Florbetapir imaging in cerebral amyloid angiopathy-related hemorrhages

Raposo, Nicolas; Planton, Mélanie; Péran, Patrice; Payoux, Pierre; Bonneville, Fabrice; Lyoubi, Aïcha; Albucher, Jean François; Acket, Blandine; Salabert, Anne‐Sophie; Olivot, Jean Marc; Hitzel, Anne; Chollet, François; Pariente, Jérémie

doi:10.1212/wnl.0000000000004228

Cited by 28 publications

(37 citation statements)

References 30 publications

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“…20 Moreover, cortical florbetapir-PET levels were higher in patients with CAA-related acute ICH and lobar microbleeds compared to patients with hypertension-related acute ICH and deep microbleeds. 21 However, the correlation between microbleed numbers and Aβ levels within CAA cases has not been assessed to date, likely due to the relatively small number of patients who have undergone PET imaging. 22 Here, we confirmed the known predilection of microbleeds for posterior brain areas, which corresponded to greater CAA severity in parietal and occipital cortex.…”

Section: Discussionmentioning

confidence: 99%

Different microvascular alterations underlie microbleeds and microinfarcts

Veluw

Scherlek

Freeze

et al. 2019

Annals of Neurology

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Objective: Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid β (Aβ) in the walls of cortical vessels and the accrual of microbleeds and microinfarcts over time. The relationship between CAA severity and microbleeds and microinfarcts as well as the sequence of events that lead to lesion formation remain poorly understood. Methods: We scanned intact formalin-fixed hemispheres of 12 CAA cases with magnetic resonance imaging (MRI), followed by histopathological examination in predefined areas and serial sectioning in targeted areas with multiple lesions. Results: In total, 1,168 cortical microbleeds and 472 cortical microinfarcts were observed on ex vivo MRI. Increasing CAA severity at the whole-brain or regional level was not associated with the number of microbleeds or microinfarcts. However, locally, the density of Aβ-positive cortical vessels was lower surrounding a microbleed compared to a simulated control lesion, and higher surrounding microinfarcts. Serial sectioning revealed that for (n = 28) microbleeds, both Aβ (4%) and smooth muscle cells (4%) were almost never present in the vessel wall at the site of bleeding, but Aβ was frequently observed upstream or downstream (71%), as was extensive fibrin(ogen) buildup (87%). In contrast, for (n = 22) microinfarcts, vascular Aβ was almost always observed at the core of the lesion (91%, p < 0.001) as well as upstream or downstream (82%), but few vessels associated with microinfarcts had intact smooth muscle cells (9%). Interpretation: These observations provide a model for how a single neuropathologic process such as CAA may result in hemorrhagic or ischemic brain lesions potentially through 2 different mechanistic pathways.

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Section: Discussionmentioning

confidence: 99%

Different microvascular alterations underlie microbleeds and microinfarcts

Veluw

Scherlek

Freeze

et al. 2019

Annals of Neurology

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“…Participants were recruited as part of two clinical research projects on ICH and AD. The recruitment procedure has been previously described [4,6]. Briefly, we included two groups of participants in this study: CAA-ICH and MCI-AD.…”

Section: Participantsmentioning

confidence: 99%

“…Sporadic cerebral amyloid angiopathy (CAA) is a cerebral small-vessel disease characterized by the deposition of amyloid-␤ (A␤) in the walls of cortical and leptomeningeal vessels, leading to loss of smooth muscle cells [1]. Positron-emission tomography (PET) amyloid radiotracers binds to parenchymal A␤ deposits in Alzheimer's disease (AD) but also to vascular A␤ in CAA patients [2][3][4]. Global amyloid tracer uptake is increased in CAA patients with or without intracerebral hemorrhage (ICH) relative to healthy controls and to patients with hypertension relative ICH (HT-ICH) [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…Positron-emission tomography (PET) amyloid radiotracers binds to parenchymal A␤ deposits in Alzheimer's disease (AD) but also to vascular A␤ in CAA patients [2][3][4]. Global amyloid tracer uptake is increased in CAA patients with or without intracerebral hemorrhage (ICH) relative to healthy controls and to patients with hypertension relative ICH (HT-ICH) [4,5]. However, this global uptake was reported as lower in CAA than in AD patients [3,5] in two studies that compared these populations using [ 11 C]Pittsburgh compound B (PiB).…”

Section: Introductionmentioning

confidence: 99%

“…In the present study, we pooled individual data from two independent cohorts [4,6] to compare the in vivo uptake of the PET amyloid tracer [ 18 F]florbetapir in patients with CAA-related ICH (CAA-ICH) and mild cognitive impairment due to AD (MCI-AD). Standard uptake values ratio (SUVr) were obtained and regional as well as voxel-wise approaches for florbetapir quantification were performed.…”

Section: Introductionmentioning

confidence: 99%

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Florbetapir Regional Distribution in Cerebral Amyloid Angiopathy and Alzheimer’s Disease: A PET Study

Planton

Saint‐Aubert

Raposo

et al. 2020

JAD

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Background: Sporadic cerebral amyloid angiopathy shows progressive amyloid-␤ deposition in the wall of small arterioles and capillaries of the leptomeninges and cerebral cortex. Objective: To investigate whether amyloid load and distribution, assessed by florbetapir positron emission tomography (PET), differs between patients with probable CAA-related intracerebral hemorrhage (CAA-ICH) and mild cognitive impairment due to Alzheimer's disease (MCI-AD). Methods: We assessed [ 18 F]florbetapir uptake in 15 patients with probable CAA-ICH and 20 patients with MCI-AD patients. Global and regional florbetapir retention were assessed using standard uptake values ratio (SUVr) in region-based and voxelwise approaches. Visual reading of florbetapir scans was performed for all participants. Group comparisons were performed using univariate and multivariate analysis. Results: Global florbetapir retention was lower in patients with CAA-ICH than MCI-AD (median SUVr, 1.33 [1.21-1.41] versus 1.44 [1.35-1.66]; p = 0.032). In the region-based analysis, regional florbetapir distribution was similar between the two groups. There was a trend for an increased occipital/global ratio in CAA-ICH patients compared to MCI-AD (p = 0.060). In the voxel-wise approach, two clusters, one in parietal regions and the other in temporal regions, had higher uptake in MCI-AD relative to CAA patients. Conclusions: Patients with CAA-ICH had a lower global florbetapir PET burden than patients with MCI-AD. Relative florbetapir retention in the posterior regions tended to be higher in CAA patients in region-based analysis but was not statistically different between groups. Investigation on differences in amyloid deposits distribution between groups required a fine-grained voxel-wise analysis. In future studies, selective amyloid tracers are needed to differentiate vascular from parenchymal amyloid.

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Mid‐life and late‐life vascular risk factor burden and neuropathology in old age

Conner

Pase

Carneiro

et al. 2019

Ann Clin Transl Neurol

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ObjectiveTo determine whether vascular risk factor burden in mid‐ or late‐life associates with postmortem vascular and neurodegenerative pathologies in a community‐based sample.MethodsWe studied participants from the Framingham Heart Study who participated in our voluntary brain bank program. Overall vascular risk factor burden was calculated using the Framingham Stroke Risk Profile (FSRP). Mid‐life FSRP was measured at 50 to 60 years of age. Following death, brains were autopsied and semi‐quantitatively assessed by board‐certified neuropathologists for cerebrovascular outcomes (cortical infarcts, subcortical infarcts, atherosclerosis, arteriosclerosis) and Alzheimer’s disease pathology (Braak stage, cerebral amyloid angiopathy, and neuritic plaque score). We estimated adjusted odds ratios between vascular risk burden (at mid‐life and before death) and neuropathological outcomes using logistic and proportional‐odds logistic models.ResultsThe median time interval between FSRP and death was 33.4 years for mid‐life FSRP and 4.4 years for final FSRP measurement before death. Higher mid‐life vascular risk burden was associated with increased odds of all cerebrovascular pathology, even with adjustment for vascular risk burden before death. Late‐life vascular risk burden was associated with increased odds of cortical infarcts (OR [95% CI]: 1.04 [1.00, 1.08]) and arteriosclerosis stage (OR [95% CI]: 1.03 [1.00, 1.05]). Mid‐life vascular risk burden was not associated with Alzheimer’s disease pathology, though late‐life vascular risk burden was associated with increased odds of higher Braak stage (OR [95% CI]: 1.03 [1.01, 1.05]).InterpretationMid‐life vascular risk burden was predictive of cerebrovascular but not Alzheimer’s disease neuropathology, even after adjustment for vascular risk factors before death.

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Florbetapir imaging in cerebral amyloid angiopathy-related hemorrhages

Cited by 28 publications

References 30 publications

Different microvascular alterations underlie microbleeds and microinfarcts

Different microvascular alterations underlie microbleeds and microinfarcts

Florbetapir Regional Distribution in Cerebral Amyloid Angiopathy and Alzheimer’s Disease: A PET Study

Mid‐life and late‐life vascular risk factor burden and neuropathology in old age

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