title: Memory, executive, and multidomain subtle cognitive impairment: clinical and biomarker findings.
abstract: OBJECTIVE
  We studied the biomarker signatures and prognoses of 3 different subtle cognitive impairment (SCI) groups (executive, memory, and multidomain) as well as the subjective memory complaints (SMC) group.
  
  
  METHODS
  We studied 522 healthy controls in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cutoffs for executive, memory, and multidomain SCI were defined using participants who remained cognitively normal (CN) for 7 years. CSF Alzheimer disease (AD) biomarkers, composite and region-of-interest (ROI) MRI, and fluorodeoxyglucose-PET measures were compared in these participants.
  
  
  RESULTS
  Using a stringent cutoff (fifth percentile), 27.6% of the ADNI participants were classified as SCI. Most single ROI or global-based measures were not sensitive to detect differences between groups. Only MRI-SPARE-AD (Spatial Pattern of Abnormalities for Recognition of Early AD), a quantitative MRI pattern-based global index, showed differences between all groups, excluding the executive SCI group. Atrophy patterns differed in memory SCI and SMC. The CN and the SMC groups presented a similar distribution of preclinical dementia stages. Fifty percent of the participants with executive, memory, and multidomain SCI progressed to mild cognitive impairment or dementia at 7, 5, and 2 years, respectively.
  
  
  CONCLUSIONS
  Our results indicate that (1) the different SCI categories have different clinical prognoses and biomarker signatures, (2) longitudinally followed CN subjects are needed to establish clinical cutoffs, (3) subjects with SMC show a frontal pattern of brain atrophy, and (4) pattern-based analyses outperform commonly used single ROI-based neuroimaging biomarkers and are needed to detect initial stages of cognitive impairment.
authors.affiliation: From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco.
authors.forename: Jon B
authors.initials: JB
authors.lastname: Toledo
authors.affiliation: From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco.
authors.forename: Maria
authors.initials: M
authors.lastname: Bjerke
authors.affiliation: From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco.
authors.forename: Kewei
authors.initials: K
authors.lastname: Chen
authors.affiliation: From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco.
authors.forename: Martin
authors.initials: M
authors.lastname: Rozycki
authors.affiliation: From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.affiliation: From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Arnold
authors.affiliation: From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
authors.affiliation: From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco.
authors.forename: Christos
authors.initials: C
authors.lastname: Davatzikos
authors.affiliation: From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.affiliation: From the Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research (J.B.T., M.B., L.M.S., J.Q.T.), and Department of Psychiatry (S.E.A.), University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Banner Alzheimer's Institute (K.C., E.M.R.), Phoenix, AZ; Center for Biomedical Image Computing and Analytics (M.R., C.D.), Philadelphia, PA; Mayo Clinic College of Medicine (C.R.J.), Rochester, MN; and Center for Imaging of Neurodegenerative Diseases (M.W.W.), Department of Radiology, San Francisco VA Medical Center/University of California San Francisco. trojanow@mail.med.upenn.edu.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology*; D003072:Cognition Disorders / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000473:pathology*; D018450:Disease Progression; D056344:Executive Function; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000473:pathology*; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography
chemical_list: D015415:Biomarkers