Fulvio Lauretani

Frailty, cognitive impairment, depression, functional dependency, low physical performance, and undernutrition are highly prevalent in older adults referred for cancer treatment, cardiovascular interventions, neurological therapies, and orthopaedic surgery, and each independently predicts treatment toxicity, post-procedural complications, and mortality. Comprehensive Geriatric Assessment (CGA) is the most accurate predictor of treatment outcomes in older patients, yet it remains structurally absent from most speciality pathways, contributing to overtreatment of biologically frail patients and undertreatment of biologically robust ones. In this Viewpoint, we propose and operationalise the FIT–FRAIL–DISABLE multidimensional geriatric stratification model as a conceptual framework for translating CGA findings into proportional, speciality-specific treatment recommendations across oncology, cardiology, neurogeriatrics, and orthogeriatrics. The model integrates six validated CGA instruments—the Mini-Mental State Examination (MMSE), the 15-item Geriatric Depression Scale (GDS-15), basic and instrumental Activities of Daily Living (ADL, IADL), the Short Physical Performance Battery (SPPB), and the Mini Nutritional Assessment Short Form (MNA-SF)—into three actionable categories (FIT, FRAIL, DISABLE) aligned with full-intensity, risk-adapted, and symptom-focused care, and is explicitly positioned in relation to the deficit-based frailty paradigm and the WHO Intrinsic Capacity (ICOPE) framework, which it complements rather than replaces. We specify a provisional, a priori decision rule for combining domain scores and describe how each stratification category should inform—but not dictate—goal-concordant treatment intensity within a shared decision-making process. FIT–FRAIL–DISABLE is presented as a proposed, hypothesis-generating framework: its composite thresholds and domain weighting have not yet been empirically derived, and the model has not undergone prospective validation. Retrospective calibration on existing CGA cohorts and prospective multicentre validation are being designed within the GERIA-NET research consortium. If validated, the framework has the potential to reduce both overtreatment-related harm and undertreatment-related therapeutic deprivation in older adults undergoing active treatment.

Background: Adverse drug reactions (ADRs) represent a major and often underestimated source of morbidity, hospitalization, and functional decline in older adults. The convergence of age-related pharmacokinetic and pharmacodynamic changes, multimorbidity, polypharmacy, and frailty creates a clinical environment in which ADR risk is not static but evolves along progressive trajectories—from mild, early manifestations toward severe, potentially irreversible outcomes. Understanding these trajectories is essential for rational geriatric prescribing. Methods: This narrative review synthesizes evidence from epidemiological studies, systematic reviews, Cochrane analyses, and clinical trials published between 2000 and 2025, focusing on adults aged 65 years and older with two or more chronic conditions. Sources were identified through a structured, non-systematic literature search of PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus using the terms ‘adverse drug reactions’, ‘polypharmacy’, ‘multimorbidity’, ‘frailty’, ‘deprescribing’, and ‘pharmacokinetics’ in older adults, alone and in combination. Evidence quality was assessed narratively, distinguishing trial evidence from observational and expert consensus data. Results: ADRs in older adults are best classified using complementary frameworks—the augmented Type A to withdrawal Type E and failure-of-therapy Type F taxonomy (Types A–F), the Dose-Time-Susceptibility (DoTS) classification, and the EIDOS mechanistic scheme—which together capture the heterogeneity of drug-related harm in this population. Age-related pharmacokinetic changes (altered absorption, increased volume of distribution of lipophilic drugs, reduced hepatic and renal clearance) and pharmacodynamic shifts (heightened receptor sensitivity, baroreflex impairment, increased blood–brain barrier permeability) interact with polypharmacy and frailty to amplify ADR trajectories from mild to severe. Anticholinergic burden, prescribing cascades, and inappropriate polypharmacy function as structural accelerators of these trajectories. Medication review and deprescribing improve prescribing quality but evidence for hard outcome benefits remains of low to very low certainty. Emerging AI-enabled digital tools show promising accuracy for identifying frailty and pharmacological vulnerability, but this performance relates to frailty classification and has not yet been shown to prevent ADR trajectories; they require validation for routine clinical use. Conclusions: Recognizing ADRs in older adults as dynamic trajectories rather than isolated events repositions prescribing review and deprescribing from optional to essential clinical acts. An integrated approach combining pharmacological vigilance, comprehensive geriatric assessment, structured deprescribing, and emerging digital decision-support tools offers the most realistic pathway to reduce the trajectory-related burden of drug-related harm in complex older patients.

Background: The Emergency Department (ED) is a ‘strategic crossroads’ for geriatric care, as older adults represent nearly 50% of ED visits resulting in hospital admissions. It is therefore essential to integrate geriatric expertise within the ED to address their complex needs and improve outcomes. Aims: This study evaluated whether implementing a Geriatric Team (GT) comprising geriatricians, nurses, social workers, tasked with conducting Comprehensive Geriatric Assessment and delivering tailored interventions in the ED, could reduce unnecessary hospital admissions and repeated ED visits compared to standard practice. Materials and methods: A multicentre, parallel, unblinded, superiority randomised study was conducted on people aged 75 years or older who scored ≥2 on the Triage Risk Stratification Tool upon ED admission. Randomisation was computer-generated and applied to calendar weeks. The primary outcome was hospital admission at the index ED visit. The secondary outcomes were ED readmissions; hospitalisations; mortality at 7, 30 and 90 days; and functional status at 30 and 90 days. Results: The study included 624 participants, 314 (50.3%) in the GT group and 310 (49.7%) in the usual care group. Hospital admissions at the index ED visit were 13.7% in the GT and 56.8% in the usual care group. ED readmission and hospitalisation rates were similar across groups. All-cause 30-day mortality was similar across groups, while 90-day mortality was lower in the intervention group. Functional decline was attenuated at both 30 and 90 days in the GT group. Conclusions: By relieving pressure on inpatient services, the GT integration into ED workflows represents a scalable strategy for health systems facing demographic shifts and rising demand for age-sensitive care.

Neurodegenerative diseases are among the most consequential disorders of later life, not only because of their increasing prevalence, rising from approximately 1–2% at age 65 to over 30% by age 85, but also because they develop within the broader clinical context of ageing, multimorbidity, frailty, and polypharmacy. In older adults, these conditions rarely present as isolated and static diagnostic entities; rather, they unfold as dynamic clinical trajectories involving the progressive interaction of cognitive decline, behavioural-neuropsychiatric symptoms, and extrapyramidal-motor dysfunction. In this review, we propose a trajectory-based framework for the interpretation and management of major neurodegenerative disorders in later life, including Alzheimer’s disease, frontotemporal dementia, Parkinson’s disease and Parkinson’s disease dementia, dementia with Lewy bodies, and vascular cognitive impairment. Building on a conceptual model organized around three major symptom spheres: cognitive, behavioural-neuropsychiatric, and extrapyramidal-motor, we argue that each disorder can be understood according to the relative predominance and temporal evolution of these domains. Alzheimer’s disease is typically cognition-led, frontotemporal dementia behaviour-led, and Parkinsonian syndromes motor-led, whereas dementia with Lewy bodies shows early multidomain convergence across all three spheres simultaneously. Vascular and mixed dementias follow more heterogeneous trajectories shaped by lesion burden, network disruption, and copathology. This framework has direct implications for diagnosis, prognostic stratification, and treatment selection, because interventions targeting one sphere may destabilize another and generate prescription cascades, delirium, or functional decline. We further discuss how biomarker-based diagnosis, disease-modifying therapies, non-pharmacological interventions, multidisciplinary care, deprescribing strategies, and palliative planning can be integrated within a trajectory-based approach. Interpreting neurodegeneration through clinical trajectories rather than diagnostic labels alone offers a more realistic and therapeutically useful model for precision geriatric neurology across the full course of disease.

Ageing is associated with neuromuscular decline, and emerging evidence suggests that sex may influence the time course of motor unit adaptations. This study examined age- and sex-related differences in motor unit firing behaviour across young (YG), middle-aged (MA), and older adults (OLD), by integrating high-density EMG motor unit analysis with muscle morphology and daily physical activity measurements. The analysis of single motor unit activity during submaximal isometric contractions of the vastus lateralis revealed that older adults had lower firing rates and a reduced capacity to modulate discharge frequency during force-increasing contractions. In the YG and MA groups, females showed higher motor unit firing rates and variability than males, while in OLD these sex differences were no longer present. Females also demonstrated a steeper decline in firing rate modulation between MA and OLD. Reductions in muscle cross-sectional area and thickness were similar between sexes. Physical activity levels declined with age in both sexes. These findings reveal distinct, sex-specific trajectories of neuromuscular ageing, with females showing greater motor neuron function decline between MA and OLD, in the absence of sex-related differences in the rate of morphological deterioration. The attenuation of sex differences in older age suggests a convergence of neuromuscular profiles with ageing. While physical activity may contribute to the observed sex-specific patterns, other mechanisms related to hormonal shifts warrant further investigation. These insights underscore the importance of considering age and sex in the study of motor control and in the development of targeted interventions to preserve muscle function across the lifespan.

Sufficient levels of physical activity are fundamental for preventing cardiovascular disease, dementia, and ultimately disability in older persons, yet this protective factor is nullified when excessive hours are spent in continuous sitting. Balancing physical activity and sedentary behavior is crucial for influencing metabolic parameters and vascular patterns, both central and peripheral, thereby reducing the risk of cardiovascular diseases, vascular dementia, and cognitive impairment. The primary goal of geriatric medicine is to improve quality of life and prevent disability by promptly identifying frail older individuals, thus mitigating both cognitive and motor impairments. Achieving this objective requires not only the optimization of pharmacological treatments but also the active promotion of a healthy lifestyle. In this context, investigating preclinical stages of disability, such as Motoric Cognitive Risk (MCR) Syndrome, which integrates physical and cognitive components of decline, becomes essential. However, despite robust evidence supporting these interventions, greater efforts are needed from the geriatric medical community to bridge the gap between scientific recommendations and everyday clinical practice. Integrating these guidelines into routine care is pivotal for delivering personalized interventions that address both physical inactivity and prolonged sedentary behavior. More research should aim to strengthen this balance, providing clearer, actionable strategies for clinicians to implement, thereby fostering the formation of evidence-based public health guidelines on physical activity specifically tailored for older persons.

Atrial Fibrillation can be considered a geriatric syndrome for its prevalence and incidence, its impact on patients’ quality of life, and Health Systems’ economy. The European Society of Cardiology 2024 guidelines introduce a recommendation for maintaining vitamin K antagonist therapy over switching to direct oral anticoagulants in clinically stable elderly patients with atrial fibrillation. This article explores the implications of this indication for the geriatric clinical context. The focus will also be devoted to the need for the stratification of older patients with atrial fibrillation, making an appropriate distinction between frailty and disability.

Background: Age-related loss of skeletal muscle strength and mass is linked to adverse postoperative outcomes in older individuals with sarcopenia. Half of patients suffer from severe associated osteoarthritis requiring orthopedic interventions. Mitigating the onset and progression of sarcopenia before surgery is essential to improve the prognosis and reduce surgical complications. The aim of this research was to innovatively explore whether the preoperative period could be the appropriate timeframe to empower surgical resilience, through prehabilitation and dietary supplementation, in older sarcopenic patients undergoing knee arthroplasty. Methods: The current literature concerning the effectiveness of prehabilitation and dietary supplementation before knee arthroplasty in sarcopenic older individuals was reviewed, following the SANRA criteria, between December 2023 and February 2024. The study inclusion criteria were as follows: (1) prehabilitation and/or dietary supplementation interventions; (2) human participants aged 65 years and older; (3) relevant outcome reporting (functional status, postoperative complications, and patient-reported outcomes); and (4) articles written in English The extracted information included study characteristics, demographics, intervention details, outcomes, and the main findings. Results: Merged prehabilitation and dietary supplementation strategies extrapolated from the current literature and involving strength, resistance, balance, and flexibility training, as well as essential amino acids, iron, vitamin D, adenosine triphosphate, and glucosamine sulphate supplementation, could improve the functional capacity, ability to withstand the upcoming surgical stressors, and postoperative outcomes in older people undergoing knee arthroplasty. Conclusions: Addressing complex links between knee osteoarthritis and sarcopenia in older individuals undergoing knee arthroplasty requires a multidimensional approach. Prehabilitation emerges as a crucial preliminary step, allowing the optimization of surgical outcomes. Nutraceutical integration, included in a comprehensive care plan, could have a synergic effect in achieving prehabilitation goals. Those interventions are essential for surgical resilience, in terms of muscle function preservation, recovery acceleration, and overall quality of life enhancement. Intensive collaboration among specialists could advance knowledge and the sharable consensus concerning the critical and evolutive field of perioperative care.

Dopamine is a key neurotransmitter involved in physiological processes such as motor control, motivation, reward, cognitive function, and maternal and reproductive behaviors. Therefore, dysfunctions of the dopaminergic system are related to a plethora of human diseases. Dopamine, via different circuitries implicated in compulsive behavior, reward, and habit formation, also represents a key player in substance use disorder and the formation and perpetuation of mechanisms leading to addiction. Here, we propose dopamine as a model not only of neurotransmission but also of neuromodulation capable of modifying neuronal architecture. Abuse of substances like methamphetamine, cocaine, and alcohol and their consumption over time can induce changes in neuronal activities. These modifications lead to synaptic plasticity and finally to morphological and functional changes, starting from maladaptive neuro-modulation and ending in neurodegeneration.

Introduction and aim. Atypical or mixed presentations of neurodegenerative disorders may postpone or confound the final diagnosis. Molecular imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) radioligands provide target-specific information and may anticipate the diagnosis by “in vivo” detection of the neuro pathological substrate, as Aβ deposition, nigrostriatal dopaminergic depletion or tau inclusions. This concise review will dis cuss the potential of PET and SPECT imaging as a solid guide to better characterize atypical phenotypes of neurodegeneration in the clinical routine, with the potential to drive personalized interventions, improve cohort uniformity for clinical trials, and serve as biomarkers for targeted molecular therapies. Material and methods. Literature search was performed focusing on the role of PET and SPECT imaging in assessing atypical phenotypes of neurodegeneration, using the electronic source of database PubMed/MEDLINE and the web-based search engines Google, Google Scholar. Analysis of the literature. New disease-modifying drugs may increase their effect with early initiation, which is especially im portant in working persons and younger subjects presenting atypical symptoms. In older individuals, the coexistence of neu rodegeneration, age-related changes, cerebrovascular lesions, or depression makes challenging a definitive diagnosis. Quantitative tools able to measure tracer distribution increase the accuracy of molecular neuroimaging creating topographic maps that compare subject’s data with healthy controls databases. Conclusion. Atypical phenotypes may be associated with quantitative key-pattern allowing a more precise and early diagnosis of the neurodegenerative disorder. Finally, quantitative assessment of the pathological substrates allows us to track the disease process and measure treatment response.