Prognostic Nutritional Index, Circulating Bacterial and Viral DNA, and Neurocognitive Vulnerability in Geriatric Inpatients: A Cross-Sectional Study

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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Publication Details

Journal
Nutrients
Published
2026-10-15
DOI
https://doi.org/10.3390/nu18203387
Primary Topic
Nutrition and Health in Aging
Type
article
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article

Prognostic Nutritional Index, Circulating Bacterial and Viral DNA, and Neurocognitive Vulnerability in Geriatric Inpatients: A Cross-Sectional Study

Anna Rita Bonfigli, Sonia Fantone, Maurizio Cardelli, Mirko Di Rosa et al.
Nutrients
Nutrition and Health in Aging
article

Prognostic Nutritional Index, Circulating Bacterial and Viral DNA, and Neurocognitive Vulnerability in Geriatric Inpatients: A Cross-Sectional Study

Anna Rita Bonfigli, Sonia Fantone, Maurizio Cardelli, Mirko Di Rosa, Fabrizia Lattanzio, Marco Malavolta, Antonio Cherubini, Chiara Giordani, Laura Cianfruglia, Giuseppe Passarino, Rina Recchioni, Dina Bellizzi, Francesco Piacenza, Leonardo Biscetti, Giuseppe Pelliccioni, Rosanna Maniscalco, Pietro Giorgio Spezia, Matilde Sbriscia, Robertina Giacconi, Fabrizio Maggi, Marta Balietti, Olivieri Fabiola, Carlo Fortunato, Patrizia D’Aquila, Gretta Veronica Badillo Pazmay, Tiziana Casoli, Federica Novazzi, Giulia Matacchione, Dolores Limongi, Carla Prezioso, Francesca Marchegiani
article en

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.

NutrientsVol. 18(20)
University of Insubria (IT), Marche Polytechnic University (IT), Vita-Salute San Raffaele University (IT), San Raffaele University of Rome (IT), Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani (IT), ATS Sardegna (Italy) (IT), IRCCS Ospedale San Raffaele (IT), Fondazione Audiologica Varese (IT), Istituto Nazionale di Riposo e Cura per Anziani (IT), University of Calabria (IT)
Good health and well-being
Openalex Percentile: Top 14%
Nutrition and Health in Aging
DOIOpen Access PDFOpenAlex
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