Functional constipation is associated with a decline in word recognition 2 years later in community-dwelling older adults: The Korean Frailty and Aging Cohort Study

Abstract

Background: Constipation is one of the most common health problems among the elderly, and cognitive impairment is also a major health problem among the elderly. Identifying risk factors for cognitive impairment is important to prevent many cognitive disorders. Though studies on cognitive decline in patients with Parkinson’s disease are available, no study has explored the predictive effect of functional constipation on cognitive decline in non-Parkinson’s elderly individuals. This study aimed to determine the association between constipation and cognitive decline in community-dwelling older adults.

Methods: This is a 2-year longitudinal analysis of cohort study data, including 851 community-dwellers as participants at the baseline survey who took part in the Korean Frailty and Aging Cohort Study and completed a follow-up survey. 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 were used to evaluate comprehensive cognitive function. Functional constipation was defined according to the ROME IV criteria. Analysis of covariance was used to identify the association between functional constipation and cognitive decline statistically.

Results: Among the 851 participants, 8.9% had functional constipation. The mean age of the functional constipation group (78.6 ± 3.9) was higher than that of the non-constipation group (77.5 ± 3.8). Patients in the functional constipation group were more likely to have low physical activity (15.8% vs. 8.8%), polypharmacy (61.8% vs. 45.5%), and depression (30.3% vs. 17.4%). After adjusting for potential confounding factors, including age, low physical activity, polypharmacy, type 2 diabetes mellitus, depressive disorder, and baseline cognitive function test score, the mean changes in word recognition test scores from 2018 to 2020 were -0.071 and -0.524 in the no-constipation and constipation groups, respectively (P=0.009). Changes in other cognitive function tests showed a tendency to be lower in the constipation group (memory -0.138 vs. -0.489, recall -0.296 vs. -0.407, digit span -0.248 vs. -0.379, frontal assessment battery 0.281 vs. 0.12, trail making test 0.143 vs. 5.38), but were not significantly different.

Conclusions: Functional constipation at baseline was associated with a decline in word recognition after two years. 

Introduction

Constipation is an unsatisfactory defecation disorder characterized by infrequent stools, difficult stool passage, or both, and it is one of the most common health problems encountered in older adults (1–3). Functional constipation is defined by the Rome Foundation to help standardize the diagnosis of chronic constipation without physiological abnormalities identified by routine diagnostic examinations, as deemed clinically appropriate (4). The worldwide prevalence of functional constipation in adults is 10.1% (5), and the prevalence of functional constipation increases with age. Functional constipation has been reported in 30–40% of older adults worldwide (6), and 19.6% in Korea in those aged 72–86 years (7).

Cognitive impairment is a major personal and public health problem among elderly individuals. Identifying the risk factors for cognitive impairment is important for the prevention of many cognitive disorders and can help promote successful cognitive aging (8).

As an important manifestation of autonomic nerve dysfunction, constipation is well known to be the most common non-motor complication of Parkinson’s disease. Garcia et al. found that constipation predicts cognitive decline in Parkinson’s disease (9). Recently, Wang et al. showed that a higher prevalence of constipation was associated with dementia and non-amnestic mild cognitive impairment in a cross-sectional population-based cohort study (10). However, no prospective cohort study has explored the predictive effects of functional constipation on cognitive decline. Therefore, we investigated the relationship between functional constipation and cognitive decline in community-dwelling older adults using the longitudinal database of the Korean Frailty and Aging Cohort Study (KFACS).

Materials And Methods

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.

Results

General characteristics of the study population

The baseline characteristics of the subjects are presented in Table 1. Among the 851 participants, 8.9% (n = 76) had functional constipation. The mean age of the functional constipation group (78.6 ± 3.9) was higher than that of the non-constipation group (77.5 ± 3.8). The functional constipation group was more likely to have a higher rate of low physical activity (15.8% vs. 8.8%), polypharmacy (61.8% vs. 45.5%), and depression (30.3% vs. 17.4%). No statistically significant differences were found for the other variables.

Mean differences in cognitive function tests

As shown in Table 2, we evaluated the association between functional constipation and decline in cognitive function for 2 years after controlling for confounders using the ANCOVA test. The confounding variables were selected from the statistically significant variables for functional constipation (Table 1), which included age, low physical activity, polypharmacy, and depressive disorder. The baseline measures of each cognitive function test in 2018 were also included as confounding variables. 

In the ANCOVA analysis, the recognition test score declined more significantly in the constipation group (-0.524) than in the non-constipation group (-0.071) (P = 0.009) after adjusting for potential confounding factors. Other cognitive function tests (MMSE, memory, recall, span, FAB, TMT) did not show any difference in decline between the two groups (P >0.05).

Discussion

Our study showed that functional constipation predicts a decline in word list recognition in cognitive function tests in community-dwelling older adults. The proposed mechanism of the effect of constipation on cognitive impairment is that constipation can indirectly affect cognitive status through irritability and aggression caused by constipation, as well as pain and discomfort (17). In some studies, medications, such as antipsychotics, used to control behavioral disorders may cause undiagnosed constipation, which aggravates cognitive decline (18). We suggest a brain-gut axis hypothesis regarding the association of functional constipation with recognition decline. In the brain-gut axis theory, the gut is connected to the brain through the gut-brain axis (19); that is, the central nervous system communicates with the enteric nervous system, intestinal mucosa, and muscle layer through two-sided (afferent and efferent) pathways. Pathological changes in any component of the gut-brain axis may affect intestinal activity and lead to constipation. Some pathological studies have demonstrated that α-synuclein deposits can originate from the intestinal plexus and develop along the vagus nerve, eventually reaching the brain and resulting in the development of dementia (20). In other studies on the brain-gut axis theory, the parietal lobe of the brain was associated with constipation in children (21), and the parietal lobe is known to be related to short-term memory (22) and recognition function (23). Therefore, parietal lobe function may be connected to constipation and recognition. However, there are no studies about this connection yet; therefore, further investigation is needed. The initial and most prominent cognitive deficits are usually amnestic rather than non-amnestic, and the finding that constipation is associated with a decline in word-list recognition seems reasonable.

This study has some limitations. First, our study participants were ambulatory community-dwelling older adults, and hospitalized, institutionalized or bedridden elderly individuals were excluded, so our results may not be generalizable to other population settings. Second, the detailed medication history of participants was not investigated in this study. Medications such as antipsychotics can be associated with both constipation and cognitive impairment. However, we excluded those who had been taking narcotics and those with a history of dementia. In addition, the prevalence of psychiatric disorders did not differ between the two groups at baseline.

Nevertheless, this study has several strengths. First, our study was a two-year longitudinal retrospective cohort-based study with a more appropriate temporal relationship than previous cross-sectional studies. To the best of our knowledge, this is the first longitudinal study to show an association between functional constipation and cognitive function. Second, we used KFACS data, which included a relatively large number of community-dwelling older adults aged 72 to 86 from 10 nationwide centers, including urban and rural areas.

Conclusion

Functional constipation at baseline was associated with a decline in word list recognition 2 years later.

Abbreviations

CERAD-K, the consortium to establish a registry for Alzheimer's disease assessment battery; DM, diabetes mellitus; CI, confidence intervals; TMT, trail-making test; FAB, frontal assessment battery; MMSE, mini-mental state examination; ANCOVA, analysis of covariance; MNA, mini nutritional assessment; BMI, body mass index; IPAQ, International physical activity questionnaires; KFACS, the Korean frailty and aging cohort study; IRB, institutional review board; GDS, geriatric depression scale; SD, standard deviation

Declarations

Ethics approval and consent to participate: 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.

Consent for publication: Not applicable.

Availability of data and material: The data and material presented in this study are available from the corresponding authors (Chang Won Won, [email protected]) upon reasonable request.

Competing interests: The researchers claim no conflicts of interest. 

Funding: This study was funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HI15C3153). This study was supported by a grant from the Korea Health Technology R&D Project through the Korean Health Industry Development Institute (KHIDI). 

Informed consent statement: Informed consent was obtained from all the subjects involved in the study.

Author Contributions: Conceptualization, CWW, SK; Data curation, HSJ, SK; Funding acquisition, CWW; Investigation, CWW, SK; Methodology, CWW, SK, HSJ; Writing-original draft, HSJ, SK; Writing-review and editing, all.

Acknowledgments: The authors gratefully acknowledge the cooperation of all participants in this study.

Authors' information (optional): Not applicable

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Tables

Table 1. Baseline characteristics of study subjects according to functional constipation

All values are presented as the mean ± standard deviation or number (%). Depression implies that the Korean version of the short form of the Geriatric Depression Scale (SGDS-K) score is higher than 5. Independent living implies that people can live without help from others, and not in nursing homes or hospitals. Low physical activity implies that IPAQ-based weekly physical activity (kcal/week) is less than 495.65 kcal/week in males, 283.5 kcal/week in females, and less than the 20% threshold in KFACS; polypharmacy implies taking five or more prescribed medications; malnutrition implies a MNA score < 17. High-risk drinking implies two or more alcoholic drinks weekly (once seven cups for males and five cups for females). MMSE, TMT (out of 360 seconds, increasingly worse), Span (Digit Span Test, total score of 28), FAB (total score of 18), recall test (total score of 10), and recognition test (total score of 10).

SGDS-K, the Korean version of short form of geriatric depression scale; KFACS, Korean frailty and aging cohort study; MMSE, mini-mental state examination; TMT, trail-making test; MNA, mini nutritional assessment; FAB, frontal assessment battery; BMI, body mass index; DM, diabetes mellitus; IPAQ, International physical activity questionnaires

The level of statistical significance was set at P < 0.05.

Table2. Adjusted mean differences in cognitive function test scores between baseline and two years later

ANCOVA was used to identify associations between functional constipation and cognitive decline, adjusted for age, low physical activity, polypharmacy, type 2 DM, depression, and baseline cognitive function test scores in 2018. 

DM, diabetes mellitus; CI, confidence intervals; TMT, trail-making test; FAB, frontal assessment battery; MMSE, mini-mental state examination; ANCOVA, analysis of covariance

The level of statistical significance was set at P < 0.05.