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. 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.
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.
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