Vascular contributions to Alzheimer's disease

Eisenmenger, Laura; Peret, Anthony; Famakin, Bolanle M.; Spahic, Alma; Roberts, Grant S.; Bockholt, Jeremy; Johnson, Kevin M.; Paulsen, Jane S.

doi:10.1016/j.trsl.2022.12.003

Cited by 38 publications

(36 citation statements)

References 234 publications

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“…The close relationships of individual metabolic and cardiovascular diseases with VaD and naMCI have been observed in previous studies 17,35–37 . Of the five multimorbidity clusters, we found that metabolic and cardiac‐MSK clusters were associated with VaD and naMCI, which could be partly due to shared common vascular injury mechanisms such as endothelial dysfunction, inflammation, and vascular remodeling, 35,36,38 and these mechanisms could also contribute to Alzheimer's pathology and neurodegeneration 39,40 . In the biomarker subsample, we did find that the metabolic cluster was associated with increased plasma NfL and the cardiac‐MSK cluster was associated with increased plasma Aβ42, which partially supports this pathway.…”

Section: Discussionsupporting

confidence: 78%

Multimorbidity, cognitive phenotypes, and Alzheimer's disease plasma biomarkers in older adults: A population‐based study

Ren,

Li,

Tian

et al. 2023

Alzheimer's & Dementia

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INTRODUCTIONTo examine the burden and clusters of multimorbidity in association with mild cognitive impairment (MCI), dementia, and Alzheimer's disease (AD)‐related plasma biomarkers among older adults.METHODSThis population‐based study included 5432 participants (age ≥60 years); of these, plasma amyloid beta (Aβ), total tau, and neurofilament light chain (NfL) were measured in a subsample (n = 1412). We used hierarchical clustering to generate five multimorbidity clusters from 23 chronic diseases. We diagnosed dementia and MCI following international criteria. Data were analyzed using logistic and linear regression models.RESULTSThe number of chronic diseases was associated with dementia (multivariable‐adjusted odds ratio = 1.22; 95% confidence interval [CI] = 1.11 to 1.33), AD (1.13; 1.01 to 1.26), vascular dementia (VaD) (1.44; 1.25 to 1.64), and non‐amnestic MCI (1.25; 1.13 to 1.37). Metabolic cluster was associated with VaD and non‐amnestic MCI, whereas degenerative ocular cluster was associated with AD (p < 0.05). The number of chronic diseases was associated with increased plasma Aβ and NfL (p < 0.05).DISCUSSIONMultimorbidity burden and clusters are differentially associated with subtypes of dementia and MCI and AD‐related plasma biomarkers in older adults.Highlights We used hierarchical clustering to generate five clusters of multimorbidity. The presence and load of multimorbidity were associated with dementia and mild cognitive impairment. Multimorbidity clusters were differentially associated with subtypes of dementia and Alzheimer's disease plasma biomarkers.

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Section: Discussionsupporting

confidence: 78%

Multimorbidity, cognitive phenotypes, and Alzheimer's disease plasma biomarkers in older adults: A population‐based study

Ren,

Li,

Tian

et al. 2023

Alzheimer's & Dementia

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“…This is linked with the development of a vicious cycle between microvascular damage and beta-amyloid aggregates that contribute to AD development. Brain imaging supports these observations, as well as chronic cerebral hypoperfusion, microvascular dysfunction, and perivascular space enlargement – hallmarks of small vessel disease – precede cognitive decline and changes in conventional biomarkers [276]. These mechanisms of small vessel disease are shared between vascular dementia and AD: assessment of retinal microvasculature has shown apparent microvascular dysfunction and remodelling in neurodegenerative diseases [278,279].…”

Section: Microvascular Inflammation Across the Age-related Diseases C...mentioning

confidence: 80%

“…The most prevalent form of dementia, AD, is marked by a steady decline in cognitive function and neurodegeneration. The vascular hypothesis suggests that cerebral microvascular alterations are central to the pathogenesis of AD, providing a link with CV disease [276]. Possible mechanisms include neurovascular coupling imbalances and BBB disruption [276].…”

Section: Microvascular Inflammation Across the Age-related Diseases C...mentioning

confidence: 99%

“…The vascular hypothesis suggests that cerebral microvascular alterations are central to the pathogenesis of AD, providing a link with CV disease [276]. Possible mechanisms include neurovascular coupling imbalances and BBB disruption [276]. Impaired removal of beta-amyloid may be a consequence of these neurovascular changes: vascular changes may precede the development of tau pathology [277].…”

Section: Microvascular Inflammation Across the Age-related Diseases C...mentioning

confidence: 99%

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The importance of microvascular inflammation in ageing and age-related diseases: a position paper from the ESH working group on small arteries, section of microvascular inflammation

Mengozzi

Ciuceis

Georgiopoulos

et al. 2023

Journal of Hypertension

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Microcirculation is pervasive and orchestrates a profound regulatory cross-talk with the surrounding tissue and organs. Similarly, it is one of the earliest biological systems targeted by environmental stressors and consequently involved in the development and progression of ageing and age-related disease. Microvascular dysfunction, if not targeted, leads to a steady derangement of the phenotype, which cumulates comorbidities and eventually results in a nonrescuable, very high-cardiovascular risk. Along the broad spectrum of pathologies, both shared and distinct molecular pathways and pathophysiological alteration are involved in the disruption of microvascular homeostasis, all pointing to microvascular inflammation as the putative primary culprit. This position paper explores the presence and the detrimental contribution of microvascular inflammation across the whole spectrum of chronic age-related diseases, which characterise the 21st-century healthcare landscape. The manuscript aims to strongly affirm the centrality of microvascular inflammation by recapitulating the current evidence and providing a clear synoptic view of the whole cardiometabolic derangement. Indeed, there is an urgent need for further mechanistic exploration to identify clear, very early or disease-specific molecular targets to provide an effective therapeutic strategy against the otherwise unstoppable rising prevalence of age-related diseases.

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“…4 Potential direction: Chinese herbal medicine targeting mitochondrial dysfunction for CCH related neurodegeneration pathology CCH is an independent exacerbating reason for impairment in learning and memory of PD and AD (Eisenmenger et al, 2022;Fan et al, 2022). CCH mediated mitochondrial dysfunction is one of the fundamental causes for both neurovascular damages, as well as neurodegeneration pathology aggravation.…”

Section: Restoring Mitochondrial Self-regulationmentioning

confidence: 99%

Insights of Chinese herbal medicine for mitochondrial dysfunction in chronic cerebral hypoperfusion induced cognitive impairment: Existed evidences and potential directions

Wang

Wang²,

Li³

et al. 2023

Front. Pharmacol.

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Chronic cerebral hypoperfusion (CCH) is one of the main pathophysiological markers of cognitive impairment in central nervous system diseases. Mitochondria are cores of energy generation and information process. Mitochondrial dysfunction is the key upstream factors of CCH induced neurovascular pathology. Increasing studies explored the molecular mechanisms of mitochondrial dysfunction and self-repair for effective targets to improve CCH-related cognitive impairment. The clinical efficacy of Chinese herbal medicine in the treatment of CCH induced cognitive impairment is definite. Existed evidences from pharmacological studies have further proved that, Chinese herbal medicine could improve mitochondrial dysfunction and neurovascular pathology after CCH by preventing calcium overload, reducing oxidative stress damage, enhancing antioxidant capacity, inhibiting mitochondria-related apoptosis pathway, promoting mitochondrial biogenesis and preventing excessive activation of mitophagy. Besides, CCH mediated mitochondrial dysfunction is one of the fundamental causes for neurodegeneration pathology aggravation. Chinese herbal medicine also has great potential therapeutic value in combating neurodegenerative diseases by targeting mitochondrial dysfunction.

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Vascular contributions to Alzheimer's disease

Cited by 38 publications

References 234 publications

Multimorbidity, cognitive phenotypes, and Alzheimer's disease plasma biomarkers in older adults: A population‐based study

Multimorbidity, cognitive phenotypes, and Alzheimer's disease plasma biomarkers in older adults: A population‐based study

The importance of microvascular inflammation in ageing and age-related diseases: a position paper from the ESH working group on small arteries, section of microvascular inflammation

Insights of Chinese herbal medicine for mitochondrial dysfunction in chronic cerebral hypoperfusion induced cognitive impairment: Existed evidences and potential directions

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