Sporadic Cerebral Small Vessel Disease: A Growing Concern in Aging Societies

As the global population ages, the prevalence of age-related sporadic cerebral small vessel disease (CSVD) is on the rise. This condition, often overlooked due to its subtle early symptoms, can have a profound impact on the health and well-being of older adults. In this article, we will explore the pathology, pathophysiology, detection methods, and clinical manifestations of sporadic CSVD, highlighting its significance as a “pandemic” of the aging society.

Introduction

With an aging population, the prevalence of age-related sporadic CSVD is increasing. Community prevalence of confluent white matter hyperintensities (WMH), lacunes, and cerebral microbleeds varies, and CSVD is commonly asymptomatic or associated with subtle changes in mental and/or motor functions. It may progress slowly and become “malignant” with precipitating events, presenting as stroke or stroke-like episodes, leading to dementia and disability. Age is a major risk factor, and CSVD is often found in patients with other age-related brain diseases like Alzheimer’s disease (AD), with recent studies suggesting an etiological role in AD.

Pathology and Pathophysiology

Anatomy

Cerebral small vessels include intracranial perforating arteries, arterioles, capillaries, and venules. Capillaries form the blood-brain barrier (BBB) and are part of the neurovascular units (NVU).

Small Vessel Changes

Affected arterioles show loss of smooth muscle cells, subintimal deposits, thickening, and possible rupture. Venules may have collagenosis, and capillary density may be lost.

Brain Parenchymal Changes

Changes include infarcts, hemorrhages, enlarged perivascular space (ePVS), and white matter changes (WMC). Early hypotheses suggested arteriosclerotic occlusion leading to infarcts, but recent evidence points to endothelial dysfunctions, BBB breakdown, and other pathological processes as more important. With time, secondary loss of white and grey matter occurs.

Risk Factors

Sporadic CSVD is related to aging, vascular diseases (e.g., hypertension, smoking), and genetic susceptibility. Genetic factors may explain differences in disease development among individuals with similar risk factors. Population studies show ethnic differences in WMH prevalence.

In Vivo Detection

Direct Visualization

Direct visualization of small vessels is difficult, but advanced techniques like 7.0-Tesla MR angiopathy or three-dimensional rotational angiography may help.

Other Methods

Transcranial Doppler ultrasound (TCD) and retinal imaging can assess cerebral small vessel measures. TCD’s pulsatility index (PI) reflects vascular resistance, and retinal imaging correlates with CSVD markers.

Neuroimaging

Conventional assessment uses brain MRI (or CT) to evaluate related brain parenchymal changes. The STandards for ReportIng Vascular changes on nEuroimaging describes MRI characteristics. Other techniques like diffusion tensor imaging (DTI) and functional MRI can detect additional changes. Biomarkers in cerebrospinal fluid (CSF) or blood may reflect pathophysiological processes.

Clinical Manifestations

Stroke

Sporadic CSVD commonly presents as stroke (lacunar or deep ICH) or transient ischemic attack (TIA). Acute lesions can cause various clinical syndromes, and cognitive decline may occur if the lesion involves a cognitive relevant site. The presence of cerebral microbleeds increases the risk of ICH, and subclinical CSVD increases stroke and mortality risks.

Cognitive Impairment

Even without overt stroke, CSVD can cause cognitive impairment. The “subcortical” type is characterized by slow processing speed, executive dysfunction, and reduced attention span. Cognitive assessment should include tests sensitive to these domains. The association with cognitive impairment depends on factors like CSVD severity, site, brain network disruption, atrophy, and concurrent pathologies. Cognition can decline progressively, and CSVD increases the risk of dementia in stroke and AD contexts.

Others

Apathy and depression are common behavioral disturbances. Other manifestations include parkinsonism (lower body involvement, minimal levodopa response) and urinary incontinence (at advanced stages). Severe CSVD can lead to pseudobulbar palsy and multiple impairments.

Conclusion

Sporadic CSVD is a significant health issue in aging societies. Understanding its pathology, detection, and clinical manifestations is crucial for early diagnosis and management. Further research is needed to explore genetic and environmental factors, develop better detection methods, and improve treatment strategies. As the population ages, addressing CSVD becomes increasingly important to reduce its impact on individuals and society.

doi: 10.1097/CM9.0000000000001320

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