Longitudinal Accumulation of Cerebral Microhemorrhages in Dominantly Inherited Alzheimer Disease

• Autores: 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 Francisco; 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
• Año de publicación: 2021
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: DIAD; autosomal dominant Alzheimer disease; cerebral microhemoorrhages; cerebral microbleeds
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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.
Fil: Joseph Mathurin, Nelly. Washington University in St. Louis; Estados Unidos
Fil: Wang, Guoqiao. Washington University in St. Louis; Estados Unidos
Fil: Kantarci, Kejal. Mayo Clinic Cancer Center; Estados Unidos
Fil: Jack, Clifford R.. Mayo Clinic Cancer Center; Estados Unidos
Fil: McDade, Eric. Washington University in St. Louis; Estados Unidos
Fil: Hassenstab, Jason. Washington University in St. Louis; Estados Unidos
Fil: Blazey, Tyler M.. Washington University in St. Louis; Estados Unidos
Fil: Gordon, Brian A.. Washington University in St. Louis; Estados Unidos
Fil: Su, Yi. Banner Alzheimers Institute; Estados Unidos
Fil: Chen, Gengsheng. Washington University in St. Louis; Estados Unidos
Fil: Massoumzadeh, Parinaz. Washington University in St. Louis; Estados Unidos
Fil: Hornbeck, Russ C.. Washington University in St. Louis; Estados Unidos
Fil: Allegri, Ricardo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Ances, Beau M.. Washington University in St. Louis; Estados Unidos
Fil: Berman, Sarah B.. University of Pittsburgh; Estados Unidos
Fil: Brickman, Adam M.. Columbia University; Estados Unidos
Fil: Brooks, William S.. University of New South Wales; Australia
Fil: Cash, David M.. UK Dementia Research Institute; Reino Unido. University College London; Estados Unidos
Fil: Chhatwal, Jasmeer P.. Harvard Medical School. Department of Medicine. Massachusetts General Hospital; Estados Unidos
Fil: Chui, Helena C.. University of Southern California; Estados Unidos
Fil: Correia, Stephen. University Brown; Estados Unidos. Butler Hospital; Estados Unidos
Fil: Cruchaga, Carlos. Washington University in St. Louis; Estados Unidos
Fil: Farlow, Martin R.. Indiana University. School of Medicine; Estados Unidos
Fil: Fox, Nick C.. UK Dementia Research Institute; Reino Unido. University College London; Estados Unidos
Fil: Fulham, Michael. University of Sydney; Australia. Royal Prince Alfred Hospital; Australia
Fil: Ghetti, Bernardino. Indiana University. School of Medicine; Estados Unidos
Fil: Graff Radford, Neill R.. Mayo Clinic Cancer Center; Estados Unidos
Fil: Johnson, Keith A.. Harvard Medical School. Department of Medicine. Massachusetts General Hospital; Estados Unidos
Fil: Karch, Celeste M.. Washington University in St. Louis; Estados Unidos
Fil: Laske, Christoph. Eberhard Karls Universität Tübingen; Alemania