Data from: 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
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.