Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a leading cause of death and disability among older adults. Modifiable vascular risk factors for AD (VRF) include obesity, hypertension, type 2 diabetes mellitus, sleep apnea, and metabolic syndrome. Here, interactions between cerebrovascular function and development of AD are reviewed, as are interventions to improve cerebral blood flow and reduce VRF. Atherosclerosis and small vessel cerebral disease impair metabolic regulation of cerebral blood flow and, along with microvascular rarefaction and altered trans-capillary exchange, create conditions favoring AD development. Although currently there are no definitive therapies for treatment or prevention of AD, reduction of VRFs lowers the risk for cognitive decline. There is increasing evidence that brief repeated exposures to moderate hypoxia, i.e. intermittent hypoxic training (IHT), improve cerebral vascular function and reduce VRFs including systemic hypertension, cardiac arrhythmias, and mental stress. In experimental AD, IHT nearly prevented endothelial dysfunction of both cerebral and extra-cerebral blood vessels, rarefaction of the brain vascular network, and the loss of neurons in the brain cortex. Associated with these vasoprotective effects, IHT improved memory and lessened AD pathology. IHT increases endothelial production of nitric oxide (NO), thereby increasing regional cerebral blood flow and augmenting the vaso-and neuroprotective effects of endothelial NO. On the other hand, in AD excessive production of NO in microglia, astrocytes, and cortical neurons generates neurotoxic peroxynitrite. IHT enhances storage of excessive NO in the form of S-nitrosothiols and dinitrosyl iron complexes. Oxidative stress plays a pivotal role in the pathogenesis of AD, and IHT reduces oxidative stress in a number of experimental pathologies. Beneficial effects of IHT in experimental neuropathologies other than AD, including dyscirculatory encephalopathy, ischemic stroke injury, audiogenic epilepsy, spinal cord injury, and alcohol withdrawal stress have also been reported. Further research on the potential benefits of IHT in AD and other brain pathologies is warranted.

10-Week Hatha Yoga Increases Right Hippocampal Density Compared to Active and Passive Control Groups: A Controlled Structural cMRI Study

“…This fits very well with the results of Bousama et al [108] who postulated in their work intermittent hypoxia as the key factor for neurogenesis modulation in the hippocampus. They hypothesized that activation of neurogenesis is a reaction to hypoxia-induced neuronal loss, thereby contributing relative hypoxia as a neuroprotective mechanism [109][110][111].…”

“…The effect of augmented breaths [112] as well as effects of Yoga breathing practices [68] has shown to be associated with changes in blood pressure and heart rate. Breath frequency and indurance are found to be strongly influenced by negative and positive emotions [110,113]. Therefore, it is tempting to speculate that the breathing element in Hatha Yoga practice represents an important role for the effect on the hippocampus by influencing circuits between neurons of the ventral hippocampus and brainstem nuclei [112].…”

Intermittent Hypoxic Conditioning Alleviates Post-Traumatic Stress Disorder-Induced Damage and Dysfunction of Rat Visceral Organs and Brain

“…Endogenous defense systems can be enhanced by intermittent hypoxia conditioning (IHC), which has been shown to be efficient, safe, and free of side effects [8]. In particular, IHC is highly cardio-, vaso-, and neuroprotective [11,12]. In clinical and experimental studies, IHC prevented behavioral disorders and cerebral neuronal damage in epilepsy [13], Parkinson disease [14], and Alzheimer's disease [12,15].…”

Nanotherapy for Alzheimer's disease and vascular dementia: Targeting senile endothelium

“…In fact, vascular cognitive impairment and dementia (VCID) is the second leading cause of dementia behind Alzheimer's disease, and is a frequent comorbidity in the Alzheimer's patient (Cooper and Mitchell 2016;Dichgans and Leys 2017;Greenberg et al [for MarkVCID consortium] 2017;Kalaria 2016;Perrotta et al 2016;Sudduth et al 2017). On a worldwide basis, 36 million people had dementia in 2010; of these dementia patients, 60%-80% have Alzheimer's disease (Bhat et al 2015;Dichgans and Leys 2017;Manukhina et al 2016).…”