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Shared mechanisms for cognitive impairment and physical frailty: A model for complex systems.

ABSTRACT: Introduction:We describe findings from a large study that provide empirical support for the emerging construct of cognitive frailty and put forth a theoretical framework that may advance the future study of complex aging conditions. While cognitive impairment and physical frailty have long been studied as separate constructs, recent studies suggest they share common etiologies. We aimed to create a population predictive model to gain an understanding of the underlying biological mechanisms for the relationship between physical frailty and cognitive impairment. Methods:Data were obtained from the longitudinal "Invecchaiare in Chianti" (Aging in Chianti, InCHIANTI Study) with a representative sample (n = 1453) of older adults from two small towns in Tuscany, Italy. Our previous work informed the candidate 132 single nucleotide polymorphisms (SNPs) and 155 protein biomarkers we tested in association with clinical outcomes using a tree boosting, machine learning (ML) technique for supervised learning analysis. Results:We developed two highly accurate predictive models, with a Model I area under the curve (AUC) of 0.88 (95% confidence interval [CI] 0.83-0.90) and a Model II AUC of 0.86 (95% CI 0.80-0.90). These models indicate cognitive frailty is driven by dysregulation across multiple cellular processes including genetic alterations, nutrient and lipid metabolism, and elevated levels of circulating pro-inflammatory proteins. Discussion:While our results establish a foundation for understanding the underlying biological mechanisms for the relationship between cognitive decline and physical frailty, further examination of the molecular pathways associated with our predictive biomarkers is warranted. Our framework is in alignment with other proposed biological underpinnings of Alzheimer's disease such as genetic alterations, immune system dysfunction, and neuroinflammation.

SUBMITTER: Sargent L

PROVIDER: S-EPMC7362211 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Shared mechanisms for cognitive impairment and physical frailty: A model for complex systems.

Sargent Lana L Nalls Mike M Amella Elaine J EJ Slattum Patricia W PW Mueller Martina M Bandinelli Stefania S Tian Qu Q Swift-Scanlan Theresa T Lageman Sarah K SK Singleton Andrew A

Alzheimer's & dementia (New York, N. Y.) 20200715 1

<h4>Introduction</h4>We describe findings from a large study that provide empirical support for the emerging construct of cognitive frailty and put forth a theoretical framework that may advance the future study of complex aging conditions. While cognitive impairment and physical frailty have long been studied as separate constructs, recent studies suggest they share common etiologies. We aimed to create a population predictive model to gain an understanding of the underlying biological mechanis ...[more]

PMID: 32685657

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Project description:Physical frailty and impaired cognition are common in patients with cirrhosis. Physical frailty can be assessed using performance-based tests, but the extent to which impaired cognition may impact performance is not well characterized. We assessed the relationship between impaired cognition and physical frailty in patients with cirrhosis. We enrolled 1,623 ambulatory adult patients with cirrhosis waiting for liver transplantation at 10 sites. Frailty was assessed with the liver frailty index (LFI; "frail," LFI ≥ 4.4). Cognition was assessed at the same visit with the number connection test (NCT); continuous "impaired cognition" was examined in primary analysis, with longer NCT (more seconds) indicating worse impaired cognition. For descriptive statistics, "impaired cognition" was NCT ≥ 45 seconds. Linear regression associated frailty and impaired cognition; competing risk regression estimated subhazard ratios (sHRs) of wait-list mortality (i.e., death/delisting for sickness). Median NCT was 41 seconds, and 42% had impaired cognition. Median LFI (4.2 vs. 3.8) and rates of frailty (38% vs. 20%) differed between those with and without impaired cognition. In adjusted analysis, every 10-second NCT increase associated with a 0.08-LFI increase (95% confidence interval [CI], 0.07-0.10). In univariable analysis, both frailty (sHR, 1.63; 95% CI, 1.43-1.87) and impaired cognition (sHR, 1.07; 95% CI, 1.04-1.10) associated with wait-list mortality. After adjustment, frailty but not impaired cognition remained significantly associated with wait-list mortality (sHR, 1.55; 95% CI, 1.33-1.79). Impaired cognition mediated 7.4% (95% CI, 2.0%-16.4%) of the total effect of frailty on 1-year wait-list mortality. Conclusion: Patients with cirrhosis with higher impaired cognition displayed higher rates of physical frailty, yet frailty independently associated with wait-list mortality while impaired cognition did not. Our data provide evidence for using the LFI to understand mortality risk in patients with cirrhosis, even when concurrent impaired cognition varies.

Project description:BackgroundLittle is known about the heterogeneous clinical profile of physical frailty and its association with cognitive impairment in older U.S. nursing home (NH) residents.MethodsMinimum Data Set 3.0 at admission was used to identify older adults newly-admitted to nursing homes with life expectancy ≥6 months and length of stay ≥100 days (n = 871,801). Latent class analysis was used to identify physical frailty subgroups, using FRAIL-NH items as indicators. The association between the identified physical frailty subgroups and cognitive impairment (measured by Brief Interview for Mental Status/Cognitive Performance Scale: none/mild; moderate; severe), adjusting for demographic and clinical characteristics, was estimated by multinomial logistic regression and presented in adjusted odds ratios (aOR) and 95% confidence intervals (CIs).ResultsIn older nursing home residents at admission, three physical frailty subgroups were identified: "mild physical frailty" (prevalence: 7.6%), "moderate physical frailty" (44.5%) and "severe physical frailty" (47.9%). Those in "moderate physical frailty" or "severe physical frailty" had high probabilities of needing assistance in transferring between locations and inability to walk in a room. Residents in "severe physical frailty" also had greater probability of bowel incontinence. Compared to those with none/mild cognitive impairment, older residents with moderate or severe impairment had slightly higher odds of belonging to "moderate physical frailty" [aOR (95%CI)moderate cognitive impairment: 1.01 (0.99-1.03); aOR (95%CI)severe cognitive impairment: 1.03 (1.01-1.05)] and much higher odds to the "severe physical frailty" subgroup [aOR (95%CI)moderate cognitive impairment: 2.41 (2.35-2.47); aOR (95%CI)severe cognitive impairment: 5.74 (5.58-5.90)].ConclusionsFindings indicate the heterogeneous presentations of physical frailty in older nursing home residents and additional evidence on the interrelationship between physical frailty and cognitive impairment.

Project description:Background/objectivesTo obtain national and regional estimates of prevalence of frailty with or without cognitive impairment, and cognitive impairment with or without frailty among older adults in the United States, and to identify profiles of characteristics that distinguish their joint versus separate occurrence.DesignCross-sectional.SettingCommunity or non-nursing home residential care settings.ParticipantsA U.S. nationally representative sample of 7,497 older adults aged 65 and older from the National Health and Aging Trends Study.MeasurementsFrailty was measured by the physical frailty phenotype. Cognitive impairment was assessed by cognitive performance testing of executive function and memory or by proxy reports. Multinomial logistic regression was used to identify profiles of demographic, socioeconomic, health, behavioral, and psychosocial characteristics that distinguish four subgroups: not-frail and cognitively intact ("neither"), not-frail and cognitively impaired ("Cog. only"), frail and cognitively intact ("frailty only"), and frail and cognitively impaired ("both").ResultsThe prevalence of "Cog. only," "frailty only," and "both" was 25.5%, 5.6%, and 8.7%, respectively. Individuals with"frailty only" had the highest prevalence of obesity, current smoking, comorbidity, lung disease, and history of surgery. The "both" group had the highest prevalence of dementia, depression, cardiovascular diseases, and disability. No significant differences were found between the "Cog. only" group and the "neither" group with respect to history of surgery and comorbidity burden. The prevalence of dementia in the "Cog. only" was less than half of that in the "both" group.ConclusionThe finding of sizable subgroups having physical frailty but not cognitive impairment, and vice versa, suggests that the two cannot be considered necessarily as antecedent or sequela of one another. The study provided empirical data supporting the prioritization of comorbidity, obesity, surgery history, and smoking status in clinical screening of frailty and cognitive impairment before formal diagnostic assessments.

Project description:BackgroundU.S. nursing homes provide long-term care to over 1.2 million older adults, 60% of whom were physically frail and 68% had moderate or severe cognitive impairment. Limited research has examined the longitudinal experience of these two conditions in older nursing home residents.MethodsThis national longitudinal study included newly-admitted non-skilled nursing care older residents who had Minimum Data Set (MDS) 3.0 (2014-16) assessments at admission, 3 months, and 6 months (n = 266,001). Physical frailty was measured by FRAIL-NH and cognitive impairment by the Brief Interview for Mental Status. Separate sets of group-based trajectory models were fitted to identify the trajectories of physical frailty and trajectories of cognitive impairment, and to estimate the association between older residents' characteristics at admission with each set of trajectories. A dual trajectory model was used to quantify the association between the physical frailty trajectories and cognitive impairment trajectories.ResultsOver the course of the first six months post-admission, five physical frailty trajectories ["Consistently Frail" (prevalence: 53.0%), "Consistently Pre-frail" (29.0%), "Worsening Frailty" (7.6%), "Improving Frailty" (5.5%), and "Consistently Robust" (4.8%)] and three cognitive impairment trajectories ["Consistently Severe Cognitive Impairment" (35.5%), "Consistently Moderate Cognitive Impairment" (31.8%), "Consistently Intact/Mild Cognitive Impairment" (32.7%)] were identified. One in five older residents simultaneously followed the trajectories of "Consistently Frail" and "Consistently Severe Cognitive Impairment". Characteristics associated with higher odds of the "Improving Frailty", "Worsening Frailty", "Consistently Pre-frail" and "Consistently Frail" trajectories included greater at-admission cognitive impairment, age ≥ 85 years, admitted from acute hospitals, cardiovascular/metabolic diagnoses, neurological diagnoses, hip or other fractures, and presence of pain. Characteristics associated with higher odds of the "Consistently Moderate Cognitive Impairment" and "Consistently Severe Cognitive Impairment" included worse at-admission physical frailty, neurological diagnoses, hip fracture, and receipt of antipsychotics.ConclusionsFindings provided information regarding the trajectories of physical frailty, the trajectories of cognitive impairment, the association between the two sets of trajectories, and their association with residents' characteristics in older adults' first six months post-admission to U.S. nursing homes. Understanding the trajectory that the residents would most likely follow may provide information to develop a comprehensive care approach tailored to their specific healthcare goals.

Project description:ObjectivesTo examine whether physical frailty onset before, after, or in concert with cognitive impairment is differentially associated with fall incidence in community-dwelling older adults.DesignA longitudinal observational study.Setting and participantsData from 1337 older adults age ≥65 years and free of physical frailty or cognitive impairment at baseline were obtained from the National Health Aging Trends Study (2011‒2017), a nationally representative cohort study of US older adult Medicare beneficiaries.MethodsParticipants were assessed annually for frailty (physical frailty phenotype) and cognitive impairment (bottom quintile of clock drawing test or immediate and delayed recall; or proxy-report of diagnosis of dementia or AD8 score of ≥2). Incident falls were ascertained annually via self-report. Multinomial logistic regression was performed to estimate the association between order of first onset of cognitive impairment and/or frailty and incident single or repeated falls in the 1-year interval following their first onset.ResultsOf the 1,337, 832 developed cognitive impairment first (termed "CI first"), 286 developed frailty first (termed "frailty first") and 219 had co-occurrence of cognitive impairment and frailty within one year (termed "CI-frailty co-occurrence") over 5 years. Overall, 491 (34.5%) had at least 1 fall during the 1-year interval following the onset of physical frailty and/or cognitive impairment. After adjustment, "CI-frailty co-occurrence" was associated with a more than 2-fold increased risk of repeated falls than "CI first" (odds ratio 2.35, 95% confidence interval 1.51‒3.67; P < .001). No significant difference was found between participants with "frailty first" and "CI first" (P = .07). In addition, the order of onset was not associated with risk of a single fall.Conclusions and implicationsOlder adults experiencing "CI-frailty co-occurrence" had the greatest risk of repeated falls compared with those with "CI first" and "frailty first". Fall risk screening should consider the order and timing of onset of physical frailty and cognitive impairment.

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Shared mechanisms for cognitive impairment and physical frailty: A model for complex systems.

Publications

Shared mechanisms for cognitive impairment and physical frailty: A model for complex systems.

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