TY - JOUR
T1 - Longitudinal Accumulation of Cerebral Microhemorrhages in Dominantly Inherited Alzheimer Disease
AU - Dominantly Inherited Alzheimer Network
AU - Joseph-Mathurin, Nelly
AU - Wang, Guoqiao
AU - Kantarci, Kejal
AU - Jack, Clifford R.
AU - McDade, Eric
AU - Hassenstab, Jason
AU - Blazey, Tyler M.
AU - Gordon, Brian A.
AU - Su, Yi
AU - Chen, Gengsheng
AU - Massoumzadeh, Parinaz
AU - Hornbeck, Russ C.
AU - Allegri, Ricardo F.
AU - Ances, Beau M.
AU - Berman, Sarah B.
AU - Brickman, Adam M.
AU - Brooks, William S.
AU - Cash, David M.
AU - Chhatwal, Jasmeer P.
AU - Chui, Helena C.
AU - Correia, Stephen
AU - Cruchaga, Carlos
AU - Farlow, Martin R.
AU - Fox, Nick C.
AU - Fulham, Michael
AU - Ghetti, Bernardino
AU - Graff-Radford, Neill R.
AU - Johnson, Keith A.
AU - Karch, Celeste M.
AU - Laske, Christoph
AU - Lee, Athene K.W.
AU - Levin, Johannes
AU - Masters, Colin L.
AU - Noble, James M.
AU - O'Connor, Antoinette
AU - Perrin, Richard J.
AU - Preboske, Gregory M.
AU - Ringman, John M.
AU - Rowe, Christopher C.
AU - Salloway, Stephen
AU - Saykin, Andrew J.
AU - Schofield, Peter R.
AU - Shimada, Hiroyuki
AU - Shoji, Mikio
AU - Suzuki, Kazushi
AU - Villemagne, Victor L.
AU - Xiong, Chengjie
AU - Morris, John C.
AU - Bateman, Randall J.
AU - Benzinger, Tammie L.S.
N1 - Publisher Copyright:
© 2020 American Academy of Neurology.
PY - 2021/3/23
Y1 - 2021/3/23
N2 - Objective: To investigate the inherent clinical risks associated with the presence of cerebral microhemorrhages (CMHs) or cerebral microbleeds and characterize individuals at high risk for developing hemorrhagic amyloid-related imaging abnormality (ARIA-H,), we longitudinally evaluated families with dominantly inherited Alzheimer disease (DIAD). Methods: Mutation carriers (n = 310) and noncarriers (n = 201) underwent neuroimaging, including gradient echo MRI sequences to detect CMHs, and neuropsychological and clinical assessments. Cross-sectional and longitudinal analyses evaluated relationships between CMHs and neuroimaging and clinical markers of disease. Results: Three percent of noncarriers and 8% of carriers developed CMHs primarily located in lobar areas. Carriers with CMHs were older, had higher diastolic blood pressure and Hachinski ischemic scores, and more clinical, cognitive, and motor impairments than those without CMHs. 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 not composite cognitive measure, cortical thickness, hippocampal volume, or white matter lesions. Critically, the presence of 2 or more CMHs was associated with a significant risk for development of additional CMHs over time (8.95 ± 10.04 per year). Conclusion: Our study highlights factors associated with the development of CMHs in individuals with DIAD. CMHs are a part of the underlying disease process in DIAD and are significantly associated with dementia. This highlights that in participants in treatment trials exposed to drugs, which carry the risk of ARIA-H as a complication, it may be challenging to separate natural incidence of CMHs from drug-related CMHs.
AB - Objective: To investigate the inherent clinical risks associated with the presence of cerebral microhemorrhages (CMHs) or cerebral microbleeds and characterize individuals at high risk for developing hemorrhagic amyloid-related imaging abnormality (ARIA-H,), we longitudinally evaluated families with dominantly inherited Alzheimer disease (DIAD). Methods: Mutation carriers (n = 310) and noncarriers (n = 201) underwent neuroimaging, including gradient echo MRI sequences to detect CMHs, and neuropsychological and clinical assessments. Cross-sectional and longitudinal analyses evaluated relationships between CMHs and neuroimaging and clinical markers of disease. Results: Three percent of noncarriers and 8% of carriers developed CMHs primarily located in lobar areas. Carriers with CMHs were older, had higher diastolic blood pressure and Hachinski ischemic scores, and more clinical, cognitive, and motor impairments than those without CMHs. 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 not composite cognitive measure, cortical thickness, hippocampal volume, or white matter lesions. Critically, the presence of 2 or more CMHs was associated with a significant risk for development of additional CMHs over time (8.95 ± 10.04 per year). Conclusion: Our study highlights factors associated with the development of CMHs in individuals with DIAD. CMHs are a part of the underlying disease process in DIAD and are significantly associated with dementia. This highlights that in participants in treatment trials exposed to drugs, which carry the risk of ARIA-H as a complication, it may be challenging to separate natural incidence of CMHs from drug-related CMHs.
UR - http://www.scopus.com/inward/record.url?scp=85103474053&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000011542
DO - 10.1212/WNL.0000000000011542
M3 - Article
C2 - 33495373
AN - SCOPUS:85103474053
SN - 0028-3878
VL - 96
SP - E1632-E1645
JO - Neurology
JF - Neurology
IS - 12
ER -