Isometric Exercise Training for Managing Vascular Risk Factors in Mild Cognitive Impairment and Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is the most common form of dementia diagnosed amongst the elderly. Mild cognitive impairment (MCI) is a condition often indicative of the earliest symptomatology of AD with 10%-15% of MCI patients reportedly progressing to a diagnosis of AD. Individuals with a history of vascular risk factors (VRF's) are considered high risk candidates for developing cognitive impairment in later life. Evidence suggests that vascular injury resulting from untreated VRF's promotes progression from MCI to AD and exacerbates the severity of dementia in AD, and neuroimaging studies have found that the neurodegenerative processes associated with AD are heavily driven by VRF's that promote cerebral hypoperfusion. Subsequently, common links between vascular disorders such as hypertension and neurodegenerative disorders such as AD include compromised vasculature, cerebral hypoperfusion and chronic low grade inflammation (a hallmark of both hypertension and AD). Exercise has been demonstrated to be an effective intervention for blood pressure management, chronic low grade inflammation and improvements in cognition. Data from recent analyses suggests that isometric exercise training (IET) may improve vascular integrity and elicit blood pressure reductions in hypertensives greater than those seen with dynamic aerobic and resistance exercise. IET may also play an effective role in the management of VRF's at the MCI stage of AD and may prove to be a significant strategy in the prevention, attenuation or delay of progression to AD. A plausible hypothesis is that the reactive hyperemia stimulated by IET initiates a cascade of vascular, neurotrophic and neuro-endocrine events that lead to improvements in cognitive function.

Keywords: Alzheimers disease; blood pressure; hypertension; isometric exercise training; mild cognitive impairment; reactive hyperemia; vascular risk factors.

Figure 1

Alzheimer’s disease (AD) is responsible for severe cortical atrophy in selective regions of the brain such as the frontal and prefrontal cortex, and the temporal, medial-temporal and limbic areas. Neural structures associated with these regions include the thalamus, basal ganglia, cingulate cortex, fornix, hypothalamus, amygdala, hippocampus and entorhinal cortex. One of the earliest indicators of AD, identified by imaging studies, is the presence of cerebral hypoperfusion in temporoparietal regions such as the entorhinal and hippocampal areas.

Figure 2

Vascular risk factors (VRF’s) such as hypertension, atherosclerosis, hyperlipidemia and cerebrovascular disease are linked to cognitive disorders such as vascular dementia (VaD) and sporadic AD. Vascular damage associated with aging, hypertension and other VRF’s is thought to; inhibit both the delivery of nutrients to the brain and the clearance of toxic metabolites, compromise the integrity of the blood brain barrier (BBB) promoting the accumulation and propagation of the hallmark proteogenic pathologies associated with AD. VaD is not accompanied by these same hallmark neurodegenerative processes. In both VaD and AD, the homeostatic disruption of altered cerebral vasculature is believed to promote cellular disruption, cell death and cognitive impairment ultimately resulting in dementia.