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RESEARCH PAPER ANALYSIS

Frailty index predicts the risk of 17 health outcomes in distinct ways: prospective findings from the Moli-sani Study.

In a prospective cohort of ~20,000 adults followed for a median of 15 years, a 29-item frailty index predicted higher risk of multiple outcomes including Parkinson's disease (HR 1.25 per SD), non-Alzheimer dementia, cardiometabolic events, hospitalisations, and mortality.

PMID41967035
JournalAge and ageing
Publication Date2026-04-04
Ingested2026-04-28 08:58 PM
EXECUTIVE SUMMARY

What the AI sees

In a prospective cohort of ~20,000 adults followed for a median of 15 years, a 29-item frailty index predicted higher risk of multiple outcomes including Parkinson's disease (HR 1.25 per SD), non-Alzheimer dementia, cardiometabolic events, hospitalisations, and mortality.

WHY IT MATTERS

Research significance

This establishes frailty as a useful population-level risk stratification marker that could help identify individuals for surveillance or preventive interventions relevant to Parkinson's disease, but it offers little mechanistic insight or direct therapeutic targets for drug discovery.

ABSTRACT

Source abstract

BACKGROUND: Frailty reflects systemic vulnerability and is a major public health concern in ageing. This study examined how frailty relates to risk of death, hospitalisation and major chronic diseases. METHODS: We analysed data from 20 975 adults (≥35 years, 52% women) recruited in 2005-10 from the population-based Moli-sani Study (Italy) and followed for a median of 15 years. Frailty was assessed using a multidimensional 29-item frailty index (FI). Cox models accounting for competing risks estimated hazard ratios (HR) for 17 incident outcomes, adjusted for age, sex and common covariates, including social status indicators. RESULTS: Frailty was associated with increased risk of several adverse outcomes. Per 1-SD increase in FI, the risk of type-2 diabetes and coronary heart disease rose by 82% (HR = 1.82; 95% confidence interval 1.73-1.92; 1541 events) and 33% (HR = 1.33; 1.23-1.44; 756). FI was also associated with an increased risk of Parkinson's disease (HR = 1.25; 1.05-1.47; 158) and non-Alzheimer dementia (HR = 1.31; 1.11-1.54; 150). Cancer associations varied by site. FI also predicted hospitalisations for any cause (HR = 1.31; 1.28-1.34; 11 193), and all-cause mortality (HR = 1.35; 1.30-1.40; 2631). Analyses comparing frail and prefrail with fit categories, excluding early events, and stratified by sex showed consistent results, with indications of somewhat stronger associations among individuals younger than 65 years in certain outcomes. CONCLUSION: FI predicts a wide range of chronic diseases, especially cardiometabolic and neurodegenerative outcomes, and their negative consequences, including hospitalisation and mortality. These findings reinforce the importance of frailty assessment in preventive strategies, risk stratification and integrated surveillance in the general population.

SUPPORTING PAPER SET

32 more papers to review

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1 The cGAS-STING-Glymphatic-gut Axis in Parkinson's disease: A proposed self-amplifying triad of Neuroinflammation and therapeutic opportunity. International immunopharmacology 91.0 2 Immunosenescence and Inflammaging as Drivers of Neurodegeneration: Cellular Mechanisms, Neuroimmune Crosstalk, and Therapeutic Implications. Cells 91.0 3 Flavonoids improve neurotransmitters for Parkinson's treatment: mechanism and therapeutic potential. Frontiers in pharmacology 88.0 4 Alpha-Lipoic Acid and Biotin in Neurodegenerative Diseases: Convergent Mechanistic Insights from Preclinical Models to Clinical Perspectives. Neurology international 78.0 5 The Gut Microbiota in Parkinson's Disease: Mechanistic Insights into Microbial-Host Interactions. Microorganisms 85.0 6 Linking inflammation, metabolic dysfunction, and neurodegeneration: a comprehensive review of TLR2 pathways in type 2 diabetes. Frontiers in clinical diabetes and healthcare 80.0 7 Neuroprotective effects of GLP-2 and a GLP-2/GIP dual receptor agonist in an MPTP-induced mouse model of Parkinson's disease. Peptides 86.0 8 TNF alpha unmasks enteric malate aspartate shuttle dysfunction bridging Parkinson disease and intestinal inflammation. Nature communications 91.5 9 Lipid Metabolism and Neurodegeneration: Mechanistic Insights and Therapeutic Targets. Ageing research reviews 82.0 10 Shared functional microbiome signatures in Parkinson's disease and constipation predominate irritable bowel syndrome despite taxonomic divergence. Brain, behavior, & immunity - health 80.0 11 Benzimidazole as a Versatile Scaffold for Developing Neurotherapeutics Against Neurodegenerative Diseases. ChemMedChem 74.0 12 Biomimicking neuromelanin reverses the gait deficits and dopaminergic neuronal loss in the Parkinson's disease. Colloids and surfaces. B, Biointerfaces 86.0 13 Neuroprotective roles of klotho: Molecular pathways and therapeutic implications for cognitive health in neurological and psychiatric diseases. Experimental physiology 84.0 14 Flavonoid Rutin Reduces Intestinal Inflammation in an Experimental Model of Parkinson's Disease. Neurotoxicity research 70.0 15 Nanostructured Lipid Carriers Enhance Brain Delivery and Antioxidant Efficacy of a Small-Molecule MAO B Inhibitor for Neurodegenerative Disease Therapy. Molecular pharmaceutics 78.0 16 Pathophysiological Role of the Gut Brain Axis in Parkinson's Disease: From Microbial Metabolites and Intestinal Permeability to Central Neuroinflammation. Current neurovascular research 86.0 17 Parkinson's Disease: From Metabolism to Genetics-A Comprehensive Review. Current issues in molecular biology 86.0 18 Navigating the cholesterol maze: Key insights on use of statins in neurodegenerative disorders. Neuroprotection (Chichester, England) 76.0 19 Integrative network pharmacology delineates dual GPCR and non-GPCR mechanisms of blended and individual Taikong Blue lavender and Pingyin rose essential oils in neurodegenerative and psychiatric disorders. Computers in biology and medicine 65.0 20 Models of neuroprotection in Parkinson's disease: Exploring cellular, molecular, and microenvironmental targets. Experimental neurology 78.0 21 Hyaluronic acid: emerging roles and biomaterial innovations in Alzheimer's and Parkinson's disease therapy. Frontiers in pharmacology 75.2 22 Molecular mechanisms underlying Parkinson's disease and role of phytochemicals, α-synuclein, sirtuins, and incretin mimetics in potential therapy. Frontiers in pharmacology 75.0 23 Lipid droplets in neurodegenerative diseases: pathological drivers and therapeutic vulnerabilities. Cell death discovery 82.0 24 Brain-gut-microbiota axis: a review on the bidirectional regulatory mechanisms between gut microbiota and brain and their disease interactions. Frontiers in microbiology 74.0 25 Long non-coding RNAs in neurodegenerative diseases - Molecular mechanisms, liquid biopsy biomarkers, and therapeutic targets: A review. Biomolecules & biomedicine 84.0 26 Neurosyphilis and Parkinsonism: Overlapping Pathophysiology and Emerging Therapeutic Insights. Current neurovascular research 76.0 27 Molecular biochemistry of soluble epoxide hydrolase in lipid mediator pathways and neuroinflammatory responses. The Journal of steroid biochemistry and molecular biology 82.0 28 Multifaceted role of CNPY2 beyond ER stress: Disease implications and therapeutic potential. Cell stress 83.3 29 Neuroprotective Role of Exercise-based Physiotherapy Combined with Pharmacological Agents in Parkinson's Disease. Central nervous system agents in medicinal chemistry 64.0 30 Distinct metabolomic and proteomic signatures in Parkinson's disease patients with REM sleep behavior disorder. Signal transduction and targeted therapy 84.0 31 HMGB1-mediated neuroinflammation: molecular mechanisms and emerging therapeutic approaches. Inflammopharmacology 78.0 32 Beyond acid-base dyshomeostasis: Dynamic instability of neuronal lysosomal pH as a pathogenic mechanism and therapeutic target in neurological diseases. Biochemical pharmacology 88.0
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