White matter lesions, cognition, and recurrent hemorrhage in lobar intracerebral hemorrhage

Smith, Edward E.; Gurol, M. Edip; Eng, Jessica A.; Engel, Chana; Nguyen, Thanh N.; Rosand, Jonathan; Greenberg, Steven M.

doi:10.1212/01.wnl.0000142966.22886.20

Cited by 216 publications

(190 citation statements)

References 59 publications

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“…There is an inverse correlation between CAA presence and cognitive function that has been reported in both case series [39] as well as in the population based studies. In the MRC study, severe CAA was identified in 36.5% of individuals with dementia compared to 7% without dementia, OR 7.7 (95% CI, 3.3 to 20.4) [7].…”

Section: Cognitive Impairment and Dementiasupporting

confidence: 54%

“…White matter disease is associated with increased cognitive decline in about 20% of the patients, particularly those where it is severe. Patients with WMD have a high incidence of concomitant petechial hemorrhages that can negatively affect their cognitive performance [39]. Though not specifically addressed, it is presumed that the involvement of the subcortical and particularly periventricular white matter, and the concomitant circuit disruption leads to a pattern of cognitive decline where apathy, impaired executive function and psychomotor slowing predominating over impaired episodic memory.…”

Section: Cognitive Impairment and Dementiamentioning

confidence: 99%

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Clinical phenotypes of Cerebral Amyloid Angiopathy

Maia¹,

Feldman

2007

Journal of the Neurological Sciences

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The term Cerebral Amyloid Angiopathy (CAA) is used to describe the pathological changes occurring in cerebral blood vessels, both leptomeningeal and cortical that result from the deposition of amyloid proteins. This CNS vasculopathy is associated with a spectrum of clinical phenotypes that include both ischemic and hemorrhagic presentations. Dementia, cognitive impairment and transient neurological symptoms or signs are also being increasingly recognized as part of the CAA clinical spectrum.This review covers the clinical, pathological and neuroimaging aspects of CAA.

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Section: Cognitive Impairment and Dementiasupporting

confidence: 54%

Section: Cognitive Impairment and Dementiamentioning

confidence: 99%

Clinical phenotypes of Cerebral Amyloid Angiopathy

Maia¹,

Feldman

2007

Journal of the Neurological Sciences

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“…118 In that study, preICH cognitive impairment was associated with advanced WMH on CT or MRI. However, cognitive impairment was assessed with a standardized questionnaire, without quantitative assessment of cognition.…”

Section: Lobar Microbleeds and Cognitionmentioning

confidence: 81%

Ischemic brain injury in cerebral amyloid angiopathy

Reijmer

Veluw

Greenberg

2015

J Cereb Blood Flow Metab

123

102

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Cerebral amyloid angiopathy (CAA) is a common form of cerebral small vessel disease and an important risk factor for intracerebral hemorrhage and cognitive impairment. While the majority of research has focused on the hemorrhagic manifestation of CAA, its ischemic manifestations appear to have substantial clinical relevance as well. Findings from imaging and pathologic studies indicate that ischemic lesions are common in CAA, including white-matter hyperintensities, microinfarcts, and microstructural tissue abnormalities as detected with diffusion tensor imaging. Furthermore, imaging markers of ischemic disease show a robust association with cognition, independent of age, hemorrhagic lesions, and traditional vascular risk factors. Widespread ischemic tissue injury may affect cognition by disrupting white-matter connectivity, thereby hampering communication between brain regions. Challenges are to identify imaging markers that are able to capture widespread microvascular lesion burden in vivo and to further unravel the etiology of ischemic tissue injury by linking structural magnetic resonance imaging (MRI) abnormalities to their underlying pathophysiology and histopathology. A better understanding of the underlying mechanisms of ischemic brain injury in CAA will be a key step toward new interventions to improve long-term cognitive outcomes for patients with CAA.

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“…The subjects were recruited from an ongoing single-center prospective longitudinal cohort study of the natural history of CAA. 13 Detailed information including demographics, clinical status, risk factors, and characteristics of the presenting event were prospectively recorded at the time of cohort entry. None of the 11 subjects had dementia and all were free of symptoms suggestive of new stroke for 1 year prior to PiB-PET.…”

Section: Methods Study Subjectsmentioning

confidence: 99%

Predicting sites of new hemorrhage with amyloid imaging in cerebral amyloid angiopathy

Gurol

Dierksen

Betensky³

et al. 2012

Neurology

Self Cite

110

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Objective: We aimed to determine whether amyloid imaging can help predict the location and number of future hemorrhages in cerebral amyloid angiopathy (CAA). Methods:We performed a longitudinal cohort study of 11 patients with CAA without dementia who underwent serial brain MRIs after baseline amyloid imaging with Pittsburgh compound B (PiB). Mean distribution volume ratio (DVR) of PiB was determined at the sites of new micro/ macrobleeds identified on follow-up MRI and compared with PiB retention at "simulated" hemorrhages, randomly placed in the same subjects using a probability distribution map of CAA-hemorrhage location. Mean PiB retention at the sites of observed new bleeds was also compared to that in shells concentrically surrounding the bleeds. Finally the association between number of incident bleeds and 3 regional amyloid measures were obtained.Results: Nine of 11 subjects had at least one new microbleed on follow-up MRI (median 4, interquartile range [IQR] 1-9) and 2 had 5 new intracerebral hemorrhages. Mean DVR was greater at the sites of incident bleeds (1.34, 95% confidence interval [CI] 1.23-1.46) than simulated lesions (1.14, 95% CI 1.07-1.22, p Ͻ 0.0001) in multivariable models. PiB retention decreased with increasing distance from sites of observed bleeds (p Ͻ 0.0001). Mean DVR in a superior frontal/ parasagittal region of interest correlated independently with number of future hemorrhages after adjustment for relevant covariates (p ϭ 0.003). Conclusions:Our results provide direct evidence that new CAA-related hemorrhages occur preferentially at sites of increased amyloid deposition and suggest that PiB-PET imaging may be a useful tool in prediction of incident hemorrhages in patients with CAA. Neurology ® 2012;79:320-326 GLOSSARY A␤ ϭ ␤-amyloid; CAA ϭ cerebral amyloid angiopathy; CI ϭ confidence interval; DVR ϭ distribution volume ratio; IQR ϭ interquartile range; PiB ϭ Pittsburgh compound B; ROI ϭ region of interest; SWI ϭ susceptibility-weighted imaging.Small vessel brain disease is associated with a range of brain lesions including white matter T2 hyperintensities, cerebral microbleeds, lacunar lesions, and cerebral microinfarcts.1-3 The precise relationship between location of the small vessel pathology and the resultant brain lesions has been difficult to establish, however, largely because of inability to image the small vessels during life. An important advance in this regard was the development of the thioflavin T derivative Pittsburgh compound B (PiB) for in vivo imaging of fibrillar ␤-amyloid (A␤). A series of studies have demonstrated that PiB labels not only parenchymal A␤ in senile plaques 4 but also the cerebrovascular A␤ deposits 5-9 that define cerebral amyloid angiopathy (CAA). A spatial relationship between vascular amyloid and lobar bleeds in CAA has been suggested by neuropathologic studies 10,11 and one cross-sectional radiologic analysis using PiB-PET imaging. 12 There are no prospective studies of patients with CAA followed over time, however, making it difficult...

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White matter lesions, cognition, and recurrent hemorrhage in lobar intracerebral hemorrhage

Abstract: White matter damage in lobar ICH is common and is associated with cognitive impairment. These data support the possibility that an underlying vasculopathy in lobar ICH patients, possibly cerebral amyloid angiopathy, can cause clinically important vascular dysfunction.

Cited by 216 publications

References 59 publications

Clinical phenotypes of Cerebral Amyloid Angiopathy

Clinical phenotypes of Cerebral Amyloid Angiopathy

Ischemic brain injury in cerebral amyloid angiopathy

Predicting sites of new hemorrhage with amyloid imaging in cerebral amyloid angiopathy

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