Longitudinal Accumulation of Cerebral Microhemorrhages in Dominantly Inherited Alzheimer Disease

JOSEPH-MATHURIN, NELLY; WANG, GUOQIAO; KANTARCI, KEJAL; JACK, CLIFFORD R.; MCDADE, ERIC; HASSENSTAB, JASON; BLAZEY, TYLER M.; GORDON, BRIAN A.; SU, YI; CHEN, GENGSHENG; MASSOUMZADEH, PARINAZ; HORNBECK, RUSS C.; ALLEGRI, RICARDO F.; ANCES, BEAU M.; BERMAN, SARAH B.; BRICKMAN, ADAM M.; BROOKS, WILLIAM S.; CASH, DAVID M.; CHHATWAL, JASMEER P.; CHUI, HELENA C.; CORREIA, STEPHEN; CRUCHAGA, CARLOS; FARLOW, MARTIN R.; FOX, NICK C.; FULHAM, MICHAEL; GHETTI, BERNARDINO; GRAFF-RADFORD, NEILL R.; JOHNSON, KEITH A.; KARCH, CELESTE M.; LASKE, CHRISTOPH; LEE, ATHENE K.W.; LEVIN, JOHANNES; MASTERS, COLIN L.; NOBLE, JAMES M.; O'CONNOR, ANTOINETTE; PERRIN, RICHARD J.; PREBOSKE, GREGORY M.; RINGMAN, JOHN M.; ROWE, CHRISTOPHER C.; SALLOWAY, STEPHEN; SAYKIN, ANDREW J.; SCHOFIELD, PETER R.; SHIMADA, HIROYUKI; SHOJI, MIKIO; SUZUKI, KAZUSHI; VILLEMAGNE, VICTOR L.; XIONG, CHENGJIE; YAKUSHEV, IGOR; MORRIS, JOHN C.; BATEMAN, RANDALL J.; BENZINGER, TAMMIE L.S.

NEUROLOGY

LIPPINCOTT WILLIAMS & WILKINS

Año: 2021

0028-3878

Objective: To investigate the inherent clinical risks associated with the presence of cerebralmicrohemorrhages (CMHs) or cerebral microbleeds (CMBs) and characterize individuals at highrisk for developing hemorrhagic amyloid-related imaging abnormality (ARIA-H), we evaluatedlongitudinally families affected by dominantly inherited Alzheimer disease (DIAD).Methods: Mutation carriers (n=310) and non-carriers (n=201) underwent neuroimaging,including gradient echo MR sequences to detect CMHs, neuropsychological, and clinicalassessments. Cross-sectional and longitudinal analyses evaluated relationships between CMHsand neuroimaging and clinical marker of disease.Results: Three percent of non-carriers and eight percent of carriers developed CMHs primarilylocated in lobar areas. Carriers with CMHs were older, had higher diastolic blood pressure andHachinski ischemic scores, and more clinical, cognitive, and motor impairments than thosewithout CMH. APOE-ε4 status was not associated with the prevalence or incidence of CMHs.Prevalent or incident CMHs predicted faster change in clinical dementia rating although notcomposite cognitive measure, cortical thickness, hippocampal volume, or white matter lesions.Critically, the presence of two or more CMHs was associated with a significant risk fordevelopment of additional CMHs over time (8.95±10.04 per year).Conclusion: Our study highlights factors associated with the development of CMHs inindividuals with DIAD. CMHs are a part of the underlying disease process in DIAD and aresignificantly associated with dementia. This highlights that in participants in treatment trialsexposed to drugs, which carry the risk of ARIA-H as a complication, it may be challenging toseparate natural incidence of CMHs from drug related CMHs.