Terminology
- Cerebral small vessel disease (CSVD): a broad term describing heterogeneous conditions, such as hypertensive vasculopathy and cerebral amyloid angiopathy (CAA), affecting blood vessels with diameters ranging 50-500 \(\mu\)m.
Consequences of CSVD
- Cognitive impairment and possible mechanisms:
- CBF↓
- Blood brain function (BBB) integrity damage (low evidence level), leaked substances that may damage brain parenchyma are unknown, e.g., frbrinogen leakage → activation of microglia, blockage of oligodendrocyte replacement
- Vasoreactivity, may lead to chronic or intermittent hypoperfusion
- Abnormal diffusion and perfusion patterns
- White matter hyperintensity (WMH)
- Oligodendrocyte precurser cell progression, inhibited by endothelial dysfunction
- Symmetric parkinsonism
Magnetic resonance imaging (MRI) markers of CSVD:
- WMH, most clearly associated with dementia
- Recent small subcortical infarcts, lacunae of vascular origin, and microbleeds (most specific and clinically available markers at present)
- BBB dysfunction measures: dynamic contrast-enhanced MRI, cerebral spinal fluid/serum albumin ratio
Challenges of determing implications of CSVD
- Making premortem diagnosis for vascular cognitive impairment and dementia (VCID) associated with CSVD
- Lack of clear neuropathological consensus criteria
- Scarcity of sensitive and specific in-vivo biomarkers
- Lack of distinct clinical syndromes
- More challenging in the presence of neurodegenerative diseases, e.g., 80%-100% people with amyloid plaques have CAA
Management
- Antihyperyensive treatment-WMH↓
- Antiplatelet therapy-concerns with bleeding
- Statin-silent infarcts↓ and WMH↓
- Diabetes control
- Cholinersterase inhibitors-modest benefit and undesirable side effects
Reference:
Bos D, Wolters FJ, Darweesh SKL, Vernooij MW, de Wolf F, Ikram MA, Hofman A. Cerebral small vessel disease and the risk of dementia: A systematic review and meta-analysis of population-based evidence. Alzheimers Dement. 2018 Nov;14(11):1482-1492.
Elahi FM, Wang MM, Meschia JF. Cerebral Small Vessel Disease-Related Dementia: More Questions Than Answers. Stroke. 2023 Mar;54(3):648-660.