title: Amyloid burden, neuronal function, and cognitive decline in middle-aged adults at risk for Alzheimer's disease.
abstract: The relative influence of amyloid burden, neuronal structure and function, and prior cognitive performance on prospective memory decline among asymptomatic late middle-aged individuals at risk for Alzheimer's disease (AD) is currently unknown. We investigated this using longitudinal cognitive data from 122 middle-aged adults (21 "Decliners" and 101 "Stables") enrolled in the Wisconsin Registry for Alzheimer's Prevention who underwent multimodality neuroimaging [11C-Pittsburgh Compound B (PiB), 18F-fluorodeoxyglucose (FDG), and structural/functional magnetic resonance imaging (fMRI)] 5.7 ± 1.4 years (range = 2.9-8.9) after their baseline cognitive assessment. Covariate-adjusted regression analyses revealed that the only imaging measure that significantly distinguished Decliners from Stables (p = .027) was a Neuronal Function composite derived from FDG and fMRI. In contrast, several cognitive measures, especially those that tap episodic memory, significantly distinguished the groups (p's<.05). Complementary receiver operating characteristic curve analyses identified the Brief Visuospatial Memory Test-Revised (BVMT-R) Total (.82 ± .05, p < .001), the BVMT-R Delayed Recall (.73 ± .06, p = .001), and the Reading subtest from the Wide-Range Achievement Test-III (.72 ± .06, p = .002) as the top three measures that best discriminated the groups. These findings suggest that early memory test performance might serve a more clinically pivotal role in forecasting future cognitive course than is currently presumed.
authors.affiliation: 1 Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison, Wisconsin.
authors.forename: Ozioma C
authors.initials: OC
authors.lastname: Okonkwo
authors.affiliation: 1 Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison, Wisconsin.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Oh
authors.affiliation: 3 Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Koscik
authors.affiliation: 3 Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Erin
authors.initials: E
authors.lastname: Jonaitis
authors.affiliation: 1 Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison, Wisconsin.
authors.forename: Caitlin A
authors.initials: CA
authors.lastname: Cleary
authors.affiliation: 2 Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: N Maritza
authors.initials: NM
authors.lastname: Dowling
authors.affiliation: 1 Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison, Wisconsin.
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Bendlin
authors.affiliation: 3 Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Asenath
authors.initials: A
authors.lastname: Larue
authors.affiliation: 2 Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Hermann
authors.affiliation: 6 Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.affiliation: 6 Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Dhanabalan
authors.initials: D
authors.lastname: Murali
authors.affiliation: 2 Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Howard A
authors.initials: HA
authors.lastname: Rowley
authors.affiliation: 1 Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison, Wisconsin.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Carlsson
authors.affiliation: 1 Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison, Wisconsin.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Gallagher
authors.affiliation: 1 Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison, Wisconsin.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Asthana
authors.affiliation: 2 Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Sager
authors.affiliation: 2 Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Brad T
authors.initials: BT
authors.lastname: Christian
authors.affiliation: 1 Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison, Wisconsin.
authors.forename: Sterling C
authors.initials: SC
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism*; D000704:Analysis of Variance; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D012372:ROC Curve; D011877:Radionuclide Imaging; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000682:Amyloid; D053327:Apolipoprotein E4; D010100:Oxygen