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Data from: Longitudinal cognitive and biomarker changes in dominantly inherited Alzheimer disease


McDade, Eric et al. (2019), Data from: Longitudinal cognitive and biomarker changes in dominantly inherited Alzheimer disease, Dryad, Dataset,


Objective: To assess the onset, sequence and rate of progression of comprehensive biomarker and clinical measures across the spectrum of Alzheimer disease using the Dominantly Inherited Alzheimer Network (DIAN) study and compare these to cross-sectional estimates. Methods: We conducted longitudinal clinical, cognitive, cerebrospinal fluid (CSF) and neuroimaging assessments (mean of 2.7 (+/- 1.1) visits) in 217 DIAN participants. Linear mixed effects models were used to assess changes in each measure relative to individuals’ estimated years to symptom onset and to compare mutation carriers and non-carriers. Results: Longitudinal amyloid-ß measures changed first (starting 25 years before estimated symptom onset), followed by declines in measures of cortical metabolism (approximately 7-10 years later), then cognition and hippocampal atrophy (approximately 20 years later). There were significant differences in the estimates of CSF p-tau181 and tau, with elevations from cross-sectional estimates preceeding longitudinal estimates by over 10 years; further, longitudinal estimates identifed a significant decline in CSF p-tau181 near symptom onset as opposed to continued elevations. Conclusion: These longitudinal estimates clarify the sequence and temporal dynamics of presymptomatic pathological changes in ADAD –information critical to a better understanding of the disease. The pattern of biomarker changes identified here also suggests that, if left unchecked, once β-amyloidosis begins additional non-β-amyloid-pathologies may begin to develop less than 10 years later, but more than 15 years before sympotom onset, an important consideration for interventions meant to alter the disease course.

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