title: Amyloid burden, cortical thickness, and cognitive function in the Wisconsin Registry for Alzheimer's Prevention.
abstract: There is a growing interest in understanding how amyloid-β (Aβ) accumulation in preclinical Alzheimer's disease relates to brain morphometric measures and cognition. Existing investigations in this area have been primarily conducted in older cognitively-normal (CN) individuals. Therefore, not much is known about the associations between Aβ burden, cortical thickness, and cognition in midlife. We examined this question in 109, CN, late-middle-aged adults (mean age=60.72±5.65 years) from the Wisconsin Registry for Alzheimer's Prevention. They underwent Pittsburgh Compound B (PiB) and anatomical magnetic resonance (MR) imaging, and a comprehensive cognitive exam. Blinded visual rating of the PiB scans was used to classify the participants as Aβ+ or Aβ-. Cortical thickness measurements were derived from the MR images. The Aβ+ group exhibited significant thinning of the entorhinal cortex and accelerated age-associated thinning of the parahippocampal gyrus compared with the Aβ- group. The Aβ+ group also had numerically lower, but nonsignificant, test scores on all cognitive measures, and significantly faster age-associated cognitive decline on measures of Speed & Flexibility, Verbal Ability, and Visuospatial Ability. Our findings suggest that early Aβ aggregation is associated with deleterious changes in brain structure and cognitive function, even in midlife, and that the temporal lag between Aβ deposition and the inception of neurodegenerative/cognitive changes might be narrower than currently thought.
authors.affiliation: Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison WI ; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Doherty
authors.affiliation: Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison WI ; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Schultz
authors.affiliation: Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison WI ; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Oh
authors.affiliation: Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Koscik
authors.affiliation: Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI ; Department of Biostatistics & Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: N Maritza
authors.initials: NM
authors.lastname: Dowling
authors.affiliation: Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.affiliation: Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Dhanabalan
authors.initials: D
authors.lastname: Murali
authors.affiliation: Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison WI ; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI ; Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Gallagher
authors.affiliation: Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison WI ; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI ; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Carlsson
authors.affiliation: Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison WI ; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI ; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Bendlin
authors.affiliation: Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Asenath
authors.initials: A
authors.lastname: LaRue
authors.affiliation: Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI ; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI ; Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Hermann
authors.affiliation: Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI ; Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Howard A
authors.initials: HA
authors.lastname: Rowley
authors.affiliation: Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison WI ; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI ; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Asthana
authors.affiliation: Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI ; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Sager
authors.affiliation: Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI ; Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Brad T
authors.initials: BT
authors.lastname: Christian
authors.affiliation: Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison WI ; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI ; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Sterling C
authors.initials: SC
authors.lastname: Johnson
authors.affiliation: Geriatric Research Education and Clinical Center, William S. Middleton Memorial VA Hospital, Madison WI ; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI ; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Ozioma C
authors.initials: OC
authors.lastname: Okonkwo
keywords: Preclinical AD; amyloid; cognition; cortical thickness