecular Imaging and Nuclear Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment (P.V., R.E.A., G.A.M., K.A.J., D.M.R., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; and Berenson-Allen Center for Noninvasive Brain Stimulation and Division for Cognitive Neurology (A.P.-L.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. patrizia@nmr.mgh.harvard.edu.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Vannini
authors.affiliation: From the Department of Neurology (P.V., B.H., C.E.M., K.A.J., D.M.R., K.A.H., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (P.V., B.H., K.A.J., R.A.S.), Department of Psychiatry (P.V., B.H., K.A.J., R.A.S.), and Department of Radiology (B.H., K.A.J.), Division of Molecular Imaging and Nuclear Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment (P.V., R.E.A., G.A.M., K.A.J., D.M.R., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; and Berenson-Allen Center for Noninvasive Brain Stimulation and Division for Cognitive Neurology (A.P.-L.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Bernard
authors.initials: B
authors.lastname: Hanseeuw
authors.affiliation: From the Department of Neurology (P.V., B.H., C.E.M., K.A.J., D.M.R., K.A.H., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (P.V., B.H., K.A.J., R.A.S.), Department of Psychiatry (P.V., B.H., K.A.J., R.A.S.), and Department of Radiology (B.H., K.A.J.), Division of Molecular Imaging and Nuclear Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment (P.V., R.E.A., G.A.M., K.A.J., D.M.R., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; and Berenson-Allen Center for Noninvasive Brain Stimulation and Division for Cognitive Neurology (A.P.-L.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Munro
authors.affiliation: From the Department of Neurology (P.V., B.H., C.E.M., K.A.J., D.M.R., K.A.H., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (P.V., B.H., K.A.J., R.A.S.), Department of Psychiatry (P.V., B.H., K.A.J., R.A.S.), and Department of Radiology (B.H., K.A.J.), Division of Molecular Imaging and Nuclear Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment (P.V., R.E.A., G.A.M., K.A.J., D.M.R., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; and Berenson-Allen Center for Noninvasive Brain Stimulation and Division for Cognitive Neurology (A.P.-L.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Amariglio
authors.affiliation: From the Department of Neurology (P.V., B.H., C.E.M., K.A.J., D.M.R., K.A.H., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (P.V., B.H., K.A.J., R.A.S.), Department of Psychiatry (P.V., B.H., K.A.J., R.A.S.), and Department of Radiology (B.H., K.A.J.), Division of Molecular Imaging and Nuclear Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment (P.V., R.E.A., G.A.M., K.A.J., D.M.R., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; and Berenson-Allen Center for Noninvasive Brain Stimulation and Division for Cognitive Neurology (A.P.-L.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Gad A
authors.initials: GA
authors.lastname: Marshall
authors.affiliation: From the Department of Neurology (P.V., B.H., C.E.M., K.A.J., D.M.R., K.A.H., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (P.V., B.H., K.A.J., R.A.S.), Department of Psychiatry (P.V., B.H., K.A.J., R.A.S.), and Department of Radiology (B.H., K.A.J.), Division of Molecular Imaging and Nuclear Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment (P.V., R.E.A., G.A.M., K.A.J., D.M.R., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; and Berenson-Allen Center for Noninvasive Brain Stimulation and Division for Cognitive Neurology (A.P.-L.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Dorene M
authors.initials: DM
authors.lastname: Rentz
authors.affiliation: From the Department of Neurology (P.V., B.H., C.E.M., K.A.J., D.M.R., K.A.H., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (P.V., B.H., K.A.J., R.A.S.), Department of Psychiatry (P.V., B.H., K.A.J., R.A.S.), and Department of Radiology (B.H., K.A.J.), Division of Molecular Imaging and Nuclear Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment (P.V., R.E.A., G.A.M., K.A.J., D.M.R., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; and Berenson-Allen Center for Noninvasive Brain Stimulation and Division for Cognitive Neurology (A.P.-L.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pascual-Leone
authors.affiliation: From the Department of Neurology (P.V., B.H., C.E.M., K.A.J., D.M.R., K.A.H., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (P.V., B.H., K.A.J., R.A.S.), Department of Psychiatry (P.V., B.H., K.A.J., R.A.S.), and Department of Radiology (B.H., K.A.J.), Division of Molecular Imaging and Nuclear Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment (P.V., R.E.A., G.A.M., K.A.J., D.M.R., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; and Berenson-Allen Center for Noninvasive Brain Stimulation and Division for Cognitive Neurology (A.P.-L.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Johnson
authors.affiliation: From the Department of Neurology (P.V., B.H., C.E.M., K.A.J., D.M.R., K.A.H., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (P.V., B.H., K.A.J., R.A.S.), Department of Psychiatry (P.V., B.H., K.A.J., R.A.S.), and Department of Radiology (B.H., K.A.J.), Division of Molecular Imaging and Nuclear Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment (P.V., R.E.A., G.A.M., K.A.J., D.M.R., R.A.S.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; and Berenson-Allen Center for Noninvasive Brain Stimulation and Division for Cognitive Neurology (A.P.-L.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D053327:Apolipoprotein E4 / Q000235:genetics; D001931:Brain Mapping; D005260:Female; D019788:Fluorodeoxyglucose F18; D006624:Hippocampus / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D008032:Limbic System / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism*; D008609:Mental Status Schedule; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012146:Rest; D011795:Surveys and Questionnaires; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D019275:Radiopharmaceuticals; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18