Table 1.

Summary of current evidence and promising future research directions for novel factors related to AD.

Items	Summary of main evidence	Priorities for future research
Sleep	There exists a bi-directional relationship between sleep disturbances and dementia, but it remains unclear whether sleep disturbances are early signs or risk factors for AD.	Future research to uncover potential mechanisms and to explore the use of sleep interventions for the prevention and treatment of AD among high-risk older adults.
Hypoxia	Chronic hypoxia is one of the important environmental factors contributing to the pathogenesis of AD.	Further research is needed to determine whether prospective prevention and treatment of hypoxia may be helpful to delay or ameliorate the progression of AD by any mechanism.
Diet	Certain nutrients (eg, antioxidants) and dietary patterns (eg, Mediterranean diet) might have neuroprotective effects, but results have been inconsistent.	Larger adequately powered intervention and prospective studies in diverse populations with clinically relevant endpoints as well as sensitive neurocognitive tests and brain biomarkers associated with preclinical AD risk are required to understand the effect of diet on AD from the earliest to later stages of disease.
Gut microbiome	Numerous evidences have been obtained on the relationship between gut microbiota and AD from clinical studies, animal experiments, and mechanism exploration.	Whether some specific bacteria or combinations of bacteria in the gut microbiota have a role in the prevention and treatment of AD remains to be further clarified.
Hearing loss	Peripheral and central hearing loss are associated with lower regional brain volumes and dementia risk	Studies to determine mechanisms and direction of associations. Clinical trial to test if hearing rehabilitation affects cognition.

AD: Alzheimer disease.