Age-accelerated cognitive decline in asymptomatic adults with CSF β-amyloid


Clark LR, Berman SE, Norton D, Koscik RL, Jonaitis EM, Blennow K, Bendlin BB, Asthana S, Johnson SC, Zetterberg H, Carlsson CM.

Neurology. 2018 Mar 9. pii: 10.1212/WNL.0000000000005291. [Epub ahead of print]

Abstract

Objective Compare cognitive and hippocampal volume trajectories in asymptomatic middle-aged and older adults with positive CSF markers of β-amyloid (Aβ) or tau to adults without an Alzheimer disease (AD)-associated biomarker profile. Methods Three hundred ninety-two adults enrolled in a longitudinal cohort study (Wisconsin Registry for Alzheimer’s Prevention or Wisconsin Alzheimer’s Disease Research Center) completed a lumbar puncture and at least 2 biennial or annual neuropsychological evaluations. Cutoffs for Aβ42, total tau, and phosphorylated tau were developed via receiver operating characteristic curve analyses on a sample of 78 participants (38 dementia, 40 controls). These cutoffs were applied to a separate sample of 314 cognitively healthy adults (mean age at CSF collection = 61.5 years), and mixed-effects regression analyses tested linear and quadratic interactions of biomarker group × age at each visit on cognitive and hippocampal volume outcomes. Results Two hundred fifteen participants (69%) were biomarker negative (preclinical AD stage 0), 46 (15%) were Aβ+ only (preclinical AD stage 1), 25 (8%) were Aβ+ and tau+ (preclinical AD stage 2), and 28 (9%) were tau+ only. Both stage 1 and stage 2 groups exhibited greater rates of linear decline on story memory and processing speed measures, and nonlinear decline on list-learning and set-shifting measures compared to stage 0. The tau+ only group did not significantly differ from stage 0 in rates of cognitive decline. Conclusion In an asymptomatic at-risk cohort, elevated CSF Aβ (with or without elevated tau) was associated with greater rates of cognitive decline, with the specific pattern of decline varying across cognitive measures.

Contributing Lab Members