Contribution of cerebral microvascular mechanisms to age-related cognitive impairment and dementia

Area of Science:

• Neurology
• Vascular Biology
• Gerontology

Background:

• Alzheimer's disease and related dementias (AD/ADRD) pose significant global health challenges.
• Aging, hypertension, and diabetes are key risk factors for AD/ADRD, with no current effective treatments.
• Emerging evidence links cerebral vascular dysfunction and hypoperfusion to AD/ADRD pathogenesis, preceding other pathological hallmarks.

Purpose of the Study:

• To highlight emerging concepts and mechanisms of microvascular contribution to AD/ADRD.
• To explore hypotheses involving anterograde and retrograde cerebral vascular pathways.
• To discuss the roles of cerebral capillaries and the venous system in AD/ADRD.

Main Methods:

• Commentary synthesizing current evidence on microvascular roles in AD/ADRD.
• Discussion of underlying mechanisms including vascular endothelial dysfunction, oxidative stress, inflammation, and cellular senescence.
• Exploration of impacts on cerebral blood flow autoregulation and neurovascular coupling.

Main Results:

• Microvascular dysfunction is increasingly recognized as a critical factor in AD/ADRD.
• Impaired cerebral blood flow, neurovascular coupling, and capillary/venous system dysfunction are implicated.
• Multiple pathways including endothelial dysfunction, oxidative stress, and inflammation contribute to vascular pathology in AD/ADRD.

Conclusions:

• The microvasculature plays a significant, yet not fully understood, role in the development of AD/ADRD.
• Targeting microvascular pathways presents a potential therapeutic avenue for AD/ADRD.
• Further research into cerebral vascular dysfunction is essential for advancing AD/ADRD treatment strategies.