Frailty is associated with the clinical expression of neuropsychological deficits in older adults.

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.

Frailty and Risk of Dementia in Mild Cognitive Impairment Subtypes.

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.

Frailty, lifestyle, genetics and dementia risk.

OBJECTIVE: To optimise dementia prevention strategies, we must understand the complex relationships between lifestyle behaviours, frailty and genetics. METHODS: We explored relationships between frailty index, healthy lifestyle and polygenic risk scores (all assessed at study entry) and incident all-cause dementia as recorded on hospital admission records and death register data. RESULTS: The analytical sample had a mean age of 64.1 years at baseline (SD=2.9) and 53% were women. Incident dementia was detected in 1762 participants (median follow-up time=8.0 years). High frailty was associated with increased dementia risk independently of genetic risk (HR 3.68, 95% CI 3.11 to 4.35). Frailty mediated 44% of the relationship between healthy lifestyle behaviours and dementia risk (indirect effect HR 0.95, 95% CI 0.95 to 0.96). Participants at high genetic risk and with high frailty had 5.8 times greater risk of incident dementia compared with those at low genetic risk and with low frailty (HR 5.81, 95% CI 4.01 to 8.42). Higher genetic risk was most influential in those with low frailty (HR 1.31, 95% CI 1.22 to 1.40) but not influential in those with high frailty (HR 1.09, 95% CI 0.92 to 1.28). CONCLUSION: Frailty is strongly associated with dementia risk and affects the risk attributable to genetic factors. Frailty should be considered an important modifiable risk factor for dementia and a target for dementia prevention strategies, even among people at high genetic risk.

Cumulative health deficits, APOE genotype, and risk for later-life mild cognitive impairment and dementia.

OBJECTIVE: To determine whether health-deficit accumulation is associated with the risks of mild cognitive impairment (MCI) and dementia independently of APOE genotype. METHODS: A frailty index was calculated using the deficit-accumulation approach in participants aged 50 years and older from the National Alzheimer's Coordinating Center. Cognitive status was determined by clinical evaluation. Using multistate transition models, we assessed the extent to which an increasing degree of frailty affected the probabilities of transitioning between not cognitively impaired (NCI), MCI, and dementia. RESULTS: Participants (n=14 490) had a mean age of 72.2 years (SD=8.9 years; range=50-103 years). Among those NCI at baseline (n=9773), each 0.1 increment increase in the frailty index was associated with a higher risk of developing MCI and a higher risk of progressing to dementia. Among those with MCI at baseline (n=4717), higher frailty was associated with a higher risk of progressing to dementia, a lower probability of being reclassified as NCI, and a higher likelihood of returning to MCI in those that were reclassified as NCI. These risk effects were present and similar in both carriers and non-carriers of the APOE ε4 allele. CONCLUSION: Among older Americans, health-deficit accumulation affects the likelihood of progressive cognitive impairment and the likelihood of cognitive improvement independently of a strong genetic risk factor for dementia. Frailty represents an important risk factor for cognitive dysfunction and a marker of potential prognostic value.

Validation of the Pictorial Fit-Frail Scale in a memory clinic setting.

OBJECTIVE: To assess the feasibility, reliability, and validity of the Pictorial Fit-Frail Scale (PFFS) among patients, caregivers, nurses, and geriatricians in an outpatient memory clinic. DESIGN: Observational study. SETTING: A Canadian referral-based outpatient memory clinic. PARTICIPANTS: Fifty-one consecutive patients and/or their caregivers, as well as attending nurses and geriatricians. MEASUREMENTS: Participants (patients, caregivers, nurses, and geriatricians) were asked to complete the PFFS based on the patient's current level of functioning. Time-to-complete and level of assistance required was recorded. Participants also completed a demographic survey and patients' medical history (including the Mini-Mental State Examination [MMSE], and Comprehensive Geriatric Assessment [CGA]) was obtained via chart review. RESULTS: Patient participants had a mean age of 77.3±10.1 years, and average MMSE of 22.0±7.0, and 53% were female. Participants were able to complete the PFFS with minimal assistance, and their average times to completion were 4:38±2:09, 3:11±1:16, 1:05±0:19, and 0:57±0:30 (mins:sec) for patients, caregivers, nurses, and geriatricians, respectively. Mean PFFS scores as rated by patients, caregivers, nurses, and geriatricians were 9.0±5.7, 13.1±6.6, 11.2±4.5, 11.9±5.9, respectively. Patients with low MMSE scores (0-24) took significantly longer to complete the scale and had higher PFFS scores. Inter-rater reliability between nurses and geriatricians was 0.74, but it was lower when assessments were done for patients with low MMSE scores (0.47, p<0.05). The correlation between PFFS and a Frailty Index based on the CGA was moderately high and statistically significant for caregivers, nurses, and geriatricians (r=0.66, r=0.59, r=0.64, respectively), but not patients. CONCLUSIONS: The PFFS is feasible, even among people with some slight cognitive impairment, though it may be less useful when patients with severe dementia administer it to themselves. Further, the PFFS may help inform clinicians about areas of concern as identified by patients, enabling them to contribute more to diagnostic and treatment decisions or helping with health tracking and care planning.

Investigating the feasibility and reliability of the Pictorial Fit-Frail Scale.

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.

Social vulnerability as a predictor of mortality and disability: cross-country differences in the survey of health, aging, and retirement in Europe (SHARE).

BACKGROUND: Social factors are important for health; the concept of social vulnerability considers them holistically and can be quantified using a social vulnerability index (SVI). AIMS: Investigate the SVI in relation to mortality and disability, independent of frailty, in middle-aged and older European adults, and examine how this relationship differs across countries. METHODS: 18,289 community-dwelling participants 50 years and older from SHARE wave 1 (2004) were included in our sample. A 32-item SVI and a 57-item frailty index were calculated for individuals as the proportion of deficits present out of the total number considered. Countries were grouped based on their social model: Nordic (Denmark, Netherlands, Sweden), Continental (France, Austria, Belgium, Germany) and Mediterranean (Greece, Italy, Spain). Outcome measures were 5-year mortality and disability (≥1 dependency with activities of daily living) at wave 4 (2011-2012). RESULTS: High social vulnerability (highest quartile) predicted mortality (HR = 1.25, 95 % CI 1.07-1.45), and disability (OR = 1.36, 95 % CI 1.15-1.62) after controlling for age, sex, baseline disability and frailty level. When analyses were split by social model, social vulnerability remained a significant predictor of mortality for Continental (HR = 1.36, CI 1.05-1.77) and Mediterranean (HR = 1.33, CI 1.03-1.72) countries, but not the Nordic (HR = 1.02, CI 0.76-1.37) countries; the same pattern was observed for disability (Nordic OR = 1.06, CI 0.72-1.55; Continental OR = 1.53, CI 1.20-1.96; Mediterranean OR = 1.58, CI 1.13-2.23). DISCUSSION/CONCLUSIONS: Social vulnerability was a significant predictor of mortality and disability, though when controlling for frailty, this relationship varied by the social model of the country.

Physical demands at work and physical activity are associated with frailty in retirement.

BACKGROUND: The relationship between occupational physical activity and frailty is complex and understudied. OBJECTIVE: We explore whether moderate-vigorous physical activity (MVPA) in retirement and main lifetime occupation physical demands (OPD) are associated with frailty in retirement. METHODS: Retired adults aged 50 + who participated in waves 3-4 of the Survey of Health, Ageing and Retirement in Europe were included. We constructed a 65-item frailty index (FI; Wave 4). Linear regressions tested the independent associations between OPD (Wave 3) and retirement MVPA (Wave 4) with FI (B: 95% CI) controlling for occupation characteristics (Wave 3) and demographics (Wave 4). These models were repeated across country groups (Nordic; Mediterranean; Continental) and sexes. RESULTS: We included 8,411 adults (51.1% male) aged 72.4 years (SD 8.0). Frequent MVPA was consistently associated with lower FI (-0.09 : 0.10--0.08, p < .001) while OPD was associated with higher FI (0.02 : 0.01-0.03, p < .001). The MVPA*OPD interaction (-0.02: -0.04--0.00, p = .043) was weakly associated with FI, but did not explain additional model variance or was significant among any country group or sex. CONCLUSIONS: For a sample of European community-dwelling retirees, a physically demanding main lifetime occupation independently predicts worse frailty, even in individuals who are physically active in retirement.

10-year frailty trajectory is associated with Alzheimer's dementia after considering neuropathological burden.

MAIN PROBLEM: Frailty is an established risk factor for cognitive decline and Alzheimer's disease. Few studies have examined the longitudinal relationship between frailty and cognition. METHODS: Participants of Rush Memory and Aging project (n = 625, 67.5% female, 83.2 ± 5.9 years at baseline) underwent annual clinical evaluations (average follow-up 5.6 ± 3.7 years) followed by neuropathologic assessment after death. A frailty index was calculated from 41 health variables at each evaluation. Clinical diagnosis of MCI and/or dementia was ascertained by clinical data review (blinded to neuropathological data) after death. Age, sex, education, and neuropathological burden (10-item index) were evaluated as covariates. Frailty trajectories were calculated using a mixed effects model. RESULTS: At baseline the mean frailty index = 0.24 ± 0.12 and increased at rate of 0.026 or ~1 deficit per year. At death, 27.7% of the sample had MCI, and 38.6% had dementia. Frailty trajectories were significantly steeper among those individuals who were ultimately diagnosed as clinically impaired prior to death, even after controlling for age, sex, education, and neuropathological index. CONCLUSIONS: Findings suggest a strong link between health status (frailty index) and dementia, even after considering neuropathology. Frailty trajectories were associated with risk for MCI and dementia, underscoring the importance of addressing frailty to manage dementia risk.

CCCDTD5: Reducing the risk of later-life dementia. Evidence informing the Fifth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD-5).

The Fifth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD-5) was a year-long process to synthesize the best available evidence on several topics. Our group undertook evaluation of risk reduction, in eight domains: nutrition; physical activity; hearing; sleep; cognitive training and stimulation; social engagement and education; frailty; and medications. Here we describe the rationale for the undertaking and summarize the background evidence-this is also tabulated in the Appendix. We further comment specifically on the relationship between age and dementia, and offer some suggestions for how reducing the risk of dementia in the seventh decade and beyond might be considered if we are to improve prospects for prevention in the near term. We draw to attention that a well-specified model of success in dementia prevention need not equate to the elimination of cognitive impairment in late life.

Neuropathologic burden and the degree of frailty in relation to global cognition and dementia.

OBJECTIVE: To test the hypothesis that degree of frailty and neuropathologic burden independently contribute to global cognition and odds of dementia. METHODS: This was a secondary analysis of a prospective cohort study of older adults living in Illinois. Participants underwent an annual neuropsychological and clinical evaluation. We included 625 participants (mean age 89.7 ± 6.1 years; 67.5% female) who died and underwent autopsy. We quantified neuropathology using an index measure of 10 neuropathologic features: ß-amyloid deposition, hippocampal sclerosis, Lewy bodies, tangle density, TDP-43, cerebral amyloid angiopathy, arteriolosclerosis, atherosclerosis, and gross and chronic cerebral infarcts. Clinical consensus determined dementia status, which we coded as no cognitive impairment, mild cognitive impairment, or dementia. A battery of 19 tests spanning multiple domains quantified global cognition. We operationalized frailty using a 41-item frailty index. We employed regression analyses to model relationships between neuropathology, frailty, and dementia. RESULTS: Both frailty and a neuropathology index were independently associated with global cognition and dementia status. These results held after controlling for traditional pathologic measures in a sample of participants with Alzheimer clinical syndrome. Frailty improved the fit of the model for dementia status (χ2[2] 72.64; p < 0.0001) and explained an additional 11%-12% of the variance in the outcomes. CONCLUSION: Dementia is a multiply determined condition, to which both general health, as captured by frailty, and neuropathology significantly contribute. This integrative view of dementia and health has implications for prevention and therapy; specifically, future research should evaluate frailty as a means of dementia risk reduction.

Investigation of frailty as a moderator of the relationship between neuropathology and dementia in Alzheimer's disease: a cross-sectional analysis of data from the Rush Memory and Aging Project.

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.

Lower Frailty Is Associated with Successful Cognitive Aging Among Older Adults with HIV.

Aging with HIV poses unique and complex challenges, including avoidance of neurocognitive disorder. Our objective here is to identify the prevalence and predictors of successful cognitive aging (SCA) in a sample of older adults with HIV. One hundred three HIV-infected individuals aged 50 and older were recruited from the Modena HIV Metabolic Clinic in Italy. Participants were treated with combination antiretroviral therapy for at least 1 year and had suppressed plasma HIV viral load. SCA was defined as the absence of neurocognitive impairment (as defined by deficits in tasks of episodic learning, information processing speed, executive function, and motor skills) depression, and functional impairment (instrumental activities of daily living). In cross-sectional analyses, odds of SCA were assessed in relation to HIV-related clinical data, HIV-Associated Non-AIDS (HANA) conditions, multimorbidity (≥2HANA conditions), and frailty. A frailty index was calculated as the number of deficits present out of 37 health variables. SCA was identified in 38.8% of participants. Despite no differences in average chronologic age between groups, SCA participants had significantly fewer HANA conditions, a lower frailty index, and were less likely to have hypertension. In addition, hypertension (odds ratio [OR] = 0.40, p = .04), multimorbidity (OR = 0.35, p = .05), and frailty (OR = 0.64, p = .04) were significantly associated with odds of SCA. Frailty is associated with the likelihood of SCA in people living with HIV. This defines an opportunity to apply knowledge from geriatric population research to people aging with HIV to better appreciate the complexity of their health status.

Predictors of transitions in frailty severity and mortality among people aging with HIV.

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.

Modifications to the frailty phenotype criteria: Systematic review of the current literature and investigation of 262 frailty phenotypes in the Survey of Health, Ageing, and Retirement in Europe.

We conducted a systematic review to determine variability in how the criteria of the frailty phenotype (grip strength, weight loss, exhaustion, walking speed, physical activity) were assessed. We then evaluated the impact on estimating prevalence and mortality of modifying the criteria, using the Survey of Health, Ageing, & Retirement in Europe (SHARE). Five databases were searched for original research articles published after 2000, which evaluated frailty using the phenotypic criteria. Among the 264 included studies, 24 studies provided enough information to demonstrate that all criteria were assessed as proposed in the original frailty phenotype study by Fried et al. (2001). Physical inactivity and weight loss were the criteria most often modified. We then created 262 phenotypes from SHARE based on common modifications found in the review. Among these phenotypes, frailty prevalence ranged from 12.7% to 28.2%. Agreement with the primary frailty phenotype ranged from 0.662 to 0.967 and internal consistency ranged from 0.430 to 0.649. Women had 2.1-16.3% higher frailty prevalence than men. Areas under receiver operating characteristic curves for discriminating five-year mortality ranged from 0.607 (95% CI: 0.583-0.630) to 0.668 (0.645-0.691). The frailty phenotype often has been modified, and these modifications have important impact on its classification and predictive ability.

Accumulation of non-traditional risk factors for coronary heart disease is associated with incident coronary heart disease hospitalization and death.

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.