Time-restricted feeding (TRF) for prevention of age-related vascular cognitive impairment and dementia

Abstract Aging-induced pathological alterations of the circulatory system play a critical role in morbidity and mortality of older adults. While the importance of cellular and molecular mechanisms of arterial aging for increased cardiovascular risk in older adults is increasingly appreciated, aging processes of veins are much less studied and understood than those of arteries. In this review, age-related cellular and morphological alterations in the venous system are presented. Similarities and dissimilarities between arterial and venous aging are highlighted, and shared molecular mechanisms of arterial and venous aging are considered. The pathogenesis of venous diseases affecting older adults, including varicose veins, chronic venous insufficiency, and deep vein thrombosis, is discussed, and the potential contribution of venous pathologies to the onset of vascular cognitive impairment and neurodegenerative diseases is emphasized. It is our hope that a greater appreciation of the cellular and molecular processes of vascular aging will stimulate further investigation into strategies aimed at preventing or retarding age-related venous pathologies.

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Role of age-related alterations of the cerebral venous circulation in the pathogenesis of vascular cognitive impairment

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00776.2018 ◽

2019 ◽

Vol 316 (5) ◽

pp. H1124-H1140 ◽

Cited By ~ 14

Author(s):

Gabor A. Fulop ◽

Stefano Tarantini ◽

Andriy Yabluchanskiy ◽

Andrea Molnar ◽

Calin I. Prodan ◽

...

Keyword(s):

Cognitive Impairment ◽

Cerebral Arteries ◽

Vascular Cognitive Impairment ◽

Cerebral Veins ◽

Older Individuals ◽

Low Velocity ◽

Venous Circulation ◽

Age Related ◽

The Brain

There has been an increasing appreciation of the role of vascular contributions to cognitive impairment and dementia (VCID) associated with old age. Strong preclinical and translational evidence links age-related dysfunction and structural alterations of the cerebral arteries, arterioles, and capillaries to the pathogenesis of many types of dementia in the elderly, including Alzheimer’s disease. The low-pressure, low-velocity, and large-volume venous circulation of the brain also plays critical roles in the maintenance of homeostasis in the central nervous system. Despite its physiological importance, the role of age-related alterations of the brain venous circulation in the pathogenesis of vascular cognitive impairment and dementia is much less understood. This overview discusses the role of cerebral veins in the pathogenesis of VCID. Pathophysiological consequences of age-related dysregulation of the cerebral venous circulation are explored, including blood-brain barrier disruption, neuroinflammation, exacerbation of neurodegeneration, development of cerebral microhemorrhages of venous origin, altered production of cerebrospinal fluid, impaired function of the glymphatics system, dysregulation of cerebral blood flow, and ischemic neuronal dysfunction and damage. Understanding the age-related functional and phenotypic alterations of the cerebral venous circulation is critical for developing new preventive, diagnostic, and therapeutic approaches to preserve brain health in older individuals.

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Clinical presentations and epidemiology of vascular dementia

Clinical Science ◽

10.1042/cs20160607 ◽

2017 ◽

Vol 131 (11) ◽

pp. 1059-1068 ◽

Cited By ~ 57

Author(s):

Eric E. Smith

Keyword(s):

Cognitive Impairment ◽

Brain Injury ◽

Cardiovascular Diseases ◽

Small Vessel Disease ◽

Later Life ◽

Vascular Cognitive Impairment ◽

Large Artery ◽

Age Related ◽

Clinical Syndromes ◽

Artery Disease

Cerebrovascular and cardiovascular diseases cause vascular brain injury that can lead to vascular cognitive impairment (VCI). VCI is the second most common neuropathology of dementia and mild cognitive impairment (MCI), accounting for up to one-third of the population risk. It is frequently present along with other age-related pathologies such as Alzheimer's disease (AD). Multiple etiology dementia with both VCI and AD is the single most common cause of later life dementia. There are two main clinical syndromes of VCI: post-stroke VCI in which cognitive impairment is the immediate consequence of a recent stroke and VCI without recent stroke in which cognitive impairment is the result of covert vascular brain injury detected only on neuroimaging or neuropathology. VCI is a syndrome that can result from any cause of infarction, hemorrhage, large artery disease, cardioembolism, small vessel disease, or other cerebrovascular or cardiovascular diseases. Secondary prevention of further vascular brain injury may improve outcomes in VCI.

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Integrative Role of Hyperbaric Oxygen Therapy on Healthspan, Age-Related Vascular Cognitive Impairment, and Dementia

Frontiers in Aging ◽

10.3389/fragi.2021.678543 ◽

2021 ◽

Vol 2 ◽

Author(s):

Priya Balasubramanian ◽

Jordan Delfavero ◽

Adam Nyul-Toth ◽

Amber Tarantini ◽

Rafal Gulej ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Hyperbaric Oxygen ◽

Hyperbaric Oxygen Therapy ◽

Oxygen Therapy ◽

Vascular Cognitive Impairment ◽

The Body ◽

World Population ◽

Age Related

Growing life expectancy will contribute to the on-going shift towards a world population increasingly comprised of elderly individuals. This demographic shift is associated with a rising prevalence of age-related diseases, among all age-related pathologies it has become crucial to understand the age-associated cognitive changes that remain a major risk factor for the development of vascular cognitive impairment and dementia (VCID). Furthermore, age-related Alzheimer’s disease and other neurogenerative diseases with vascular etiology are the most prominent contributing factors for the loss of cognitive function observed in aging. Hyperbaric Oxygen Therapy (HBOT) achieves physiologic effects by increasing oxygen tension (PO2), raising oxygen tissue levels, decreasing intracranial pressure and relieving cerebral edema. Many of the beneficial effects of HBOT exert their protective effects at the level of the microcirculation. Furthermore, the microcirculation’s exquisite pervasive presence across every tissue in the body, renders it uniquely able to influence the local environment of most tissues and organs, including the brain. As such, treatments aimed at restoring aging-induced functional and structural alterations of the cerebral microcirculation may potentially contribute to the amelioration of a range of age-related pathologies including vascular cognitive impairment, Alzheimer’s disease, and vascular dementias. Despite the presented evidence, the efficacy and safety of HBOT for the treatment of age-related vascular cognitive impairment and dementia remains understudied. The present review aims to examine the existing evidence indicative of a potential therapeutic role for HBOT-induced hyperoxia against age-related cerebromicrovascular pathologies contributing to cognitive impairment, dementia and decreased healthspan in the elderly.

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Can oligodendrocyte precursor cells be a therapeutic target for mitigating cognitive decline in cerebrovascular disease?

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x20929432 ◽

2020 ◽

Vol 40 (8) ◽

pp. 1735-1736 ◽

Cited By ~ 2

Author(s):

Ken Arai

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Memory Deficits ◽

Vascular Cognitive Impairment ◽

Precursor Cells ◽

Oligodendrocyte Precursor Cells ◽

Age Related ◽

White Matter Development ◽

Oligodendrocyte Precursor ◽

Novel Therapeutic

Oligodendrocyte precursor cells (OPCs) give rise to mature myelin-forming oligodendrocytes during white matter development. In adult brains, some populations of OPCs remain to renew oligodendrocyte pools and myelin. Two recent studies highlight the importance of OPCs in white matter homeostasis. Genetic tracing studies suggest that age-related decline in OPCs may contribute to diminished myelin renewal and memory deficits in mouse models. Single cell transcriptomics and imaging may now define specific subsets of OPCs involved in process elaboration, motility and myelination. These advances raise the possibility of pursuing OPCs as novel therapeutic targets for vascular cognitive impairment.

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Inhibitory control deficits in vascular cognitive impairment revealed using the MILO task.

10.31234/osf.io/zhmbv ◽

2020 ◽

Author(s):

Emma Richards ◽

Ian Michael Thornton ◽

Anthony Bayer ◽

Andrea Tales

Keyword(s):

Cognitive Impairment ◽

Visual Search ◽

Inhibitory Control ◽

Vascular Cognitive Impairment ◽

Error Rates ◽

Localization Task ◽

Control Groups ◽

Inhibitory Deficit ◽

Age Related ◽

Serial Reaction

We used the MILO (Multi-Item Localization) task to characterise the performance of a group of older adults diagnosed with mild to moderate vascular cognitive impairment (VCI). The MILO task is designed to explore the temporal context of visual search and in addition to measuring overall completion time, provides a profile of serial reaction time (SRT) patterns across all items in a sequence. Of particular interest here, is the Vanish/Remain MILO manipulation that can identify problems with inhibitory control during search. Typically, the slope of the SRT functions are identical, regardless of whether items Vanish or Remain visible when selected, indicating an ability to ignore previously selected targets. Based on the distributed nature of VCI-related pathology and previous visual search studies from our group, we speculated that MILO performance would be compromised in this group of participants when items remained visible after being selected relative. Compared to cognitively healthy, age-matched control participants, the performance of VCI participants was characterised by overall slowing, increased error rates, and crucially, a compromised ability to use inhibitory tagging. As predicted, VCI participants had a significantly shallower Remain versus Vanish SRT function, whereas slopes were identical for control groups. Overall, our findings suggest that the MILO task could be a useful tool for identifying non-age-related changes in behaviour with patient populations, and clearly hints at a specific inhibitory deficit in VCI.

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