On frailty as a geriatric concept

Frailty as a geriatric concept has been considered as the beginning of a rapid downward spiral towards death. Nevertheless, the French word "fragilité" is different from frailty?-?and probably an erroneous translation. Furthermore, frailty can be considered as belonging to the human condition as such.     

Oral frailty and neurodegeneration in Alzheimer’s disease

Frailty is a critical intermediate status of the aging process with a multidimensional and multisystem nature and at higher risk for adverse health-related outcomes,including falls,disability,hospitalizations,institutionalization,mortality,dementia,and Alzheimer’s disease.Among different frailty phenotypes,oral frailty has been recently suggested as a novel construct defined as a decrease in oral function with a coexisting decline in cognitive and physical functions.We briefly reviewed existing evidence on operational definitions of oral frailty,assessment and screening tools,and possible relationships among oral frailty,oral microbiota,and Alzheimer’s disease neurodegeneration.Several underlying mechanism may explain the oral health-frailty links including undernutrition,sarcopenia linked to both poor nutrition and frailty,psychosocial factors,and the chronic inflammation typical of oral disease.Oral microbiota may influence Alzheimer’s disease risk through circulatory or neural access to the brain and the interplay with periodontal disease,often causing tooth loss also linked to an increased Alzheimer’s disease risk.On this bases,COR388,a bacterial protease inhibitor targeting Porphyromonas gingivalis implicated in periodontal disease,is now being tested in a double-blind,placebocontrolled Phase II/III study in mild-to-moderate Alzheimer’s disease.Therefore,oral status may be an important contributor to general health,including Alzheimer’s disease and latelife cognitive disorders,suggesting the central role of preventive strategies targeting the novel oral frailty phenotype and including maintenance and improvement of oral function and nutritional status to reduce the burden of both oral dysfunction and frailty.     

Vascular depression: An early warning sign of frailty

Objectives: Frailty is a common geriatric disorder associated with activities of daily living (ADL) impairment, hospitalization, and death. Phenomenological evidence suggests that late-life depression (Katz, 2004 Katz, IR. 2004. Depression and frailty: The need for multidisciplinary research. American Journal of Geriatric Psychiatry, 12(1): 1–6. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]), particularly vascular depression, may be a risk factor for frailty. This study tests that hypothesis.

Methods: We identified a sample of stroke-free women over the age of 80 from the Health and Retirement Survey. The sample included 984 respondents in 2000 (incidence sample). Of these, 459 were non-frail at baseline and still alive in 2004 (prevalence sample). Frail respondents experienced at least three of the following: wasting, exhaustion, weakness, slowness, and falls. Vascular depression was represented using two dummy variables. The first represented respondents with either high cerebrovascular burden (CVB; at least two cerebrovascular risk factors) or probable depression (score ≥3 on the 8-item Center for Epidemiological Studies Depression Scale (CES-D)), and the second represented respondents with both high CVB and probable depression.

Results: At baseline, the prevalence of frailty was 31.5%. Over four years the incidence of frailty was 31.8%. After controlling for age, education, ADL and IADL disability, arthritis, pulmonary disorders, cancer, and self-rated health, respondents with either high CVB or probable depression were more likely to be frail at baseline, and those with both were at even higher risk. Of those who were not frail at the 2000 wave, respondents who reported both high CVB and probable depression were more likely to become frail by 2004.

Discussion: These findings suggest that vascular depression is a prodrome for frailty.     

Physical frailty: vulnerability of patients suffering from late-life depression

Objectives: Frailty, a state of increased risk of negative health outcomes, is increasingly recognized as a relevant concept for identifying older persons in need of preventative geriatric interventions. Even though broader concepts of frailty include psychological characteristics, frailty is largely neglected in mental health care. The aim of the present study is to examine the prevalence of physical frailty in depressed older patients and its potential overlap with depression criteria.

Method: Cross-sectional observational study including 378 depressed and 132 non-depressed adults aged ≥60 years according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. Physical frailty was defined as ≥3 out of 5 criteria (handgrip strength, weight loss, poor endurance, walking speed, low physical activity).

Results: Prevalence rates of physical frailty were 27.2% and 9.1% among depressed and non-depressed participants, respectively, which remained significant after controlling for relevant covariates (odds ratio [OR] = 2.66 [95% confidence interval [C.I.] = 1.36, 5.24], p = .004). Physical frailty in depression was associated with more severe depressive symptoms; this association remained significant in subsequent analyses with purely physical proxies for frailty (hand grip strength, walking speed) and different severity measures of depressive symptoms.

Conclusion: A quarter of depressed older patients is physically frail, especially the most depressed group. This cannot be explained by overlap in criteria and should be examined in future studies, primarily on its presumed clinical relevance.     

Depression and frailty: concurrent risks for adverse health outcomes

Objectives: This study used latent growth curve modeling (LGCM) to estimate the independent and joint associations between frailty and depression trajectories and likelihood of nursing home admission and falls resulting in injury.

Methods: Data come from five waves (2004–2012) of the Health and Retirement Study. Community-dwelling individuals aged 51 and older (N = 13,495) were analyzed using LGCM. Frailty was measured using a frailty index consisting of 30 deficits. Depressive symptoms were measured using the eight-item Centers for Epidemiologic Studies – Depression scale. Adverse health outcomes included nursing home admissions and falls resulting in injury.

Results: Prevalence of frailty increased over the study period (24.1%–32.1%), while the prevalence of depression was relatively constant over time (approximately 13%). Parallel process LGCM showed that more rapid increases of frailty and depressive symptoms were associated with higher odds of both nursing home admission and serious falls over time (Frailty: OR_{Nursing home} = 1.33, 95% CI: 1.09–1.66; OR_Fall = 1.52, 95% CI: 1.12–2.08; Depression: OR_{Nursing home} = 3.63, 95% CI: 1.29–9.97; OR_Fall = 1.16, 95% CI: 1.01–1.34). Associations between frailty and adverse outcomes were attenuated, and in some cases were no longer statistically significant, after accounting for concurrent depression.

Conclusion: Frailty trajectories may be important indicators of risk for nursing home admissions and falls, independent of baseline frailty status; however, concurrent depression trajectories are associated with adverse outcomes to a similar degree as frailty. Focus should be given to distilling elements of the frailty index which confer most risk for poor health outcomes.     

Sleep disturbances and risk of frailty and mortality in older men

ObjectiveTo test the hypothesis that non-frail older men with poorer sleep at baseline are at increased risk of frailty and death at follow-up.MethodsIn this prospective cohort study, subjective (questionnaires) and objective sleep parameters (actigraphy, in-home overnight polysomnography) were measured at baseline in 2505 non-frail men aged ?67 years. Repeat frailty status assessment performed an average of 3.4 years later; vital status assessed every four months. Sleep parameters expressed as dichotomized predictors using clinical cut-points. Status at follow-up exam classified as robust, intermediate (pre-frail) stage, frail, or died in interim.ResultsNone of the sleep disturbances were associated with the odds of being intermediate/frail/dead (vs. robust) at follow-up. Poor subjective sleep quality (multivariable odds ratio [MOR] 1.26, 95% CI 1.01–1.58), greater nighttime wakefulness (MOR 1.31, 95% CI 1.04–1.66), and greater nocturnal hypoxemia (MOR 1.47, 95% CI 1.02–2.10) were associated with a higher odds of frailty/death at follow-up (vs. robust/intermediate). Excessive daytime sleepiness (MOR 1.60, 95% CI 1.03–2.47), greater nighttime wakefulness (MOR 1.57, 95% CI 1.12–2.20), severe sleep apnea (MOR 1.74, 95% CI 1.04–2.89), and nocturnal hypoxemia (MOR 2.28, 95% CI 1.45–3.58) were associated with higher odds of death (vs. robust/intermediate/frail at follow-up). The association between poor sleep efficiency and mortality nearly reached significance (MOR 1.48, 95% CI 0.99–2.22). Short sleep duration and prolonged sleep latency were not associated with frailty/death or death at follow-up.ConclusionsAmong non-frail older men, poor subjective sleep quality, greater nighttime wakefulness, and greater nocturnal hypoxemia were independently associated with higher odds of frailty or death at follow-up, while excessive daytime sleepiness, greater nighttime wakefulness, severe sleep apnea and greater nocturnal hypoxemia were independently associated with an increased risk of mortality.     

Reduced cerebellar gray matter is a neural signature of physical frailty

Physical frailty has been recognized as a clinical syndrome resulting from declines in various physiological systems; however, the role of the central nervous system in the pathophysiology of frailty remains unclear. The I‐Lan Longitudinal Aging Study randomly sampled community‐dwelling people aged 50 or older for a brain magnetic resonance imaging study. All participants were assessed for frailty status (robust, prefrail, and frail) based on the presence of five frailty components: slow walking speed, muscle weakness, low physical activity, exhaustion and weight loss (Fried criteria). Gray matter volume (GMV) changes associated with frailty status and individual frailty components were examined. Overall, 456 participants (64.0 ± 8.5 years, 47.6% women) were included in this study. The prefrail (n = 178, 39.0%) and frail (n = 19, 4.2%) subjects were grouped for analysis. The prefrail–frail group showed reduced GMV, compared to the robust group (n = 259, 56.8%), in the cerebellum, hippocampi, middle frontal gyri, and several other cerebral regions (corrected P < 0.05). Each frailty component was associated with GMV changes in functionally related brain areas. Hierarchical cluster analysis categorized these components into three subsets. Motor‐related components, including weakness, low activity, and slowness, comprised one subset with a common cerebellar involvement. Exhaustion and weight loss were the other two subsets without cerebellar changes. To conclude, physical frailty is associated with a decreased reserve in specific brain regions, especially cerebellum. Further longitudinal studies are needed to explore if the cerebellum‐ and noncerebellum‐based frailty components reflect a distinctive future risk for developing frailty. Hum Brain Mapp 36:3666–3676, 2015. © 2015 Wiley Periodicals, Inc .     

Sex frailty differences in ageing mice: Neuropathologies and therapeutic projections

It is well‐established that females live longer than males. Paradoxically, women tend to have poorer health, a condition often named sex frailty. The aim of this study was to evaluate possible frailty predictors in older mice in a sex‐specific manner, in order to employ these predictors to follow‐up therapy efficiency. To further evaluate therapy effects, we also investigated the use of neurotrophic insulin‐like growth factor 1 (IGF‐1) gene therapy and its correlation with the expression of this frailty and emotional behaviour. In order to evaluate frailty, we employed two different approaches. We performed a frailty assessment through a 31‐Item Clinical Frailty Index and through a Performance‐Based 8‐Item Frailty Index. Our results show that both indexes are in concordance to evaluate sex differences, but they do not correlate when evaluating IGF‐1 therapy effects. Moreover, in order to reduce test‐to‐test variability for measures of dependent variables, we compared open field results across studies assessing sex and treatment by means of the z‐score normalization. The data show that regular open field parameters submitted to z‐score normalization analysis could be a useful tool to identify sex differences in ageing mice after growth factor therapies. Taking this into account, sex is a factor that influences the incidence and/or nature of all major complex diseases; the main outcome of our investigation is the development of an efficient tool that compares the use of different frailty index calculations. This represents an important strategy in order to identify sex differences and therapy efficiency in ageing models.     

A cost utility analysis of treating different adult spinal deformity frailty states

The aim of this study was to investigate the cost utility of treating non-frail versus frail or severely frail adult spinal deformity (ASD) patients. 79 surgical ASD patients >18 years with available frailty and ODI data at baseline and 2-years post-surgery (2Y) were included. Utility data was calculated using the ODI converted to the SF-6D. QALYs utilized a 3% discount rate to account for decline to life expectancy (LE). Costs were calculated using the PearlDiver database. ICER was compared between non-operative (non-op.) and operative (op.) NF and F/SF patients at 2Y and LE. When compared to non-operative ASD, the ICER was $447,943.96 vs. $313,211.01 for NF and F/SF at 2Y, and $68,311.35 vs. $47,764.61 for NF and F/SF at LE. Frail and severely frail patients had lower cost per QALY compared to not frail patients at 2Y and life expectancy, and had lower ICER values when compared to a non-operative cohort of ASD patients. While these results support operative correction of frail and severely frail patients, it is important to note that these patients are often at worse baseline disability, which is closely related to frailty scores, and have more opportunity to improve postoperatively. Furthermore, there may be a threshold of frailty that is not operable due to the risk of severe complications that is not captured by this analysis. While future research should investigate economic outcomes at extended follow up times, these findings support the cost effectiveness of ASD surgery at all frailty states.     

A new physical-cognitive scale for assessment of frailty in Chinese Han elderly

ABSTRACT

Objective: To develop a physical- cognitive scale for assessment of frailty and compare the clinical features between the new scale and the conventional Fried criteria.

Methods: 1757 individuals aged 70–84 were analyzed. Participants reporting three or more Fried phenotypes were grouped as frail patients (FP) whereas others as non-frail (NF). A score of Hasegawa’s dementia scale (HDS-R) higher than 21.5 were classified as non-cognitive impairment group (NCI) group. By combining the cognitive and frailty criteria, participants manifesting three or more positive components out of the six were categorized into the Physical-cognitive frailty group (Pc-F) while others into non- Pc-F (Pc-NF).

Results: Of all the participants, 46.7% (820) were males and 53.3% (937) were females. The mean age was 75.33 ± 3.90. 10.1% (178/1757) were evaluated as FP patients. The prevalence of CI was 53.2%; CI was much higher in the frail group (77.0%) than in the non-frail group (50.5%). Based on the new Pc-F scale, 163 out of 1579 NF participants were identified as Pc-F, and the prevalence of Pc-F reached 19.4% (341/1757). In the Pc-F group, there are more females, patients of advanced age, diabetes, stroke, CHD, CKD, metabolic syndrome, and high hs-CRP. Within the Pc-F group, patients with CI showed a higher incidence of exhaustion, low activity, weakness, and slowness than those without CI.

Conclusions: Our study revealed a significantly worse status in frail participants with CI than without. Our new scale shows a stronger correlation between frailty and complications than the classic phenotype.