Cerebral amyloidosis associated with cognitive decline in autosomal dominant Alzheimer disease

Objective: To investigate the associations of cerebral amyloidosiswith concurrent cognitiveperformance and with longitudinal cognitive declinein asymptomatic and symptomatic stages of autosomal dominant Alzheimer disease (ADAD). Methods: Two hundred sixty-three participants enrolled in the Dominantly Inherited Alzheimer Network observational study underwent neuropsychologicalevaluation as well as PET scans with Pittsburgh compound B. One hundred twenty-one participants completed at least 1 follow-up neuropsychologicalevaluation. Four composite cognitivemeasures representing global cognition, episodic memory, language, and working memory were generated using z scores from a battery of 13 standard neuropsychologicaltests. General linear mixed-effects models were used to investigate the relationship between baseline cerebral amyloidosisand baseline cognitiveperformance and whether baseline cerebral amyloidosispredicts cognitivechange over time (mean follow-up 2.32 years ± 0.92, range 0.89–4.19) after controlling for estimated years from expected symptom onset, APOE e4 allelic status, and education. Results: In asymptomatic mutation carriers, amyloid burden was not associated with baseline cognitivefunctioning but was significantly predictive of longitudinal declinein episodic memory. In symptomatic mutation carriers, cerebral amyloidosiswas correlated with worse baseline performance in multiple cognitivecomposites and predicted greater declineover time in global cognition, working memory, and Mini-Mental State Examination. Conclusions: Cerebral amyloidosispredicts longitudinal episodic memory declinein presymptomatic ADAD and multidomain cognitive declinein symptomatic ADAD. These findings imply that amyloidosisin the brain is an indicator of early cognitive declineand provides a useful outcome measure for early assessment and prevention treatmenttrials.