DOI: 10.1002/alz.076415 ISSN: 1552-5260

Association of waist‐to‐hip ratio with Alzheimer’s disease and neuroinflammation biomarkers in cognitively unimpaired adults

Núria Tort‐Colet, Gonzalo Sánchez‐Benavides, Carolina Minguillon, Gwendlyn Kollmorgen, Margherita Carboni, Henrik Zetterberg, Kaj Blennow, Juan Domingo Gispert, Marc Suarez‐Calvet, Oriol Grau‐Rivera
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Obesity is associated with higher risk of Alzheimer’s disease (AD) and other dementias. This association could be mediated by a pro‐inflammatory effect of abdominal adiposity. Here, we used the waist‐to‐hip ratio (WHR) as a proxy for central adiposity to explore its association with AD and neuroinflammation biomarkers, as well as its interaction with sex in cognitively unimpaired adults from the ALFA+ cohort.


We analyzed data from 353 participants (61.2% females; 64.3% β‐amyloid [Aβ]+; 61.04 ± 4.77 years on average). We measured CSF p‐tau and t‐tau with the Elecsys® immunoassays and CSF Aβ42, Aβ40 and neuroinflammation biomarkers (sTREM2, GFAP, YKL40, S100 and IL‐6) with the exploratory Roche NeuroToolKit robust prototype assays. We used separated linear regression models to analyze associations of WHR with CSF AD and neuroinflammation biomarkers while adjusting by age, sex, APOE status, education years, mean blood pressure and triglycerides. We ran interaction analyses between WHR and sex.


We did not find significant main effects of WHR on CSF AD or neuroinflammation biomarkers. We found a significant interaction between WHR and sex on IL‐6 (p = 0.008; correcting by multiple hypotheses, p_adjusted = 0.067). After stratifying by sex, WHR was associated with IL‐6 in the male group (p = 0.032; p_adjusted = 0.242), but not in the female group (p = 0.596).


WHR is positively associated with IL‐6 levels in males. The effect of sex, and the role of neuroinflammation as a potential mediator in the association between obesity and dementia risk warrant further research.

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