Body Mass Index and Leptin Are Related to Cognitive Performance Over 10 Years in Women With and Without HIV Infection

J Clin Endocrinol Metab. 2022 Feb 17;107(3):e1126-e1135. doi: 10.1210/clinem/dgab759.


Context: It is not yet understood whether people living with HIV infection have an increased risk of Alzheimers Disease and Related Dementias due to enhanced survivorship with highly effective antiretroviral therapies and/or increasing adiposity with aging.

Objective: This work aimed to determine whether body mass index (BMI) and leptin were longitudinally associated over 10 years with neuropsychological performance (NP) among middle-aged women with HIV (WWH) vs without HIV.

Methods: Women's Interagency HIV Study (WIHS) participants (301 WWH, 113 women without HIV from Brooklyn, New York City, and Chicago had baseline and 10-year BMI and fasting plasma leptin levels using commercial enzyme-linked immunosorbent assay (ng/mL); and demographically adjusted NP T scores (attention/working memory, executive function [EF], processing speed, memory, learning, verbal fluency, motor function, global) at 10-year follow-up. Multivariable linear regression analyses, stratified by HIV serostatus, examined associations between BMI, leptin, and NP.

Results: Over 10 years, women (baseline age 39.8 ± 9.2 years, 73% Black, 73% WWH) transitioned from average overweight (29.1 ± 7.9) to obese (30.5 ± 7.9) BMI. Leptin increased 11.4 ± 26.4 ng/mL (P < .001). Higher baseline BMI and leptin predicted poorer 10-year EF among all women (BMI β = -6.97, 95% CI (-11.5 to -2.45) P = .003; leptin β = -1.90, 95% CI (-3.03 to -0.76), P = .001); higher baseline BMI predicted better memory performance (β = 6.35, 95% CI (1.96-10.7), P = .005). Greater 10-year leptin increase predicted poorer EF (P = .004), speed (P = .03), and verbal (P = .02) and global (P = 0.005) performance among all women, and WWH. Greater 10-year BMI increase predicted slower processing speed (P = .043) among all women; and among WWH, poorer EF (P = .01) and global (P = .04) performance.

Conclusion: In middle-aged WIHS participants, 10-year increases in BMI and leptin were associated with poorer performance across multiple NP domains among all women and WWH. Trajectories of adiposity measures over time may provide insight into the role of adipose tissue in brain health with aging.

Keywords: HIV; body mass index; cognition; leptin; obesity; overweight; women.

Publication types

  • Observational Study
  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity
  • Adult
  • Aging / blood
  • Aging / metabolism*
  • Body Mass Index*
  • Case-Control Studies
  • Cognition*
  • Female
  • Follow-Up Studies
  • HIV Infections / blood
  • HIV Infections / complications*
  • HIV Infections / metabolism
  • Humans
  • Leptin / blood*
  • Leptin / metabolism
  • Longitudinal Studies
  • Middle Aged
  • Neuropsychological Tests / statistics & numerical data
  • Prospective Studies


  • LEP protein, human
  • Leptin