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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.
Glossary
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- HCV=
- hippocampal volume;
- LM=
- Logical Memory;
- LP=
- lumbar puncture;
- MCI=
- mild cognitive impairment;
- p-tau=
- phosphorylated tau;
- RAVLT=
- Rey Auditory Verbal Learning Test;
- TMT-B=
- Trail Making Test Part B;
- t-tau=
- total tau;
- WADRC=
- Wisconsin Alzheimer's Disease Research Center;
- WRAP=
- Wisconsin Registry for Alzheimer's Prevention
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received July 12, 2017.
- Accepted in final form January 8, 2018.
- © 2018 American Academy of Neurology
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