Molecular Neuroimaging in Vascular Cognitive Impairment

Gurol, M. Edip

doi:10.1161/strokeaha.115.007958

Cited by 13 publications

(11 citation statements)

References 48 publications

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“…The lacunar stroke group may be a more homogenous SVD group compared with the mVCI group as some of the mVCI patients may have coexisting pathologies such as amyloid angiopathy or Alzheimer pathology that also can affect cognitive function. 34 We found no association between microstructural integrity and cognitive function in SVD patients. Age and educational level had a strong confounding effect.…”

Section: Discussioncontrasting

confidence: 55%

Intravoxel Incoherent Motion Imaging in Small Vessel Disease

Zhang

Wong

Uiterwijk

et al. 2017

Stroke

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The exact pathophysiology of cognitive deterioration in SVD remains unclear. It has been proposed that microstructural damage and reduced cerebral perfusion may play an integral part in this process. Diffusion tensor imaging studies found diminished microstructural integrity and network efficiency of the white matter in SVD patients compared with controls. 4 Moreover, lower microstructural integrity in the white matter was found to be associated with lower cognitive function. 5,6 In addition to microstructural changes, multiple studies showed reduced cerebral perfusion in patients with SVD.7-9 Most of these studies examined perfusion differences between patients with cognitive impairment and a control group, whereas studies on the direct relationship between cognition and perfusion in patients with SVD are scarce. Intravoxel incoherent motion (IVIM) imaging is a diffusion-weighted magnetic resonance imaging (MRI) techniqueBackground and Purpose-Cerebral small vessel disease (SVD) is associated with cognitive impairment. This may be because of decreased microstructural integrity and microvascular perfusion, but data on these relationships are scarce. We determined the relationship between cognition and microvascular perfusion and microstructural integrity in SVD patients, using intravoxel incoherent motion imaging-a diffusion-weighted magnetic resonance imaging technique designed to determine microvascular perfusion and microstructural integrity simultaneously. Methods-Seventy-three patients with SVD and 39 controls underwent intravoxel incoherent motion imaging and neuropsychological assessment. Parenchymal diffusivity D (a surrogate measure of microstructural integrity) and perfusion-related measure fD* were calculated for the normal appearing white matter, white matter hyperintensities, and cortical gray matter. The associations between cognitive performance and D and fD* were determined. Results-In SVD patients, multivariable analysis showed that lower fD* in the normal appearing white matter and cortical gray matter was associated with lower overall cognition (P=0.03 and P=0.002, respectively), lower executive function (P=0.04 and P=0.01, respectively), and lower information-processing speed (P=0.04 and P=0.01, respectively). D was not associated with cognitive function. In controls, no association was found between D, fD*, and cognition. Conclusions-In SVD patients, lower cognitive performance is associated with lower microvascular perfusion in the normal appearing white matter and cortical gray matter. Our results support recent findings that both cortical gray matter and normal appearing white matter perfusion may play a role in the pathophysiology of cognitive dysfunction in SVD. Clinical Trial Registration-URL: http://www.trialregister.nl. Unique identifier: NTR3786.

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Section: Discussioncontrasting

confidence: 55%

Intravoxel Incoherent Motion Imaging in Small Vessel Disease

Zhang

Wong

Uiterwijk

et al. 2017

Stroke

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“…27 Amyloid PET imaging can shed light on the presence/absence of severe vascular amyloid in patients with mixed ICH. 28,29 Our study has important clinical implications. Nineteen percent of our large primary ICH cohort (total n = 391) evaluated with MRI showed ICH/microbleed in both lobar and deep locations, so this is a rather prevalent condition.…”

Section: Discussionmentioning

confidence: 83%

Mixed-location cerebral hemorrhage/microbleeds

et al. 2018

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“…[7][8][9][10] This PET tracer was shown to bind vascular amyloid by radiologic-pathologic correlation in both the common sporadic form of CAA and Iowa-type hereditary CAA, a form of the disorder with little or no plaque deposits of fibrillar Ab. 11,12 Amyloid imaging using PiB-PET has already made important contributions to our understanding of CAA-related hemorrhagic and ischemic disease mechanisms, 2,7,8,13,14 such as prediction of future hemorrhages. 7 Despite these promising results obtained with PiB, its clinical application and regulatory approval have been limited by its short half-life, requiring onsite synthesis.…”

Section: Classification Of Evidencementioning

confidence: 99%

Florbetapir-PET to diagnose cerebral amyloid angiopathy

et al. 2016

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Objective: We hypothesized that florbetapir, a Food and Drug Administration-approved PET tracer, could distinguish cerebral amyloid angiopathy (CAA)-related intracerebral hemorrhage (ICH) from hypertensive ICH (HTN-ICH). Methods:We prospectively enrolled survivors of primary ICH related to probable CAA (per Boston Criteria, n 5 10) and HTN-ICH (n 5 9) without dementia. All patients underwent florbetapir-PET and multimodal MRI, and patients with CAA had additional Pittsburgh compound B (PiB) PET. Amyloid burden was assessed quantitatively (standard uptake value ratio [SUVR]) and visually classified as positive or negative. Results:The CAA and HTN-ICH groups had similar age (66.9 vs 67.1), sex, and leukoaraiosis volumes (31 vs 30 mL, all p . 0.8). Florbetapir uptake and PiB retention strongly correlated in patients with CAA both globally within cerebral cortex (r 5 0.96, p , 0.001) and regionally in lobar cortices (all r . 0.8, all p # 0.01). Mean global cortical florbetapir uptake was substantially higher in CAA than HTN-ICH (SUVR: 1.41 6 0.17 vs 1.15 6 0.08, p 5 0.001), as was mean occipital SUVR (1.44 6 0.12 vs 1.17 6 0.08, p , 0.001), even after correcting for global SUVR (p 5 0.03). Visual rating for positive/negative florbetapir demonstrated perfect interrater agreement (k 5 1) and was positive for all 10 patients with CAA vs 1 of 9 HTN-ICH patients (sensitivity 100%, specificity 89%).Conclusions: Florbetapir appears to label vascular amyloid in patients with CAA-related ICH. The approved florbetapir binary visual reading method can have diagnostic value in appropriate clinical settings. Classification of evidence:This study provides Class II evidence that florbetapir-PET provides a sensitivity of 100% (95% confidence interval [CI] 66%-100%) and specificity of 89% (95% CI 51%-99%) for determination of probable CAA among cognitively normal patients. Cerebral amyloid angiopathy (CAA), characterized by accumulation of b-amyloid (Ab) proteins in the walls of cortical/leptomeningeal vessels, is a common cause of vessel wall breakdown and vascular dysfunction in older adults, making it a major contributor to fatal or disabling intracerebral hemorrhages (ICH) as well as ischemic injury and dementia. 1,2 There currently is no specific treatment for CAA, in part because of our inability to identify this condition at early phases prior to appearance of multiple hemorrhagic brain lesions. 3 Accurate early diagnosis of CAA also has direct implications for stroke prevention, as this pathology is an important cause of anticoagulant-associated ICH and might dictate use of alternative nonpharmaceutical approaches such as left atrial appendage closure for patients with nonvalvular atrial fibrillation. 4,5

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Molecular Neuroimaging in Vascular Cognitive Impairment

Cited by 13 publications

References 48 publications

Intravoxel Incoherent Motion Imaging in Small Vessel Disease

Intravoxel Incoherent Motion Imaging in Small Vessel Disease

Mixed-location cerebral hemorrhage/microbleeds

Florbetapir-PET to diagnose cerebral amyloid angiopathy

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