Cerebral circulation in aging

Nagata, Ken; Yamazaki, Takashi; Takano, Daiki; Maeda, Tetsuya; Fujimaki, Yumi; Nakase, Taizen; Sato, Yuichi

doi:10.1016/j.arr.2016.06.001

Cited by 73 publications

(58 citation statements)

References 102 publications

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“…We will first discuss the relation of T2D with large artery disease, namely atherosclerosis. Cerebral hypoperfusion, of which atherosclerotic stenosis is a primary cause is one posited contributor to the pathogenic process in AD. Both AD and atherosclerosis share several common risk factors including T2D, APOE ε4 and dyslipidaemia .…”

Section: Cerebral Vascular Disease Pathologymentioning

confidence: 99%

Review: Relationship of type 2 diabetes to human brain pathology

Pruzin

Nelson

Abner

et al. 2018

Neuropathology Appl Neurobio

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Type 2 diabetes (T2D) and Alzheimer's disease (AD) are both highly prevalent diseases worldwide, and each is associated with high-morbidity and high-mortality. Numerous clinical studies have consistently shown that T2D confers a two-fold increased risk for a dementia, including dementia attributable to AD. Yet, the mechanisms underlying this relationship, especially nonvascular mechanisms, remain debated. Cerebral vascular disease (CVD) is likely to be playing a role. But increased AD neuropathologic changes (ADNC), specifically neuritic amyloid plaques (AP) and neurofibrillary tangles (NFT), are also posited mechanisms. The clinicopathological studies to date demonstrate T2D to be consistently associated with infarcts, particularly subcortical lacunar infarcts, but not ADNC, suggesting the association of T2D with dementia may largely be mediated through CVD. Furthermore, growing interest exists in insulin resistance (IR), particularly IR within the brain itself, which may be an associated but distinct phenomenon from T2D, and possibly itself associated with ADNC. Other mechanisms largely related to protein processing and efflux in the central nervous system with altered function in T2D may also be involved. Such mechanisms include islet amyloid polypeptide (or amylin) deposition, co-localized with beta-amyloid and found in more abundance in the AD temporal cortex, blood-brain barrier breakdown and dysfunction, potentially related to pericyte degeneration, and disturbance of brain lymphatics, both in the glial lymphatic system and the newly discovered discrete central nervous system lymph vessels. Medical research is ongoing to further disentangle the relationship of T2D to dementia in the ageing human brain.

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Section: Cerebral Vascular Disease Pathologymentioning

confidence: 99%

Review: Relationship of type 2 diabetes to human brain pathology

Pruzin

Nelson

Abner

et al. 2018

Neuropathology Appl Neurobio

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“…Internal carotid arteries (ICA) and basilar artery (BA) join to form the Circle of Willis which gives rise to cerebral arteries: anterior (ACA), middle (MCA) and posterior (PCA) cerebral arteries. Used with permission from (189). …”

Section: Figurementioning

confidence: 99%

Impact of Metabolic Diseases on Cerebral Circulation: Structural and Functional Consequences

Coucha

Abdelsaid

Ward

et al. 2018

Comprehensive Physiology

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Metabolic diseases including obesity, insulin resistance, and diabetes have profound effects on cerebral circulation. These diseases not only affect the architecture of cerebral blood arteries causing adverse remodeling, pathological neovascularization, and vasoregression but also alter the physiology of blood vessels resulting in compromised myogenic reactivity, neurovascular uncoupling, and endothelial dysfunction. Coupled with the disruption of blood brain barrier (BBB) integrity, changes in blood flow and microbleeds into the brain rapidly occur. This overview is organized into sections describing cerebrovascular architecture, physiology, and BBB in these diseases. In each section, we review these properties starting with larger arteries moving into smaller vessels. Where information is available, we review in the order of obesity, insulin resistance, and diabetes. We also tried to include information on biological variables such as the sex of the animal models noted since most of the information summarized was obtained using male animals. © 2018 American Physiological Society. Compr Physiol 8:773-799, 2018.

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“…This is also consistent with glucose hypometabolism seen in the brains of individuals with advanced AD (Daulatzai 2016; Silverman et al 2001). It is important to note that these mechanisms are shared by both vascular dementia and AD (Nagata et al 2016). …”

Section: Hypoxia-inducible Factor Cerebral Blood Flow and Memorymentioning

confidence: 99%

The Role of Hypoxia-Inducible Factor 1 in Mild Cognitive Impairment

et al. 2016

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Neuroinflammation and reactive oxygen species are thought to mediate the pathogenesis of Alzheimer’s disease (AD), suggesting that mild cognitive impairment (MCI), a prodromal stage of AD, may be driven by similar insults. Several studies document that hypoxia-inducible factor 1 (HIF-1) is neuroprotective in the setting of neuronal insults, since this transcription factor drives the expression of critical genes that diminish neuronal cell death. HIF-1 facilitates glycolysis and glucose metabolism, thus helping to generate reductive equivalents of NADH/NADPH that counter oxidative stress. HIF-1 also improves cerebral blood flow which opposes the toxicity of hypoxia. Increased HIF-1 activity and/or expression of HIF-1 target genes, such as those involved in glycolysis or vascular flow, may be an early adaptation to the oxidative stressors that characterize MCI pathology. The molecular events that constitute this early adaptation are likely neuroprotective, and might mitigate cognitive decline or the onset of full-blown AD. On the other hand, prolonged or overwhelming stressors can convert HIF-1 into an activator of cell death through agents such as Bnip3, an event that is more likely to occur in late MCI or advanced Alzheimer’s dementia.

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Cerebral circulation in aging

Cited by 73 publications

References 102 publications

Review: Relationship of type 2 diabetes to human brain pathology

Review: Relationship of type 2 diabetes to human brain pathology

Impact of Metabolic Diseases on Cerebral Circulation: Structural and Functional Consequences

The Role of Hypoxia-Inducible Factor 1 in Mild Cognitive Impairment

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