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

Clark, L.; Berman, S.; Norton, D.; Koscik, R.; Jonaitis, E.; Blennow, K.; Bendlin, B.; Asthana, S.; Johnson, S.; Zetterberg, H.; Carlsson, C.

doi:10.1101/220756

bioRxiv · 10.1101/220756

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

Clark, L.·Berman, S.·Norton, D.·Koscik, R.·Jonaitis, E.·Blennow, K.·Bendlin, B.·Asthana, S.·Johnson, S.·Zetterberg, H.·Carlsson, C.

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Abstract

ObjectiveCompare cognitive and hippocampal volume (HCV) trajectories in asymptomatic middle-aged and older adults with positive cerebrospinal fluid (CSF) markers of {beta}-amyloid (A{beta}) or tau to adults without an AD-associated biomarker profile.\n\nMethod392 adults enrolled in a longitudinal cohort study (Wisconsin Registry for Alzheimers Prevention or Wisconsin Alzheimers Disease Research Center) completed a lumbar puncture and at least two biennial or annual neuropsychological evaluations. Cutoffs for A{beta}42, 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) and mixed-effects regression analyses tested linear and quadratic interactions of biomarker group x age at each visit on cognitive and HCV outcomes.\n\nResults215 participants (69%) were biomarker negative (preclinical AD Stage 0), 46 (15%) were A{beta}+ only (preclinical AD Stage 1), 25 (8%) were A{beta}+ 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 non-linear 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.\n\nConclusionIn an asymptomatic at-risk cohort, elevated CSF A{beta} (with or without elevated tau) was associated with greater rates of cognitive decline, with the specific pattern of decline varying across cognitive measures.

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Clark, L., Berman, S., Norton, D., Koscik, R., Jonaitis, E., Blennow, K., Bendlin, B., Asthana, S., Johnson, S., Zetterberg, H., Carlsson, C.. 2017-11-16. Age-accelerated cognitive decline in asymptomatic adults with CSF β-amyloid. https://doi.org/10.1101/220756

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