Study population
The KFACS is a nationwide multicenter longitudinal study with a baseline survey conducted in 2016 and 2017 to identify the factors that contribute to frailty and aging in community-dwelling individuals aged 70–84 years. The baseline survey for the cohort study was conducted at 10 centers, with 1,559 participants in 2016 and 1,455 participants in 2017 (11). Participants were recruited from urban, suburban, and rural communities nationwide. To investigate the prevalence of frailty among the three age groups and to consider the higher attrition rate in the oldest age group, the KFACS cohort adopted quota sampling stratified by age (70–74, 75–79, and 80–84 years, with a ratio of 6:5:4). This quota sampling is based on oversampling of the older group using population distribution data from the Korean Population and Housing Census conducted by Statistics Korea in 2015 (distributions of 43.5%, 33.8%, and 22.7% for adults aged 70–74, 75–79, and 80–84 years, respectively) (12). The participants were recruited from diverse settings (local senior welfare centers, community health centers, apartments, housing complexes, and outpatient clinics) to minimize selection bias. All participants were ambulatory, with or without the use of walking aids. Follow-ups have been conducted at 2-year intervals. A questionnaire for evaluating functional constipation was first included in a follow-up survey in 2018. Out of 1,292 participants aged 72–86 years who participated in the follow-up survey in 2018, 1,273 participants revisited the center after 2 years for the second follow-up survey in 2020.
Of the 1,273 participants, those without available prescription information (n = 356) and those who were diagnosed with dementia or cerebrovascular disease (n = 66) were excluded, and 851 subjects were enrolled in the analysis (Figure 1).
The KFACS protocol was approved by the Institutional Review Board (IRB) of the Clinical Research Ethics Committee of Kyung Hee University Medical Center (IRB number: 2015-12-103), and all participants provided written informed consent. Data anonymization was performed to protect the privacy of participants. This study was conducted in accordance with the consensus ethical principles derived from the guidelines, including the Declaration of Helsinki.
Assessment of Functional Constipation
Functional constipation is a functional bowel disorder that presents with obvious low frequency or incomplete defecation (13). Functional constipation was assessed based on the Rome IV criteria for functional constipation.
1. Must include two or more of the following:
A. Straining during more than one-fourth (25%) of defecations.
B. Lumpy or hard stools (Bristol stool scale 1–2) in more than one-fourth (25%) of the defecations.
C. Sensation of incomplete evacuation in more than one-fourth (25%) of defecation cases.
D. Sensation of anorectal obstruction or blockage in more than one-fourth (25%) of defecation cases.
E. Manual maneuvers to facilitate more than one-fourth (25%) of defecation.
F. Fewer than three spontaneous bowel movements per week.
2. Loose stools are rarely present without the use of laxatives.
3. Insufficient criteria for irritable bowel syndrome.
Assessment of Cognitive Function
A neuropsychological test (CERAD-K, the Consortium to Establish a Registry for Alzheimer's Disease Assessment Battery) and the Korean version of the Frontal Assessment Battery (FAB) were used to evaluate comprehensive cognitive function. The CERAD-K is a standardized clinical and neuropsychological assessment battery for the evaluation of patients with Alzheimer’s disease (14). The CERAD-K initially consisted of eight tests (verbal fluency, modified Boston naming, Korean version of mini-mental state examination (MMSE-KC), word list memory, constructional praxis, word list recall, word list recognition, and constructional praxis recall), but in this study, word list, memory, recall, word list recognition, digit span (forward, backward), trail-making test (TMT) A, and MMSE-KC were included (14).
Word list memory is a test that assesses memory for new information learning. It consists of presenting 10 commonly used words at intervals of two seconds and reading the words aloud, followed by immediate recall of as many words as possible for 90 s. The total score was 30 points, with 10 points per session. The word list recall test evaluates the ability to recall the given 10 words from the word list memory task. A maximum of 90 s was allowed, and the maximum score was 10. The word list recognition test measures recognition ability. The goal was to distinguish between the 10 words presented in the word list memory test and 10 new words. The maximum possible score was 10. The TMT A assesses attention, ordering, executive function, time-space search, and mental motion velocity. Patients were asked to draw a line connecting the numbers from 1 to 25 in ascending order, and the time taken was recorded. Participants who did not complete it in over 360 seconds were excluded. The digit span test assesses short-term memory, working memory, and attention by recalling the number sequence after hearing the numbers forward and backward. Digit spans forward and backward were composed of seven digit questions and presented with two trials. One point was scored when each digit was correctly recalled, and the total score was 14 points for each digit span forward and backward. The digit span total is the combined score of the digit span forward and backward(14).
The FAB is a test that assesses executive functions such as planning, working memory, mental flexibility, and inhibition. It consists of similarities (conceptualization), lexical-verbal fluency (mental flexibility), motor series (programming), conflicting instructions (sensitivity to interference), Go–No Go (inhibitory control), and prehension behavior (environmental autonomy), with a total score of 18; higher scores indicate better frontal lobe function (15).
Other Measurements
Demographic information, including age, sex, independent living, marriage, years of education, medical benefits, alcohol consumption, and smoking habits, was investigated through a face-to-face interview in 2018. Malnutrition was defined as a mini nutritional assessment (MNA) score < 17 (16). Physical activity was assessed using the metabolic equivalent of task minutes per week and kcal per week, calculated using the International Physical Activity Questionnaire (11). Polypharmacy implies taking five or more prescribed medications. A Geriatric Depression Scale (GDS) short form was used to define depression and a score higher than 5 was classified as depression. A history of chronic diseases including hypertension, type 2 diabetes mellitus, dyslipidemia, depressive disorder, dementia, cerebrovascular disease, other psychiatric disorders, renal disorder, thyroid disorder, and malignancy were assessed in 2018 for analysis.
Statistical Analyses
Data are presented in the form of mean ± standard deviation (SD) or percentages. Continuous variables were compared using the independent t-test, and categorical variables were compared using the chi-squared test. Analysis of covariance (ANCOVA) was used to identify associations between functional constipation and cognitive decline, adjusted for age, low physical activity, polypharmacy, type 2 diabetes mellitus, depressive disorder, and baseline cognitive function test scores. All statistical analyses were performed using IBM SPSS Statistics for Windows version 25 (IBM Corp., Armonk, N.Y., USA). The level of statistical significance was set at P < 0.05.