Subacute Ischemic Stroke Is Associated With Focal ¹¹ C PiB Positron Emission Tomography Retention But Not With Global Neocortical Aβ Deposition

Abstract

Background and Purpose-Conflicting evidence exists as to whether focal cerebral ischemia contributes to cerebral amyloid deposition. We aimed to look at A␤ deposits, detected by N-methyl-2-(4Ј-methylaminophenyl)-6-hydroxybenzothiazole (PiB) positron emission tomography, in patients with recent ischemic stroke. Specifically, we hypothesized that patients with recent ischemic stroke have higher local and neocortical PiB positron emission tomography retention and that this may be associated with major vascular risk factors. Methods-Ischemic stroke patients were studied using PiB positron emission tomography within 30 days and compared to age-matched controls. Distribution volume ratio maps were created using Logan graphical analysis with the cerebellar cortex as a reference. Results-Among the 21 ischemic stroke patients (median age, 76 years; interquartile range, 68 -77), the ipsilateral peri-infarct region PiB retention was higher compared to the contralateral mirror region, with a PiB distribution volume ratio difference of 0.29 (95% CI, 0.2-0.44; Pϭ0.001) at median 10 (interquartile range, 7-14) days after stroke. Two patients also had higher PiB retention within the infarct compared to the contralateral side. There was no difference in the neocortical PiB retention elsewhere in the brain among ischemic stroke patients compared with 22 age-matched normal controls (Pϭ0.22). Among the risk factors in the ischemic stroke patients, diabetes was associated with a higher neocortical PiB retention (Spearman Rhoϭ0.48; 95% CI, 0.28 -0.72). Conclusions-PiB retention was higher in the peri-infarct region among patients with recent ischemic stroke. This did not translate into a higher global neocortical PiB retention except possibly in patients with diabetes. The cause of the focal PiB retention is uncertain and requires further investigation. (Stroke. 2012;43:1341-1346.)

Cerebrovascular Disease, Amyloid Plaques, and Dementia

“…59 Moreover, the possibility that the observed increase in local PiB retention being a result of leakage of free PiB because of the blood-brain barrier damage could not be excluded. 30 Overall, thus far, there is no solid evidence of a significant interaction between cerebral infarcts and global amyloid burden. …”

“…59 Moreover, the possibility that the observed increase in local PiB retention being a result of leakage of free PiB because of the blood-brain barrier damage could not be excluded. 30 Overall, thus far, there is no solid evidence of a significant interaction between cerebral infarcts and global amyloid burden. Амилоидные бляшки представляют собой отложе-ния белка β-амилоида (Аβ) в веществе головного мозга и считаются одним из нейропатологических диагнос-тических признаков болезни Альцгеймера (БА) [1].…”

“…29 In patients with recent ischemic stroke, although a relatively increased PiB retention was found in peri-infarct region comparing to the contralateral mirror region, this increased regional PiB retention did not translate into a higher global PiB retention. 30 In experimental stroke models in transgenic mouse with amyloid deposition (APPswe/PS1dE9), increase in new amyloid plaques around the infarcted area was only transient, in which the accumulation most probably reflected an impaired amyloid clearance pathway caused by infarcted tissue. 59 Moreover, the possibility that the observed increase in local PiB retention being a result of leakage of free PiB because of the blood-brain barrier damage could not be excluded.…”

“…22 Amyloid PET can detect comorbid amyloid deposition in patients with high vascular burden. 23 We reviewed the potential interactions between CVD and amyloid plaques and their relationships with cognitive impairment, with reference to in-vivo clinical studies using amyloid PET imaging [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] and autopsy studies measuring amyloid plaques.…”

The link between cardiovascular risk, Alzheimer's disease, and mild cognitive impairment: support from recent functional neuroimaging studies

“…In a recent study, PiB-PET was performed a few days after stroke, and, in 20 out of 21 individuals, there was higher PiB retention in the ipsilateral peri-infarct brain region than in the contralateral side. 158 In one recent longitudinal study, baseline severity of white matter lesions correlated with increased PiB retention after a mean follow-up interval of 28 months. 78 The authors suggested that the association between WMH --a sign of CVD --and progression of amyloid load might be mediated by impaired amyloid clearance due to vascular damage.…”