Brain Vascular and Neurocognitive Health

Neurocognitive conditions and diseases including cognitive dysfunction, Alzheimer's disease and related dementias (ADRD) are among the fastest growing causes of morbidity and mortality. ADRDs impact \> 5 million people in the United States alone and \> 47 million people worldwide. The physiological reasons for these conditions are multifactorial but one contributing factor is impaired cerebral vascular function/health. Importantly, impaired cerebral vascular function/health results in cerebral hypoperfusion thereby contributing to neuronal damage and neurodegenerative processes ultimately contributing to the aforementioned neurocognitive impairments. Furthermore, it is critical to investigate therapeutic strategies to combat this elevated risk. One promising approach is Transcranial Photobiomodulation (tPBM) which is a novel and non-invasive strategy that utilizes low-level laser therapy to activate intracellular enzymatic pathways leading to an increase in mitochondrial activity, cerebral oxygenation, and thus neural and overall brain function. Importantly, this approach improves cognitive function in various animal models and limited human populations. Furthermore, there is limited evidence to suggest that these neurocognitive improvements are in-part related to increases in cerebral blood flow and cerebral vascular function/health. However, information regarding the mechanisms and effectiveness of tPBM are still relatively unknown - which represents a critical knowledge gap in the literature. Therefore, the overall research objective is of this proposal is to determine the impact of tPBM on indices of neurocognitive and cerebral vascular health. The following objectives / aims will be explored: 1. Primary Aim - The primary endpoint is the effect of acute (i.e. one-time) and repeated (i.e. up to 8 times in a 4-week period) exposure to tPBM on outcomes associated with elevated risk for various neurocognitive and pathophysiological conditions/diseases. These outcomes include neurocognitive function and indices cerebral blood vessel function/health. 2. It is hypothesized that both acute and repeated exposure to tPBM will have a beneficial impact on the outcome variables of neurocognitive function and indices cerebral blood vessel function/health.