Background: Due to its common association with chronic pain experience, cognitive impairment (CI) has never been evaluated in patients with burning mouth syndrome (BMS). The purpose of this study is to assess the prevalence of CI in patients with BMS and to evaluate its relationship with potential predictors such as pain, mood disorders, blood biomarkers, and white matter changes (WMCs).Methods: A case-control study was conducted by enrolling 40 patients with BMS and an equal number of healthy controls matched for age, gender, and education. Neurocognitive assessment [Mini Mental State Examination (MMSE), Digit Cancellation Test (DCT), the Forward and Backward Digit Span task (FDS and BDS), Corsi Block-Tapping Test (CB-TT), Rey Auditory Verbal Learning Test (RAVLT), Copying Geometric Drawings (CGD), Frontal Assessment Battery (FAB), and Trail Making A and B (TMT-A and TMT-B)], psychological assessment [Hamilton Rating Scale for Depression and Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and 36-Item Short Form Health Survey (SF-36)], and pain assessment [Visual Analogic Scale (VAS), Total Pain Rating index (T-PRI), Brief Pain Inventory (BPI), and Pain DETECT Questionnaire (PD-Q)] were performed. In addition, blood biomarkers and MRI of the brain were recorded for the detection of Age-Related WMCs (ARWMCs). Descriptive statistics, the Mann-Whitney U-test, the Pearson Chi-Squared test and Spearman’s correlation analysis were used.Results: Patients with BMS had impairments in most cognitive domains compared with controls (p < 0.001**) except in RAVLT and CGD. The HAM-D, HAM-A, PSQI, ESS, SF-36, VAS, T-PRI, BPI and PD-Q scores were statistically different between BMS patients and controls (p < 0.001**) the WMCs frequency and ARWMC scores in the right temporal (RT) and left temporal (LT) lobe were higher in patients with BMS (p = 0.023*).Conclusions: Meanwhile, BMS is associated with a higher decline in cognitive functions, particularly attention, working memory, and executive functions, but other functions such as praxis-constructive skills and verbal memory are preserved. The early identification of CI and associated factors may help clinicians to identify patients at risk of developing time-based neurodegenerative disorders, such as Alzheimer’s disease (AD) and vascular dementia (VD), for planning the early, comprehensive, and multidisciplinary assessment and treatment.

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