We analyzed the records of participants in the Aging Study of Pyeongchang Rural Area (ASPRA) cohort, a population-based, prospective cohort study originally established in 2014 that included community-dwelling adult residents of Pyeongchang-gun, Gangwon Province, South Korea who were aged 65 years and older. Detailed information on the original study design and measurements in the ASPRA has been published elsewhere.²¹⁾ During annual assessments, the study population continuously increased with the expansion of the covered region of ASPRA among Pyeongchang-gun, with the inclusion and exclusion criteria remaining the same. Individuals were eligible for participation if they were (1) aged 65 years or older, (2) registered in the Community Healthcare Service, (3) ambulatory with or without an assistive device, (4) living at home, and (5) able to provide informed consent by themselves or their legal proxies. We excluded participants who were (1) living in nursing homes, (2) hospitalized, or (3) bedridden and receiving nursing home level care at home at the time of enrollment.

Between December 2014 and December 2017, 1,295 community-dwelling individuals were enrolled in the ASPRA cohort, which included over 90% of eligible people living in the study area. Among these older adults, we used records of 1,292 people who completed the K-FRAIL questionnaire. All participants underwent a comprehensive geriatric assessment every 12 months, while health-related outcomes, including death, institutionalization, and disability, were recorded every 3 months. The characteristics of the original ASPRA population were generally comparable to those of the general Korean rural population based on the Korea National Health and Nutrition Examination Survey.²¹⁾ The study protocol of the ASPRA cohort was approved by the Institutional Review Board of the Asan Medical Center (No. 2015-0673). Written informed consent was obtained from all participants.

We used the K-FRAIL questionnaire as a screening measure for frailty status. The K-FRAIL is based on the original FRAIL scale,¹³⁾ which has been validated in various populations and translated into Korean.¹⁶⁾ This simple screening tool of five self-reported items can be assessed in 2–3 minutes with no requirement for special equipment or sophisticated training. The questionnaire comprises five items:

(1) Fatigue (responses of “all of the time” or “most of the time” to the following question): “How much of the time during the past 4 weeks did you feel tired?”

(2) Resistance (positive response to the question): “By yourself and not using aids, do you have any difficulty in walking up 10 steps without resting?”

(3) Ambulation (positive response to the question): “By yourself and not using aids, do you have any difficulty in walking 300 m?”

(4) Illnesses (five or more self-reported physician diagnoses of hypertension, diabetes, cancer excluding minor skin cancer, chronic lung disease, heart attack, congestive heart failure, angina, asthma, arthritis, stroke, or kidney disease), and

(5) Loss of weight (>5% in the past year).

We calculated the K-FRAIL score by combining the number of positive items and classified the participants as robust (0 points), prefrail (1–2 points), or frail (3–5 points).

Trained nurses performed comprehensive geriatric assessments (CGAs) to evaluate geriatric conditions. Multimorbidity was defined as having two or more of the 11 physician-diagnosed illnesses such as angina, arthritis, asthma, cancer, chronic lung disease, congestive heart failure, diabetes, hypertension, heart attack, kidney disease, and stroke. Polypharmacy was defined as regularly taking five or more medications.²²⁾ Cognitive impairment was defined as a Korean version of the Mini-Mental State Examination score of <24.²³⁾ Depressive mood was defined as a Korean version of the Center for Epidemiological Studies Depression scale score of >20.²⁴⁾ Malnutrition risk was defined as a Mini-Nutritional Assessment-Short Form score of ≤11.²⁵⁾ To assess physical function, we measured handgrip strength (kg) using a dynamometer (T.K.K. 5401 Grip-D; Takei, Tokyo, Japan) and averaged two measurements of the dominant hand.²¹⁾ We defined dysmobility as a slow gait (usual gait speed <0.6 m/s from a timed 4-m walk).²⁶⁾ We calculated the Short Physical Performance Battery (SPPB) score from three components: the ability to stand for up to 10 seconds with feet positioned in three ways (together side-by-side, semi-tandem, and tandem), the time to complete a 4-m walk, and the time to rise from a chair five times. The resultant SPPB scores ranged from 0 to 12, with higher scores indicating a higher level of function.²⁷⁾ Sarcopenia was defined according to the Asian Working Group for Sarcopenia as follows: decreased muscle mass (decreased handgrip strength of <26 kg for men and <18 kg for women) and decreased physical performance (slow gait of <0.8 m/s).²⁸⁾ Disability was defined as requiring assistance in performing any of the seven activities of daily living (ADL; bathing, continence, dressing, eating, toileting, transferring, and washing face and hands) or 10 instrumental activities of daily living (IADL; food preparation, household chores, going out on a short distance, grooming, handling finances, laundry, managing own medications, shopping, transportation, and using a telephone).²¹⁾

This study defined major adverse health outcomes as death, institutionalization, and incidence of disability during the 3-year follow-up period. We defined disability as the requirement for assistance from another person in performing any one of the ADL or IADL.²¹⁾ Health-related quality of life was assessed during the follow-up period using the EuroQol-5D (EQ-5D).²⁹⁾ An EQ-5D score decline over 3 years of >0.2 was considered clinically meaningful.³⁰⁾ To assess these outcome measures, all participants underwent structured interviews via phone calls every 3 months on institutionalization, death, and annualized follow-up assessments, including CGAs for ADL, IADL, and EQ-5D.

To compare variables for baseline characteristics according to the frailty status derived from the K-FRAIL scale, we used Kruskal–Wallis and chi-square tests for continuous and discrete variables, respectively. To cross-sectionally assess the association between prevalent frailty and geriatric syndrome, we used logistic regression analysis with common geriatric syndromes as dependent variables and frailty status (robust, prefrail, and frail) as independent variables after adjusting for age and sex. For longitudinal outcome analysis, we used logistic regression analysis for health outcomes of mortality, long-term institutionalization, incidence of disability, and decline in EQ-5D score at 3 years from baseline, with frailty status (robust, prefrail, and frail) as dependent variables after adjusting age and sex. Mortality was further analyzed using Kaplan–Meier analysis, with log-rank tests and Cox proportional hazard regression analysis used to examine the statistical differences in survival according to the baseline frailty status. The restricted mean survival time was estimated as death at 40 months. Two-sided p-values <0.05 indicated statistical significance in all analyses. Statistical analyses were performed using IBM SPSS Statistics for Windows, version 21.0 (IBM Corp., Armonk, NY, USA).

As shown in Table 1, 471 (36.5%) participants were classified as robust, 524 (40.5%) as prefrail, and 297 (23%) as frail according to the K-FRAIL scale. The frail group was older, more likely to be female, more likely to be living alone, and had lower income than the other two groups (p<0.001). The frail group also had a higher burden of multimorbidity and polypharmacy and was more likely to have depression and cognitive impairment than the other two groups (p<0.001). Physical performance was worse and the prevalence of disability was higher in the frail group than in the other two groups (p<0.001).

In Table 2, frailty according to the FRAIL scale was associated with geriatric conditions after adjusting for age and sex. The frail group showed a significant association with multimorbidity (odds ratio [OR]=2.24; 95% confidence interval [CI], 1.57–3.21), dysmobility (OR=5.35; 95% CI, 3.58–7.97), malnutrition (OR=4.09; 95% CI, 2.83–5.90), cognitive impairment (OR=3.52; 95% CI, 2.36–5.25), depression (OR=27.50; 95% CI, 11.09–68.19), and disability (OR=3.12; 95% CI, 2.18–4.46).

Longitudinal analysis showed that baseline frailty status significantly increased the risks of mortality (OR=3.57; 95% CI, 1.69–7.54), institutionalization (OR=2.42; 95% CI, 1.30–4.51), and disability at 3 years (OR=3.04; 95% CI, 1.91–4.85) but not the deterioration of the quality of life (Table 3). The differences in 3-year mortality according to the FRAIL scale are shown in Fig. 1. The frail group had significantly lower estimated median survival (203 months) than the prefrail (410 months) and robust (357 months) groups at 30 months follow-up (all p<0.05).