authors: Wang F, Gordon BA, Ryman DC, Ma S, Xiong C, Hassenstab J, Goate A, Fagan AM, Cairns NJ, Marcus DS, McDade E, Ringman JM, Graff-Radford NR, Ghetti B, Farlow MR, Sperling R, Salloway S, Schofield PR, Masters CL, Martins RN, Rossor MN, Jucker M, Danek A, Förster S, Lane CA, Morris JC, Benzinger TL, Bateman RJ summary/abstract:
To investigate the associations of cerebral amyloidosis with concurrent cognitive performance and with longitudinal cognitive decline in asymptomatic and symptomatic stages of autosomal dominant Alzheimer disease (ADAD).
Two hundred sixty-three participants enrolled in the Dominantly Inherited Alzheimer Network observational study underwent neuropsychological evaluation as well as PET scans with Pittsburgh compound B. One hundred twenty-one participants completed at least 1 follow-up neuropsychological evaluation. Four composite cognitive measures representing global cognition, episodic memory, language, and working memory were generated using z scores from a battery of 13 standard neuropsychological tests. General linear mixed-effects models were used to investigate the relationship between baseline cerebral amyloidosis and baseline cognitive performance and whether baseline cerebral amyloidosis predicts cognitive change 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 ε4 allelic status, and education.
In asymptomatic mutation carriers, amyloid burden was not associated with baseline cognitive functioning but was significantly predictive of longitudinal decline in episodic memory. In symptomatic mutation carriers, cerebral amyloidosis was correlated with worse baseline performance in multiple cognitive composites and predicted greater decline over time in global cognition, working memory, and Mini-Mental State Examination.
Cerebral amyloidosis predicts longitudinal episodic memory decline in presymptomatic ADAD and multidomain cognitive decline in symptomatic ADAD. These findings imply that amyloidosis in the brain is an indicator of early cognitive decline and provides a useful outcome measure for early assessment and prevention treatment trials.organization:
Washington University School of Medicine, USA; University of Pittsburgh, USA; Mayo Clinic, USA; Indiana University School of Medicine,USA; Massachusetts General Hospital,USA; Brown University, Australia; University of New South Wales, Australia; University of Melbourne, Australia; School of Exercise, Australia; UCL Institute of Neurology, UK; Hertie Institute for Clinical Brain Research, Germany; Technische Universität München,Germany; Xuan Wu Hospital, China DOI:
10.1212/WNL.0000000000001903 full text source