Vascular and Metabolic Factors in Alzheimer’s Disease and Related Dementias: Introduction

Iadecola, Costantino

doi:10.1007/s10571-015-0319-y

Cited by 45 publications

(40 citation statements)

References 45 publications

(48 reference statements)

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“…This might theoretically depend on the higher prevalence of previous stroke in the MCI group (similar to MIX); however, TRAIL levels were not higher in MCI patients with previous stroke (data not shown). More generally, by highlighting the possible link between TRAIL and the diagnosis of MCI [29,30,31], our data might support previous results of other groups underlining the important role of vascular factors in the pathogenesis of cognitive impairment in the elderly, independent of the final etiological diagnosis. …”

Section: Discussionsupporting

confidence: 87%

Serum Soluble Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Levels in Older Subjects with Dementia and Mild Cognitive Impairment

Tisato

Rimondi

Brombo

et al. 2016

Dement Geriatr Cogn Disord

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Background: The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been involved in both physiological and pathological conditions, including vascular pathologies and pathologies of the central nervous system. Nonetheless, the knowledge about the role of systemic TRAIL in patients affected by different types of dementia and mild cognitive impairment (MCI) is still limited. Objective: We assessed serum TRAIL levels in a large cohort of older individuals (n = 644) including patients with late-onset Alzheimer's disease (LOAD), vascular dementia (VAD), ‘mixed' dementia (MIX), MCI, and healthy controls. Methods: Circulating TRAIL was measured by ELISA. Results: At univariate analysis, TRAIL levels were higher in VAD, MIX, and MCI patients compared with LOAD patients and controls. Using the multiple linear regression model, we found that TRAIL levels were associated with VAD and MCI, but not MIX, independent of potential confounding factors. Conclusion: The finding of high levels of circulating TRAIL in VAD and MCI seems to suggest that both of these conditions are characterized by a significant vascular damage with respect to LOAD.

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Section: Discussionsupporting

confidence: 87%

Serum Soluble Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Levels in Older Subjects with Dementia and Mild Cognitive Impairment

Tisato

Rimondi

Brombo

et al. 2016

Dement Geriatr Cogn Disord

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“…Although the mechanisms that contribute to dementia remain unclear, attention has shifted from the solitary amyloid hypothesis toward a complex cause that acknowledges the vascular contribution in the pathogenesis of mild cognitive impairment and dementia, including Alzheimer disease. [1][2][3] In support of this paradigm shift, there is extensive overlap between traditional cardiovascular disease and cerebrovascular disease risk factors, such as older age, hypertension, diabetes mellitus, higher body mass index, and increased risk of cognitive impairment and dementia. More recently, elevated aortic stiffness has been identified as a novel risk factor associated with cognitive impairment among older adults with and without hypertension independent of other cardiovascular disease risk factors.…”

mentioning

confidence: 99%

Higher Aortic Stiffness Is Associated With Lower Global Cerebrovascular Reserve Among Older Humans

DuBose¹,

Ponto²,

Moser³

et al. 2018

Hypertension

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Abstract-Greater aortic stiffness and pulse pressure are associated with cerebrovascular remodeling, reduced white matter microstructure, and cognitive performance with aging in humans. However, it is unclear whether aortic stiffness and pulse pressure are associated with reduced basal global cerebral blood flow (CBF) and cerebrovascular reserve among older adults. Global CBF was quantified in 205 adults (range, 19-87 years; mean±SE: 30.6±1.3 years) using quantitative [ 15 O] water brain positron emission tomography imaging. In a subset of older adults (n=24; 70.0±2.0 years), aortic stiffness (carotid femoral pulse wave velocity) and cerebrovascular reserve (change in global CBF after intravenous infusion of acetazolamide) were assessed. In the entire cohort, global CBF was lower in older compared with young adults (36.5±1.1 versus 50.5±0.7 mL/min per 100 mL; P<0.001). Global CBF was higher in young women compared with young men (51.0±0.30 versus 47.4±0.03 mL/min per 100 mL; P<0.001) but did not differ between older women and men (P=0.63). In older adults, greater carotid femoral pulse wave velocity was associated with lower cerebrovascular reserve (r=−0.68; P=0.001 adjusted for age, sex, and mean arterial pressure) but not global CBF (r=0.13; P=0.60). Brachial pulse pressure was not associated with lower cerebrovascular reserve (r=−0.37; P=0.159) when adjusted for age and sex. These data indicate that the age-related increases in aortic stiffness may contribute, in part, to the brain's impaired ability to augment blood flow in response to a stimulus with aging in humans. (Hypertension. 2018;72:476-482.

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“…Historically, these pathologies have been considered distinct from each other, even mutually exclusive (Iadecola, 2010; Roseberg et al, 2016; Erkinjutti and Gauthier, 2009). However there is a growing awareness of the similarities between the two illnesses, with a growing number of AD patients also exhibiting VCI pathology such as cerebrovascular lesions as well as reduced vascular reactivity and CBF (Calabrese et al, 2016; Binnewijzend et al, 2016; Cantin et al, 2011; Iadecola, 2016; Ruitenberg et al, 2005). While a causative relationship between the two pathologies is of debate, the Nun Study did highlight that of the participants who met the criteria of AD, those with ischemic lesions had poorer cognitive function than those with no brain lesions (Marchant et al, 2013; Wang et al, 2016; Snowdon et al, 1997).…”

Section: Cerebrovascular Pathology and Cytochrome P450 Eicosanoidsmentioning

confidence: 99%

Cytochrome P450 eicosanoids in cerebrovascular function and disease

Davis

Liu

Alkayed

2017

Pharmacology & Therapeutics

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Cytochrome P450 eicosanoids play important roles in brain function and disease through their complementary actions on cell-cell communications within the neurovascular unit (NVU) and mechanisms of brain injury. Epoxy- and hydroxyeicosanoids, respectively formed by cytochrome P450 epoxygenases and ω-hydroxylases, play opposing roles in cerebrovascular function and in pathological processes underlying neural injury, including ischemia, neuroinflammation and oxidative injury. P450 eicosanoids also contribute to cerebrovascular disease risk factors, including hypertension and diabetes. We summarize studies investigating the roles P450 eicosanoids in cerebrovascular physiology and disease to highlight the existing balance between these important lipid signaling molecules, as well as their roles in maintaining neurovascular homeostasis and in acute and chronic neurovascular and neurodegenerative disorders.

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Vascular and Metabolic Factors in Alzheimer’s Disease and Related Dementias: Introduction

Cited by 45 publications

References 45 publications

Serum Soluble Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Levels in Older Subjects with Dementia and Mild Cognitive Impairment

Serum Soluble Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Levels in Older Subjects with Dementia and Mild Cognitive Impairment

Higher Aortic Stiffness Is Associated With Lower Global Cerebrovascular Reserve Among Older Humans

Cytochrome P450 eicosanoids in cerebrovascular function and disease

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