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@ARTICLE{JosephMathurin:155387,
      author       = {Joseph-Mathurin, Nelly and Wang, Guoqiao and Kantarci,
                      Kejal and Jack, Clifford R and McDade, Eric and Hassenstab,
                      Jason and Blazey, Tyler M and Gordon, Brian A and Su, Yi and
                      Chen, Gengsheng and Massoumzadeh, Parinaz and Hornbeck, Russ
                      C and Allegri, Ricardo F and Ances, Beau M and Berman, Sarah
                      B and Brickman, Adam M and Brooks, William S and Cash, David
                      M and Chhatwal, Jasmeer P and Chui, Helena C and Correia,
                      Stephen and Cruchaga, Carlos and Farlow, Martin R and Fox,
                      Nick C and Fulham, Michael and Ghetti, Bernardino and
                      Graff-Radford, Neill R and Johnson, Keith A and Karch,
                      Celeste M and Laske, Christoph and Lee, Athene K W and
                      Levin, Johannes and Masters, Colin L and Noble, James M and
                      O'Connor, Antoinette and Perrin, Richard J and Preboske,
                      Gregory M and Ringman, John M and Rowe, Christopher C and
                      Salloway, Stephen and Saykin, Andrew J and Schofield, Peter
                      R and Shimada, Hiroyuki and Shoji, Mikio and Suzuki, Kazushi
                      and Villemagne, Victor L and Xiong, Chengjie and Yakushev,
                      Igor and Morris, John C and Bateman, Randall J and
                      Benzinger, Tammie L S},
      collaboration = {Network, Dominantly Inherited Alzheimer},
      title        = {{L}ongitudinal {A}ccumulation of {C}erebral
                      {M}icrohemorrhages in {D}ominantly {I}nherited {A}lzheimer
                      {D}isease.},
      journal      = {Neurology},
      volume       = {96},
      number       = {12},
      issn         = {1526-632X},
      address      = {[S.l.]},
      publisher    = {Ovid},
      reportid     = {DZNE-2021-00627},
      pages        = {e1632 - e1645},
      year         = {2021},
      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.},
      keywords     = {Adult / Alzheimer Disease: complications / Alzheimer
                      Disease: pathology / Brain: pathology / Cerebral Hemorrhage:
                      epidemiology / Cerebral Hemorrhage: etiology / Cerebral
                      Hemorrhage: pathology / Female / Humans / Longitudinal
                      Studies / Magnetic Resonance Imaging / Male / Middle Aged},
      cin          = {Core ICRU / Clinical Dementia Research München / München
                      common},
      ddc          = {610},
      cid          = {I:(DE-2719)1240005 / I:(DE-2719)1111016 /
                      I:(DE-2719)6000016},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33495373},
      pmc          = {pmc:PMC8032370},
      doi          = {10.1212/WNL.0000000000011542},
      url          = {https://pub.dzne.de/record/155387},
}