Neuropsychological changes in asymptomatic persons with Alzheimer disease neuropathology.
Sarah E Monsell, Charles Mock, Jason Hassenstab, Catherine M Roe, Nigel J Cairns, John C Morris, Walter Kukull
Author Information
Sarah E Monsell: From the National Alzheimer's Coordinating Center (S.E.M., C.M., W.K.), University of Washington, Seattle; and Knight Alzheimer's Disease Research Center (J.H., C.M.R., N.J.C., J.C.M.), Department of Neurology, Washington University School of Medicine, St. Louis, MO. smonsell@u.washington.edu.
Charles Mock: From the National Alzheimer's Coordinating Center (S.E.M., C.M., W.K.), University of Washington, Seattle; and Knight Alzheimer's Disease Research Center (J.H., C.M.R., N.J.C., J.C.M.), Department of Neurology, Washington University School of Medicine, St. Louis, MO.
Jason Hassenstab: From the National Alzheimer's Coordinating Center (S.E.M., C.M., W.K.), University of Washington, Seattle; and Knight Alzheimer's Disease Research Center (J.H., C.M.R., N.J.C., J.C.M.), Department of Neurology, Washington University School of Medicine, St. Louis, MO.
Catherine M Roe: From the National Alzheimer's Coordinating Center (S.E.M., C.M., W.K.), University of Washington, Seattle; and Knight Alzheimer's Disease Research Center (J.H., C.M.R., N.J.C., J.C.M.), Department of Neurology, Washington University School of Medicine, St. Louis, MO.
Nigel J Cairns: From the National Alzheimer's Coordinating Center (S.E.M., C.M., W.K.), University of Washington, Seattle; and Knight Alzheimer's Disease Research Center (J.H., C.M.R., N.J.C., J.C.M.), Department of Neurology, Washington University School of Medicine, St. Louis, MO.
John C Morris: From the National Alzheimer's Coordinating Center (S.E.M., C.M., W.K.), University of Washington, Seattle; and Knight Alzheimer's Disease Research Center (J.H., C.M.R., N.J.C., J.C.M.), Department of Neurology, Washington University School of Medicine, St. Louis, MO.
Walter Kukull: From the National Alzheimer's Coordinating Center (S.E.M., C.M., W.K.), University of Washington, Seattle; and Knight Alzheimer's Disease Research Center (J.H., C.M.R., N.J.C., J.C.M.), Department of Neurology, Washington University School of Medicine, St. Louis, MO.
OBJECTIVE: To determine whether asymptomatic persons with Alzheimer disease (AD) neuropathologic change differ in the trajectory of their cognitive performance compared to asymptomatic persons without AD neuropathologic change. METHODS: Longitudinal performance on standard neuropsychological tests was examined in participants who died within 2 years of their last cognitive assessment and who were never diagnosed with mild cognitive impairment or dementia (Clinical Dementia Rating global score of 0 at all assessments). Using cognitive and neuropathologic data collected between 2005 and 2013 from the 34 National Institute on Aging-sponsored Alzheimer's Disease Centers, cognitive trajectories were compared for persons with and without evidence of AD neuropathologic change. We evaluated rates of decline in 4 domains (episodic memory, language, attention/working memory, executive function). The significance of the differences (β) in rates of decline was tested using linear regression, adjusting for age, education, sex, and other neuropathologic lesions. RESULTS: Participants who had low to high levels of AD neuropathologic change (n = 131) showed a greater rate of decline on the attention/working memory domain score (β = -0.11; 95% confidence interval = -0.19, -0.02; p = 0.02) when compared to 80 participants who died without evidence of AD neuropathologic change. CONCLUSIONS: Clinically normal individuals who come to autopsy with AD neuropathologic change exhibit subtle evidence of declining cognitive trajectories for attention/working memory.
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