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. 2025 May;105(1):90-106.
doi: 10.1177/13872877251326060. Epub 2025 Apr 17.

Leptin, adiponectin, body mass index, and incident cognitive impairment

Affiliations

Leptin, adiponectin, body mass index, and incident cognitive impairment

Evan L Thacker et al. J Alzheimers Dis. 2025 May.

Abstract

BackgroundDisordered metabolism affects risk for cognitive decline, Alzheimer's disease, and other dementias, likely through pathways involving adipokines.ObjectiveAnalyze incident cognitive impairment in relation to leptin, adiponectin, body mass index, and other risk factors.MethodsNested case-control study within the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort of 30,239 adults in the US. Cases with incident cognitive impairment (n = 489) scored >1.57 SD below demographically adjusted means on ≥2 of 3 cognitive tests: word list learning, word list delayed recall, and category fluency. Cognitively intact controls (n = 583) were randomly selected within demographic strata. Leptin and adiponectin were assayed in thawed blood that had been stored at baseline.ResultsIn participants with normal weight, lower leptin was associated with higher odds of cognitive impairment. Relative to leptin = 25 ng/mL, adjusted ORs were 1.5 (95% CI: 1.2, 1.9) at leptin = 15 ng/mL, 0.8 (0.8, 0.9) at leptin = 30 ng/mL, and 0.5 (0.4, 0.8) at leptin = 45 ng/mL. In participants with obesity, higher adiponectin was associated with higher odds of cognitive impairment. Relative to adiponectin = 25 ng/mL, adjusted ORs were 0.8 (95% CI: 0.7, 1.0) at adiponectin = 15 ng/mL, 1.1 (1.0, 1.2) at adiponectin = 30 ng/mL, and 1.3 (1.0, 1.7) at adiponectin = 45 ng/mL. Associations of adipokines with cognitive impairment varied across levels of other risk factors.ConclusionsAdipokines, in concert with body mass index, play complex roles in cognitive health, with many avenues open for further investigation.

Keywords: Alzheimer's disease; adipokines; adiponectin; biomarkers; body mass index; cognitive dysfunction; epidemiology; leptin; obesity; overweight.

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Conflict of interest statement

Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Jorge R. Kizer owns stock in Abbott, AbbVie, Bristol Myers Squibb, Johnson & Johnson, Lily, Medtronic, Merck, and Pfizer. The remaining authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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