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Review
. 2022 Oct;70(10):3021-3029.
doi: 10.1111/jgs.17985. Epub 2022 Aug 8.

Mediation effects of diabetes and inflammation on the relationship of obesity to cognitive impairment in African Americans

Rola Abi Saleh  1 , Seth T Lirette  2 , Emelia J Benjamin  3   4 , Myriam Fornage  5 , Stephen T Turner  6 , Pamela I Hammond  7 , Thomas H Mosley  1 , Michael E Griswold  1 , B Gwen Windham  1
Affiliations
Review

Mediation effects of diabetes and inflammation on the relationship of obesity to cognitive impairment in African Americans

Rola Abi Saleh et al. J Am Geriatr Soc. 2022 Oct.

Abstract

Background: Whether diabetes and adipokine-driven inflammation explain the association of obesity to cognitive impairment is unknown.

Methods: Structural equation models estimated the total effects of waist circumference on cognitive outcomes among African American participants cross-sectionally (index exam) and longitudinally. Total effects were deconstructed into direct pathways of waist circumference to cognitive impairment and indirect mediation pathways through leptin, soluble tumor necrosis factor receptor 2 (sTNFR2), and diabetes. Waist circumference, leptin, and sTNFR2 were standardized. Cognitive impairment was defined as MMSE <21 or a z-score < -1.5 standard deviation (SD). Incident cognitive impairment was defined among those without cognitive impairment at the index exam as follow-up MMSE<21, z- score < -1.5, MMSE decline >1 point/year, or z-score decline of >0.1 SD/year.

Results: Among 1008 participants (70% women, mean age 62.9 years, 14.5% with obesity, 26% with diabetes), 132 (13%) had baseline cognitive impairment. Each SD higher waist circumference was associated with higher odds of cognitive impairment, odds ratio (OR) = 1.63; (95% confidence interval: 1.17, 2.24), with mediating pathways explaining 65% of the total effect (58% from diabetes; 7% from inflammation). At follow-up (mean 6.8 years), 106 of 535 (19.8%) had developed cognitive impairment. Each SD higher waist circumference was associated with higher odds of developing cognitive impairment (OR = 1.87; 95%CI: 1.18, 2.74); the direct effect of waist circumference explained 37% of the total effect and mediating pathways explained 63% (61% from diabetes; 2% from inflammation), although individual pathways were not statistically supported in the smaller sample.

Conclusion: Diabetes, and to a lesser degree, adiposity-driven inflammation, appear to explain a substantial proportion of abdominal adiposity relationships with cognitive impairment. The impact of preventing and treating obesity on cognitive outcomes merits study.

Keywords: cardiovascular; cognitive aging; health disparities.

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Conflict of interest statement

Conflict of Interest

None

Figures

Figure 1.
Figure 1.
Total effects of obesity on prevalent cognitive impairment (A) and incident cognitive impairment (B) displayed as direct and indirect pathways.
See this image and copyright information in PMC

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