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Objective: Due to the high clinical heterogeneity of epilepsy, there is a critical need for novel metrics aimed at capturing its biological and phenotypic complexity. Frailty is increasingly recognized in various medical disciplines as a useful construct to understand differences in susceptibility to adverse outcomes. Here, we develop a frailty index (FI) for patients with epilepsy (PwE) and explore its association with demographic and clinical features., Methods: In this cross-sectional study, we consecutively enrolled 153 PwE from an outpatient epilepsy clinic. Participants were assessed for various health deficits to calculate the FI. Associations between FI and demographic/clinical features, antiseizure medications (ASMs), and patient-reported outcomes were analyzed using general linear models and Spearman correlation., Results: The median age at the time of study visit was 47 years (interquartile range = 33-60), and 89 (58.2%) patients were females. Multiple linear regression revealed that the developed 33-item FI showed an independent association with age, female sex, higher body mass index, family history of epilepsy, intellectual disability, and the number of ASMs used. A robust analysis of covariance showed higher FI levels in patients using cytochrome P450 3A4-inducer ASMs. We found a moderate positive correlation between FI and psychological distress, lower quality of life, and physical frailty, measured by the Hospital Anxiety and Depression Scale, Quality of Life in Epilepsy Inventory-10, and handgrip strength, respectively. Finally, a weak association was observed between higher FI scores and an increased number of epileptic falls., Significance: This study highlights the significance of frailty as a comprehensive health measure in epilepsy. It suggests that frailty in this specific population is not only a manifestation of aging but is inherently linked to epilepsy and treatment-related factors. Future research is warranted to validate and refine the FI in diverse epilepsy populations and investigate its impact on specific adverse outcomes in longitudinal studies., (© 2024 International League Against Epilepsy.)

Background and Purpose: The aim was to determine whether frailty is associated with the relationship between neuropsychological markers and global cognition in older adults., Methods: Cross-sectional analyzes were conducted of baseline data from three large cohort studies: National Alzheimer's Coordinating Center (NACC), Rush Memory and Aging Project (MAP) and Alzheimer's Disease Neuroimaging Initiative (ADNI). Studies recruited North American participants along the spectrum of cognitive functioning (44% no cognitive impairment at baseline). A frailty index was computed in each dataset. Frailty indices, neuropsychological tests (including measures of processing speed, episodic, semantic and working memory) and Mini-Mental State Examination (MMSE) scores were the variables of interest, with age, sex, education and apolipoprotein E ε4 evaluated as confounders., Results: Across all studies, 23,819 participants aged 55-104 (57% female) were included in analyzes. Frailty index scores were significantly and inversely associated with MMSE scores and significantly moderated relationships between neuropsychological test scores and MMSE scores. In participants with higher frailty index scores, lower neuropsychological test scores were more strongly associated with lower MMSE scores (standardized interaction coefficients ranged from -0.19 to -1.17 in NACC, -0.03 to -2.27 in MAP and -0.04 to -0.38 in ADNI, depending on the neuropsychological test). These associations were consistent across the different databases and were mostly independent of the composition of frailty indices (i.e., after excluding possible symptoms of dementia)., Conclusions: Amongst older Americans, frailty is associated with the cognitive expression of neuropsychological deficits. Implementation of frailty assessment in routine neurological and neuropsychological practice should be considered to optimize care outcomes for older adults., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Frailty is an age-related state of increased risk for health-related adverse outcomes that reflects multisystem physiological changes and likely influences the clinical expression and disease progression of neurodegenerative disorders. The aim of the present study was to assess the potential relationship between frailty, as assessed by a frailty index (FI), and motor symptom severity, motor subtypes, and non-motor domains in Parkinson's disease (PD)., Methods: We consecutively enrolled 150 PD patients. We administered an FI specifically designed for PD that included 50 age-related multidimensional biological deficits. Patients underwent a clinical assessment that evaluated motor and non-motor manifestations of PD. Using the FI score, we classified PD patients as relatively fit (FI ≤ 0.10), less fit (0.10 < FI ≤ 0.21), or frail (FI > 0.21). A linear regression model was designed to explore possible associations between frailty level and PD motor and non-motor manifestations., Results: Frail patients showed greater motor symptom severity and motor complications than fitter patients. A trend towards a higher prevalence of the postural instability/gait disorder subtype was also observed in frail versus relatively fit and less fit patients. The global burden of non-motor symptoms was higher in frail patients. Increased frailty was associated with more severe motor and non-motor symptoms, as well as with more pronounced cognitive deficits. These associations remained significant even when "traditional" predictors of PD severity (age, disease duration, and levodopa equivalent daily dose) were considered., Conclusions: The present findings indicate that the FI is associated with both motor and non-motor features of PD., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Frailty is an age-related status of increased vulnerability to stressors caused by the accumulation of multiple health deficits. This construct may allow to capture the clinical complexity of patients with multiple sclerosis (MS)., Objective: To investigate the relationship between frailty and the clinical manifestations of MS., Methods: Patients with MS were consecutively enrolled at five tertiary dedicated services. Disability and fatigue were assessed. The phenotypes of MS were also identified. Frailty was measured using a frailty index (FI), computed by cumulatively considering 42 age-related multidimensional health deficits., Results: Overall, 745 MS patients (mean age = 48.2 years, standard deviation = 11.7 years; women 68%) were considered. The median FI value was 0.12 (interquartile range = 0.05-0.19) and the 99th percentile was 0.40. FI scores were associated with MS disease duration, disability, fatigue, as well as with the number of previous disease-modifying treatments and current symptomatic therapies. A logistic regression analysis model showed that FI score was independently associated with the secondary progressive phenotype., Conclusion: Frailty is significantly associated with major characteristics of MS. The findings of the present cross-sectional investigation should be explored in future longitudinal studies.

The present study aimed at investigating if the main biomarkers of Alzheimer's disease (AD) neuropathology and their association with cognitive disturbances and dementia are modified by the individual's frailty status. We performed a cross-sectional analysis of data from participants with normal cognition, mild cognitive impairment (MCI), and AD dementia enrolled in the Alzheimer's Disease Neuroimaging Initiative 2 (ADNI2) study. Frailty was operationalized by computing a 40-item Frailty Index (FI). The following AD biomarkers were considered and analyzed according to the participants' frailty status: CSF Aβ 1-42 , 181 P-tau, and T-tau; MRI-based hippocampus volume; cortical glucose metabolism at the FDG PET imaging; amyloid deposition at the 18 F-AV-45 PET imaging. Logistic regression models, adjusted for age, sex, and education, were performed to explore the association of biomarkers with cognitive status at different FI levels. Subjects with higher FI scores had lower CSF levels of Aβ 1-42 , hippocampus volumes at the MRI, and glucose metabolism at the FDG PET imaging, and a higher amyloid deposition at the 18 F-AV-45 PET. No significant differences were observed among the two frailty groups concerning ApoE genotype, CSF T-tau, and P-tau. Increasing frailty levels were associated with a weakened relationship between dementia and 18 F-AV-45 uptake and hippocampus volume and with a stronger relationship of dementia with FDG PET. Frailty contributes to the discrepancies between AD pathology and clinical manifestations and influences the association of AD pathological modifications with cognitive changes. AD and dementia should increasingly be conceived as "complex diseases of aging," determined by multiple, simultaneous, and interacting pathophysiological processes.

Background: Serious mental illnesses may be characterized by accelerated biological aging, and over the last years the research on the topic has been stimulated by studies exploring the molecular underpinnings of senescence., Methods: In the present manuscript we propose that measuring frailty, a general product of organismal ageing, through the "Frailty Index" (FI), a recently-emerged macroscopic indicator of functional status and biological age, adds an important marker to the measurements currently implemented in the study of accelerated biological age in psychiatric illnesses., Results: The FI quantifies functional negative health attributes and measures their cumulative effect, thus providing a useful estimate of the individual's biological age and risk profile. Recent studies in older adults have observed significant associations between FI and molecular measures of aging., Limitations: High FI values can be driven by causes different from aging per se, so FI may be a sensitive but not specific measure of biological aging., Conclusions: FI, which is extensively used in geriatrics and gerontology but it has rarely been used in relation to mental health, may be of relevance in the evaluation of age-related phenomena associated with psychiatric diseases., Competing Interests: Declaration of Competing Interest All authors have no actual or past potential conflict of interest to disclose, including any financial, personal or other relationships with other people or organizations that could inappropriately have influenced the results presented in this paper., (Copyright © 2020. Published by Elsevier B.V.)

In the present study, we explored the relationship between multimorbidity and frailty in a population of older individuals with cognitive disturbances attending a memory clinic. All subjects consecutively attending the Memory Clinic of the Department of Human Neuroscience, "Sapienza" University of Rome, between January 2017 and April 2018 for a first neurological evaluation were considered for the present analysis. Multimorbidity was defined as the simultaneous presence of two or more diseases in the same individual. A Frailty Index was computed by considering 44 age-related, multidimensional health deficits. Overall, 185 subjects were recruited in the study. A condition of multimorbidity was detected in 87.6% of the sample, whereas only the 44.6% of the study population was considered as frail. A poor agreement was observed between multimorbidity and frailty. The present findings confirm that counting diseases or health deficits may provide discordant information concerning the risk profile of older subjects.

Frailty is defined as a decline in an organism's physiological reserves resulting in increased vulnerability to stressors. In humans, a single continuous variable, the so-called Frailty Index (FI), can be obtained by multidimensionally assessing the biological complexity of an ageing organism. Here, we evaluate this variability in dogs and compare it to the data available for humans. In dogs, there was a moderate correlation between age and the FI, and the distribution of the FI increased with age. Deficit accumulation was strongly related to mortality. The effect of age, when combined with the FI, was negligible. No sex-related differences were evident. The FI could be considered in epidemiological studies and/or experimental trials to account for the potential confounding effects of the health status of individual dogs. The age-related deficit accumulation reported in dogs is similar to that demonstrated in humans. Therefore, dogs might represent an excellent model for human aging studies.

Neuropsychological tests, besides reflecting the cognitive reserves and deficits of the tested individual, might also be differently affected by his/her underlying biological asset. In this context, the construct of frailty may offer an opportunity for better weighting the results of traditional tests. We evaluated the relationships between a set neuropsychological measures and a 35-item Frailty Index (FI). The role played by the FI in the relationship between neuropsychological tests and global cognition was also explored. Data from the first neurological and neuropsychological assessments of 79 subjects attending our university memory clinic because complaining cognitive disturbances were considered for the present analysis. A statistically significant correlation between FI and Trail Making Test-B was observed (Spearman's rho 0.33; p = 0.02). The relationship between the performance at the Rey Complex Figure and global cognition (as measured by the Mini Mental State Examination) was influenced by the FI. In fact, participants with higher FI levels had a weakened association linking constructional/visual memory abilities and general cognitive functioning. The interpretation of the neuropsychological assessment can be biased by the frailty status of the tested individual. It can be hypothesized the need of developing new models of correction, that may better reflect the person's biology and complexity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Frailty is an age-related status of increased vulnerability to stressors caused by the accumulation of multiple health deficits. This construct may allow to capture the clinical complexity of patients with multiple sclerosis (MS). Objective: To investigate the relationship between frailty and the clinical manifestations of MS. Methods: Patients with MS were consecutively enrolled at five tertiary dedicated services. Disability and fatigue were assessed. The phenotypes of MS were also identified. Frailty was measured using a frailty index (FI), computed by cumulatively considering 42 age-related multidimensional health deficits. Results: Overall, 745 MS patients (mean age = 48.2 years, standard deviation = 11.7 years; women 68%) were considered. The median FI value was 0.12 (interquartile range = 0.05–0.19) and the 99th percentile was 0.40. FI scores were associated with MS disease duration, disability, fatigue, as well as with the number of previous disease-modifying treatments and current symptomatic therapies. A logistic regression analysis model showed that FI score was independently associated with the secondary progressive phenotype. Conclusion: Frailty is significantly associated with major characteristics of MS. The findings of the present cross-sectional investigation should be explored in future longitudinal studies. [ABSTRACT FROM AUTHOR]

The early identification of fragile populations in the Covid-19 era would help governments to allocate resources and plan strategies to contain consequences of the pandemic. Beyond frailty, social vulnerability to environmental stressors, such as the social distancing enforced to reduce the SARS-CoV2 contagion, can modify long-term disease risk and induce health status changes in the general population. We assessed frailty and social vulnerability indices in 1,258 Italian residents during the first lockdown phase via an on-line survey. We compared indices taking into account age categories and gender. While frailty showed a linear increase with age and was greater in females than in males, social vulnerability was higher in young adults and elders compared to middle aged and older adults, and in males than females. Both frailty and social vulnerability contributed in explaining the individual perception of the impact of Covid-19 emergency on health, which was further influenced by proactive attitudes/behaviors and social isolation. Social isolation and loneliness following the Covid-19 outbreak may exert dramatic psychosocial effects in the general population. The early detection of vulnerable categories, at risk to become ill and develop long-lasting health status changes, would help to prevent consequences on general well-being by allocating resources to targeted interventions managing psychosocial distress and increasing young adults and elderly resilience toward the post-Covid-19 crisis. [ABSTRACT FROM AUTHOR]

To date, the external validity of randomized controlled trials (RCTs) on Alzheimer's disease (AD) has been assessed only considering monodimensional variables. Nevertheless, looking at isolated and single characteristics cannot guarantee a sufficient level of appreciation of the AD patients' complexity. The only way to understand whether the two worlds (i.e., research and clinics) deal with the same type of patients is to adopt multidimensional approaches more holistically reflecting the biological age of the individual. In the present study, we compared measures of frailty/biological aging [assessed by a Frailty Index (FI)] of a sample of patients with AD resulted eligible and subsequently included in phase III RCTs compared to patients referring to the same clinical service, but not considered for inclusion. The "RCT sample" and the "real world sample" were found to be statistically similar for all the considered sociodemographic and clinical variables. Nevertheless, the "real world sample" was found to be significantly frailer compared to the "RCT sample," as indicated by higher FI scores [0.28 (SD 0.1) vs. 0.17 (SD 0.1); p < 0.001, respectively]. Moreover, when assessing the relationship between FI and age, we found that the correlation was almost null in the "RCT sample" (Spearman's r = 0.01; p = 0.98), while it was statistically significant in the "real world sample" (r = 0.49; p = 0.02). The application of too rigid designs may result in the poor representativeness of RCT samples. It may even imply the study of a condition biologically different from that observed in the "real world." The adoption of multidimensional measures capable to capture the individual's biological age may facilitate evaluating the external validity of clinical studies, implicitly improving the interpretation of the results and their translation in the clinical arena. [ABSTRACT FROM AUTHOR]

For instance, it is likely that if an index had been created considering only biological abnormalities (i.e. a biological FI),[4] thus capable of capturing and measuring subclinical frailty, higher FI scores would have been observed among our MS patients. The FI values obtained in our study cannot be automatically translated to other populations of MS patients with different sociodemographic and clinical characteristics. We thank Zanotto et al. for their interest in our paper "Operationalization of a frailty index in patients with multiple sclerosis: A cross-sectional investigation", in which we investigated the relationship between frailty and the clinical expression of multiple sclerosis (MS) in a large population of patients by applying a specifically designed Frailty Index (FI).[1] The reflections on the results obtained by measuring the individual degree of frailty through an FI cannot be separated from an accurate evaluation of (1) how the index was computed, and (2) to which population it was applied. [Extracted from the article]

The survival of HIV-infected persons has been increasing over the last years, thanks to the implementation of more effective pharmacological and non-pharmacological interventions. Nevertheless, HIV-infected persons are often “biologically” older than their “chronological” age due to multiple clinical, social, and behavioral conditions of risk. The detection in this population of specific biological features and syndromic conditions typical of advanced age has made the HIV infection an interesting research model of accelerated and accentuated aging. Given such commonalities, it is possible that “biologically aged” HIV-positive persons might benefit from models of adapted and integrated care developed over the years by geriatricians for the management of their frail and complex patients. In this article, possible strategies to face the increasingly prevalent geriatric syndromes in HIV-infected persons are discussed. In particular, it is explained the importance of shifting from the traditional disease-oriented approach into models of care facilitating a multidisciplinary management of frailty. [ABSTRACT FROM AUTHOR]

The authors discuss the relevance of the horse-racing effect in the conduction of randomized controlled trials (RCTs) in older people. They indicate that the horse-racing effect advocated in observational studies of aging represents a major source of confounding in RCTs. They suggest the need for researchers to become aware about the necessity of shifting from a disease-oriented approach to a function-oriented one in order to design an informative RCTs in older person.

Background The Frailty Index (FI), proposed by Rockwood and Mitniski, measures the deficits accumulation occurring with aging, and can be generated from the results of a comprehensive clinical assessment. Its construct (based on pure arithmetical assumptions) may represent a unique feature for supporting unbiased comparisons among clinical facilities/services. Objective To propose an example depicting how the FI may support health economic evaluations and provide insights for public health. Design Observational study. Setting Nine nursing homes participating in the “Incidence of pNeumonia and related ConseqUences in nursing home Residents” (INCUR) study. Subjects A sample of 345 older persons living in nursing homes. Methods A 30-item FI was generated from clinical data retrieved from medical charts. Health care expenditures that occurred over 12 months of follow-up for each participant were obtained from the Caisse Primaire d'Assurance Maladie . Descriptive analyses describing the relationships between the FI of residents with the annual health care expenditures according to nursing home are presented. Results Mean age of the study sample was 86.0 (SD 7.9) years. The median annual cost per patient was 27,717.75 (interquartile range, IQR 25,917.60–32,118.02) Euros. The median FI was 0.33 (IQR 0.27–0.43). Results are graphically presented to highlight clinical and economic differences across nursing homes, so as to identify potential discrepancies between clinical burden and consumed resources. Conclusions In this article, an example on how the FI may support health economic analyses and promote an improved allocation of healthcare resources is presented. [ABSTRACT FROM AUTHOR]