Objective To explore the factors affecting the cognition of elderly women with white matter lesions (WML) and to look for potential biological markers of dementia in this population. Methods A total of 149 elderly woman patients with WML and 48 elderly woman patients without WML who were treated in the outpatient department and ward in Department of Neurology, The First Affiliated Hospital of Naval Medical University (Second Military Medical University) and Kongjiang Hospital of Yangpu District of Shanghai from Jan. to Jun. 2020 were enrolled. The patients were divided into non-WML group (control group, n=48), mild WML group (n=72) and moderate to severe WML group (n=77) according to the severity of WML. WML patients were divided into dementia group (n=58) and non-dementia group (n=91) according to the mini-mental state exam (MMSE) scores. The levels of interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α), 25-hydroxyvitamin D (25(OH)D) and prolactin were compared between groups, and logistic regression model was used to analyze the correlations between these factors and the occurrence of dementia in elderly women with WML. In addition, receiver operating characteristics (ROC) curve was drawn to study the diagnostic value of 25(OH)D combined with prolactin for dementia in elderly women with WML. Results Compared with the control group, the serum 25(OH)D levels of patients in the mild and moderate to severe WML groups were significantly lower ([13.34±3.85] ng/mL,[12.73±3.77] ng/mL vs[15.82±4.07] ng/mL, P<0.01). The serum inflammatory factor levels of patients in the mild and moderate to severe WML groups were increased significantly compared with those of patients in the control group, such as IL-1β ([75.14±16.03] pg/mL,[75.42±14.38] pg/mL vs[53.96±13.55] pg/mL, P<0.01), IL-6 (35.70[28.92, 40.67] pg/mL, 35.29[28.97, 43.41] pg/mL vs 22.38[18.04, 27.20] pg/mL, P<0.01), TNF-α (72.72[55.68, 88.63] pg/mL, 71.52[60.26, 85.85] pg/mL vs 50.93[38.93, 60.48] pg/mL, P<0.01). The levels of serum 25(OH)D, uric acid, prolactin and cortisol in the dementia group were lower than those in the non-dementia group (25(OH)D:[11.77±3.63] ng/mL vs[13.83±3.72] ng/mL, P<0.01; uric acid:[331.02±150.31] μmol/L vs[380.16±128.02] μmol/L, P<0.05; prolactin:[231.72±79.39] μIU/mL vs[276.84±99.66] μIU/mL, P<0.01; cortisol:[287.38±149.58] nmol/L vs[358.45±155.32] nmol/L, P<0.01). The results of multivariate logistic regression analysis suggested that serum 25(OH)D (odds ratio[OR]=0.821, 95% confidence interval[CI] 0.717-0.940, P=0.004) and prolactin (OR=0.994,95% CI 0.989-1.000, P=0.042) were protective factors for dementia in elderly women with WML after adjusting for age. The combination of 25(OH)D and prolactin had moderate diagnostic value for dementia in elderly women with WML, and the area under ROC curve was 0.745 (P<0.001). Conclusion Serum 25(OH)D and prolactin levels are associated with dementia in elderly women with WML, and are expected to be potential biomarkers for early diagnosis of dementia in this population.