Association between the Naples Prognostic Score and cognitive function in older adults: validation in Alzheimer’s disease and vascular dementia

Background Accumulating evidence indicates that systemic inflammation and metabolic dysregulation might contribute to cognitive impairment. The Naples Prognostic Score (NPS), a composite measure integrating albumin, total cholesterol (TC), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR), provides a succinct profile of systemic inflammatory-metabolic status. This study investigated the association between the NPS and cognitive impairment in elderly Americans. Methods We analyzed data from 2,595 participants (age ≥60) in the 2011–2014 National Health and Nutrition Examination Survey (NHANES). Cognitive function was evaluated using Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), Animal Fluency Test (CFDAST), and Digit Symbol Substitution Test (CFDDS). Cognitive impairment was defined as scoring in the lowest quartile. Multivariate logistic regression, linear trend analysis, and subgroup analysis were used to assess the association between NPS and cognitive impairment. Furthermore, the distribution of NPS across different dementia subtypes was validated in an independent clinical cohort comprising 189 clinically diagnosed patients. Results After full adjustment, higher NPS scores were associated with an increased risk of cognitive impairment. A significant association was observed specifically with executive function assessed by CFDAST (OR = 2.03, 95% CI: 1.18–3.51). Significant dose–response relationships were found for both CFDAST and CFDDS ( P for trend = 0.007 and 0.025, respectively). In the clinical cohort, NPS levels were similarly elevated in patients with Alzheimer’s disease (AD) and vascular dementia (VaD) (mean 3.11 vs. 3.03, p = 0.432), suggesting that systemic inflammatory-metabolic dysregulation may constitute a common pathological mechanism across multiple subtypes of dementia. Conclusion Higher NPS scores are independently associated with executive dysfunction in older adults. Although this scoring system has limited specificity in differentiating dementia subtypes, it shows potential as a screening tool for identifying populations at high risk of executive dysfunction. This underscores the potential of interventions targeting underlying inflammatory and metabolic pathways as a transdiagnostic strategy. Nevertheless, the predictive utility of the NPS requires comprehensive validation through prospective studies.