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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. [ABSTRACT FROM AUTHOR]

Risk factors for developing dementia from mild cognitive impairment (MCI) probably differ between MCI subtypes. We investigated how frailty relates to dementia risk in amnestic MCI (a-MCI; n = 2,799) and non-amnestic MCI (na-MCI; n = 629) in the National Alzheimer's Coordinating Center database. Although higher frailty increased dementia risk for people with either a-MCI or na-MCI, the larger risk was in na-MCI (interaction hazard ratio = 1.35 [95% confidence interval = 1.15-1.59], p < 0.001). Even after the onset of clinically significant cognitive impairment, poor general health, quantified by a high degree of frailty, is a significant risk for dementia. ANN NEUROL 2021;89:1221-1225. [ABSTRACT FROM AUTHOR]

Background: Some people with substantial Alzheimer's disease pathology at autopsy had shown few characteristic clinical symptoms or signs of the disease, whereas others with little Alzheimer's disease pathology have been diagnosed with Alzheimer's dementia. We aimed to examine whether frailty, which is associated with both age and dementia, moderates the relationship between Alzheimer's disease pathology and Alzheimer's dementia.Methods: We did a cross-sectional analysis of data from participants of the Rush Memory and Aging Project, a clinical-pathological cohort study of older adults (older than 59 years) without known dementia at baseline, living in Illinois, USA. Participants in the cohort study underwent annual neuropsychological and clinical evaluations. In the present cross-sectional analysis, we included those participants who did not have any form of dementia or who had Alzheimer's dementia at the time of their last clinical assessment and who had died and for whom complete autopsy data were available. Alzheimer's disease pathology was quantified by a summary measure of neurofibrillary tangles and neuritic and diffuse plaques. Clinical diagnosis of Alzheimer's dementia was based on clinician consensus. Frailty was operationalised retrospectively using health variable information obtained at each clincial evaluation using the deficit accumulation approach (41-item frailty index). Logistic regression and moderation modelling were used to assess relationships between Alzheimer's disease pathology, frailty, and Alzheimer's dementia. All analyses were adjusted for age, sex, and education.Findings: Up to data cutoff (Jan 20, 2017), we included 456 participants (mean age at death 89·7 years [SD 6·1]; 316 [69%] women). 242 (53%) had a diagnosis of possible or probable Alzheimer's dementia at their last clinical assessment. Frailty (odds ratio 1·76, 95% CI 1·54-2·02; p<0·0001) and Alzheimer's disease pathology (4·81, 3·31-7·01; p<0·0001) were independently associated with Alzheimer's dementia, after adjusting for age, sex, and education. When frailty was added to the model for the relationship between Alzheimer's disease pathology and Alzheimer's dementia, model fit improved (p<0·0001). There was a significant interaction between frailty and Alzheimer's disease pathology (odds ratio 0·73, 95% CI 0·57-0·94; pinteraction=0·015). People with an increased frailty score had a weakened direct link between Alzheimer's disease pathology and Alzheimer's dementia; that is, people with a low amount of frailty were better able to tolerate Alzheimer's disease pathology, whereas those with higher amounts of frailty were more likely both to have more Alzheimer's disease pathology and for it to be expressed as dementia.Interpretation: The degree of frailty among people of the same age modifies the association between Alzheimer's disease pathology and Alzheimer's dementia. That frailty is related to both odds of Alzheimer's dementia and disease expression has implications for clinical management, since individuals with even a low level of Alzheimer's disease pathology might be at risk for dementia if they have high amounts of frailty. Further research should assess how frailty and cognition change over time to better elucidate this complex relationship.Funding: None. [ABSTRACT FROM AUTHOR]

Background: Assessing multiple traditional risk factors improves prediction for late-life diseases, including coronary heart disease (CHD). It appears that non-traditional risk factors can also predict risk. The objective was to investigate contributions of non-traditional risk factors to coronary heart disease risk using a deficit accumulation approach. Methods: Community-dwelling adults with no known history of CHD (n = 2195, mean age 46.9±18.7 years, 51.8% women) participated in the 1995 Nova Scotia Health Survey. Three risk factor indices were constructed to quantify the proportion of deficits present in individuals: 1) a 17-item Non-Traditional Risk Factor Index (e.g. sinusitis, arthritis); 2) a 9-item Traditional Risk Factor Index (e.g. hypertension, diabetes); and 3) a frailty index (25 items combined from the other two index measures). Ten-year risks of CHD events (defined as CHD-related hospitalization and CHD-related mortality) were evaluated. Results: The Non-Traditional Risk Factor Index, made up of health deficits unrelated to CHD, was independently associated with incident CHD events over 10 years after controlling for age, sex, and the Traditional Risk Factor Index [adjusted {adj.} Hazard Ratio {HR} = 1.31; Confidence Interval {CI} 1.14–1.51]. When all health deficits, both those related and unrelated to CHD, were included in a frailty index the corresponding adjusted hazard ratio was 1.61; CI 1.40–1.85. Conclusion: Both traditional and non-traditional risk factor indices are independently associated with incident CHD events. CHD risk assessment may benefit from consideration of general health information as well as from traditional risk factors. [ABSTRACT FROM AUTHOR]

Background the Pictorial Fit-Frail Scale (PFFS) was designed as a simple and practical approach to the identification of frailty. Objectives To investigate the feasibility and reliability of this visual image-based tool, when used by patients, caregivers and healthcare professionals (HCPs) in clinical settings. Design observational study. Setting three outpatient geriatric healthcare settings. Subjects patients (n  = 132), caregivers (n  = 84), clinic nurses (n  = 7) and physicians (n  = 10). Methods the PFFS was administered to all patients. Where available, HCPs and caregivers completed the scale based on the patients' health. In the geriatric day hospital, the PFFS was completed on admission and administered again within 7–14 days. Time and level of assistance needed to complete the scale were recorded. Intraclass correlation coefficients (ICCs) and 95% confidence intervals (CIs) were used to assess test−retest and inter-rater reliability. Results mean time to complete the scale (minutes:seconds ± SD) was 4:30 ± 1:54 for patients, 3:13 ± 1:34 for caregivers, 1:28 ± 0:57 for nurses and 1:32 ± 1:40 for physicians. Most patients were able to complete the scale unassisted (64%). Mean patient PFFS score was 11.1 ± 5.3, mean caregiver score was 13.2 ± 6.3, mean nurse score was 10.7 ± 4.5 and mean physician score was 11.1 ± 5.6; caregiver scores were significantly higher than patient (P  < 0.01), nurse (P  < 0.001) and physician (P  < 0.01) scores. Test−retest reliability was good for patients (ICC = 0.78, [95%CI = 0.67–0.86]) and nurses (ICC = 0.88 [0.80–0.93]). Inter-rater reliability between HCPs was also good (ICC = 0.75 [0.63–0.83]). Conclusion the PFFS is a feasible and reliable tool for use with patients, caregivers and HCPs in clinical settings. Further research on the validity and responsiveness of the tool is necessary. [ABSTRACT FROM AUTHOR]

Background: People aging with HIV show variable health trajectories. Our objective was to identify longitudinal predictors of frailty severity and mortality among a group aging with HIV. Methods: Exploratory analyses employing a multistate transition model, with data from the prospective Modena HIV Metabolic Clinic Cohort Study, based in Northern Italy, begun in 2004. Participants were followed over four years from their first available visit. We included all 963 participants (mean age 46.8±7.1; 29% female; 89% undetectable HIV viral load; median current CD4 count 549, IQR 405–720; nadir CD4 count 180, 81–280) with four-year data. Frailty was quantified using a 31-item frailty index. Outcomes were frailty index score or mortality at four-year follow-up. Candidate predictor variables were baseline frailty index score, demographic (age, sex), HIV-disease related (undetectable HIV viral load, current CD4+ T-cell count, nadir CD4 count, duration of HIV infection, and duration of antiretroviral therapy [ARV] exposure), and behavioral factors (smoking, injection drug use (IDU), and hepatitis C virus co-infection). Results: Four-year mortality was 3.0% (n = 29). In multivariable analyses, independent predictors of frailty index at follow-up were baseline frailty index (RR 1.06, 95% CI 1.05–1.07), female sex (RR 0.93, 95% CI 0.87–0.98), nadir CD4 cell count (RR 0.96, 95% CI 0.93–0.99), duration of HIV infection (RR 1.06, 95% CI 1.01–1.12), duration of ARV exposure (RR 1.08, 95% CI 1.02–1.14), and smoking pack-years (1.03, 1.01–1.05). Independent predictors of mortality were baseline frailty index (OR 1.19, 1.02–1.38), current CD4 count (0.34, 0.20–0.60), and IDU (2.89, 1.30–6.42). Conclusions: Demographic, HIV-disease related, and social and behavioral factors appear to confer risk for changes in frailty severity and mortality among people aging with HIV. [ABSTRACT FROM AUTHOR]