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High amyloid load is associated with episodic memory decline and incident mild cognitive impairment in middle-aged adults in the wisconsin registry for Alzheimer’s prevention (WRAP)

  • Lindsay R. Clark
    Affiliations
    Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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  • Annie M. Racine
    Affiliations
    Institute on Aging, University of Wisconsin, Madison, WI, USA

    Neuroscience Training Program, University of Wisconsin, Madison, WI, USA

    Neuroscience and Public Policy Program, University of Wisconsin, Madison, WI, USA
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  • Rebecca L. Koscik
    Affiliations
    Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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  • Ozioma C. Okonkwo
    Affiliations
    Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Wisconsin Alzheimer's Institute, 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
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  • Christopher R. Nicholas
    Affiliations
    Wisconsin 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
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  • Cynthia M. Carlsson
    Affiliations
    Wisconsin 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
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  • Sanjay Asthana
    Affiliations
    Wisconsin Alzheimer's Institute, 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

    University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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  • Mark A. Sager
    Affiliations
    Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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  • Bradley T. Christian
    Affiliations
    Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI, USA

    University of Wisconsin, Madison, Madison, WI, USA
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  • Sterling C. Johnson
    Affiliations
    Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Wisconsin Alzheimer's Institute, 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
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      Background

      This study investigated the relationship between amyloid burden and cognition in a cohort of late middle-aged participants enriched for family history of Alzheimer’s disease (AD) enrolled in the WRAP Study.

      Methods

      182 WRAP participants completed a PET-PiB scan approximately 5 years after baseline cognitive testing. A composite cortical measure of amyloid burden was calculated and a DVR cutpoint of 1.12 (derived from an ROC analysis) was used to classify participants as PiB+ (n= 41) or PiB- (n=141). Additionally, participants were classified as having psychometric mild cognitive impairment (MCI; n=37) if at least two neuropsychological performances within a cognitive domain or least one measure in three cognitive domains (immediate memory, delayed memory, executive functioning) were ≤ 1.5 standard deviations below the mean of a robust normative group. Rates of PiB positivity by cognitive group (MCI or cognitively normal [CN]) were compared and a linear mixed-effects regression model examined longitudinal trajectories on the Rey Auditory Verbal Learning Test (RAVLT) by PiB and MCI status. The model included fixed effects for amyloid group (PiB+/PiB-), amyloid group x time, age, and gender, and random effects for participant and time. Outcome variables were either RAVLT total trials 1-5 or RAVLT delayed recall raw scores.

      Results

      The MCI group had a greater proportion of PiB+ participants compared with the CN group (X2=4.23; p<.05; see Figure 1). Linear mixed-effects models revealed a significant interaction between amyloid group and time on RAVLT delayed recall (β = -.34, p<.05), indicating steeper decline in the PiB+ group (see Figure 2). Other significant fixed effects included age (β =-.08, p<.01) and female sex (β =2.14, p<.001). There was a trend in the same direction for the amyloid by time interaction on RAVLT total trials (β = -.84, p=.08; see Figure 2). Models were re-run in the MCI group only and again indicated a significant interaction between amyloid group and time on RAVLT delayed recall (β =-1.05, p<.01), but not on RAVLT total trials (see Figure 3).

      Conclusions