Neutrophil to Lymphocyte Ratio as a Predictive Biomarker of Dementia: Findings from a Prospective Cohort Study in Individuals with Mild Cognitive Impairment

Background Neuroinflammation plays a crucial role in neurodegeneration. The neutrophil-to-lymphocyte ratio (NLR), a known marker of systemic inflammation, has been investigated in patients with Alzheimer’s disease (AD) though its prognostic value in mild cognitive impairment (MCI) progression to dementia remains controversial. This study aims at evaluating the NLR as a potential prognostic biomarker for progression to dementia in a sample of individuals with MCI. Methods The study sample included 91 individuals with MCI of amnestic type. Socio-demographic, clinical, functional, neuropsychological and laboratory data of participants were collected. The NLR parameter was assessed at the baseline visit. Participants were followed up to five years and censored at the time of the onset of dementia or at drop out from the study (for any reason). The Receiver Operating Characteristic (ROC) curve analysis and the Youden Index were applied to determine the best discriminant NLR cutoff value. Based on this value, participants were divided in two groups and rates of dementia were estimated. Cox regression models were used to estimate the predictive effect of NLR on the risk of conversion to dementia. Crude and adjusted hazard ratios (HRs) and corresponding 95% Confindence Intervals (CI) were estimated from these models. Results Overall, 40 participants converted to dementia with an incidence rate of conversion of 18.7 cases per 100 person-years. The optimal threshold of NLR to predict conversion to dementia resulted 2.25, with a sensitivity of 74.4% and a specificity of 65.3% (Youden index = 0.40, Area Under the Curve (AUC) = 0.74). After adjusting for relevant confounders, a NLR higher than 2.25 was associated with an increased risk of developing dementia over three years (adj. HR = 3.58, 95% CI : 1.61–7.97; p = 0.002). Using the literature-based NLR threshold of 2.5 confirmed the association, showing a similarly increased risk of dementia (adj. HR = 2.80, 95% CI: 1.33–5.92, p = 0.007). Conclusions This study suggests that NLR, despite its limited specificity, may be a useful indicator for identifying individuals with MCI at increased risk of dementia. Larger studies are needed to validate these findings and explore its clinical applicability. Clinical trial number : not applicable