Longitudinal cognitive and biomarker changes in dominantly inherited Alzheimer disease

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 es...