Longitudinal Accumulation of Cerebral Microhemorrhages in Dominantly Inherited Alzheimer Disease
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Published:2021-01-25
Issue:12
Volume:96
Page:e1632-e1645
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ISSN:0028-3878
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Container-title:Neurology
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language:en
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Short-container-title:Neurology
Author:
Joseph-Mathurin NellyORCID, 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.ORCID, Brooks William S., Cash David M.ORCID, Chhatwal Jasmeer P., Chui Helena C., Correia Stephen, Cruchaga CarlosORCID, Farlow Martin R., Fox Nick C., Fulham MichaelORCID, Ghetti Bernardino, Graff-Radford Neill R., Johnson Keith A., Karch Celeste M.ORCID, 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.ORCID, Schofield Peter R.ORCID, Shimada Hiroyuki, Shoji MikioORCID, Suzuki Kazushi, Villemagne Victor L., Xiong Chengjie, Yakushev Igor, Morris John C., Bateman Randall J.ORCID, Benzinger Tammie L.S.,
Abstract
ObjectiveTo 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).MethodsMutation 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.ResultsThree 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).ConclusionOur 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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Neurology (clinical)
Cited by
14 articles.
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