The role of exercise in mitigating subcortical ischemic vascular cognitive impairment

Abstract

Subcortical ischemic vascular cognitive impairment (SIVCI) is the most preventable form of cognitive dysfunction. There is converging evidence from animal and human studies that indicate vascular injury as the primary cause of SIVCI. Currently, there are no curative pharmaceutical treatments for vascular dementia; however, exercise may be a promising strategy to combat SIVCI. This review will focus on the role of exercise as a strategy to prevent or slow the progression of SIVCI, with particular emphasis on the mechanisms by which exercise may improve cerebrovascular function. We propose that exercise may be an effective strategy to combat SIVCI by improving cognitive function, increasing the bioavailability of neurotrophins, stimulating endothelial function, and controlling vascular risk factors. Keywords: endothelial function, exercise, subcortical ischemic vascular cognitive impairment, white matter hyperintensities. J. Neurochem. (2018) 144, 582--594.This article is part of the Special Issue "Vascular Dementia".The World Health Organization estimates that 47.5 million people worldwide are living with dementia with an expected increase of 7.7 million new cases each year (World Health Organization 2012). Dementia is a common cause of disability and dependency among older adults; thus, the high prevalence and incidence of dementia is a great burden to health, social, and financial systems (World Health Organization 2012). Vascular cognitive impairment (VCI) is the second leading cause of cognitive impairment and dementia (van Norden et al. 2012). Vascular cognitive impairment is an umbrella term that encompasses the full spectrum of cognitive and functional impairments associated with cerebrovascular disease, from frank dementia to mild cognitive deficits (Gorelick et al. 2011). Subcortical ischemic vascular cognitive impairment (SIVCI) is the most common form of VCI and is caused by cerebral small vessel disease (SVD) (Moorhouse and Rockwood 2008). Cerebral SVD is caused by chronic and diffuse ischemia and is most often associated with damage to cerebral white matter. Specifically, it manifests as white matter hyperintensities (WMH), lacunes, enlarged perivascular spaces, and microbleeds (Wardlaw et al. 2013b).Overall, there is converging evidence from animal and human studies that indicate vascular injury as the primary cause of SIVCI (Iadecola 2013). Vascular risk factors such as Received May 29, 2017; revised manuscript received August 9, 2017; accepted August 11, 2017.Address correspondence and reprint requests to Teresa Liu-Ambrose, University of British Columbia, Djavad Mowafaghian Centre for Brain Health, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z3. USA. E-mail: teresa.ambrose@ubc.caAbbreviations used: ADAS-Cog, Alzheimer's Disease Assessment Scale-cognitive subscale; BDNF, brain-derived neurotrophic factor; CBF, cerebral blood flow; eNOS, endothelial nitric oxide synthase; fMRI, functional magnetic resonance imaging MRI; IGF-1, insulin-like growth factor 1; MCI, mild cognitive impairment; MRI, m...

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“…As there is currently no cure for WMHs (Alber et al, 2019), strategies which can mitigate the risks of WMH on falls are needed. Physical activity (PA) is an important modifiable lifestyle factor associated with both lower WMH volumes (Burzynska et al, 2014;Dao et al, 2018;Alber et al, 2019) and reduced risk of falling (Khan et al, 2001). However, whether PA moderates the burden of WMH volume on falls risk is not well established.…”

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