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Background Adipokines are hormones secreted by adipose tissue with roles in energy homeostasis and regulation of metabolism. Their dysregulation is suggested to contribute to the increased risk of dementia seen with midlife obesity, but longitudinal studies investigating this are scarce. We determined the association between plasma levels of adiponectin, leptin, and resistin with the risk of dementia. Methods We performed a case–cohort study embedded in the prospective, population-based Rotterdam Study. Plasma levels of the adiponectin, leptin, and resistin were measured at baseline (1997–1999) in a random subcohort of 945 participants without dementia, and additionally in 177 participants, who were diagnosed with dementia during follow-up (until January 1, 2018). Results Higher levels of leptin and resistin were associated with a decreased risk of dementia (adjusted hazard ratio [95% confidence interval] per SD increase of log-transformed values: 0.85 [0.72–1.00] for leptin; 0.82 [0.71–0.95] for resistin). The association of leptin with dementia was further modified by body mass index and by APOE ε4 carrier status. Adiponectin levels were not associated with the risk of dementia. Conclusions These findings support the hypothesis that adipokines have a role in the pathophysiology of dementia. Future studies are warranted to confirm the findings and to explore the underlying mechanisms.

Adiponectin, Leptin, and Resistin and the Risk of Dementia