Background/Objectives: Impaired immunonutritional status is common among hospitalized older adults and may contribute to adverse outcomes through alterations in gut-brain axis pathways involving immune, microbial, and inflammatory mechanisms. The Prognostic Nutritional Index (PNI), a composite marker based on serum albumin and lymphocyte count, may identify patients with altered immunonutritional status and increased clinical vulnerability. This cross-sectional study investigated whether PNI-defined immunonutritional impairment is associated with bacterial and viral DNAemia, inflammation, and neurocognitive conditions in 1016 geriatric patients from the Report-AGE cohort. Methods: Participants were stratified according to PNI into low- and high-PNI groups. Blood bacterial DNA (BB-DNA), Torque teno virus (TTV), herpes simplex virus (HSV-1), varicella-zoster virus (VZV), leukocyte telomere length (LTL), inflammatory and neurodegeneration-related biomarkers were evaluated. Multivariable logistic regression models were used to assess the associations of BB-DNA and PNI with cognitive impairment and interRAI-derived neurocognitive conditions. Results: Low-PNI patients exhibited a higher burden of comorbidities, frailty, and systemic inflammation, alongside increased concentrations of BB-DNA, IL-6, IL-17A, GDF15, osteopontin, FGF21, follistatin, and neurofilament light chain. Among patients with low-PNI, increasing BB-DNA tertiles were associated with progressively higher TTV, HSV-1, and VZV DNAemia, elevated NLR, IL-6, and IL-17A levels, and shorter LTL. In multivariable analyses, low-PNI was independently associated with cognitive impairment (OR: 1.39, 95% CI: 1.06-1.83), easily distracted behavior (OR: 1.75, 95% CI: 1.29-2.35), and behavioral disturbances (OR: 1.80, 95% CI: 1.05-3.06), whereas BB-DNA showed an association with acute changes in mental status (OR: 1.75, 95% CI: 1.09-2.81) and behavioral disturbances (OR: 3.09, 95% CI: 1.11-8.59). Conclusions: These findings suggest that impaired immunonutritional status, bacterial and viral burden, systemic inflammation, and neurocognitive alterations may represent interconnected features of clinical vulnerability, although the cross-sectional design does not establish temporal or causal relationships among these factors.
Prognostic Nutritional Index, Circulating Bacterial and Viral DNA, and Neurocognitive Vulnerability in Geriatric Inpatients: A Cross-Sectional Study
Novazzi F.;Maggi F.;
2026-01-01
Abstract
Background/Objectives: Impaired immunonutritional status is common among hospitalized older adults and may contribute to adverse outcomes through alterations in gut-brain axis pathways involving immune, microbial, and inflammatory mechanisms. The Prognostic Nutritional Index (PNI), a composite marker based on serum albumin and lymphocyte count, may identify patients with altered immunonutritional status and increased clinical vulnerability. This cross-sectional study investigated whether PNI-defined immunonutritional impairment is associated with bacterial and viral DNAemia, inflammation, and neurocognitive conditions in 1016 geriatric patients from the Report-AGE cohort. Methods: Participants were stratified according to PNI into low- and high-PNI groups. Blood bacterial DNA (BB-DNA), Torque teno virus (TTV), herpes simplex virus (HSV-1), varicella-zoster virus (VZV), leukocyte telomere length (LTL), inflammatory and neurodegeneration-related biomarkers were evaluated. Multivariable logistic regression models were used to assess the associations of BB-DNA and PNI with cognitive impairment and interRAI-derived neurocognitive conditions. Results: Low-PNI patients exhibited a higher burden of comorbidities, frailty, and systemic inflammation, alongside increased concentrations of BB-DNA, IL-6, IL-17A, GDF15, osteopontin, FGF21, follistatin, and neurofilament light chain. Among patients with low-PNI, increasing BB-DNA tertiles were associated with progressively higher TTV, HSV-1, and VZV DNAemia, elevated NLR, IL-6, and IL-17A levels, and shorter LTL. In multivariable analyses, low-PNI was independently associated with cognitive impairment (OR: 1.39, 95% CI: 1.06-1.83), easily distracted behavior (OR: 1.75, 95% CI: 1.29-2.35), and behavioral disturbances (OR: 1.80, 95% CI: 1.05-3.06), whereas BB-DNA showed an association with acute changes in mental status (OR: 1.75, 95% CI: 1.09-2.81) and behavioral disturbances (OR: 3.09, 95% CI: 1.11-8.59). Conclusions: These findings suggest that impaired immunonutritional status, bacterial and viral burden, systemic inflammation, and neurocognitive alterations may represent interconnected features of clinical vulnerability, although the cross-sectional design does not establish temporal or causal relationships among these factors.
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