Exploring the neuroprotective role of physical activity in cerebral small vessel disease

Abstract

Cerebral small vessel disease (cSVD) is a common neurological finding characterized by abnormalities of the small blood vessels in the brain. Previous research has established a strong connection between cSVD and stroke, as well as neurodegenerative disorders, notably Alzheimer's disease (AD) and other dementias. As the search for effective interventions continues, physical activity (PA) has emerged as a potential preventative and therapeutic avenue. This review synthesizes the human and animal literature on the influence of PA on cSVD, highlighting the importance of determining optimal exercise protocols, considering aspects such as intensity, duration, timing, and exercise type. Furthermore, the necessity of widening the age bracket in research samples is discussed, ensuring a holistic understanding of the interventions across varying pathological stages of the disease. The review also suggests the potential of exploring diverse biomarkers and risk profiles associated with clinically significant outcomes. Moreover, we review findings demonstrating the beneficial effects of PA in various rodent models of cSVD, which have uncovered numerous mechanisms of neuroprotection, including increases in neuroplasticity and integrity of the vasculature and white matter; decreases in inflammation, oxidative stress, and mitochondrial dysfunction; and alterations in amyloid processing and neurotransmitter signaling. In conclusion, this review highlights the potential of physical activity as a preventive strategy for addressing cSVD, offering insights into the need for refining exercise parameters, diversifying research populations, and exploring novel biomarkers, while shedding light on the intricate mechanisms through which exercise confers neuroprotection in both humans and animal models.

Keywords: Cerebral Small Vessel Disease; Exercise Protocols; Neurodegenerative Disease; Neuroprotection; Physical Activity; Vascular Dementia.

Fig. 1.

Impact of Physical Activity on Measures of cSVD, Stratified by Study Type. This figure visually represents the most frequently reported findings from Tables 1a and 1b regarding the influence of physical activity on measurements of cerebral small vessel disease (cSVD). Upward pointing green arrows indicate a positive association or positive effect, red downward pointing arrows indicate a negative association or negative effect, yellow dash marks represent no differences between groups in intervention studies. For a comprehensive review of findings please refer to Tables 1a and 1b. Created with BioRender.com.

Fig. 2.

Impact of Physical Activity on Neuropathology and Cognitive-Behavioral Function in Animal Models of cSVD. This figure summarizes the findings regarding the effect of physical activity from studies conducted in animal models of cSVD. Mechanisms by which exercise were found to influence neuropathology are located on each black line with arrows indicating an increase or decrease. The corresponding effects of each mechanism on various pathologies are indicated in the center column. Changes in behavioral outcomes due to exercise are represented in the final column. For a comprehensive review of findings, please refer to Table 2. Created with BioRender.com.