title: Spectrum of cognition short of dementia: Framingham Heart Study and Mayo Clinic Study of Aging.
abstract: OBJECTIVE
  To understand the neuropsychological basis of dementia risk among persons in the spectrum including cognitive normality and mild cognitive impairment.
  
  
  METHODS
  We quantitated risk of progression to dementia in elderly persons without dementia from 2 population-based studies, the Framingham Heart Study (FHS) and Mayo Clinic Study of Aging (MCSA), aged 70 to 89 years at enrollment. Baseline cognitive status was defined by performance in 4 domains derived from batteries of neuropsychological tests (that were similar but not identical for FHS and MCSA) at cut scores corresponding to SDs of ≤-0.5, -1, -1.5, and -2 from normative means. Participants were characterized as having no cognitive impairment (reference group), or single or multiple amnestic or nonamnestic profiles at each cut score. Incident dementia over the following 6 years was determined by consensus committee at each study separately.
  
  
  RESULTS
  The pattern of hazard ratios for incident dementia, rates of incident dementia and positive predictive values across cognitive test cut scores, and number of affected domains was similar although not identical across the FHS and MCSA. Dementia risks were higher for amnestic profiles than for nonamnestic profiles, and for multidomain compared with single-domain profiles.
  
  
  CONCLUSIONS
  Cognitive domain subtypes, defined by neuropsychologically derived cut scores and number of low-performing domains, differ substantially in prognosis in a conceptually logical manner that was consistent between FHS and MCSA. Neuropsychological characterization of elderly persons without dementia provides valuable information about prognosis. The heterogeneity of risk of dementia cannot be captured concisely with one test or a single definition or cutpoint.
authors.affiliation: From the Department of Neurology, Mayo Alzheimer's Disease Research Center (D.S.K., B.F.B., R.C.P., R.O.R., W.A.R.), Division of Epidemiology, Department of Health Sciences Research (R.O.R., M.M. Mielke, W.A.R., R.C.P.), Division of Biostatistics and Bioinformatics, Department of Health Sciences Research (V.S.P., J.A., R.H.C.), and Department of Psychiatry and Psychology, Division of Neurocognitive Disorders (R.J.I., M.M. Machulda, J.F.), College of Medicine, Mayo Clinic, Rochester, MN; and Departments of Neurology (A.B., S.D., R.A., S.A., P.A.W., S.S.) and Biostatistics (A.B.), Boston University Schools of Medicine and Public Health, MA. knopman@mayo.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.affiliation: From the Department of Neurology, Mayo Alzheimer's Disease Research Center (D.S.K., B.F.B., R.C.P., R.O.R., W.A.R.), Division of Epidemiology, Department of Health Sciences Research (R.O.R., M.M. Mielke, W.A.R., R.C.P.), Division of Biostatistics and Bioinformatics, Department of Health Sciences Research (V.S.P., J.A., R.H.C.), and Department of Psychiatry and Psychology, Division of Neurocognitive Disorders (R.J.I., M.M. Machulda, J.F.), College of Medicine, Mayo Clinic, Rochester, MN; and Departments of Neurology (A.B., S.D., R.A., S.A., P.A.W., S.S.) and Biostatistics (A.B.), Boston University Schools of Medicine and Public Health, MA.
authors.forename: Alexa
authors.initials: A
authors.lastname: Beiser
authors.affiliation: From the Department of Neurology, Mayo Alzheimer's Disease Research Center (D.S.K., B.F.B., R.C.P., R.O.R., W.A.R.), Division of Epidemiology, Department of Health Sciences Research (R.O.R., M.M. Mielke, W.A.R., R.C.P.), Division of Biostatistics and Bioinformatics, Department of Health Sciences Research (V.S.P., J.A., R.H.C.), and Department of Psychiatry and Psychology, Division of Neurocognitive Disorders (R.J.I., M.M. Machulda, J.F.), College of Medicine, Mayo Clinic, Rochester, MN; and Departments of Neurology (A.B., S.D., R.A., S.A., P.A.W., S.S.) and Biostatistics (A.B.), Boston University Schools of Medicine and Public Health, MA.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Machulda
authors.affiliation: From the Department of Neurology, Mayo Alzheimer's Disease Research Center (D.S.K., B.F.B., R.C.P., R.O.R., W.A.R.), Division of Epidemiology, Department of Health Sciences Research (R.O.R., M.M. Mielke, W.A.R., R.C.P.), Division of Biostatistics and Bioinformatics, Department of Health Sciences Research (V.S.P., J.A., R.H.C.), and Department of Psychiatry and Psychology, Division of Neurocognitive Disorders (R.J.I., M.M. Machulda, J.F.), College of Medicine, Mayo Clinic, Rochester, MN; and Departments of Neurology (A.B., S.D., R.A., S.A., P.A.W., S.S.) and Biostatistics (A.B.), Boston University Schools of Medicine and Public Health, MA.
authors.forename: Julie
authors.initials: J
authors.lastname: Fields
authors.affiliation: From the Department of Neurology, Mayo Alzheimer's Disease Research Center (D.S.K., B.F.B., R.C.P., R.O.R., W.A.R.), Division of Epidemiology, Department of Health Sciences Research (R.O.R., M.M. Mielke, W.A.R., R.C.P.), Division of Biostatistics and Bioinformatics, Department of Health Sciences Research (V.S.P., J.A., R.H.C.), and Department of Psychiatry and Psychology, Division of Neurocognitive Disorders (R.J.I., M.M. Machulda, J.F.), College of Medicine, Mayo Clinic, Rochester, MN; and Departments of Neurology (A.B., S.D., R.A., S.A., P.A.W., S.S.) and Biostatistics (A.B.), Boston University Schools of Medicine and Public Health, MA.
authors.forename: Rosebud O
authors.initials: RO
authors.lastname: Roberts
authors.affiliation: From the Department of Neurology, Mayo Alzheimer's Disease Research Center (D.S.K., B.F.B., R.C.P., R.O.R., W.A.R.), Division of Epidemiology, Department of Health Sciences Research (R.O.R., M.M. Mielke, W.A.R., R.C.P.), Division of Biostatistics and Bioinformatics, Department of Health Sciences Research (V.S.P., J.A., R.H.C.), and Department of Psychiatry and Psychology, Division of Neurocognitive Disorders (R.J.I., M.M. Machulda, J.F.), College of Medicine, Mayo Clinic, Rochester, MN; and Departments of Neurology (A.B., S.D., R.A., S.A., P.A.W., S.S.) and Biostatistics (A.B.), Boston University Schools of Medicine and Public Health, MA.
authors.forename: V Shane
authors.initials: VS
authors.lastname: Pankratz
authors.affiliation: From the Department of Neurology, Mayo Alzheimer's Disease Research Center (D.S.K., B.F.B., R.C.P., R.O.R., W.A.R.), Division of Epidemiology, Department of Health Sciences Research (R.O.R., M.M. Mielke, W.A.R., R.C.P.), Division of Biostatistics and Bioinformatics, Department of Health Sciences Research (V.S.P., J.A., R.H.C.), and Department of Psychiatry and Psychology, Division of Neurocognitive Disorders (R.J.I., M.M. Machulda, J.F.), College of Medicine, Mayo Clinic, Rochester, MN; and Departments of Neurology (A.B., S.D., R.A., S.A., P.A.W., S.S.) and Biostatistics (A.B.), Boston University Schools of Medicine and Public Health, MA.
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Aakre
authors.affiliation: From the Department of Neurology, Mayo Alzheimer's Disease Research Center (D.S.K., B.F.B., R.C.P., R.O.R., W.A.R.), Division of Epidemiology, Department of Health Sciences Research (R.O.R., M.M. Mielke, W.A.R., R.C.P.), Division of Biostatistics and Bioinformatics, Department of Health Sciences Research (V.S.P., J.A., R.H.C.), and Department of Psychiatry and Psychology, Division of Neurocognitive Disorders (R.J.I., M.M. Machulda, J.F.), College of Medicine, Mayo Clinic, Rochester, MN; and Departments of Neurology (A.B., S.D., R.A., S.A., P.A.W., S.S.) and Biostatistics (A.B.), Boston University Schools of Medicine and Public Health, MA.
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Cha
authors.affiliation: From the Department of Neurology, Mayo Alzheimer's Disease Research Center (D.S.K., B.F.B., R.C.P., R.O.R., W.A.R.), Division of Epidemiology, Department of Health Sciences Research (R.O.R., M.M. Mielke, W.A.R., R.C.P.), Division of Biostatistics and Bioinformatics, Department of Health Sciences Research (V.S.P., J.A., R.H.C.), and Department of Psychiatry and Psychology, Division of Neurocognitive Disorders (R.J.I., M.M. Machulda, J.F.), College of Medicine, Mayo Clinic, Rochester, MN; and Departments of Neurology (A.B., S.D., R.A., S.A., P.A.W., S.S.) and Biostatistics (A.B.), Boston University Schools of Medicine and Public Health, MA.
authors.forename: Walter A
authors.initials: WA
authors.lastname: Rocca
authors.affiliation: From the Department of Neurology, Mayo Alzheimer's Disease Research Center (D.S.K., B.F.B., R.C.P., R.O.R., W.A.R.), Division of Epidemiology, Department of Health Sciences Research (R.O.R., M.M. Mielke, W.A.R., R.C.P.), Division of Biostatistics and Bioinformatics, Department of Health Sciences Research (V.S.P., J.A., R.H.C.), and Department of Psychiatry and Psychology, Division of Neurocognitive Disorders (R.J.I., M.M. Machulda, J.F.), College of Medicine, Mayo Clinic, Rochester, MN; and Departments of Neurology (A.B., S.D., R.A., S.A., P.A.W., S.S.) and Biostatistics (A.B.), Boston University Schools of Medicine and Public Health, MA.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Mielke
authors.affiliation: From the Department of Neurology, Mayo Alzheimer's Disease Research Center (D.S.K., B.F.B., R.C.P., R.O.R., W.A.R.), Division of Epidemiology, Department of Health Sciences Research (R.O.R., M.M. Mielke, W.A.R., R.C.P.), Division of Biostatistics and Bioinformatics, Department of Health Sciences Research (V.S.P., J.A., R.H.C.), and Department of Psychiatry and Psychology, Division of Neurocognitive Disorders (R.J.I., M.M. Machulda, J.F.), College of Medicine, Mayo Clinic, Rochester, MN; and Departments of Neurology (A.B., S.D., R.A., S.A., P.A.W., S.S.) and Biostatistics (A.B.), Boston University Schools of Medicine and Public Health, MA.
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.affiliation: From the Department of Neurology, Mayo Alzheimer's Disease Research Center (D.S.K., B.F.B., R.C.P., R.O.R., W.A.R.), Division of Epidemiology, Department of Health Sciences Research (R.O.R., M.M. Mielke, W.A.R., R.C.P.), Division of Biostatistics and Bioinformatics, Department of Health Sciences Research (V.S.P., J.A., R.H.C.), and Department of Psychiatry and Psychology, Division of Neurocognitive Disorders (R.J.I., M.M. Machulda, J.F.), College of Medicine, Mayo Clinic, Rochester, MN; and Departments of Neurology (A.B., S.D., R.A., S.A., P.A.W., S.S.) and Biostatistics (A.B.), Boston University Schools of Medicine and Public Health, MA.
authors.forename: Sherral
authors.initials: S
authors.lastname: Devine
authors.affiliation: From the Department of Neurology, Mayo Alzheimer's Disease Research Center (D.S.K., B.F.B., R.C.P., R.O.R., W.A.R.), Division of Epidemiology, Department of Health Sciences Research (R.O.R., M.M. Mielke, W.A.R., R.C.P.), Division of Biostatistics and Bioinformatics, Department of Health Sciences Research (V.S.P., J.A., R.H.C.), and Department of Psychiatry and Psychology, Division of Neurocognitive Disorders (R.J.I., M.M. Machulda, J.F.), College of Medicine, Mayo Clinic, Rochester, MN; and Departments of Neurology (A.B., S.D., R.A., S.A., P.A.W., S.S.) and Biostatistics (A.B.), Boston University Schools of Medicine and Public Health, MA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ivnik
authors.affiliation: From the Department of Neurology, Mayo Alzheimer's Disease Research Center (D.S.K., B.F.B., R.C.P., R.O.R., W.A.R.), Division of Epidemiology, Department of Health Sciences Research (R.O.R., M.M. Mielke, W.A.R., R.C.P.), Division of Biostatistics and Bioinformatics, Department of Health Sciences Research (V.S.P., J.A., R.H.C.), and Department of Psychiatry and Psychology, Division of Neurocognitive Disorders (R.J.I., M.M. Machulda, J.F.), College of Medicine, Mayo Clinic, Rochester, MN; and Departments of Neurology (A.B., S.D., R.A., S.A., P.A.W., S.S.) and Biostatistics (A.B.), Boston University Schools of Medicine and Public Health, MA.
authors.forename: Rhoda
authors.initials: R
authors.lastname: Au
authors.affiliation: From the Department of Neurology, Mayo Alzheimer's Disease Research Center (D.S.K., B.F.B., R.C.P., R.O.R., W.A.R.), Division of Epidemiology, Department of Health Sciences Research (R.O.R., M.M. Mielke, W.A.R., R.C.P.), Division of Biostatistics and Bioinformatics, Department of Health Sciences Research (V.S.P., J.A., R.H.C.), and Department of Psychiatry and Psychology, Division of Neurocognitive Disorders (R.J.I., M.M. Machulda, J.F.), College of Medicine, Mayo Clinic, Rochester, MN; and Departments of Neurology (A.B., S.D., R.A., S.A., P.A.W., S.S.) and Biostatistics (A.B.), Boston University Schools of Medicine and Public Health, MA.
authors.forename: Sanford
authors.initials: S
authors.lastname: Auerbach
authors.affiliation: From the Department of Neurology, Mayo Alzheimer's Disease Research Center (D.S.K., B.F.B., R.C.P., R.O.R., W.A.R.), Division of Epidemiology, Department of Health Sciences Research (R.O.R., M.M. Mielke, W.A.R., R.C.P.), Division of Biostatistics and Bioinformatics, Department of Health Sciences Research (V.S.P., J.A., R.H.C.), and Department of Psychiatry and Psychology, Division of Neurocognitive Disorders (R.J.I., M.M. Machulda, J.F.), College of Medicine, Mayo Clinic, Rochester, MN; and Departments of Neurology (A.B., S.D., R.A., S.A., P.A.W., S.S.) and Biostatistics (A.B.), Boston University Schools of Medicine and Public Health, MA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Wolf
authors.affiliation: From the Department of Neurology, Mayo Alzheimer's Disease Research Center (D.S.K., B.F.B., R.C.P., R.O.R., W.A.R.), Division of Epidemiology, Department of Health Sciences Research (R.O.R., M.M. Mielke, W.A.R., R.C.P.), Division of Biostatistics and Bioinformatics, Department of Health Sciences Research (V.S.P., J.A., R.H.C.), and Department of Psychiatry and Psychology, Division of Neurocognitive Disorders (R.J.I., M.M. Machulda, J.F.), College of Medicine, Mayo Clinic, Rochester, MN; and Departments of Neurology (A.B., S.D., R.A., S.A., P.A.W., S.S.) and Biostatistics (A.B.), Boston University Schools of Medicine and Public Health, MA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
authors.affiliation: From the Department of Neurology, Mayo Alzheimer's Disease Research Center (D.S.K., B.F.B., R.C.P., R.O.R., W.A.R.), Division of Epidemiology, Department of Health Sciences Research (R.O.R., M.M. Mielke, W.A.R., R.C.P.), Division of Biostatistics and Bioinformatics, Department of Health Sciences Research (V.S.P., J.A., R.H.C.), and Department of Psychiatry and Psychology, Division of Neurocognitive Disorders (R.J.I., M.M. Machulda, J.F.), College of Medicine, Mayo Clinic, Rochester, MN; and Departments of Neurology (A.B., S.D., R.A., S.A., P.A.W., S.S.) and Biostatistics (A.B.), Boston University Schools of Medicine and Public Health, MA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology / Q000523:psychology*; D003071:Cognition; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000453:epidemiology / Q000523:psychology*; D015331:Cohort Studies; D003704:Dementia / Q000175:diagnosis / Q000453:epidemiology / Q000523:psychology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D011159:Population Surveillance; D012307:Risk Factors