Neurodegenerative diseases such as Alzheimer’s disease (AD) are closely linked to oxidative stress and advanced glycation end products (AGEs), two interrelated processes that exacerbate neuronal damage through mitochondrial dysfunction, protein aggregation, and chronic inflammation. This narrative review explores the metabolic interplay between reactive oxygen species (ROS) and AGEs, with a focus on the AGE-RAGE (receptor for advanced glycation end products) signaling axis as a driver of neurodegeneration. Evidence from preclinical and clinical studies highlights their combined role in disease progression and underscores potential therapeutic targets. Strategies including mitochondria-targeted antioxidants, AGE inhibitors, RAGE antagonists, and metabolic interventions are discussed, along with future directions for biomarker development and personalized treatments. This review integrates current molecular insights into a unified metabolic–inflammatory model of AD, highlighting translational therapeutic opportunities.

Background/Objectives: Malnutrition, systemic inflammation, and immune dysfunction are key determinants of adverse outcomes in older adults following acute illness. Composite biomarkers integrating these domains could enhance early risk stratification. This study investigates, for the first time in acute geriatric care, the prognostic value of the C-reactive protein–albumin–lymphocyte (CALLY) index—a composite marker of nutritional, inflammatory, and immune status—in predicting short-term survival. Methods: We retrospectively analyzed 264 patients admitted to the acute geriatrics ward of Santa Maria della Misericordia Hospital in Perugia. The CALLY index was calculated as: (Albumin × Lymphocytes)/(CRP × 10⁴). The optimal prognostic cut-off was determined using receiver operating characteristic (ROC) curve analysis. Three-month survival was assessed by Kaplan–Meier analysis. Results: The cohort included 167 women (63.3%) and 97 men (36.7%), with a mean age of 88.0 ± 6.4 years. At 3-month follow-up, 80 patients (30.3%) had died. The CALLY index showed an area under the ROC curve of 0.647 (95% CI: 0.576–0.718; p < 0.001), with a cut-off of 0.055 (sensitivity: 68.5%, specificity: 46.3%). Among deceased patients, 42.5% had a CALLY index <0.055. After multivariable adjustment, a lower CALLY index remained independently associated with increased mortality (B = −0.805; OR = 0.45; 95% CI: 0.215–0.930; p = 0.031). Kaplan–Meier analysis demonstrated significantly higher survival in patients with a CALLY index ≥ 0.055 (Log-rank test: 13.71; p < 0.001). Conclusions: The CALLY index shows a modest but statistically significant discriminative ability for predicting short-term mortality in acutely ill older adults. As a simple, low-cost marker derived from routine laboratory tests, it holds potential for integration into clinical workflows to guide nutritional, metabolic, and prognostic management strategies in geriatric acute care.

Background and Aims: Malnutrition is common in acutely ill geriatric patients, worsening immune function and clinical outcomes. Immunonutrition, containing nutrients like omega-3 fatty acids, arginin and glutamine, may improve recovery in this population. This study aimed to evaluate the impact of immunonutrition on clinical outcomes, inflammatory markers, and immune responses in frail, hospitalized older adults. Methods: This is a retrospective observational study. In total, 36 subjects, during hospitalization, received either an immunonutrition formula or isoproteic and isocaloric enteral nutrition. The primary outcome was the length of hospital stay (LOS), with secondary outcomes focused on inflammatory cytokines and immune parameters within a week of hospitalization. Results: Patients were primarily oldest-old, with a mean age of 88.6 years ± 4.9 (range 79–96). The immunonutrition group had a significantly shorter LOS (11.37 ± 4.87 vs. 16.82 ± 10.83 days, p = 0.05) and showed increases in key cytokines (G-CSF, INF-α2, IL-12p70, IL-15, IL-2, and IL-3, p < 0.05) enhanced immune function. A decrease in T cells and an increased B/T cell ratio was also observed. No significant differences in infection rates or 90-day survival were found. Conclusions: Enteral immunonutrition improved clinical outcomes by reducing LOS and modulating immune responses in frail patients, suggesting potential benefits in recovery. Further studies are needed to confirm these findings.

Neurodegenerative diseases such as Alzheimer’s are closely linked to oxidative stress and advanced glycation end products (AGEs), two interrelated processes that exacer-bate neuronal damage through mitochondrial dysfunction, protein aggregation, and chronic inflammation. This narrative review explores the metabolic interplay between reactive oxygen species (ROS) and AGEs, with a focus on the AGE-RAGE signaling ax-is as a driver of neurodegeneration. Evidence from preclinical and clinical studies highlights their combined role in disease progression and underscores potential thera-peutic targets. Strategies including mitochondria-targeted antioxidants, AGE inhibi-tors, RAGE antagonists, and metabolic interventions are discussed, along with future directions for biomarker development and personalized treatments. This review pre-sents oxidative and glycative stress as a unified pathogenic pathway with significant clinical implications.