Introduction: Dementia and cognitive loss impact a significant proportion of the global population and present almost insurmountable challenges for treatment since they stem from multifactorial etiologies. Innovative avenues for treatment are highly warranted. Methods and results: Novel work with biological clock genes that oversee circadian rhythm may meet this critical need by focusing upon the pathways of the mechanistic target of rapamycin (mTOR), the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), mammalian forkhead transcription factors (FoxOs), the growth factor erythropoietin (EPO), and the wingless Wnt pathway. These pathways are complex in nature, intimately associated with autophagy that can maintain circadian rhythm, and have an intricate relationship that can lead to beneficial outcomes that may offer neuroprotection, metabolic homeostasis, and prevention of cognitive loss. However, biological clocks and alterations in circadian rhythm also have the potential to lead to devastating effects involving tumorigenesis in conjunction with pathways involving Wnt that oversee angiogenesis and stem cell proliferation. Conclusions: Current work with biological clocks and circadian rhythm pathways provide exciting possibilities for the treating dementia and cognitive loss, but also provide powerful arguments to further comprehend the intimate and complex relationship among these pathways to fully potentiate desired clinical outcomes.