Journal Article

DZNE-2021-00627

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Longitudinal Accumulation of Cerebral Microhemorrhages in Dominantly Inherited Alzheimer Disease.

Joseph-Mathurin, N. ; Wang, G. ; Kantarci, K. ; Jack, C. R. ; McDade, E. ; Hassenstab, J. ; Blazey, T. M. ; Gordon, B. A. ; Su, Y. ; Chen, G. ; Massoumzadeh, P. ; Hornbeck, R. C. ; Allegri, R. F. ; Ances, B. M. ; Berman, S. B. ; Brickman, A. M. ; Brooks, W. S. ; Cash, D. M. ; Chhatwal, J. P. ; Chui, H. C. ; Correia, S. ; Cruchaga, C. ; Farlow, M. R. ; Fox, N. C. ; Fulham, M. ; Ghetti, B. ; Graff-Radford, N. R. ; Johnson, K. A. ; Karch, C. M. ; Laske, C.DZNE* ; Lee, A. K. W. ; Levin, J.DZNE* ; Masters, C. L. ; Noble, J. M. ; O'Connor, A. ; Perrin, R. J. ; Preboske, G. M. ; Ringman, J. M. ; Rowe, C. C. ; Salloway, S. ; Saykin, A. J. ; Schofield, P. R. ; Shimada, H. ; Shoji, M. ; Suzuki, K. ; Villemagne, V. L. ; Xiong, C. ; Yakushev, I.DZNE* ; Morris, J. C. ; Bateman, R. J. ; Benzinger, T. L. S. ; Network, D. I. A. (Collaboration Author)

2021
Ovid [S.l.]

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Please use a persistent id in citations: doi:10.1212/WNL.0000000000011542

Abstract: 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).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.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).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.

Keyword(s): Adult (MeSH) ; Alzheimer Disease: complications (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Brain: pathology (MeSH) ; Cerebral Hemorrhage: epidemiology (MeSH) ; Cerebral Hemorrhage: etiology (MeSH) ; Cerebral Hemorrhage: pathology (MeSH) ; Female (MeSH) ; Humans (MeSH) ; Longitudinal Studies (MeSH) ; Magnetic Resonance Imaging (MeSH) ; Male (MeSH) ; Middle Aged (MeSH)

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Contributing Institute(s):

1. Core ICRU (Core ICRU)
2. Clinical Dementia Research München (Clinical Dementia Research München)
3. München common (München common)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2021

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Database coverage:
; ; ; Allianz-Lizenz ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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