Beta-amyloid and cognitive decline in late middle age: Findings from the Wisconsin Registry for Alzheimer's Prevention study

Lindsay R Clark; Annie M Racine; Rebecca L Koscik; Ozioma C Okonkwo; Corinne D Engelman; Cynthia M Carlsson; Sanjay Asthana; Barbara B Bendlin; Rick Chappell; Christopher R Nicholas; Howard A Rowley; Jennifer M Oh; Bruce P Hermann; Mark A Sager; Bradley T Christian; Sterling C Johnson

doi:10.1016/j.jalz.2015.12.009

Beta-amyloid and cognitive decline in late middle age: Findings from the Wisconsin Registry for Alzheimer's Prevention study

Alzheimers Dement. 2016 Jul;12(7):805-14. doi: 10.1016/j.jalz.2015.12.009. Epub 2016 Jan 21.

Authors

Lindsay R Clark¹, Annie M Racine², Rebecca L Koscik³, Ozioma C Okonkwo⁴, Corinne D Engelman⁵, Cynthia M Carlsson⁴, Sanjay Asthana⁴, Barbara B Bendlin⁶, Rick Chappell⁷, Christopher R Nicholas⁶, Howard A Rowley⁸, Jennifer M Oh⁶, Bruce P Hermann⁹, Mark A Sager³, Bradley T Christian¹⁰, Sterling C Johnson¹¹

Affiliations

¹ Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. Electronic address: lrclark@medicine.wisc.edu.
² Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Institute on Aging, University of Wisconsin-Madison, Madison, WI, USA; Neuroscience and Public Policy Program, University of Wisconsin-Madison, Madison, WI, USA.
³ Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
⁴ Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA.
⁵ Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
⁶ Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA.
⁷ Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA; Department of Statistics, University of Wisconsin-Madison, Madison, WI, USA.
⁸ Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
⁹ Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
¹⁰ Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI, USA; Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
¹¹ Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA; Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI, USA.

Abstract

Introduction: The present study investigated the relationship between beta-amyloid (Aβ) and cognition in a late middle-aged cohort at risk for Alzheimer's disease (AD).

Methods: One eighty-four participants (mean age = 60; 72% parental history of AD) completed a [C-11]Pittsburgh compound B positron emission tomography scan and serial cognitive evaluations. A global measure of Aβ burden was calculated, and composite scores assessing learning, delayed memory, and executive functioning were computed.

Results: Higher Aβ was associated with classification of psychometric mild cognitive impairment (MCI) at follow-up (P < .01). Linear mixed effects regression results indicated higher Aβ was associated with greater rates of decline in delayed memory (P < .01) and executive functioning (P < .05). Apolipoprotein E (APOE) ε4 status moderated the relationship between Aβ and cognitive trajectories (P values <.01).

Discussion: In individuals at risk for AD, greater Aβ in late middle age is associated with increased likelihood of MCI at follow-up and steeper rates of cognitive decline.

Keywords: APOE; Alzheimer's disease; Amyloid imaging; Cognition; Mild cognitive impairment; Preclinical Alzheimer's disease.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Aged
Alzheimer Disease / metabolism*
Amyloid beta-Peptides / metabolism*
Brain / metabolism
Cognitive Dysfunction / metabolism*
Disease Progression
Female
Humans
Male
Neuropsychological Tests / statistics & numerical data
Positron-Emission Tomography / methods
Prodromal Symptoms
Registries
Wisconsin

Substances

Amyloid beta-Peptides

Abstract

Publication types

MeSH terms

Substances

Grants and funding