
==== Front
Medicine (Baltimore)
Medicine (Baltimore)
MD
Medicine
0025-7974
1536-5964
Lippincott Williams & Wilkins Hagerstown, MD

MD-D-23-09064
00063
10.1097/MD.0000000000039561
3
6700
Research Article
Observational Study
Prevalence of and factors associated with cognitive frailty in elderly patients with chronic obstructive pulmonary disease: A cross-sectional study
Ren Jie MS renjie657021@163.com
a
https://orcid.org/0009-0007-3104-9527
Zhang Weihong MR a*
Liu Yanfei MS Yanfeifei2018@163.com
a
Fan Xin MS 18737132983@163.com
a
Li Xinxin MS 17344890138@163.com
a
Song Xinying MS 13734191773@163.com
a
a School of Nursing and Health, Zhengzhou University, Zhengzhou, China.
* Correspondence: Weihong Zhang, School of Nursing and Health, Zhengzhou University, Zhengzhou 450001, China (e-mail: 1521652903@qq.com).
13 9 2024
13 9 2024
103 37 e3956116 10 2023
09 8 2024
14 8 2024
Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

The status of cognitive frailty in elderly patients with chronic obstructive pulmonary disease (COPD) and its influencing factors in China remains unclear. This study aimed to investigate the prevalence of and factors associated with cognitive frailty in elderly patients with COPD. This cross-sectional study enrolled elderly patients with stable COPD between May and November 2022 from the Respiratory Department of the First Affiliated Hospital of Zhengzhou University and the Fifth Affiliated Hospital of Zhengzhou University. Convenience sampling method was adopted. Frailty Phenotype scale, Montreal Cognitive Assessment scale, Geriatric Depression Scale, and Clinical Dementia Rating scale were used to assess the prevalence of cognitive frailty in elderly patients with COPD. Multivariable logistic regression analysis was used to explore the associated factors. A total of 406 valid questionnaires were collected, and 173 patients (35.6%) had cognitive frailty. Binary logistic regression analysis showed that sex (odds ratio [OR] = 0.009; 95%CI: 0.001–0.770; P = .038), depression (OR = 17.780; 95%CI: 1.092–289.478; P = .043), modified Medical Research Council grade 1–3 (OR = 28.394–4095.683; 95%CI: 1.086–4,592,652.211; P < .05), global initiative for chronic obstructive lung disease grade 2 and 3 (OR = 32.508–282.072; 95%CI: 1.101–12,516.874; P < .05), and frequencies of acute exacerbations of COPD and hospitalizations within 1 year of 2 times (OR = 21.907; 95%CI: 4.587–104.622; P < .001) were independently associated with cognitive frailty. The prevalence of cognitive frailty in elderly patients with stable COPD was high. Female, depression, modified Medical Research Council grade, global initiative for chronic obstructive lung disease grade, and frequencies of acute exacerbations of COPD and hospitalizations within 1 year might be the factors independently associated with cognitive frailty, educational level might be a protective associated factor for cognitive frailty.

chronic obstructive
cognitive dysfunction
cross-sectional study
elderly patients
pulmonary disease
Department of Education of Henan Province, China, the team of Zhengzhou University will conduct research on health promotion for the elderly from January 01,2022 to December 31,2024/ Not ApplicableOPEN-ACCESSTRUE
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pmc1. Introduction

Chronic obstructive pulmonary disease (COPD) has been the 5th leading cause of death in China.[1] The prevalence of COPD continued to rise substantially with the aging of the Chinese population.[2] The estimated standardized prevalence of COPD in a national survey between 2014 and 2015 was 13.6% among 66,752 adults aged 40 years or older.[3] Frailty and cognitive impairment are important risk factors that harm the life expectancy of the elderly population.[4] Physical frailty and cognitive impairment might not only lead to the deterioration of physical and cognitive functions but also severely reduce the quality of life. Many previous studies suggested a close relationship between frailty and cognitive impairment or dementia.[5,6] The International Society of Nutrition and Aging and the International Society of Gerontology organized an expert consensus group in 2013 and defined “cognitive frailty” as physical weakness and cognitive impairment after the exclusion of concurrent dementia or other types of dementia.[7] The prevalence of cognitive frailty was higher in older women.[8] Other risk factors included out-of-wedlock, poor education, nonworking sociodemographic status, poor nutritional status, and depression.[9] However, in elderly patients with COPD, the factors associated with cognitive frailty remain unknown.

Elderly patients with COPD were at higher risk of frailty and cognitive impairment compared to other age groups.[10,11] Furthermore, frailty alone increased the incidence of acute exacerbations, readmission rate, and risk of death in elderly patients with COPD, as well as decreased their quality of life. Cognitive impairment increases the risk of hypoxemia, attenuates the ability to perform activities of daily living, and reduces life expectancy in elderly patients with COPD. In addition, previous studies demonstrated that cognitive frailty in the elderly not only increased the risk of adverse health outcomes, including functional disability, lowered quality of life, and all-cause mortality, but also seriously affected cognitive function, shortened healthy life expectancy, and increased the medical burden of society and families.[12,13]

Therefore, compared with simple physical weakness or cognitive impairment, patients with COPD who were cognitively frail had a higher incidence of adverse health outcomes, as well as higher requirements and greater challenges for social pension and healthcare services.[14–16] Thus, more attention should be paid to patients with COPD who have cognitive frailty. However, few studies have globally concentrated on the status quo of cognitive frailty in elderly patients with COPD. Therefore, the present study aimed to assess the prevalence of cognitive frailty in elderly patients with stable COPD and analyze the associated factors.

2. Material and methods

2.1. Study design and participants

The cross-sectional study enrolled elderly patients with stable COPD in the Respiratory Department of the First Affiliated Hospital of Zhengzhou University and the Fifth Affiliated Hospital of Zhengzhou University between May and November 2022, and a convenience sampling method was used. The inclusion criteria were: (1) age of ≥60 and ≤89 years old; (2) patients who met the diagnostic criteria of the Guidelines for Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease (revised 2021)[17] published by the Respiratory Society of the Chinese Medical Association[18]; (3) duration of COPD of ≥6 months; and (4) conscious and able to answer questions independently. The exclusion criteria were: (1) serious vision or hearing impairment or other difficulties in communication; (2) definite diagnosis of dementia or mental disorders; (3) other serious diseases hindering them from completing the study; or (4) patients with poor respiratory function cannot complete the questionnaire (modified Medical Research Council [mMRC] grade ≥ 4 or global initiative for chronic obstructive lung disease [GOLD] grade ≥ 4). The study was approved by the Ethics Committee of Zhengzhou University (approval #2022-076). All subjects provided written informed consent.

2.2. Questionnaire

The questionnaire was self-designed according to the objective and content of the study, including sociodemographic data and disease-related data of elderly patients with COPD. Sociodemographic data included sex, age, marital status, living mode, personal monthly income, educational level, and healthcare payment method. Disease-related data included duration of COPD, comorbidities, family history of the disease, smoking status, drug use, regular exercise, years of exercise, depression, body mass index (BMI), GOLD grade,[19] frequencies of acute exacerbations of COPD and hospitalizations within 1 year, mMRC dyspnea score.[20] Among them, BMI < 18.5 kg/m2, 18.5 kg/m2 ≤ BMI < 24.0 kg/m2, 24.0 kg/m2 ≤ BMI < 28.0 kg/m2, and BMI ≥ 28.0 kg/m2 indicated low body weight, normal body weight, overweight, and obesity, respectively.[21] The criteria for regular exercise were doing exercise for more than 30 min/day or more than 150 min/week for >1 year.[22]

Frailty phenotype (FP): The original frailty phenotype table was proposed in 2001.[23] In order to fit the Asian population, a Taiwanese version of FP was adopted in the present study,[24] with the following specific contents. (1) Body weight loss: body weight loss of >3 kg or >5% in the past 6 months (without diet or exercise). (2) Decreased grip strength: grip strength (kg) depends on gender and BMI, and the evaluation criteria vary according to gender and BMI. (3) Fatigue: feeling tired, feeling laborious, or lack of energy more than 3 days a week recently. (4) Slow walking speed: timed up and go test >10 seconds, according to different height- and gender-based criteria. (5) Low definition of physical activity: male physical activity of <383 kcal/week; female physical activity of <270 kcal/week (1 kcal = 4.1840 kJ), that is, about 2.5 hours of walking for men and 2 hours of walking for women, assessed by the International Physical Activity Questionnaire-Short Form. “Yes” indicated 1 point, “No” indicated 0 points, and the total range was 0 to 5 points. Scoring 0 was classified as no frailty, 1 to 2 as pre-frailty, and ≥3 as frailty.

Montreal Cognitive Assessment (MoCA) scale: The MoCA scale was developed in 2005[25] and was mainly used to screen cases with mild cognitive impairment. In the present study, Beijing-Guangzhou 7.1 edition (Mandarin edition) was adopted, and the items included executive function, immediate recall, fluency, orientation, calculation, abstraction, delayed recall, visual perception, naming, and attention. The full score on this scale is 30 points. A MoCA score of ≥26 points indicates normal cognitive function, and a MoCA score in the range of 18 to 26 represents mild cognitive impairment.

Clinical dementia rating (CDR) scale: The CDR scale was compiled in 1982[26] and included 6 aspects: memory, orientation, judgment and problem-solving ability, social cognition, home life and hobbies, and self-care status. Scoring 0 stands for healthy, 0.5 for suspicious dementia, 1 for mild dementia, 2 for moderate dementia, and 3 for severe dementia.

Geriatric depression scale: The geriatric depression scale was developed in 1982 to assess the emotional status of respondents in the latest week,[25] with a total of 30 items. For each item, subjects were asked to answer “Yes” or “No,” with 10 items scored in reverse order (“No” indicating depression) and 20 items scored in positive order (“Yes” indicating depression). A score of 0 to 10 was considered normal, representing no depression, 11 to 20 as mild depression, and 21 to 30 as moderate-to-severe depression.

Measurement: The investigator explained the objective of the study, and after obtaining the consent of hospital staff and subjects, subjects were guided to fill in the questionnaire in the form of face-to-face, on-site distribution, and retrieval. After the questionnaire was completed, the investigator checked the questionnaire in time, and retrieved the questionnaire on the spot.

2.3. Statistical analysis

Referring to the judgment criteria of cognitive frailty proposed by the expert consensus group[7] and a previous study,[27] the evaluation criteria of cognitive frailty in this study were summarized as follows: (1) subjective sensory cognitive decline; (2) FP score of ≥3 points; (3) MoCA score of <26 points; (4) no clinical diagnosis of dementia with CDR result of 0.5 points. The patients were divided into cognitive frailty and noncognitive frailty.

According to the requirement that the sample size should be 20 times the independent variable,[28] considering the sample loss rate of 10%, 378 subjects were required.

SPSS 23.0 (IBM, Armonk, NY) was used to perform statistical analysis. Continuous data with a normal distribution were described as means ± standard deviations and analyzed using Student t test; otherwise, they were presented as medians (interquartile range) and analyzed using the Mann–Whitney U test. Categorical data were described as numbers (percentages) and analyzed using the chi-square test or Fisher exact test. The occurrence of cognitive frailty was taken as the dependent variable, and the influential factors with statistical significance (P < .05) in univariate analysis were taken as independent variables for multivariable logistic regression analysis. The criterion for inclusion in the multivariable logistic regression analysis was .05. In addition, because there was collinearity between “regular exercise” and “exercise duration,” the “regular exercise” variable was excluded, and the “exercise duration” variable was included in the analysis. Two-sided P-values <.05 were considered statistically significant.

3. Results

In total, 419 elderly patients with stable COPD were enrolled. Among them, 8 patients aged under 60 years and 5 patients with a history of depression were excluded. Finally, 406 elderly patients with COPD completed the survey, and the valid questionnaire accounted for 96.9%.

The patients aged between 60 and 89 years old (aged 69.40 ± 7.50 years). There were no patients using home long-term oxygen. There were 173 patients with cognitive frailty (aged 72.95 ± 6.00 years), and the prevalence of cognitive frailty was 35.6%. There was no significant difference in marital status, smoking status, BMI, duration of COPD, healthcare payment method, mode of living, family history, drug use, or monthly income per capita between patients with cognitive frailty and those with noncognitive frailty (Table 1, all P > .05). Compared to patients with noncognitive frailty, patients with cognitive frailty have significantly older ages, fewer males, lower educational levels, more comorbidities, more depression, less exercise, fewer years of exercise, higher GOLD grade, more acute exacerbations of COPD and hospitalizations within 1 year, and higher mMRC dyspnea score (Table 1, all P < .05). Additionally, the prevalence of asthma and COPD was about 16.3%, and the prevalence of lung cancer was 11%. The estimated prevalence of ischemic heart disease was 22.5%. The prevalence of heart failure, arrhythmia, as well as pulmonary circulation and arterial diseases, was 20.7%, 16.4%, and 15.7%, respectively. Furthermore, 21.2%, 46.9%, 12.7%, 63.8%, and 67.3% of patients with COPD had type 2 diabetes, metabolic syndrome, thyroid disease, osteoporosis, and gastrointestinal diseases, among which the most common was chronic gastritis of 53.9%. The prevalence of COPD combined with extrapulmonary tumors was 12.5%, which mainly included liver cancer, colorectal cancer, breast cancer, prostate cancer, and gastric cancer.

Table 1 Baseline characteristics.

	Cognitive frailty
(n = 173)	Noncognitive frailty
(n = 233)	P	
Age, years	72.95 ± 6.00	66.91 ± 7.41	<.001	
Sex, n (%)			<.001	
 Male	114 (65.9)	202 (86.7)		
 Female	59 (34.1)	31 (13.3)		
Marital status, n (%)			.053	
 Married	136 (78.6)	202 (86.7)		
 Divorced	19 (11.0)	20 (8.6)		
 Widowed	18 (10.4)	11 (4.7)		
Educational level, n (%)			<.001	
 Primary school or below	36 (20.8)	11 (4.7)		
 Junior high school	54 (31.2)	30 (12.9)		
 Senior high school	47 (27.2)	107 (45.9)		
 College or above	36 (20.8)	85 (36.5)		
Monthly income per capita, n (%)			.533	
 <1500 RMB	29 (16.8)	36 (15.4)		
 1500–2999 RMB	8 (4.6)	19 (8.2)		
 3000–4999 RMB	15 (8.7)	28 (12.0)		
 ≥5000 RMB	121 (69.9)	150 (64.4)		
Healthcare payment method, n (%)			.335	
 Healthcare insurance	128 (74.0)	183 (78.5)		
 New rural cooperative medical system	29 (16.8)	37 (15.9)		
 At his own expense	16 (9.2)	13 (5.6)		
Mode of living, n (%)			.050	
 Living alone	18 (10.4)	31 (13.3)		
 Living with a spouse	118 (68.2)	160 (68.7)		
 Living with children	16 (9.2)	30 (12.9)		
 Others	21 (12.1)	12 (5.1)		
Duration of COPD, n (%)			.374	
 Less than 3 years	22 (12.7)	27 (11.6)		
 3 to 6 years	57 (32.9)	91 (39.1)		
 6 to 9 years	74 (42.8)	83 (35.6)		
 More than 9 years	20 (11.6)	32 (13.7)		
Family history, n (%)			.709	
 No	163 (94.2)	212 (91.0)		
 Yes	10 (5.8)	21 (9.0)		
Drug use, n (%)			.680	
 Neither	100 (57.8)	128 (54.9)		
 Drug only	48 (27.7)	74 (31.8)		
 Both	25 (14.5)	31 (13.3)		
Number of comorbidities, n (%)			.020	
 ≤2	69 (39.9)	120 (51.5)		
 ≥3	104 (60.1)	113 (48.5)		
Regular exercise, n (%)			<.001	
 No	144 (83.2)	76 (32.6)		
 Yes	29 (16.8)	157 (67.4)		
Exercise duration, years	0.5 (0, 1.5)	5 (0, 7)	<.001	
Smoking status, n (%)			.270	
 Current	30 (17.3)	47 (20.2)		
 Previous	40 (23.2)	66 (28.3)		
 Never	103 (59.5)	120 (51.5)		
BMI, n (%)			.342	
 <18.5 kg/m2	25 (14.5)	29 (12.4)		
 18.5–23.9 kg/m2	55 (31.8)	90 (38.6)		
 24–27.9 kg/m2	71 (41.0)	79 (33.9)		
 ≥28 kg/m2	22 (12.7)	35 (15.1)		
Depression, n (%)			<.001	
 No	41 (23.7)	188 (80.7)		
 Yes	132 (76.3)	45 (19.3)		
GOLD grade, n (%)			<.001	
 Grade 1	5 (2.9)	177 (76.0)		
 Grade 2	54 (31.2)	41 (17.6)		
 Grade 3	114 (65.9)	15 (6.4)		
Frequencies of acute exacerbations of COPD and hospitalizations within 1 year, n (%)			<.001	
 0	12 (6.9)	184 (79.0)		
 1	32 (18.5)	43 (18.4)		
 2	129 (74.6)	6 (2.6)		
mMRC dyspnea score (%)			<.001	
 Grade 0	4 (2.3)	168 (72.1)		
 Grade 1	49 (28.4)	39 (16.7)		
 Grade 2	103 (59.5)	24 (10.3)		
 Grade 3	17 (9.8)	2 (0.9)		
BMI = body mass index, COPD = chronic obstructive pulmonary disease, GOLD = global initiative for chronic obstructive lung disease, mMRC = modified Medical Research Council.

The correlation analysis showed that there was no correlation between each variable (Table 2). The random forest analysis (Fig. 1) and heatmap (Fig. 2) showed that the importance of impact on cognitive frailty in elderly patients with COPD decreased from frequencies of acute exacerbations of COPD and hospitalizations within 1 year, GOLD grade, mMRC grade, age, depression, exercise duration, regular exercise, educational level, comorbidities, and sex (all Mean Decrease Gini > 1).

Table 2 Correlation analysis.

Correlation	Cognitive frailty	Age	Sex	Educational level	Comorbidities	Regular exercise	Exercise duration	Depression	mMRC grade	GOLD grade	Frequencies of acute exacerbations of COPD and hospitalizations within 1 year	
Cognitive frailty	1	0.403	‐0.248	‐0.336	0.115	‐0.502	‐0.444	0.568	0.705	0.757	0.800	
Age	0.403	1	0.051	‐0.058	‐0.075	‐0.458	‐0.174	0.587	0.182	0.202	0.295	
Sex	‐0.248	0.051	1	0.209	‐0.296	0.110	0.047	‐0.057	‐0.201	‐0.211	‐0.223	
Educational level	‐0.336	‐0.058	0.209	1	‐0.353	0.051	‐0.042	‐0.087	‐0.255	‐0.253	‐0.260	
Comorbidities	0.115	‐0.075	‐0.296	‐0.353	1	‐0.351	‐.183	0.113	0.148	0.1620	0.114	
Regular exercise	‐0.502	‐0.458	0.110	0.051	‐0.351	1	0.758	‐0.569	‐0.344	‐0.375	‐0.356	
Exercise duration	‐0.444	‐0.174	0.047	‐0.042	‐0.183	0.758	1	‐0.390	‐0.278	‐0.334	‐0.317	
Depression	0.568	0.587	‐0.057	‐0.087	0.113	‐0.569	‐0.390	1	0.305	0.402	0.433	
mMRC grade	0.705	0.182	‐0.201	‐0.255	0.148	‐0.344	‐0.278	0.305	1	0.687	0.599	
GOLD grade	0.757	0.202	‐0.211	‐0.253	0.162	‐0.375	‐0.334	0.402	0.687	1	0.649	
Frequencies of acute exacerbations of COPD and hospitalizations within 1 year	0.800	0.295	‐0.223	‐0.260	0.114	‐0.356	‐.0317	0.433	0.599	0.649	1	
COPD = chronic obstructive pulmonary disease, GOLD = global initiative for chronic obstructive lung disease, mMRC = modified Medical Research Council.

Figure 1. The results of random forest analysis. The correlation is determined by whether the importance degree >1, and the higher the importance score, the stronger the correlation between the 2 variables. The results showed that the variables positively correlated with cognitive decline were COPD acute stage, GOLD grade, mMRC grade, age, depression, and number of comorbidities. The multiple correlation variables were exercise duration, exercise persistence, education level, and gender. COPD = chronic obstructive pulmonary disease, GOLD = global initiative for chronic obstructive lung disease, mMRC = modified Medical Research Council.

Figure 2. Heatmap. The closer the color is to red, the stronger the positive correlation between the 2 variables. The closer the color is to blue, the stronger the negative correlation between the 2 variables. According to the importance score, the correlation variables were acute stage of COPD, GOLD grade, mMRC grade, age, depression, exercise duration, exercise persistence, education level, number of comorbidity, and gender. COPD = chronic obstructive pulmonary disease, GOLD = global initiative for chronic obstructive lung disease, mMRC = modified Medical Research Council.

Based on the above results, age, exercise duration, frequencies of acute exacerbations of COPD, and hospitalizations within 1 year were included as original values. The assigned values for sex, number of comorbidities, educational level, regular exercise, depression, mMRC score, and GOLD grading are shown in Table 3. Binary logistic regression analysis (Table 4) showed that sex (odds ratio [OR] = 0.009; 95%CI: 0.001–0.770; P = .038), depression (OR = 17.780; 95%CI: 1.092–289.478; P = .043), mMRC grade 1–3 (OR = 28.394–4095.683; 95%CI: 1.086–4,592,652.211; P < .05), GOLD grade 2 and 3 (OR = 32.508–282.072; 95%CI: 1.101–12,516.874; P < .05), and frequencies of acute exacerbations of COPD and hospitalizations within 1 year of 2 times (OR = 21.907; 95%CI: 4.587–104.622; P < .001) were related with cognitive frailty. The area under receiver operating characteristic was 0.999 (95% CI, 0.998–1.000), indicating good prediction ability (Fig. 3). Based on the results of binary logistic regression analysis, a nomogram of score card is constructed for important variables in order to better assess the risk of cognitive decline according to the patient’s situation (Fig. 4).

Table 3 Variables assignment methods.

Variables	Assignment	
Dependent variable		
 Cognitive frailty	No = 0; Yes = 1	
Independent variable		
 Sex	Female = 0; Male = 1	
 Educational level (primary school as a benchmark)	Primary school = 0; Junior high school = 1; Senior high school = 2; College or above = 3	
 Number of comorbidities	≤2 = 0; ≥3 = 0	
 Regular exercise	No = 0; Yes = 1	
 Depression	No = 0; Yes = 1	
 mMRC grade	Grade 0 = 0; Grade 1 = 1; Grade 2 = 2; Grade 3 = 3	
 GOLD grade	Grade 1 = 0; Grade 2 = 1; Grade 3 = 2	

Table 4 Cox regression analysis of variables related with cognitive frailty.

Variables	B	SE	Wales	Sig	Exp (B)	95% confidence interval	
Lower limit	Upper limit	
Age	0.237	0.122	3.739	0.053	1.267	0.997	1.611	
Sex	‐4.671	2.250	4.311	0.038*	0.009	<0.001	0.770	
Educational level (as a benchmark)								
 Primary school	–	–	–	–	Ref	–	–	
 Junior high school	‐1.248	4.692	0.071	0.790	0.287	<0.001	2827.832	
 Senior high school	‐3.141	4.638	0.459	0.498	0.043	<0.001	383.576	
 College or above	‐9.619	5.118	3.532	0.060	<0.001	<0.001	1.511	
Comorbidities	‐4.823	2.499	3.725	0.054	0.008	<0.001	1.077	
Regular exercise	‐4.140	3.354	1.523	0.217	0.016	<0.001	11.405	
Exercise duration	‐0.251	0.375	0.450	0.502	0.778	0.373	1.621	
Depression	2.878	1.423	4.088	0.043*	17.780	1.092	289.478	
mMRC grade								
 0	–	–	–	–	Ref	–	–	
 1	3.346	1.665	4.038	0.044*	28.394	1.086	742.294	
 2	4.918	1.819	7.308	0.007*	136.708	3.867	4833.527	
 3	8.318	3.583	5.389	0.020*	4095.683	3.652	4,592,652.211	
GOLD grade			8.504	0.014*				
 1	–	–	–	–	Ref	–	–	
 2	3.481	1.727	4.063	0.044*	32.508	1.101	959.713	
 3	5.642	1.935	8.502	0.004*	282.072	6.357	12,516.874	
Frequencies of acute exacerbations of COPD and hospitalizations within 1 year	3.087	0.798	14.973	<0.001*	21.907	4.587	104.622	
* Representatives with statistical significance.

Figure 3. The ROC analysis. ROC = receiver operating characteristic.

Figure 4. Nomogram.

4. Discussion

This study showed that the prevalence of cognitive frailty was as high as 35.6% in elderly patients with stable COPD in China. The educational level might be a protective factor for cognitive frailty. Female, depression, mMRC grade, GOLD grade, and frequencies of acute exacerbations of COPD and hospitalizations within 1 year were factors independently associated with cognitive frailty. Various aspects should be taken into consideration to prevent cognitive frailty in elderly patients with COPD.

In this study, the prevalence of cognitive frailty in elderly patients with COPD was 35.6%, indicating an unoptimistic status in China. Some studies in China reported lower frequencies of cognitive frailty: 27.1% in 303 elderly people in nursing homes,[29] 9.6% in the elderly community of Zhengzhou,[30] and 2.3% in 3202 Chinese elderly patients.[31] The higher prevalence of cognitive frailty in the present study could be related to the fact that patients in hospitals are prone to frailty and have diseases related to cognitive deficits. For example, in this study, the combined prevalence of stroke was about 16.3%, cancer and tumor 22.5%, coronary heart disease 20.7%, pulmonary circulation and artery disease 15.7%, and type 2 diabetes 21.2%. Tertiary A hospitals were considered due to high diagnostic accuracy and large sample size. In addition, patients with COPD who are treated in the hospital are more likely to have a worse overall condition than those who are treated in the community, and they may show more negative results in the survey. As cognitive frailty can increase the risk of adverse outcomes in patients with COPD, further attention should be paid to the identification and intervention of cognitive frailty in elderly patients with COPD in clinical practice. The association between COPD characteristics and cognitive frailty was discussed in a review.[32] A previous study found that in patients with COPD, around 77% of patients with hypoxemia had cognitive impairment.[33] COPD-specific factors, including hypoxemia and hypercapnia, were reported to affect cognitive impairment in elderly patients with COPD.[34,35] Furthermore, frail COPD patients also had increased dyspnea perception.[36]

In this study, sex was associated with cognitive frailty in elderly patients with COPD. Compared with females, the prevalence of cognitive frailty in male patients was lower, and female was noted as a factor associated with cognitive frailty in elderly patients with COPD, which was consistent with Lei et al’s findings.[37] There were also controversial conclusions about the higher incidence of cognitive frailty in male patients[38] and the lack of correlation between cognitive frailty and sex.[4] Additional studies are required to determine how sex impacts cognitive frailty in the elderly population. In the present study, educational level was noted as an influential factor for cognitive frailty in elderly patients with COPD, in which a higher educational level was a protective factor and an advanced age was an associated factor, which was consistent with the results in previous in China[39] and in Europe.[40] The reasons may be that people with higher educational levels had better cognitive function, brain functional connectivity, cognitive reserve,[41] and life skills, leading to attenuating risk factors that might cause damage to human health.[42] Therefore, the demographic characteristics should be fully considered in the intervention of cognitive frailty in elderly patients with COPD. Appropriate therapeutic strategies should be adopted as early as possible, particularly for patients with a low educational level.

In this study, depression was associated with cognitive frailty in elderly patients with COPD, which was consistent with previous findings.[43,44] On the other hand, a meta-analysis showed that cognitive frailty in older adults was associated with a higher risk of depression.[45] Cognitive frailty and depression shared a common pathophysiological mechanism[46] and had similar pathological processes. Depression and cognitive frailty were associated with elevated levels of some peripheral inflammatory cytokines, such as interleukin (IL)-6.[32] Up-regulation of the Th17/Treg balance is involved in the development of chronic inflammation.[47] Elevated IL-6 levels were observed in sputum[48] and were associated with increased mortality, worse six-minute walking distance performance, and poor clinical outcomes in patients with COPD.[49–51] IL-6 − 745G/C single nucleotide polymorphism was suggested to increase the risk of developing COPD[52] and further accelerate the decline of physiological function, thus increasing the risk of frailty. Depression can also lead to cognitive impairment and further develop into cognitive dysfunction.[53] With the disease progression, elderly patients with COPD were more likely to have negative emotions, such as mental stress, panic, and depression, due to functional decline, reduced endurance activity, and limited physical and social activities; as a result, the incidence of depression increased.[54] Therefore, it is suggested that healthcare providers should carry out early psychological screening for elderly patients with COPD and timely perform corresponding interventions to prevent or relieve depression.

In this study, the prevalence of acute exacerbations of COPD and hospitalizations within 1 year was an influencing factor for cognitive frailty in elderly patients with COPD. Two previous studies indicated the correlation between elevated IL-6 levels and acute exacerbations in patients with COPD.[55,56] IL-6 level was closely related to the occurrence of cognitive impairment and frailty.

The study had limitations. First, the sample size was relatively small. Second, this was a study conducted in only 2 centers. Third, the study lacks subgroup analysis, such as in different geographic regions in China, which limits its interpretation. Finally, the study was cross-sectional, preventing the assessment of causality. In addition, it is possible that cognitive frailty improved after hospitalization in some patients, but it could not be evaluated.

5. Conclusion

In conclusion, the prevalence of cognitive frailty in elderly patients with stable COPD in China was high. Female, educational level, depression, mMRC grade, GOLD grade, and frequencies of acute exacerbations of COPD and hospitalizations within 1 year were independently associated with cognitive frailty in elderly patients with stable COPD. A multicenter study with a large sample was needed to verify this result.

Author contributions

Conceptualization: Jie Ren.

Data curation: Weihong Zhang, Jie Ren, Yanfei Liu, Xin Fan.

Formal analysis: Weihong Zhang, Jie Ren.

Methodology: Jie Ren, Xin Fan.

Project administration: Jie Ren.

Resources: Yanfei Liu.

Supervision: Yanfei Liu.

Validation: Xinxin Li, Xinying Song.

Visualization: Jie Ren.

Writing – original draft: Weihong Zhang, Jie Ren.

Writing – review & editing: Weihong Zhang, Jie Ren.

Abbreviations:

BMI body mass index

CDR clinical dementia rating

COPD chronic obstructive pulmonary disease

GOLD global initiative for chronic obstructive lung disease

mMRC modified Medical Research Council

MoCA Montreal Cognitive Assessment

This study was supported by Research on the Construction and Operation Guarantee Mechanism of Home Exercise Rehabilitation Model for Community Elderly with Weakness Based on Mobile Health Technology, (Project approval number :72064038), Henan Province Science and Technology Research and Development Project (Project Approval Number: 2421023110432), Development and Empirical Study of a Community based Smart Rehabilitation Platform for Chronic Obstructive Pulmonary Disease Patients Based on Clinical Decision Support System Fund project: Henan University Science and Technology innovation team support plan (Project approval number: 22IRTSTHN027) Research direction: Health promotion for the aged.

The study was approved by the Ethics Committee of Zhengzhou University (approval #2022-076). All subjects provided written informed consent.

The authors have no conflicts of interest to disclose.

All data generated or analyzed during this study are included in this published article [and its supplementary information files].

How to cite this article: Ren J, Zhang W, Liu Y, Fan X, Li X, Song X. Prevalence of and factors associated with cognitive frailty in elderly patients with chronic obstructive pulmonary disease: A cross-sectional study. Medicine 2024;103:37(e39561).
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