Journal of integrative neuroscienceSep 8, 2025

How Problems in Brain Blood Flow and Support Cells May Contribute to Vascular Cognitive Impairment and Potential Treatments

Alzheimers & Treatments Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jan 19, 2026

Abstract

Cognitive impairment, which can progress from mild cognitive impairment to dementia, represents a significant burden on individuals and healthcare systems.

Vascular cognitive impairment (VCI) encompasses a range of conditions from subcortical ischemic VCI to mixed dementia involving vascular and Alzheimer's-type pathologies.
Endothelial dysfunction in the neurovascular unit (NVU) may initiate a cycle of dysregulation that includes impaired neurovascular coupling, blood-brain barrier breakdown, and neuroinflammation.
Emerging evidence indicates that cerebral endothelial cells are crucial for regulating nutrient transport and initiating neuroinflammatory responses.
Proactive management of vascular risk factors like hypertension and diabetes may help prevent progression from vascular injury to irreversible dementia.
Preserving the integrity of the NVU is associated with strategies to mitigate the global burden of dementia.

Simplified

Cognitive impairment represents a progressive neurodegenerative condition with severity ranging from mild cognitive impairment (MCI) to dementia and exerts significant burdens on both individuals and healthcare systems. Vascular cognitive impairment (VCI) represents a heterogeneous clinical continuum, spanning a spectrum from subcortical ischemic VCI (featuring small vessel disease, white matter lesions, and lacunar infarcts) to mixed dementia, where vascular and Alzheimer's-type pathologies coexist. While traditionally linked to macro- and microvascular dysfunction, the mechanisms underlying VCI remain complex. However, contemporary research has gone beyond structural vascular damage, highlighting the neurovascular unit (NVU) as a critical mediator. Emerging evidence demonstrates that cerebral endothelial cells within the NVU not only regulate oxygen and nutrient transport but also orchestrate neuroinflammatory signaling and neurovascular coupling (NVC). Crucially, endothelial dysfunction initiates a self-perpetuating cycle of NVU dysregulation characterized by: (1) NVC impairment through diminished nitric oxide bioavailability and calcium signaling defects, (2) blood-brain barrier (BBB) breakdown via tight-junction protein degradation and pericyte detachment, and (3) neuroinflammation driven by endothelial-derived cytokine release and leukocyte infiltration. By integrating recent advances in NVU biology, we have established a framework to inform clinical strategies for early diagnosis and targeted therapies, which we outline in this review. Moreover, proactive management of vascular risk factors (e.g., hypertension, diabetes) in presymptomatic stages may mitigate the progression from vascular injury to irreversible dementia, underscoring its preventive potential. These insights reinforce the idea that preserving NVU integrity represents a pivotal approach to mitigating the global dementia burden.

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How Problems in Brain Blood Flow and Support Cells May Contribute to Vascular Cognitive Impairment and Potential Treatments

Abstract

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