Blood-based biomarkers in hypothalamic-pituitary axes for the risk of dementia or cognitive decline: a systematic review and meta-analysis

Blood-based biomarkers are ideal candidates for dementia prediction. This systematic review and meta-analysis aimed to evaluate longitudinal relationships of blood hormones and hormone-binding proteins in hypothalamic-pituitary (HP) axes with dementia or cognitive decline. PubMed, MEDLINE, EMBASE, PsycINFO, and BIOSIS were systematically searched from 1919 to June 2020. Fifteen types of hormones and four types of hormone-binding proteins were measured in 48 prospective studies. Increased risk of dementia or cognitive decline could be predicted by elevated blood concentrations of free-thyroxine (free-T4, RR = 1.06, p = 0.001) and sex hormone-binding globulin (SHBG, RR = 1.10, p = 0.025). Lower thyroid-stimulating hormone (TSH) levels within (RR = 1.28, p < 0.001) and below (RR = 1.27, p = 0.004) the normal range were both risky. Current evidence suggests the alterations of multiple blood molecules in HP axes, especially TSH, free-T4, and SHBG precede the incidence of dementia or cognitive decline. The underpinning etiology remains to be elucidated in the future.