Peripheral vascular dysfunction significantly contributed to cognitive decline and dementia risk in aging adults, according to a recent review.
Published in the journal Aging, the review highlighted the link between cardiovascular diseases (CVD) and peripheral and cerebral vascular dysfunction, which are significant contributors to the development of dementia.
Key Findings:
- Aging and Disease Risk: Aging was identified as a major non-modifiable risk factor for diseases, including CVD and dementia. CVD in mid-life was associated with memory decline and increased dementia risk in older age.
- Vascular Dysfunction: Peripheral vascular dysfunction, such as stiffening of large elastic arteries and endothelial dysfunction, contributed to CVD and cognitive decline. This dysfunction could serve as a non-invasive method to predict dementia risk.
- Oxidative Stress: Excessive production of reactive oxygen species (ROS) due to chronic low-grade inflammation, mitochondrial dysfunction, cellular senescence, and deregulated nutrient sensing was a common factor in both peripheral and cerebral vascular dysfunction.
- Mechanistic Links: The review suggested that targeting oxidative stress and improving vascular function through lifestyle changes like aerobic exercise and dietary modifications, or pharmacological agents, might reduce dementia risk.
Types of Dementia and Vascular Dysfunction:
- Alzheimer’s Disease: The most common dementia type, linked to cerebrovascular dysfunction through Aβ plaques and tau neurofibrillary tangles, which caused vascular lesions and blood-brain barrier (BBB) disruption.
- Lewy Body Dementia: Associated with α-Synuclein aggregation, triggering neuroinflammatory responses and ROS production.
- Frontotemporal Dementia: Linked to white matter alterations and small-vessel disease in the brain.
- Vascular Dementia: Caused by diseased intracranial arteries, leading to cerebral hypoperfusion and hypoxia, contributing to cognitive decline.
Peripheral and Cerebral Vascular Health:
- Cerebrovascular Dysfunction: Aging affected the brain’s ability to coordinate blood flow, leading to cognitive decline. Increased cerebrovascular pulsatility with age could damage brain structures and lead to dementia.
- Peripheral Vascular Dysfunction: Large elastic artery stiffening increased blood flow pulsatility to the brain, damaging cerebral microvessels and promoting cognitive impairment.
Shared Molecular Mechanisms:
- Inflammation: Chronic low-grade inflammation, characterized by excessive NF-κB signaling, was a key feature of aging, contributing to ROS production and vascular dysfunction.
- Mitochondrial Dysfunction: Excessive mitochondrial ROS production with aging disrupted cellular homeostasis, leading to peripheral and cerebral vascular dysfunction.
- Cellular Senescence: Accumulation of senescent cells promoted vascular and cognitive dysfunction through the senescence-associated secretory phenotype.
- Deregulated Nutrient Sensing: Reduced NAD+ bioavailability with aging impaired vascular and cognitive function, with NAD+ boosting compounds showing promise in preclinical trials.
Therapeutic Strategies:
- Aerobic Exercise: First-line therapy for improving vascular function, reducing inflammation, and enhancing mitochondrial function, which might also benefit cognitive health.
- Dietary Approaches: Mediterranean and Japanese diets, as well as intermittent fasting, showed potential in improving vascular and cognitive function through reduced oxidative stress and inflammation.
- Pharmacological Agents: NO-boosting compounds, antihypertensives, and senolytics showed promise in preclinical models for enhancing vascular and cognitive health with aging.
The study authors emphasized the importance of addressing peripheral vascular health to mitigate dementia risk with aging. Targeting shared molecular mechanisms through lifestyle and pharmacological interventions held promise for improving both peripheral vascular and brain health, potentially offering new strategies for assessing and reducing dementia risk in older adults.
Full author disclosures can be found in the published article.