title: Amyloid, neurodegeneration, and small vessel disease as predictors of dementia in the oldest-old.
abstract: OBJECTIVE
  To examine the association between brain structural changes and β-amyloid deposition, and incident dementia in 183 elderly subjects without dementia (mean age 85.5 years) 2 years later.
  
  
  METHODS
  Subjects had a brain structural MRI scan and a PET scan with (11)C-labeled Pittsburgh compound B (PiB) in 2009, and were evaluated clinically in 2011.
  
  
  RESULTS
  At baseline evaluation, of the 183 participants (146 cognitively normal [CN]); 37 mild cognitive impairment [MCI]), 139 (76%) were PiB+, had small hippocampal volume (<25th percentile), or had high white matter lesion (WML) volume (>75th percentile). Two years later, 111 (61%) were classified as CN, 51 (28%) as MCI, and 21 (11%) as dementia. At baseline, 51% of the CN participants and 67.5% of the MCI cases were PiB+. Thirty percent of the CN and 51% of the MCI cases had small hippocampi, and 24% of the CN and 40.5% of the MCI cases had abnormal WMLs. Of the 21 participants who progressed to dementia, 20 (95%) had at least one imaging abnormality. Only 3 (14%) were only PiB+, 1 (5%) had only small hippocampi, 1 (5%) had only WMLs, 1 (5%) was biomarker negative, and the other 16 had various pairs of imaging abnormalities. Continuous variables of PiB retention, left and right hippocampal volume, and WML volume were independent predictors of dementia in a logistic regression analysis controlling for age, sex, education level, and Mini-Mental State Examination scores.
  
  
  CONCLUSIONS
  The prevalence of β-amyloid deposition, neurodegeneration (i.e., hippocampal atrophy), and small vessel disease (WMLs) is high in CN older individuals and in MCI. A combination of 2 or 3 of these factors is a powerful predictor of short-term incidence of dementia.
authors.affiliation: From the Departments of Neurology (O.L.L., J.T.B., B.S., M.I., E.M.), Psychiatry (O.L.L., W.E.K., J.T.B., H.J.A.), Radiology (C.M., R.L.C., J.P., A.C.), Pharmaceutical Sciences (C.M.), Psychology (J.T.B.), Biostatistics (L.W.), and Epidemiology, Graduate School of Public Health (L.H.K.), University of Pittsburgh, School of Medicine, PA; and Department of Neurology (S.T.D.), University of Virginia School of Medicine, Charlottesville. lopezol@upmc.edu.
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Lopez
authors.affiliation: From the Departments of Neurology (O.L.L., J.T.B., B.S., M.I., E.M.), Psychiatry (O.L.L., W.E.K., J.T.B., H.J.A.), Radiology (C.M., R.L.C., J.P., A.C.), Pharmaceutical Sciences (C.M.), Psychology (J.T.B.), Biostatistics (L.W.), and Epidemiology, Graduate School of Public Health (L.H.K.), University of Pittsburgh, School of Medicine, PA; and Department of Neurology (S.T.D.), University of Virginia School of Medicine, Charlottesville.
authors.forename: William E
authors.initials: WE
authors.lastname: Klunk
authors.affiliation: From the Departments of Neurology (O.L.L., J.T.B., B.S., M.I., E.M.), Psychiatry (O.L.L., W.E.K., J.T.B., H.J.A.), Radiology (C.M., R.L.C., J.P., A.C.), Pharmaceutical Sciences (C.M.), Psychology (J.T.B.), Biostatistics (L.W.), and Epidemiology, Graduate School of Public Health (L.H.K.), University of Pittsburgh, School of Medicine, PA; and Department of Neurology (S.T.D.), University of Virginia School of Medicine, Charlottesville.
authors.forename: Chester
authors.initials: C
authors.lastname: Mathis
authors.affiliation: From the Departments of Neurology (O.L.L., J.T.B., B.S., M.I., E.M.), Psychiatry (O.L.L., W.E.K., J.T.B., H.J.A.), Radiology (C.M., R.L.C., J.P., A.C.), Pharmaceutical Sciences (C.M.), Psychology (J.T.B.), Biostatistics (L.W.), and Epidemiology, Graduate School of Public Health (L.H.K.), University of Pittsburgh, School of Medicine, PA; and Department of Neurology (S.T.D.), University of Virginia School of Medicine, Charlottesville.
authors.forename: Rhaven L
authors.initials: RL
authors.lastname: Coleman
authors.affiliation: From the Departments of Neurology (O.L.L., J.T.B., B.S., M.I., E.M.), Psychiatry (O.L.L., W.E.K., J.T.B., H.J.A.), Radiology (C.M., R.L.C., J.P., A.C.), Pharmaceutical Sciences (C.M.), Psychology (J.T.B.), Biostatistics (L.W.), and Epidemiology, Graduate School of Public Health (L.H.K.), University of Pittsburgh, School of Medicine, PA; and Department of Neurology (S.T.D.), University of Virginia School of Medicine, Charlottesville.
authors.forename: Julie
authors.initials: J
authors.lastname: Price
authors.affiliation: From the Departments of Neurology (O.L.L., J.T.B., B.S., M.I., E.M.), Psychiatry (O.L.L., W.E.K., J.T.B., H.J.A.), Radiology (C.M., R.L.C., J.P., A.C.), Pharmaceutical Sciences (C.M.), Psychology (J.T.B.), Biostatistics (L.W.), and Epidemiology, Graduate School of Public Health (L.H.K.), University of Pittsburgh, School of Medicine, PA; and Department of Neurology (S.T.D.), University of Virginia School of Medicine, Charlottesville.
authors.forename: James T
authors.initials: JT
authors.lastname: Becker
authors.affiliation: From the Departments of Neurology (O.L.L., J.T.B., B.S., M.I., E.M.), Psychiatry (O.L.L., W.E.K., J.T.B., H.J.A.), Radiology (C.M., R.L.C., J.P., A.C.), Pharmaceutical Sciences (C.M.), Psychology (J.T.B.), Biostatistics (L.W.), and Epidemiology, Graduate School of Public Health (L.H.K.), University of Pittsburgh, School of Medicine, PA; and Department of Neurology (S.T.D.), University of Virginia School of Medicine, Charlottesville.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Aizenstein
authors.affiliation: From the Departments of Neurology (O.L.L., J.T.B., B.S., M.I., E.M.), Psychiatry (O.L.L., W.E.K., J.T.B., H.J.A.), Radiology (C.M., R.L.C., J.P., A.C.), Pharmaceutical Sciences (C.M.), Psychology (J.T.B.), Biostatistics (L.W.), and Epidemiology, Graduate School of Public Health (L.H.K.), University of Pittsburgh, School of Medicine, PA; and Department of Neurology (S.T.D.), University of Virginia School of Medicine, Charlottesville.
authors.forename: Beth
authors.initials: B
authors.lastname: Snitz
authors.affiliation: From the Departments of Neurology (O.L.L., J.T.B., B.S., M.I., E.M.), Psychiatry (O.L.L., W.E.K., J.T.B., H.J.A.), Radiology (C.M., R.L.C., J.P., A.C.), Pharmaceutical Sciences (C.M.), Psychology (J.T.B.), Biostatistics (L.W.), and Epidemiology, Graduate School of Public Health (L.H.K.), University of Pittsburgh, School of Medicine, PA; and Department of Neurology (S.T.D.), University of Virginia School of Medicine, Charlottesville.
authors.forename: Ann
authors.initials: A
authors.lastname: Cohen
authors.affiliation: From the Departments of Neurology (O.L.L., J.T.B., B.S., M.I., E.M.), Psychiatry (O.L.L., W.E.K., J.T.B., H.J.A.), Radiology (C.M., R.L.C., J.P., A.C.), Pharmaceutical Sciences (C.M.), Psychology (J.T.B.), Biostatistics (L.W.), and Epidemiology, Graduate School of Public Health (L.H.K.), University of Pittsburgh, School of Medicine, PA; and Department of Neurology (S.T.D.), University of Virginia School of Medicine, Charlottesville.
authors.forename: Milos
authors.initials: M
authors.lastname: Ikonomovic
authors.affiliation: From the Departments of Neurology (O.L.L., J.T.B., B.S., M.I., E.M.), Psychiatry (O.L.L., W.E.K., J.T.B., H.J.A.), Radiology (C.M., R.L.C., J.P., A.C.), Pharmaceutical Sciences (C.M.), Psychology (J.T.B.), Biostatistics (L.W.), and Epidemiology, Graduate School of Public Health (L.H.K.), University of Pittsburgh, School of Medicine, PA; and Department of Neurology (S.T.D.), University of Virginia School of Medicine, Charlottesville.
authors.forename: Eric
authors.initials: E
authors.lastname: McDade
authors.affiliation: From the Departments of Neurology (O.L.L., J.T.B., B.S., M.I., E.M.), Psychiatry (O.L.L., W.E.K., J.T.B., H.J.A.), Radiology (C.M., R.L.C., J.P., A.C.), Pharmaceutical Sciences (C.M.), Psychology (J.T.B.), Biostatistics (L.W.), and Epidemiology, Graduate School of Public Health (L.H.K.), University of Pittsburgh, School of Medicine, PA; and Department of Neurology (S.T.D.), University of Virginia School of Medicine, Charlottesville.
authors.forename: Steven T
authors.initials: ST
authors.lastname: DeKosky
authors.affiliation: From the Departments of Neurology (O.L.L., J.T.B., B.S., M.I., E.M.), Psychiatry (O.L.L., W.E.K., J.T.B., H.J.A.), Radiology (C.M., R.L.C., J.P., A.C.), Pharmaceutical Sciences (C.M.), Psychology (J.T.B.), Biostatistics (L.W.), and Epidemiology, Graduate School of Public Health (L.H.K.), University of Pittsburgh, School of Medicine, PA; and Department of Neurology (S.T.D.), University of Virginia School of Medicine, Charlottesville.
authors.forename: Lisa
authors.initials: L
authors.lastname: Weissfeld
authors.affiliation: From the Departments of Neurology (O.L.L., J.T.B., B.S., M.I., E.M.), Psychiatry (O.L.L., W.E.K., J.T.B., H.J.A.), Radiology (C.M., R.L.C., J.P., A.C.), Pharmaceutical Sciences (C.M.), Psychology (J.T.B.), Biostatistics (L.W.), and Epidemiology, Graduate School of Public Health (L.H.K.), University of Pittsburgh, School of Medicine, PA; and Department of Neurology (S.T.D.), University of Virginia School of Medicine, Charlottesville.
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
mesh_terms: D000369:Aged, 80 and over; D000682:Amyloid / Q000378:metabolism*; D000814:Aniline Compounds; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D059345:Cerebral Small Vessel Diseases / Q000503:physiopathology*; D060825:Cognitive Dysfunction / Q000175:diagnosis; D003704:Dementia / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D015577:Geriatric Assessment; D020441:Ginkgo biloba; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D019636:Neurodegenerative Diseases / Q000503:physiopathology*; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts / Q000627:therapeutic use; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D000814:Aniline Compounds; D010936:Plant Extracts; D013844:Thiazoles