Establishing Biological Plausibility for Cognitive Frailty

Cognitive frailty is considered a potentially reversible age-related condition characterized by the simultaneous presence of both physical frailty and cognitive decline. The concept of cognitive frailty existing in older adults is indisputable, although the mechanisms and the directional relationship behind the dynamic association remain unexplained. Mechanisms have been suggested, often linking cognitive frailty to cognitive impairment or as a component of frailty but without an understanding of the biological bases for these associations we cannot not move forward with intervention trials. This dissertation examines the biological mechanisms for cognitive frailty. The study is the first to use a large number of protein and genetic markers identified by a systematic review to define the underlying pathology for cognitive frailty. We use an innovative Boosted trees machine learning technique for developing a population based predictive model. Xgboost is based in boosted trees and provides more efficient and accurate predictive modeling with large datasets and a rapid / robust framework for feature selection. Statistical modeling is used to design, test, and validate an accurate method for and identifying and classifying the features that predict individuals with cognitive frailty. The tree boosting model is used for the evaluation of multiple variables simultaneously and provides a high predictive value with low bias. The results presented within this dissertation create a foundation of understanding for a new aging condition and encourage translational research focused on the detection and prevention of cognitive frailty

Different Cognitive Frailty Models and Health- and Cognitive-related Outcomes in Older Age: From Epidemiology to Prevention

Frailty, a critical intermediate status of the aging process that is at increased risk for negative health-related events, includes physical, cognitive, and psychosocial domains or phenotypes. Cognitive frailty is a condition recently defined by operationalized criteria describing coexisting physical frailty and mild cognitive impairment (MCI), with two proposed subtypes: potentially reversible cognitive frailty (physical frailty/MCI) and reversible cognitive frailty (physical frailty/pre- MCI subjective cognitive decline). In the present article, we reviewed the framework for the definition, different models, and the current epidemiology of cognitive frailty, also describing neurobiological mechanisms, and exploring the possible prevention of the cognitive frailty progression. Several studies suggested a relevant heterogeneity with prevalence estimates ranging 1.0–22.0% (10.7–22.0% in clinical-based settings and 1.0–4.4% in population-based settings). Cross-sectional and longitudinal population-based studies showed that different cognitive frailty models may be associated with increased risk of functional disability, worsened quality of life, hospitalization, mortality, incidence of dementia, vascular dementia, and neurocognitive disorders. The operationalization of clinical constructs based on cognitive impairment related to physical causes (physical frailty, motor function decline, or other physical factors) appears to be interesting for dementia secondary prevention given the increased risk for progression to dementia of these clinical entities. Multidomain interventions have the potential to be effective in preventing cognitive frailty. In the near future, we need to establish more reliable clinical and research criteria, using different operational definitions for frailty and cognitive impairment, and useful clinical, biological, and imaging markers to implement intervention programs targeted to improve frailty, so preventing also late-life cognitive disorders

Cognitive frailty: a conceptual systematic review and an operational proposal for future research

[Abstract] Objective. To analyze the definition of “cognitive frailty” and to study the conceptual and operational definitions used and their implications for empirical research. The relationships between this concept and cognitive reserve, the role of neuropathology and brain reserve, motor signs of aging and the reversibility of cognitive frailty are also discussed. Study design. Systematic review of empirical studies identified from Medline Advanced 1966, CINAHL, Web of Science, PsycINFO, and Scopus until August 2017. Main – outcome measures. Effect sizes. The quality of the articles was assessed by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Statement. Three independent reviewers participated in the study selection and data extraction. Results. Nineteen studies involving 31,707 participants met the inclusion criteria. Significant associations were reported between cognitive frailty and physical frailty or gait speed. Screening instruments were usually used to determine objective cognitive decline rather than extensive neuropsychological assessments. Educational level was the only indicator of cognitive reserve that was systematically included in the evaluation of cognitive frailty. Motor decline and gait variables were not systematically included in protocols for the assessment of cognitive frailty. Conclusions. A strong operational definition would benefit both the development of treatments to counter cognitive frailty and the assessment of treatment effectiveness. Nevertheless, since there is clear agreement regarding the importance of interventions for and the prevention of cognitive frailty, randomized controlled trials investigating the efficacy of preventive interventions are necessary.Xunta de Galicia; ED431C-2017/27Xunta de Galicia; ED431C 2017/49Xunta de Galicia; ED431F 2017/09Xunta de Galicia; IN607C 2016/0

molecular mechanisms in cognitive frailty potential therapeutic targets for oxygen ozone treatment

Abstract In the last decade, cognitive frailty has gained great attention from the scientific community. It is characterized by high inflammation and oxidant state, endocrine and metabolic alterations, mitochondria dysfunctions and slowdown in regenerative processes and immune system, with a complex and multifactorial aetiology. Although several treatments are available, challenges regarding the efficacy and the costs persist. Here, we proposed an alternative non-pharmacological, non-side-effect, low cost therapy based on anti-inflammation, antioxidant, regenerative and anti-pathogens properties of ozone (O3), through the activation of several molecular mechanisms (Nrf2-ARE, NF-κB, NFAT, AP-1, HIFα). We highlighted how these specific processes could be implicated in cognitive frailty to identify putative therapeutic targets for its treatment. The O2-O3 therapy has never been tested for cognitive frailty. This work provides thus wide scientific background to build a consistent rationale for testing for the first time this therapy, that could modulate the immune, inflammatory, oxidant, metabolic, endocrine, microbiota and regenerative processes impaired in cognitive frailty. Although insights are needed, the O2-O3 therapy could represent a faster, easier, inexpensive monodomain intervention, working in absence of side effects, for cognitive frailty

Cognitive frailty: an update

This review article provides an update of the empirical research on cognitive fragility conducted in the last four years. The studies retrieved were classified in four different categories. The first category includes articles relating cognitive frailty to cognitive reserve and which continue to highlight the importance of educational level. The second category includes recent research on cognitive fragility biomarkers, involving neuroimaging, metabolism and, in a novel way, microbiota. The third category includes research on how cognitive frailty is related to motor development and physical functioning, exploring e.g. the use of technology to study motor markers of cognitive frailty. Finally, in the fourth category, research clarifying the difference between reversible frailty and potentially reversible cognitive frailty has led to new interventions aimed at reducing cognitive frailty and preventing negative health outcomes. Interventions based on physical activity and multicomponent interventions are particularly emphasized. In addition, recent research explores the long-term effects of dual interventions in older adults living in nursing homes. In summary, research on cognitive frailty has increased in recent years, and applied aspects have gained importanceThis work was financially supported through FEDER founds (A way to make Europe) by the Spanish AEI (doi: 10.13039/501100011033; Refs. PID2020-114521RB-C21 and PSI2017-89389-C2-1-R) and by the Galician Government (Consellería de Cultura, Educación e Ordenación Universitaria; GI-1807-USC: Ref. ED431C 2021/04). CB was supported by a Research Initiation Grant from the University of Santiago de Compostela, co-financed by Banco Santander. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publicationS

Cognicise Would be Beneficial for the Protection of Cognitive Frailty and Motoric Cognitive Risk (MCR) Syndrome

In recent years, elderly people tend to have mild cognitive impairment (MCI) and physical frailty. For the combination, the concept “cognitive frailty” has been in focus. According to recent study, the incidence risk for long-term care after 2 years showed hazard ratio (HR) 1.0 for healthy subjects, 2.22 for decreased cognitive function, 2.40 for physical frailty, and 3.86 for cognitive frailty, respectively. Recommended exercise is “cognicise”, which is a coined word that combines cognition and exercise. For similar concept, Motoric cognitive risk (MCR) syndrome has been also in focus. Cognicise would be useful in current circumstance worldwide

Determinant Factors of Cognitive Frailty in Elderly Patients

Introduction. Physical frailty and cognitive impairment have a strong relationship and there are differences in factors associated with cognitive frailty. This research aimed to determine the prevalence of cognitive frailty and identify factors associated with cognitive frailty in the elderly population in hospital polyclinic. Methods. A cross-sectional study with secondary data on patients aged ≥60 years in the Internal Medicine Polyclinic of Atma Jaya Hospital, Jakarta, from May 2020 to May 2021. The independent variables of this study were age, cardiovascular disease, type 2 diabetes mellitus, dyslipidemia, risk of malnutrition, risk of depression, and functional status. The alternative criteria by Won et al. were used to classify cognitive frailt. Bivariate analysis (chi-square test) and multivariate analysis (logistic regression) were performed using SPSS program. Results. There were 343 subjects with a median age of 66 years, 35% had cardiovascular disease, 5.2% had a high risk of malnutrition, 9.3% had depressive symptoms, 20.4% had a low functional status (ADL-Barthel index), 55.7% were diagnosed with type 2 diabetes mellitus, and 36.4% were diagnosed with dyslipidemia. The prevalence of subjects with cognitive frailty is 1.2% and 98.8% without cognitive frailty. The determinant factor of cognitive frailty is the presence of cardiovascular disease [OR 10.17 (95% CI 0.97-106.54); p=0.05]. Conclusions. Prevalence of cognitive frailty in elderly outpatients is 1.2%. The determinant factor of cognitive frailty is cardiovascular disease

Cognitive frailty: rational and definition from an (I.A.N.A./I.A.G.G.) international consensus group.

The frailty syndrome has recently attracted attention of the scientific community and public health organizations as precursor and contributor of age-related conditions (particularly disability) in older persons. in parallel, dementia and cognitive disorders also represent major healthcare and social priorities. although physical frailty and cognitive impairment have shown to be related in epidemiological studies, their pathophysiological mechanisms have been usually studied separately. an international Consensus Group on “Cognitive Frailty” was organized by the international academy on nutrition and aging (i.a.n.a) and the international association of Gerontology and Geriatrics (i.a.G.G) on april 16th, 2013 in toulouse (France). the present report describes the results of the Consensus Group and provides the first definition of a “Cognitive Frailty” condition in older adults. specific aim of this approach was to facilitate the design of future personalized preventive interventions in older persons. Finally, the Group discussed the use of multidomain interventions focused on the physical, nutritional, cognitive and psychological domains for improving the well-being and quality of life in the elderly. the consensus panel proposed the identification of the so-called “cognitive frailty” as an heterogeneous clinical manifestation characterized by the simultaneous presence of both physical frailty and cognitive impairment. in particular, the key factors defining such a condition include: 1) presence of physical frailty and cognitive impairment (Cdr=0.5); and 2) exclusion of concurrent ad dementia or other dementias. under different circumstances, cognitive frailty may represent a precursor of neurodegenerative processes. a potential for reversibility may also characterize this entity. a psychological component of the condition is evident and concurs at increasing the vulnerability of the individual to stressors

Cognitive reserve and mental health in cognitive frailty phenotypes: Insights from a study with a Portuguese sample

Background: Research on prevalence of cognitive frailty phenotypes in community-dwelling older adults in different countries is important to estimate their prevalence and to determine the influence of cognitive reserve and mental health in order to prevent frailty. The aims of this study were to estimate the prevalence of reversible and potentially reversible cognitive frailty (R-CF, PR-CF) in a Portuguese sample of old adults and explore the associations between these phenotypes and demographic, comorbidity, social support, cognitive reserve and mental health factors. Methods: We assessed frailty (Fried criteria) in 250 community-dwelling older adults (179 women) aged 60 years or over (mean 71.04 years) without dementia, neurological or psychiatric disorders. Subjective cognitive decline and Mild cognitive impairment were diagnosed according to standard criteria. The questionnaires Charlson Index, Medical Outcomes Study Social Support, Cognitive Reserve Index and General Health were used for assessing comorbidity, social support, cognitive reserve and mental health, respectively. Results: Prevalence of R-CF was 14%, and that of PR-CF, 15.2%. Cognitive frailty profiles differed significantly in relation to education, comorbidity, mental health, and cognitive reserve, but not in age or sex. Multivariate logistic regression showed that age, sex, comorbidity, social support, mental health, and cognitive reserve together predicted R-CF and PR-CF (90% specificity 75% sensitivity) with significant OR for mental health and cognitive reserve. Discussion: Cognitive reserve and mental health are important factors predicting R-CF and PR-CF. We recommend assessing these factors for early detection of cognitive frailty and promoting psychological well-being and lifestyles that increase cognitive reserve in adultsThis work was financially supported by ERDF funds through the National Research Agency (Spanish Ministry of Science, Innovation and Universities; Projects Ref. PSI2017-89389-C2-1-R and PID2020-114521RB-C21) and the Galician Government [GRC (GI-1807-USC); Ref: ED431-2017/27; ED431C-2021/04]; all with ERDF/FEDER fundsS

Association between cognitive impairment and criteria for frailty syndrome among older adults

OBJECTIVE: The association between cognitive impairment and physical frailty has been studied in older adults. The criteria degree of frailty may be keys to associated cognitive impairment. To analyze the association between cognitive impairment and the criteria for frailty. METHODS: We cross-sectionally examined data from 667 older adults (≥60 years of age) from a study entitled 'Variables associated to cognition in elderly caregivers' involving patients in an urban and rural primary healthcare center. We defined cognitive impairment based on different groups of scores on the Mini Mental State Examination, and defined frailty and prefrailty using the criteria by the Cardiovascular Health Study. We performed multinomial regression models to analyze the association between levels of frailty and cognitive impairment. RESULTS: Similar proportions of women (54.8%) and men (45.2%) participated in the study (mean age: 71 years old). We found cognitive impairment, prefrailty and frailty in 34, 54, and 24% of the participants, respectively. Concomitant cognitive impairment and frailty was found in 13% of them. The chances of cognitive impairment increased up to 330% (Odds Ratio [OR]: 4.3; 95% confidence interval [95%CI] 2.4‒7.7; p<0.001) among frail individuals, and 70% (OR: 1.7; 95%CI 1.0‒2.8; p=0.033) among prefrail individuals compared to robust/non-frail individuals. After controlling for age, education, place of residence and functional dependence, slowness and fatigue criteria were significantly associated with cognitive impairment. CONCLUSION: Older adults with frailty have a greater likelihood of concomitant cognitive impairment than prefrail and robust older adults. The prevalence of cognitive impairment and frailty is consistent with data reported in literature. The present findings contribute to the investigation of cognitive frailty