Background and purpose: Current evidence supports the involvement of lipids in brain aging. A range of serum lipids is explored in association with brain structure and cognitive function amongst rural-dwelling older adults.

Methods: This population-based cross-sectional study included 184 rural-dwelling adults (age ≥ 65 years, 39.1% women) in Shandong, China. In 2014–2016, data on demographics, lifestyle, health conditions and serum lipids were collected. Volumes of gray matter, white matter, ventricles, hippocampus and white matter hyperintensity were automatically estimated on brain magnetic resonance imaging. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE), and mild cognitive impairment (MCI) was defined according to Petersen's criteria. Data were analyzed using the general linear regression, logistic regression and mediation models.

Results: Of the 184 participants, 47 were defined with MCI. Low high-density lipoprotein cholesterol (HDL-C; <1.55 vs. ≥1.55 mmol/l) was significantly associated with reduced volumes of total white matter (multi-adjusted β = −9.77, 95% confidence interval −19.48–0.06) and hippocampus (−0.23, −0.46–0.01), a lower MMSE score (−1.49, −2.67–0.31) and a higher likelihood of MCI (multi-adjusted odds ratio 3.21, 95% confidence interval 1.42–7.29). The mediation effects of structural brain measures on the associations between a low level of HDL-C and MMSE score or MCI were not statistically significant (p > 0.05).

Conclusions: This study suggests that low HDL-C may be involved in structural brain aging and cognitive dysfunction amongst rural-dwelling older adults in China, but the association of low HDL-C with cognitive aging phenotypes appears not to be mediated by brain structure.