Joseph-Mathurin, N;
Wang, G;
Kantarci, K;
Jack, CR;
McDade, E;
Hassenstab, J;
Blazey, TM;
... Dominantly Inherited Alzheimer Network; + view all
(2021)
Longitudinal Accumulation of Cerebral Microhemorrhages in Dominantly Inherited Alzheimer Disease.
Neurology
10.1212/WNL.0000000000011542.
(In press).
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Abstract
Objective: To investigate the inherent clinical risks associated with the presence of cerebral microhemorrhages (CMHs) or cerebral microbleeds (CMBs) and characterize individuals at high risk for developing hemorrhagic amyloid-related imaging abnormality (ARIA-H), we evaluated longitudinally 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 clinical assessments. Cross-sectional and longitudinal analyses evaluated relationships between CMHs and neuroimaging and clinical marker of disease. Results: Three percent of non-carriers and eight percent 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 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 not composite cognitive measure, cortical thickness, hippocampal volume, or white matter lesions. Critically, the presence of two 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.
| Type: | Article |
|---|---|
| Title: | Longitudinal Accumulation of Cerebral Microhemorrhages in Dominantly Inherited Alzheimer Disease |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1212/WNL.0000000000011542 |
| Publisher version: | https://doi.org/10.1212/WNL.0000000000011542 |
| Language: | English |
| Additional information: | This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | DIAD, autosomal dominant Alzheimer disease, cerebral microhemorrhages, CMHs, cerebral microbleeds, CMBs, ARIA, DIAN. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10120254 |
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