Neuropsychological changes in asymptomatic persons with Alzheimer disease neuropathology

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 (b) 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 5131) showed a greater rate of decline on the attention/working memory domain score (b 5 20.11; 95% confidence interval 5 20.19, 20.02; p 5 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.