The Relationship Between Neutrophil/Lymphocyte Ratio and the Progression and Clinical Features of Alzheimer's Disease

Objectives: This study aimed to investigate the relationship between the neutrophil-to-lymphocyte ratio (NLR), a peripheral inflammatory marker, and both baseline clinical features and short-term cognitive progression in patients with Alzheimer’s disease (AD). Specifically, we sought to determine whether NLR is associated with disease stage, cognitive performance, vascular comorbidities, and 12-month cognitive decline assessed by the Mini-Mental State Examination (MMSE).
Methods: We conducted a retrospective observational study including 100 adults diagnosed with mild, moderate, or severe AD who were followed for at least 12 months at a tertiary memory clinic. Demographic characteristics, clinical data, and serial MMSE scores (baseline, 6 months, and 12 months) were extracted from medical records. Complete blood counts from the same time points were used to calculate NLR. Descriptive statistics summarized clinical variables. Correlations between NLR and MMSE scores were analyzed using Pearson and Spearman methods. Group comparisons across disease stage, sex, and vascular comorbidity were performed using t-tests or ANOVA as appropriate. Statistical significance was defined as p<0.05.
Results: The mean age of the cohort was 72.5±9.9 years, and 62% were women. Baseline disease severity was distributed as mild (28%), moderate (26%), and severe (46%). Mean baseline NLR was 2.41±1.17, increasing to 2.87±1.47 at 6 months and 3.75±3.54 at 12 months. Baseline NLR was significantly higher in patients with vascular comorbidities (p=0.008) but did not differ across AD severity categories. Higher baseline NLR was modestly associated with lower baseline MMSE scores (r=−0.24, p=0.021). Unexpectedly, higher baseline NLR correlated with a smaller decline in MMSE over 12 months (r=0.36, p=0.005). Patients with low NLR showed greater cognitive deterioration (−3.72±3.97 points) than those with high NLR (−1.38±4.38 points; p=0.037).
Conclusion: NLR was associated with worse cognitive performance at diagnosis and increased gradually over 12 months in AD patients, supporting its role as a marker of systemic inflammation. However, the counterintuitive finding that higher baseline NLR was linked to slower short-term cognitive decline highlights the complexity of inflammatory mechanisms in established AD. These results suggest that while NLR reflects clinically relevant inflammatory status, it should not be used as a standalone predictor of disease progression but rather as part of a broader multimodal biomarker framework.

Keywords: Alzheimer disease, biomarkers, cognition, inflammation, neutrophil-lymphocyte ratio, vascular comorbidity