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bioRxiv · 10.1101/229062

Modifiable risk factors moderate the relationship between amyloid and cognition in midlife

Clark, L. R.·Koscik, R. L.·Allison, S. L.·Berman, S. E.·Carlsson, C. M.·Norton, D. L.·Bendlin, B. B.·Asthana, S.·Betthauser, T. J.·Christian, B. T.·Johnson, S. C.
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Abstract

Although evidence suggests a relationship between elevated beta-amyloid and cognitive decline, approximately 30% of older adults with positive markers of amyloid remain cognitively healthy. Our objective was to test if the presence of modifiable risk factors (i.e., central obesity, hypertension, and depressive symptoms) moderated the relationship between amyloid and longitudinal cognitive performance. Data were from 207 adults (140 females; age range=40-70) enriched for Alzheimers disease risk (73% parental history of Alzheimers disease) enrolled in the Wisconsin Registry for Alzheimers Prevention study. Participants completed at least two neuropsychological evaluations and one biomarker visit ([C11] Pittsburgh Compound B PET scan or lumbar puncture). Participants were characterized as high or low on amyloid using cutoffs developed for [C11] Pittsburgh Compound B-PET distribution volume ratio or CSF amyloid beta 1-42 values. Participants were also coded as high or low risk on obesity, hypertension, and depressive symptoms. Linear mixed effects regression models examined three-way interactions between modifiable risk factor status x amyloid group x age at each study visit on longitudinal Verbal Learning & Memory and Speed & Flexibility factor scores. Results indicated that the relationship between beta-amyloid and Verbal Learning & Memory decline was associated with hypertension status (Likelihood ratio test for significance of hypertension status age x amyloid status x visit age interaction term;{chi} 2 (1) = 5.28, p = .02). The relationship between beta-amyloid and Speed & Flexibility decline was associated with depression status (Likelihood ratio test for significance of amyloid status x depression status x visit age interaction term;{chi} 2 (1) = 7.10, p = .03). The presence of obesity did not significantly moderate the relationship between beta-amyloid status and cognitive performance, although the direction of relationship was similar to above relationships (Likelihood ratio test for significance of obesity status x amyloid status x visit age interaction term;{chi} 2 (1) = 1.52, p = .21). In this at-risk for Alzheimers disease cohort, the modifiable risk factors of hypertension and depression significantly moderated the relationship between beta-amyloid and cognitive decline. Identification and modification of these risk factors in late middle age may slow the effect of amyloid on the progression of cognitive symptoms.

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Clark, L. R., Koscik, R. L., Allison, S. L., Berman, S. E., Carlsson, C. M., Norton, D. L., Bendlin, B. B., Asthana, S., Betthauser, T. J., Christian, B. T., Johnson, S. C.. 2017-12-04. Modifiable risk factors moderate the relationship between amyloid and cognition in midlife. https://doi.org/10.1101/229062

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