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Atherosclerotic burden and cerebral small vessel disease: exploring the link through microvascular aging and cerebral
Anna Csiszar1,2,3, Anna Ungvari4, Roland Patai1
1Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Insights
Atherosclerosis accelerates aging in brain
Area of Science:
- Neuroscience
- Vascular Biology
- Gerontology
Background:
- Cerebral microhemorrhages (CMHs) are linked to cognitive decline and dementia.
- CMHs are a key feature of cerebral small vessel disease (CSVD).
- Atherosclerosis is a common large vessel disease in aging populations.
Purpose of the Study:
- To explore the hypothesis that atherosclerosis contributes to CSVD and CMHs.
- To examine the role of accelerated vascular aging in CMH development.
- To understand the link between systemic vascular health and neurovascular integrity.
Main Methods:
- Review of epidemiological data on CMHs, atherosclerosis, and CSVD.
- Analysis of shared pathophysiological mechanisms between macrovascular and microvascular aging.
- Examination of the impact of risk factors like hypertension and amyloid pathology.
Main Results:
- Evidence suggests atherosclerosis extends pathological influence to cerebral microcirculation.
- Accelerated microvascular aging, driven by similar pathways as atherogenesis, increases microvascular fragility.
- Hypertension and amyloid pathology exacerbate CMH formation.
Conclusions:
- Vascular aging is a continuum linking atherosclerosis to CSVD and CMHs.
- Shared mechanisms, including oxidative stress and inflammation, drive both large and small vessel disease.
- Understanding these links can inform future therapeutic strategies for neurovascular health.
Abstract:
Cerebral microhemorrhages (CMHs, also known as cerebral microbleeds) are a critical but frequently underestimated aspect of cerebral small vessel disease (CSVD), bearing substantial clinical consequences. Detectable through sensitive neuroimaging techniques, CMHs reveal an extensive pathological landscape. They are prevalent in the aging population, with multiple CMHs often being observed in a given individual. CMHs are closely associated with accelerated cognitive decline and are increasingly recognized as key contributors to the pathogenesis of vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). This review paper delves into the hypothesis that atherosclerosis, a prevalent age-related large vessel disease, extends its pathological influence into the cerebral microcirculation, thereby contributing to the development and progression of CSVD, with a specific focus on CMHs. We explore the concept of vascular aging as a continuum, bridging macrovascular pathologies like atherosclerosis with microvascular abnormalities characteristic of CSVD. We posit that the same risk factors precipitating accelerated aging in large vessels (i.e., atherogenesis), primarily through oxidative stress and inflammatory pathways, similarly instigate accelerated microvascular aging. Accelerated microvascular aging leads to increased microvascular fragility, which in turn predisposes to the formation of CMHs. The presence of hypertension and amyloid pathology further intensifies this process. We comprehensively overview the current body of evidence supporting this interconnected vascular hypothesis. Our review includes an examination of epidemiological data, which provides insights into the prevalence and impact of CMHs in the context of atherosclerosis and CSVD. Furthermore, we explore the shared mechanisms between large vessel aging, atherogenesis, microvascular aging, and CSVD, particularly focusing on how these intertwined processes contribute to the genesis of CMHs. By highlighting the role of vascular aging in the pathophysiology of CMHs, this review seeks to enhance the understanding of CSVD and its links to systemic vascular disorders. Our aim is to provide insights that could inform future therapeutic approaches and research directions in the realm of neurovascular health.
