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Abstract

Background

Cognitive impairment has been well described in patients with Chronic Obstructive Pulmonary Disease (COPD) in addition to cardiorespiratory disability. To reduce this impairment, researchers have recommended the use of single or combined exercise training. However, the combined effect of cognitive training (CT) and pulmonary rehabilitation (PR) program on selective cognitive abilities in patients with COPD has not been fully evaluated. Therefore, we aimed to assess the impact of PR combined with CT on 6 minutes walking test (6MWT) and cognitive parameters in Tunisian males’ patients with COPD.

Methods

Thirty-nine patients with COPD were randomly assigned to an intervention group (n = 21, age = 65.3 ± 2.79) and a control group (n = 18, age = 65.3 ± 3.2). The intervention group underwent PR combined with CT, and the control group underwent only PR, three times per week for 3 months. The primary outcomes were 6MWT (6 minutes walking test -6MWT-parameters) and cognitive performance, as evaluated by Montreal cognitive assessments (MOCA) and P300 test. Secondary outcomes were patient’s characteristics and spirometric data. These tests were measured at baseline and after 3 months of training programs.

Results

Results showed a significant improvement of the 6MWT distance after the rehabilitation period in both groups (p < .001). Moreover, both groups showed significant improvement (p < .001) in cognitive performance including MOCA score and P300 test latency in three midline electrodes. However, the improvement in cognitive performance was significantly greater in the PR+CT group than the PR group.

Conclusion

In conclusion, although PR alone improves 6MWT parameters and cognitive function, the addition of CT to PR is more effective in improving cognitive abilities in patients with COPD. This combined approach may provide clinicians with a complementary therapeutic option for improving cognitive abilities in patients with COPD.

Keywords

Pulmonary rehabilitation cognitive training chronic obstructive pulmonary diseases cognitive impairment 6 minutes walking test parameters and exercise tolerance

Introduction

Cognitive impairment (CI) is a common complication affecting 77% of hypoxemic patients with Chronic Obstructive Pulmonary disease (COPD).¹ Hypoxemia in some patients with COPD seems to be a crucial factor for CI, as it affects oxygen-dependent enzymes such as acetylcholine synthesis.² These changes may be related to structural brain abnormalities, such as gray-matter pathologic changes and the loss of white matter integrity, which can be induced by smoking.³ Besides, smoking is a known cause of the COPD and the systematically review of Forey et al.⁴ highlights the relationship between smoking and decline in forced expiratory volume in one second. Indeed, the prevalence estimates of CI are increased in patients with COPD, indicating lung dysfunction as a risk factor for CI even when data are adjusted for age, sex, smoking habits and education level.⁵ CI could also affect various cognitive domains, such as memory, attention, and speed of information processing.^5,6

Pulmonary rehabilitation (PR) is an essential part of managing COPD as it improves exercise tolerance and health-related quality of life while decreasing dyspnea, fatigue, hospital admissions, and mortality in patients with COPD.⁷ Although various methods and therapies of PR have been used in COPD patients, developing an individualized exercise training prescription is a target.⁷ A related study, showed that dropouts of PR performed worse on cognitive flexibility tests than those who completed the program.⁸ A meta-analysis also showed that aerobic exercise improves cognitive function across the adult lifespan.⁹ Additionally, aerobic training after 5 months resulted in greater benefits compared to strength training in adults.¹⁰ Moreover, cognitive rehabilitation for a person with dementia exerts many cognitive beneficial effects on their global cognitive functioning (e.g., memory, working memory, attention language and psychomotor ability).¹¹ Furthermore, it has been shown that the cognitive training (CT) has positive effects on general cognitive functioning and selected cognitive abilities in mild cognitive impairment (MCI) patients.¹² It turns out that CT could maintain and/or improve specific cognitive functions, particularly attention, episodic memory, and problem-solving skills, using guided training and repetitions of standardized tasks.^13,14 From a theoretical point of view, the combination of PR and CT in patients with COPD could simultaneously attenuate the specific effects of their disease and improve their cognitive functioning.

Yet, up to now, the effect of adding CT to PR on cognitive parameters has not been clearly investigated in patients with COPD. The combination of PR and CT could be a valuable alternative to improve exercise tolerance (6 minutes walking test -6MWT-parameters) and cognitive functions (MOCA score and P300 test latency in three midline electrodes) in patients with COPD as primary outcomes. It may be also useful for clinicians to help design new rehabilitation therapies. Therefore, the aim was to study the possible interest of PR combined to CT on exercise tolerance and cognitive functions in patients with COPD.

Materials and methods

Population

Thirty-nine patients with severe COPD were included in this study according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Classification.¹⁵ Only outpatients were recruited from department of physiology and functional explorations and department of pulmonology of the university Hospital Farhat Hached of Sousse in Tunisia. These patients were randomized to two groups that is, a control group that carried out only a rehabilitation program [PR group (n = 18, age = 65.3 ± 3.2)] and to another group that combined the same rehabilitation program and an additional cognitive training [PR+CT group (n = 21, age = 65.3 ± 2.79)]. Either group benefited two measurement periods; baseline and after 3 months of trainings (Figure 1). All patients who met the eligibility criteria attended two measurements sections. Patients were randomly assigned. The randomization sequence was generated by a researcher not involved in recruitment or assessment; it was concealed from investigators using a computer-generated random number schedule with variable block sizes of two to six. There were separate outcome assessors who were blinded to group allocation. Allocation to training groups was concealed from all investigators for carrying out the training or patients’ involvement. The allocation is done using consecutively numbered opaque sealed envelopes, opened after completion of baseline assessment with the presence of the patients. Participants were selected according to the inclusion criteria as follows: (1) Clinically stable COPD patients GOLD 3 (FEV1 post bronchodilatation between 30% and 49% of predicted) (2) patients out of exacerbations periods in the last year. The non inclusion criteria were: (1) patients with heart diseases, severe psychiatric, neurologic or musculoskeletal conditions and/or instable cardiovascular diseases. (2) The use of medication influences the cognition and (3) patient with history of brain injury and the history of stroke. Patients, who changed residence, or refused to sign consent, were removed from the study. In addition, patients who dropped out after randomization due to reasons such as receiving rehabilitation elsewhere or canceling their participation due to transport problems, and thus did not begin the intervention at all.

Figure 1.

Consort 2010 Flow diagram Patients recruitment.

Participants were informed about the purpose and protocol of the study and gave their written consent. The study was conducted according to declaration of Helsinki and was approved by the local Ethics committee of the university hospital.

The trial was registered with ClinicalTrials.gov (Identifier: NCT03907839). Once the two groups had been constituted, it was verified that there was no significant difference between them. In fact, the two groups (PR and PR+CT) were homogeneous and did not exhibit difference in terms of age, body mass index (BMI), education level, height and weight (Table 1).

Table 1.

Demographics and spirometric data of the intervention and control groups.

Demographic data
Patients characteristics	Intervention Group (n = 21)	Control group (n = 18)	p-value
Age (years)	65.2 ± 2.79	65.3 ± 3.2	0.9
Level education (years)	9.6 ± 1.4	9.2 ± 1.9	0.4
Height (cm)	170.9 ± 0.03	170.1 ± 0.04	0.5
Weight (kg)	69.4 ± 5.4	69 ± 4.4	0.8
BMI (kg/m²)	23.71 ± 1.9	24 ± 1.8	0.6
Spirometric data
FEV₁ (l)
Baseline	1.4 ± 0.2	1.3 ± 0.2	0.1
Follow-up	1.3 ± 0.2	1.3 ± 0.2	0.2
FEV₁ % (predicted)
Baseline	45.1 ± 4.2	45.4 ± 5.3	0.9
Follow-up	45.4 ± 4.6	45.4 ± 5.9	0.8
FVC (l)
Baseline	2.9 ± 0.4	2.8 ± 0.4	0.8
Follow-up	2.76 ± 0.39	2.8 ± 0.5	0.6
FEV₁/FVC% (predicted)
Baseline	48.2 ± 6.7	47.1 ± 9.9	0.9
Follow-up	49.6 ± 9.5	50.7 ± 15	0.7

Notes: BMI: body mass index; FEV₁: Forced expiratory volume in one second; FVC: forced vital capacity. The results are presented as mean ± SD.

Study design

The study was conducted in the rehabilitation center of Research Laboratory of the faculty of medicine of Sousse Tunisia. Subjects were evaluated at baseline (3 days after recruitment) and at the end of the 3-month training program. On the first day of the study, subjects were informed about the study’s purpose and agreed to participate in pulmonary function testing. On the second day, patients were assessed using a standard 6 minutes walking test (6MWT), and on the third day, approximately 1-h auditory evoked potentials measures were performed for each patient.

The rehabilitation program consisted of attending 36 sessions and patients were expected to complete all the sessions, without missing any. We encouraged all the patients to complete all their sessions and tried to be flexible with scheduling to ensure their attendance.

Measurements

Pulmonary function testing

All subjects underwent a pulmonary function test using a Spirometry Zan 100 (Inspire Health GmbH, Germany) to measure the forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) and FEV/FVC by a trained respiratory therapist, according to the European Respiratory Society recommendations.¹⁶

Six-minute walking test

The 6MWT was conducted in accordance with international recommendations.¹⁷ Subjects were instructed to walk at their own maximal pace along a 40-m long hospital corridor as far as possible for 6 min. Subjects were updated about the timer reading at each minute and were allowed to stop, but could start walking again if possible. Chairs were placed along the corridor for subject use if needed. Dyspnea was measured using the Borg scale before the start and at the end of the 6MWT. Portable Spiropalm COSMED recorded heart rate (HR) and oxygen saturation (SpO2) continuously throughout the 6MWT. At the end of the 6MWT, the total covered distance was recorded. This test was performed once at baseline.

P300 test

The P300 is a component of the human brain’s event-related potential (ERP) measured by electroencephalography (EEG) and reflects cognitive processing related to attention, working memory, and decision-making. It is elicited by an infrequent, attention-grabbing stimulus, typically a tone or a visual cue, and occurs approximately 300 milliseconds after the stimulus onset, hence the name P300.¹⁸

It has been suggested that P300 test may be a useful tool for detecting CI in patients with COPD.¹⁹ The P300 waveform consists of a positive peak followed by a negative peak, with the amplitude and latency of these peaks being the key measures of interest. The amplitude reflects the amount of attention devoted to the task, with larger amplitude indicating greater attention, while latency represents the time taken for cognitive processing, with shorter latency indicating faster processing.⁶

Scalp electrode activity was measured at all electrode sites, where Fz, Cz, and Pz were chosen for analyses because their ERP responses are the largest in the midline locations. The P3b and P3a components were identified as the largest positive deflections between 250 ms and 500 ms, respectively, in the target and novel responses. The amplitude of these components was identified by means of baseline to peak measurements.²⁰ Auditory stimulus was given binaurally through a headphone (intensity - 40 dB, stimulation rate - 0.5 Hz, number of stimuli - 30) with the “tone” as the target or rare stimulus (Frequency - 2000 Hz) and “click” as non-target or frequent stimulus (Frequency - 1000 Hz, duration - 0.1 ms). The rare stimuli were applied randomly, and the percentage of rare stimuli was set at 20% and frequent stimuli at 80% of random. The participants were asked to relax keeping their eyes open and fixed at a point to avoid alpha waves. Their task was to concentrate on the rare stimulus.²¹

We followed the recommendation of the guideline for using human ERPs to study cognition²⁰ and we used Neuropack X1 measuring system MEB-2300 NIHON KOHDEN corporation.

Montreal cognitive assessment test (MOCA)

Cognitive function was assessed using the validated Arabic version of the MOCA, which is a paper and pencil screening tool that takes approximately 10 min for a trained technician to administer. The test, scored on a scale of 0–30 points, is designed to identify CI by assessing multiple cognitive domains, including attention, concentration, executive functions, memory, language, visuospatial skills, calculation, and orientation. MOCA scores between 26 and 30 are considered normal, while scores <26 indicate CI.²²

Intervention

Both groups participated in the rehabilitation program 3 days per week for 12 weeks (36 sessions). Patients in the intervention and control groups attended PR sessions, on a different day of the week; the intervention group had a PR session combined to CT.

All patients in both groups attended the sessions in a group setting. Both groups underwent a structured PR program that included not only endurance training but also other components, such as education on COPD management, breathing techniques, symptom monitoring and medical management.

Patients assigned to the control group underwent 30 min of endurance training. The sessions were supervised by a multidisciplinary team of healthcare professionals, including a medical doctor and physiotherapists and also a rehabilitation coach. Their expertise ensured proper monitoring of participants during exercises, adherence to protocols, and immediate response to any potential medical concerns or adverse events.

Regarding the of endurance training, the intensity was set on achieving a target HR corresponding to 60%–70% of maximum HR reached during the end of 6MWT, but does not lead to excessive symptoms of dyspnea or fatigue. The intensity of the PR program was progressed throughout the intervention period. The training intensity was increased in each month from 60 to 70% of maximum HR reached during the end of 6MWT (60% in the first month, 65% in the second month and 70% in the third month)

During the sessions, the participants could monitor the intensity of training using a cardio frequency meter (Polar, V800), with alarms set to ±5 beats per minute around the target HR. The training consists of cycling work for 30 min on an ergocycle. The session ended with 10 min of relaxation exercises and stretching. On this same basis of PR sessions, patients in the PR+CT group received CT for an additional 20 min after the of endurance training.

The CT involved paper-and-pencil exercises,^11,23,24 that were graded for difficulty level, and participants were given assistance when they had difficulty with the tasks.^25,26 When a participant was able to complete a task independently, the difficulty was progressively increased. The CT consisted of four main types of exercises: (1) Attention exercise where Participants repeated a series of numbers forwards and then a different series backwards. (2) Memory exercise: where participants clapped their hands when they heard a letter from a previously listened list of letters; (3) Concentration exercise where participants identified the differences between two photos; and (4) language exercise, where participants read a short paragraph of historical statements.

Statistical analysis

Statistical analysis was performed using Statistica Software 13.0 (Software, Inc., Tulsa, USA). The normality and homogeneity of variance were respectively determined using the Shapiro-wilk and Levene tests. The assumption of normality and homogeneity of variance was confirmed for all parameters. The two-way Analysis of Variance (ANOVA) test was used to compare the two groups (PR group vs PR+CT group) and within-group effects (before and after trainings) as well as the interaction effects (group × time effect) on both primary and secondary outcomes. Then, the Bonferroni post-hoc procedures were performed. Values were expressed as means (standard deviation). The level of significance was set at the 5% critical level (p < .05). In addition, effect size (Cohen’s d) was calculated using data at baseline measure and after 3-month of training. Value for Cohen’s d of 0.2, 0.5, and 0.8 was interpreted as small, moderated, and large, respectively. Priori simple size calculation was based on previously published data on the P300 amplitude (stable COPD group data (8.87 ± 7.34).²⁷ This required a sample size of 52 patients (p < .05, power 80%). A total of 100 patients were assessed for eligibility in this study.

Results

A total of 100 patients were initially recruited in this study. Thirty-one participants who did not meet the inclusion criteria included 13 patients with a history of COPD exacerbation within the past year, seven patients with COPD classified as GOLD 2 (FEV1 post bronchodilation between 50% and 80% of predicted), and 11 patients with COPD classified as GOLD 4 (FEV1 post bronchodilation <30% of predicted).

Of the 39 patients included in the study, 21 patients in the experimental group received the allocated PR program combined with CT, while 18 patients in the control group received the allocated PR program. All patients in the control and experimental groups have completed all the numbers of sessions. Patients who dropped out after randomization due to reasons such as receiving rehabilitation elsewhere or canceling their participation due to transport problems, and thus did not begin the intervention at all.

Baseline characteristics of patients are shown in Table 1. There were no significant differences between the two groups.

Differences in the 6MWT outcomes between baseline measurement, follow-up and between the two groups are shown in Table 2.

Table 2.

The 6 minutes walking test outcomes of the intervention and the control group.

	Intervention Group (n = 21)	Control group (n = 18)	p-value	Effect size (d)
6MWD(m)
Baseline	273.2 ± 64.6	276.4 ± 63.3	0.8	0.05
Follow-up	378 ± 49.6 ***	383.9 ± 44.8 ***	1.0	0.1
SpO2 (%), Rest
Baseline	91.7 ± 1.3	91.3 ± 1.7	0.9	0.1
Follow-up	92 ± 1.09	91.5 ± 1. 5	0.9	0.3
SpO2 (%), peak
Baseline	89.2 ± 1.3	89.4 ± 1.1	1.0	0.1
Follow-up	90.4 ± 0.6 **	90.6 ± 0.9 **	0.9	0.2
Dyspnea (Borg scale),Rest
Baseline	1.8 ± 0.3	1.9 ± 0.5	0.9	0.1
Follow-up	1.6 ± 0.5	1.7 ± 0.4	1.0	0.2
Dyspnea (Borg scale),Peak
Baseline	5.8 ± 0.8	5.7 ± 0.9	0.9	0.01
Follow-up	4.5 ± 0.5 **	4.5 ± 0.8 **	0.9	0.03
FC (bpm),Rest
Baseline	82.8 ± 2.4	82.5 ± 1.7	0.7	0.1
Follow-up	81.7 ± 2.2 **	81.3 ± 2.16 **	0.9	0.1
FC (bpm),Peak
Baseline	124.04 ± 3.08	124.3 ± 2.2	1.0	0.1
Follow-up	121.2 ± 2.4 **	121.05 ± 4.8 **	1.0	0.03

Notes: ET: endurance training; CT: cognitive training; 6MWTD: six-minute Walk Test Distance; SpO₂: peripheral oxygen saturation; HR: heart rate. The results are presented as mean ± SD.

**p < .01 (vs baseline); ***p < .001 (vs baseline).

The post hoc test analysis showed significant improvement (p < .001) for 6MWD, (p < .01) for final Spo2 (%), peak dyspnea, HR rest and peak after training in both groups. Spo2 rest (%) and dyspnea rest decreased significantly (p < .05) for both groups after 12 weeks of trainings (Table 2). The effect size of Spo2 (Rest and peak) and dyspnea Rest (Cohen’s d = 0.3, 0.2, 0.2, respectively) at follow-up was small between two groups.

The post hoc test analysis showed a significant improvement (p < .001) for P300 latency in P3a and P3b in midlines electrodes (Fz, Cz and Pz) for both groups. This improvement was significantly greater (p < .001) in favor of the Intervention group. The effect size of P300 latency in P3a and P3b in midlines electrodes (Fz, Cz and Pz) (cohen’s d = 2.4, 1.4 at Fz; cohen’d = 2.01, 1.7 at Pz respectively and cohen’s d = 1.1 for p3b at Cz) at follow-up was large between two groups. In addition, the effect size of P300 latency in P3a at Cz (cohen’s d = 0.2) was small at follow-up between two groups (Table 3).

Table 3.

Cognitive outcomes of the intervention and the control group.

	Intervention Group (n = 21)	Control group (n = 18)	p-value	Effect size (d)
Latency of P300 at Fz P3a (ms)
Baseline	338.6 ± 14.4	339.5 ± 11.7	0.9	0.07
Follow-up	281.3 ± 8.4 ***	304.1 ± 10.1 ***	<0.001	2.4
Latency of P300 at Fz P3b (ms)
Baseline	369.2 ± 11	368.4 ± 15.4	0.9	0.05
Follow-up	322.6 ± 20.4 ***	349.5 ± 18.5	<0.001	1.4
Latency of P300 at Cz P3a (ms)
Baseline	335.6 ± 13.3	333 ± 14.7	0.9	0.2
Follow-up	293.3 ± 8.08***	309.11 ± 8.9***	0.001	0.2
Latency of P300 at Cz P3b (ms)
Baseline	378.09 ± 17.2	379.4 ± 18. 8	1.0	0.07
Follow-up	326.2 ± 22.02***	351.7 ± 22.2***	<0.001	1.1
Latency of P300 at Pz P3a (ms)
Baseline	344.2 ± 23.08	344.4 ± 23.3	0.9	0.01
Follow-up	301.09 ± 6.4***	320.9 ± 12.8***	<0.001	2.01
Latency of P300 at Pz P3b (ms)
Baseline	381.8 ± 17.05	381.2 ± 11.9	1.0	0.04
Follow-up	343.3 ± 28.7***	362.9 ± 11.4***	0.001	1.7
Amplitude of P300 at Fz and Cz Fz (µv)
Baseline	11.4 ± 3.6	11.65 ± 4	0.7	0.06
Follow-up	11.9 ± 2.4	11.9 ± 3.7	0.2	0.03
Amplitude of P300 at Fz and Cz Cz (µv)
Baseline	11.7 ± 2.3	11.8 ± 3.4	0.9	0.1
Follow-up	11.8 ± 3.7	12.3 ± 3.03	0.7	0.1
Amplitude of P300 at Fz and Cz Pz (µv)
Baseline	12.8 ± 3.9	12.8 ± 2.8	1.0	0.01
Follow-up	12.8 ± 3.9	12.89 ± 2.9	0.7	0.02

Notes: MOCA: Montreal Cognitive Assessment; Fz: frontal (z: median line); Cz: central (z: median line) P3a, P3b the sub-parameters of the P300 wave. (ms): meters second; (μv): microvolts. The results are presented as mean ± SD.

***p < .001 (vs baseline).

Finally, the results was founded no significant effect for the amplitude in Fz, Cz and Pz in the same group and between two groups before and after 3 months of training.

For MOCA test, there were no significant differences between the two groups before the rehabilitation programs. The post hoc test showed a significant increase in MOCA score (p < .001) after 3 months of rehabilitation in both groups. This increase was higher in the intervention group than in the control group (p < .001) (Figure 2). The effect size of MOCA test (cohen’s d = 3.8) at follow-up was large between groups.

Figure 2.

MOCA test histogram. Notes: MOCA: Montreal Cognitive Assessment; ***Significant at (p < .001) within group differences before and after training; ^$ Significant at (p < .001): between-group differences after training.

Discussion

The aim of this study was to examine the effect of adding CT to PR program in patients with COPD. The main findings of this study demonstrated that combined training, improved the global cognitive functioning (MOCA) notably attention, and working memory (P300) compared to PR without CT in patients with COPD.

The results showed a significant improvement in 6MWT parameters (6MWD, SpO2, dyspnea and HR) in both groups, the increase in walking performance could be explained by a decrease in dyspnea sensation related to an improvement in aerobic fitness following rehabilitation²⁸ that may lead to better survival in individuals.²⁹ However, no significant difference was observed between the two groups. This may be not surprising since both groups performed aerobic training program improving performance of walking. In this context, the evaluation of exercise capacity via the 6MWT yielded a similar significant increase of the walking distance in both groups with COPD after aerobic training.³⁰

Our results, further demonstrated increased global cognitive functions, including visio-spatial, memory, verbal fluency, attention, concentration, language, and orientation, in both groups. This may surprising since the control group performed only aerobic training. We can suppose that PR sessions improves global cognitive function parameters because PR sessions based on aerobic exercises are likely to increase in brain volume, and functional connectivity between part of the frontal posterior and temporal cortices.³¹ These results are consistent with previous studies in healthy, sedentary, and adult patients, which suggest that aerobic training could significantly improve working memory and executive functions.^32,33 These improvements are characterized by reduced loss of cortical gray matter and white matter and could be also associated to a better level of cardiorespiratory fitness such as VO2max.³⁴ Indeed, cardiorespiratory fitness is associated to cerebral blood output and flow which would facilitate the integrity of cognitive processes and support executive functions.³⁵ In this context, the comprehensive review of Paillard et al.³⁶ brought out that cognitive improvement were related to physical exercise, which raises the cardiac output in response to increased needs for oxygen and energetic substrates compared to the state of rest. There would be an inversely proportional relationship between the amount of physical activity undertaken and the risk of cognitive decline and/or the development of neurodegenerative disease.^37,38

Furthermore, results of this study reported that the improvement in cognitive abilities based on the MOCA score was higher in the intervention group than the control group. First, this finding confirms results of Auffray et al.³⁷ concerning the beneficial effect of CT on cognitive performance in memory tests in older subjects³⁷ suggesting that CT should be included in seniors care program. Second, aerobic training may improve global cognitive abilities but selective cognitive abilities need a specific treatment that could be assured by adapted CT. The mean change of MOCA test was 3.87 points for the intervention group and 1.62 points for the control group. The mean change for the intervention group exceed the Minimal Clinically Important Difference estimated for MOCA test which lies between two and three points according to previous studies.³⁹

To our knowledge, this is the first study that implemented the P300 test to evaluate the effect of PR combined with CT on cognitive ability in patients with COPD. The present results showed an improvement in cognitive abilities by reducing the latency of the P300 wave at Fz (P3a and P3b), Cz (P3a and P3b), and Pz (P3a and P3b) in both groups. Reduced latency observed in both groups may be related to an increase of certain neutrophins.³⁸ In this context, several studies have reported that in rats, the level of certain neurotrophins, such as the brain neurotrophic factor (BDNF), increased after a PR program.³⁸ This may lead to synaptogenesis and neurogenesis in brain regions with typically little neuronal proliferation.⁴⁰ In addition, researchers have observed that an increase in the aerobic (race-induced) condition increased the uptake of choline (precursor of acetylcholine) at the cortical level and promoted the density of dopamine receptors in the brain of older rats⁴¹ suggesting that aerobic training improves vascularization of brain tissue that could explain in part enhancement of human cognitive abilities.^42,43 Moreover, latency of the P300 wave at Fz, Cz and Pz were greater in the intervention group compared to the control group indicating greater cognitive abilities improvement in participants performed the combined program. In addition, Gajewski PD and Falkenstein M⁴⁴ examined the effect of three different types of training regiments (physical, cognitive and relaxation) on cognitive improvement in older subjects and found that the improvement was more significant in the group that performed CT. Although the positive effect of aerobic training on cognitive abilities has been proven, the addition of cognitive exercise to PR sessions would deserve to be implemented in the rehabilitation program in order to optimize their therapeutic effects. This may offer to clinician need to take this consideration into account, in order to refine intervention programs, particularly for people with cognitive disorders such as neurodegenerative’ diseases.

However, regarding the amplitude of P300 at Fz and Cz, the present results showed no significant difference after physical and cognitive rehabilitation in both groups. These results can be explained by the factors responsible for the variability of the P300 latency, such as age, intra-individual variability, psychoactive substances, and psychological influence.^45,46 These results are in agreement with the study of Kirkil et al.²⁷ showing no significant difference in the amplitude of P300 between, a healthy control group, a group of patients with severe COPD, and a group of patients with stable COPD.

There are some limitations to this study. First, the absence of female patients in this study due to the higher prevalence of COPD in Tunisian males, as well as the differences in smoking behavior between males and females. Second, the training program was performed during 3 months. Further analyses are therefore needed to determine the long-term effect of adding specific CT to PR.

Conclusion

The intervention group and the control group improved cognitive abilities in patients with COPD. However, the CT added to the PR program (regarding the intervention group) improved cognitive abilities more than the only PR program (regarding the control group). The change of three points or more on the MOCA score could be considered a meaningful difference in patients with COPD. This may offer to clinician a complementary approach to improve cognitive abilities in patients with COPD. Further studies are needed to know if the additional gains in cognitive function after CT impacted on the quality of life for patients with COPD.

Footnotes

Acknowledgements

The authors would like to thank the study volunteers for their participation.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Amal Acheche

References

Grant

Heaton

McSweeny

, et al. Neuropsychologic findings in hypoxemic chronic obstructive pulmonary disease. Arch Intern Med. 1982;142(8):1470–1476.

Heaton

Grant

McSweeny

, et al. Psychologic effects of continuous and nocturnal oxygen therapy in hypoxemic chronic obstructive pulmonary disease. Arch Intern Med 1983;143(10):1941–1947.

Cleutjens

Janssen

Ponds

, et al. COgnitive-pulmonary disease. BioMed research international. 2014.

Forey

Thornton

Lee

. Systematic review with meta-analysis of the epidemiological evidence relating smoking to COPD, chronic bronchitis and emphysema. BMC Pulm Med. 2011;11(1):36–61.

Dodd

Charlton

van den Broek

, et al. Cognitive dysfunction in patients hospitalized with acute exacerbation of COPD. Chest 2013;144(1):119–127. doi:10.1378/chest.12-2099

Dodd

Getov

Jones

. Cognitive function in COPD. Eur Respir J. 2010;35(4):913–922.

McCarthy

Casey

Devane

, et al. Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2015;2:CD003793.

Emery

Schein

Hauck

, et al. Psychological and cognitive outcomes of a randomized trial of exercise among patients with chronic obstructive pulmonary disease. Health Psychol, 1998;17(3):232–240. doi:10.1037//0278-6133.17.3.232

Kamijo

Hayashi

Sakai

, et al. Acute effects of aerobic exercise on cognitive function in older adults. J Gerontol B Psychol Sci Soc Sci. 2009;64(3):356–363. doi:10.1093/geronb/gbp030

10.

Smiley-Oyen

Lowry

Francois

, et al. Exercise, fitness, and neurocognitive function in older adults: the “selective improvement” and “cardiovascular fitness” hypotheses. Ann Behav Med. 2008;36(3):280–291. doi:10.1007/s12160-008-9064-5

11.

Davis

Massman

Doody

. Cognitive intervention in Alzheimer disease: a randomized placebo-controlled study. Alzheimer disease and associated disorders. 2001;15(1):1–9.

12.

Bahar-Fuchs

Martyr

Goh

, et al. Cognitive training for people with mild to moderate dementia. Cochrane Database Syst Rev 2019;3:Cd013069. doi:10.1002/14651858.CD013069.pub2

13.

Buschert

Bokde

Hampel

. Cognitive intervention in Alzheimer disease. Nat Rev Neurol 2010;6(9):508–517. doi:10.1038/nrneurol.2010.113

14.

Reijnders

van Heugten

van Boxtel

. Cognitive interventions in healthy older adults and people with mild cognitive impairment: a systematic review. Ageing Res Rev 2013;12(1):263–275. doi:10.1016/j.arr.2012.07.003

15.

Global Initiative for Chronic Obstructive Lung Disease . Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease, 2017. https://goldcopd.org/2017

16.

Quanjer

Tammeling

Cotes

, et al. Lung volumes and forced ventilatory flows. Eur Respir J. 1993;16(Suppl 16):5–40. doi:10.1183/09041950.005s1693

17.

Singh

Puhan

Andrianopoulos

, et al. An official systematic review of the European Respiratory Society/American Thoracic Society: measurement properties of field walking tests in chronic respiratory disease. Eur Respir J. 2014;44(6):1447–1478. doi:10.1183/09031936.00150414

18.

Polich

(2007). Updating P300: an integrative theory of P3a and P3b. Clin Neurophysiol, 118(10), 2128–2148. doi: 10.1016/j.clinph.2007.04.019

19.

Ghanbari

Shadmehr

Mohammadi

, et al. (2019). Effects of pulmonary rehabilitation combined with cognitive training on cognitive function and serum BDNF levels in patients with COPD. Int J Chronic Obstr Pulm Dis, 14, 1925–1935. doi: 10.2147/COPD.S211223

20.

Picton

Bentin

Berg

, et al. Guidelines for using human event-related potentials to study cognition: recording standards and publication criteria. Psychophysiology. 2000;37(2):127-152.

21.

Sharma

Subramanian

Rajendran

. Comparison of cognitive auditory event related potentials and executive functions in adolescent athletes and non-athletes - A cross sectional study. Int J Physiol Pathophysiol Pharmacol. 2019;11(6):274–282.

22.

Nasreddine

Phillips

Bédirian

, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53(4):695–699.

23.

De Vreese

Neri

Fioravanti

, et al. Memory rehabilitation in Alzheimer’s disease: a review of progress. Int J Geriatr Psychiatry. 2001;16(8):794–809.

24.

Quayhagen

Corbeil

, et al. Coping with dementia: evaluation of four nonpharmacologic interventions. Int Psychogeriatr 2000;12(2):249–265.

25.

Bahar-Fuchs

Clare

Woods

. Cognitive training and cognitive rehabilitation for mild to moderate Alzheimer’s disease and vascular dementia. Cochrane Database Syst Rev. 2013;(2013):Cd003260. doi:10.1002/14651858.CD003260.pub2

26.

Beck

Heacock

Mercer

, et al. The impact of cognitive skills remediation training on persons with Alzheimer’s disease or mixed dementia. J Geriatr Psychiatry. 1988;21(1):73–88.

27.

Kirkil

Tug

Ozel

, et al. The evaluation of cognitive functions with P300 test for chronic obstructive pulmonary disease patients in attack and stable period. Clin Neurol Neurosurg 2007;109(7):553–560. doi:10.1016/j.clineuro.2007.03.013

28.

Vallet

Ahmaidi

Serres

, et al. Comparison of two training programmes in chronic airway limitation patients: standardized versus individualized protocols. Eur Respir J. 1997;10(1):114–122.

29.

Bowen

Votto

Thrall

, et al. Functional status and survival following pulmonary rehabilitation. Chest. 2000;118(3):697–703.

30.

Würtemberger

Bastian

. [Functional effects of different training in patients with COPD]. Pneumologie. 2001;55(12):553–562. doi:10.1055/s-2001-19001

31.

Suzuki

Shimada

Makizako

, et al. A randomized controlled trial of multicomponent exercise in older adults with mild cognitive impairment. PLoS One. 2013;8(4):e61483. doi:10.1371/journal.pone.0061483

32.

Colcombe

Kramer

. Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychol Sci 2003;14(2):125-130. doi:10.1111/1467-9280.t01-1-01430

33.

Kluding

Tseng

Billinger

. Exercise and executive function in individuals with chronic stroke: a pilot study. J Neurol Phys Ther 2011;35(1):11–17.

34.

Colcombe

Kramer

Erickson

, et al. Cardiovascular fitness, cortical plasticity, and aging. Proc Natl Acad Sci U S A. 2004;101(9):3316–3321. doi:10.1073/pnas.0400266101

35.

Paillard

. Preventive effects of regular physical exercise against cognitive decline and the risk of dementia with age advancement. Sports Med Open. 2015;1(1):20. doi:10.1186/s40798-015-0016-x

36.

Paillard

Rolland

de Souto Barreto

. Protective effects of physical exercise in Alzheimer’s disease and Parkinson’s disease: a narrative review. J Clin Neurol. 2015;11(3):212–219.

37.

Auffray

Juhel

. Effets généraux et différentiels d’un programme d’entraînement cognitif multimodal chez la personne âgée. Psy. 2001;101(1):65–89.

38.

Russo-Neustadt

Ramirez

, et al. Physical activity–antidepressant treatment combination: impact on brain-derived neurotrophic factor and behavior in an animal model. Behav Brain Res. 2001;120(1):87–95.

39.

France

Orme

Greening

, et al. Cognitive function following pulmonary rehabilitation and post-discharge recovery from exacerbation in people with COPD. Respir Med. 2021;176:106249.

40.

Pencea

Bingaman

Wiegand

, et al. Infusion of brain-derived neurotrophic factor into the lateral ventricle of the adult rat leads to new neurons in the parenchyma of the striatum, septum, thalamus, and hypothalamus. J Neurosci. 2001;21(17):6706–6717.

41.

Fordyce

Farrar

. Physical activity effects on hippocampal and parietal cortical cholinergic function and spatial learning in F344 rats. Behav Brain Res. 1991;43(2):115–123.

42.

Dustman

Emmerson

Ruhling

, et al. Age and fitness effects on EEG, ERPs, visual sensitivity, and cognition. Neurobiol Aging. 1990;11(3):193–200.

43.

Rogers

Meyer

Mortel

. After reaching retirement age physical activity sustains cerebral perfusion and cognition. J Am Geriatr Soc 1990;38(2):123–128.

44.

Gajewski

Falkenstein

. Training-induced improvement of response selection and error detection in aging assessed by task switching: effects of cognitive, physical, and relaxation training. Front Hum Neurosci. 2012;6:130. doi:10.3389/fnhum.2012.00130

45.

Hansenne

. [The p300 cognitive event-related potential. I. Theoretical and psychobiologic perspectives]. Neurophysiol Clin. 2000;30(4):191–210. doi:10.1016/s0987-7053(00)00223-9

46.

Hansenne

. [The p300 cognitive event-related potential. II. Individual variability and clinical application in psychopathology]. Neurophysiol Clin. 2000;30(4):211–231. doi:10.1016/s0987-7053(00)00224-0

Effect of a pulmonary rehabilitation program combined with cognitive training on exercise tolerance and cognitive functions among Tunisian male patients with chronic obstructive pulmonary disease: A randomized controlled trial

Abstract

Background

Methods

Results

Conclusion

Keywords

Introduction

Materials and methods

Population

Study design

Measurements

Pulmonary function testing

Six-minute walking test

P300 test

Montreal cognitive assessment test (MOCA)

Intervention

Statistical analysis

Results

Discussion

Conclusion

Footnotes

Acknowledgements

Declaration of conflicting interests

Funding

ORCID iD

References