Cerebrovascular Disease, Amyloid Plaques, and Dementia

Abstract

Absence of vascular dementia in an autopsy series from a dementia clinic. J Am Geriatr Soc. 1998;46:597-604. 6. Seno H, Ishino H, Inagaki T, Iijima M, Kaku K, Inata T. A neuropathological study of dementia in nursing homes over a 17-year period, in Shimane Prefecture, Japan. Gerontology. 1999;45:44-48. 7 However, an unresolved issue remains on the temporal relationship between the development of vascular and amyloid pathologies as other potential factors, such as the overproduction of Aβ caused by genetic mutations in APP and presenilin genes might also take part in the abnormal amyloid accumulation. Atherosclerosis and Amyloid PlaquesAtherosclerosis in large cerebral arteries can compromise cerebral blood flow and cause cerebral hypoperfusion. Patients with AD had a higher proportion and more pronounced atherosclerosis in the circle of Willis than those patients with non-AD dementias (except VaD) as shown in autopsy studies. 41,[55][56][57][58] Moreover, there was a high concordance between the ratings of atherosclerosis with amyloid plaques and CAA ratings. 41Through [18F] AV-45 PET examination, amyloid deposition in patients with dementia having unilateral carotid artery stenosis was increased. More importantly, the distribution of the amyloid disposition was found to be lateralized to the side of stenosis.26 Together, these clinical and pathological findings suggest that there is a shared cause between atherosclerosis and amyloid deposition. Infarcts and Amyloid PlaquesMost amyloid PET studies did not find significant relationships between infarcts and amyloid deposition. 27,28 In fact, a study showed that in patients with subcortical vascular cognitive impairment, the number of lacunes was negatively related with the PiB retention ratio. 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. 30 Overall, thus far, there is no solid evidence of a significant interaction between cerebral infarcts and global amyloid burden. Sources of Funding

Synergistic Effect of Depression and Cerebrovascular Disease in Mid- to Late-life on the Risk for Dementia: A Nationwide Population-based Cohort Study

“…Our results reinforce the claim that individuals with depression or CVD are more vulnerable to subsequent dementia, with the same hazards seen in previous research that examined the association between depression [16,22,32,33] or CVD [4,7,34,35] with cognitive declines. We replicated prior ndings with a large population-based sample, and also tested the generalizability of our results.…”

“…Cerebrovascular disease (CVD), including cerebral ischemia and hemorrhage, is a widely known independent risk factor for dementia [3][4][5][6][7][8]. Vascular dysfunction is known to cause cognitive decline through changes in the blood supply [9,10], in ammation [11][12][13], and in the immune system [14], as well as through brain parenchymal damage [3,7,15]. Depression has also been suggested as a risk factor for dementia.…”

Amyloid β deposition in subcortical stroke patients and effects of educational achievement: A pilot study

“…However, whether Aβ deposits are present in or around the infarct in [ 11 C] Pittsburgh compound B (PiB)–positron emission tomography (PET) analysis remains uncertain . Indeed, a direct causal relationship between cerebrovascular risk factors/lesions and Aβ deposition has yet to be shown …”

Update on the Neurobiology of Vascular Cognitive Impairment: From Lab to Clinic

“…Dysfunction of the neurovascular unit may contribute to the amyloid accumulation in addition to a direct neuronal damage, i.e., through the disruption of the BBB and a decrease in cerebral blood flow (CBF) [60][61][62]. Further, changes of the brain glucose metabolism were particularly evident in the frontal lobe of VaD patients, thus providing a metabolic pattern of cognitive impairment different from that observed in AD [27].…”