Impact of cognitive capacity on physical performance in chronic obstructive pulmonary disease patients: A scoping review

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is often accompanied by impaired cognitive and physical function. However, the role of cognitive function on motor control and purposeful movement is not well studied. The aim of the review was to determine the impact of cognition on physical performance in COPD. Methods: Scoping review methods were performed including searches of the databases: MEDLINE, EMBASE, Cochrane Systematic Reviews, Cochrane (CENTRAL), APA PsycINFO, and CINAHL. Two reviewers independently assessed articles for inclusion, data abstraction, and quality assessment. Results: Of 11,252 identified articles, 44 met the inclusion criteria. The review included 5743 individuals with COPD (68% male) with the forced expiratory volume in one second range of 24–69% predicted. Cognitive scores correlated with strength, balance, and hand dexterity, while 6-min walk distance (n = 9) was usually similar among COPD patients with and without cognitive impairment. In 2 reports, regression analyses showed that delayed recall and the trail making test were associated with balance and handgrip strength, respectively. Dual task studies (n = 5) reported impaired balance or gait in COPD patients compared to healthy adults. Cognitive or physical Interventions (n = 20) showed variable improvements in cognition and exercise capacity. Conclusions: Cognition in COPD appears to be more related to balance, hand, and dual task function, than exercise capacity.

Keywords

Cognition exercise lung disease obstructive dual tasking pulmonary rehabilitation

Introduction

Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction.¹ In 2019, COPD had an estimated global prevalence of 391 million² and was the third leading cause of death worldwide.³ The clinical features of airflow limitation, lung hyperinflation, respiratory muscle weakness, and dyspnea, contribute to the exercise intolerance often present in COPD.⁴ Exercise capacity as measured by the 6-min walk test (6MWT)^5,6 and the level of physical activity⁷ are predictors of mortality in COPD patients.

Along with the respiratory manifestations described, COPD is a systemic disease that is often accompanied by extrapulmonary sequela including cognitive dysfunction.⁸ The reported prevalence of cognitive impairment in COPD patients is variable ranging between 10 to 61%,⁹ and as high as 77% in hypoxemic populations.¹⁰ Moreover, impairment ranges from mild to severe cognitive impairment and dementia, as well as deficits in both global and specific cognitive domains.^11–13 Regarding specific cognitive domains, two systematic reviews both corroborate the frequent prevalence of memory and attention-related deficits in COPD.^13,14

Related to diminished cognitive performance is dual tasking, an experimental paradigm used to evaluate decrements in cognition when an individual is required to perform a cognitive and motor task simultaneously. Dual task interference arises when there is reduced performance in either task relative to their single task equivalent.¹⁵ There are several cognitive theories postulated to explain the reduced performance observed relative to single tasks.¹⁶ One of the theories, the central capacity sharing model, posits that internal processing of the concurrent events is capacity-limited due to the requirements of parallel processing.^17,18 Importantly, processing speed is correlated with broad cognitive measures, such as fluid intelligence.¹⁹ Thus, a systematic review evaluating older adults with mild cognitive impairment (MCI) observed greater dual task interference during walking relative to healthy controls.²⁰ Furthermore, individuals with MCI display worse postural, gait, and fine motor control relative to their non-MCI counterparts.²¹

Given the heightened prevalence of cognitive decline in COPD, and the apparent relationship of MCI and worsened dual task performance and motor control in non-COPD, it is pertinent to evaluate how cognitive capacity influences motor control in COPD patients. Additionally, as COPD patients almost invariantly exhibit dyspnea,²² it is critical to include dyspnea within our conceptual definition of physical performance. Indeed, dyspnea is not only a physical symptom but also an interoceptive stimuli that requires cortical and subcortical processing.^23,24 In COPD, hypoxemia may lead to cognitive dysfunction through neuronal injury.²⁵ The aim of this scoping review was to investigate the relationship between cognitive function and motor control in COPD patients, and whether treatments improve cognitive and physical function. As cortical control is necessary for purposeful movement,²⁶ we hypothesize that COPD patients that exhibit cognitive impairments will have more impaired motor control compared to those without cognitive impairments.

Methods

Protocol

The draft protocol and finalized review utilize the established scoping review framework set by Arksey and O’Malley and their updated enhancements.^27–29 The draft protocol was registered prospectively with Open Science Framework on 6 September 2021 (https://osf.io/ng765/). Draft revisions were conducted after consultation and feedback from the review team.

Identifying the research question

The primary objective addressed by this scoping review was to examine how cognitive capacity influences physical performance in COPD patients. The following sub-questions were addressed: 1) what is the relationship between cognitive test measures and physical performance; 2) did physical performance indicators differ when COPD patients were stratified by cognitive test scores; 3) does dual tasking influence physical performance in COPD relative to healthy adults; and 4) does baseline cognition influence cognitive and physical changes with interventions?

Information sources and search strategy

The search strategy was developed by a research librarian (AO-C) with the following key concepts: COPD, cognition, and exercise capacity. The search was executed on 20 July 2021, and a second search on 14 February 2022, in the databases: Ovid MEDLINE; Ovid Embase; Cochrane Database of Systematic Reviews; Cochrane Central Register of Controlled Trials (CENTRAL); APA PsycINFO; CINAHL complete (EBSCOhost). Conference and book materials were removed from Embase. The reference lists of retrieved publications were also examined. The searches were not limited to study design and year but were limited to humans, adults, and English language. Please see the Supplementary Appendix for the comprehensive search strategy.

Eligibility criteria

The following studies were included if they examined COPD patients of any severity: 1) by evaluating the relationship between their cognition and physical performance; 2) compared their physical performance according to stratification of their cognitive test scores; 3) examined dual task paradigms; 4) assessed cognition and physical outcomes after an intervention; and 5) evaluated the relationship between baseline cognition with physical changes with an intervention. Exclusion criteria used: 1) regression models that had cognition as an outcome variable; 2) COPD lung transplant recipients; 3) intervention studies that did not include both cognitive and physical post-treatment scores unless inclusion criterion above was met; and 4) non-English language studies. Case series, grey literature, conference proceedings and abstracts, and dissertations were excluded.

Study selection

Search results were imported into EndNote 20 and duplicates were removed using EndNote’s automation tool. Pairs of reviewers (PR, SA, EF, UM, RLFF, MK) independently screened the titles and abstracts and subsequently the selected full-text articles for inclusion. Disagreement among reviewers were resolved by a third reviewer.

Data charting process

Pairs of reviewers (PR, SA, EF, UM, RLFF, MK) independently abstracted data from the full-text articles and disagreements were resolved by a third reviewer. Data abstraction included: study design, study location, inclusion and exclusion criteria, baseline characteristics (age, sex, number of participants, COPD severity, comorbidities), study protocol, and outcome measures (correlation coefficients, hypothesis testing outcomes, beta-coefficients, dual task results, and treatment outcomes).

Quality assessment

Quality assessment was performed using a 15-item modified Downs and Black checklist³⁰ or the full Downs and Black³¹ checklist (27-items)³¹ depending on study design, the latter was used for randomized trials, randomized controlled trials (RCTs), or non-randomized controlled trials. This checklist queries study quality, external and internal validity, and power. Quality assessment was conducted by pairs of independent reviewers (PR, SA, EF, UM, MK) and disagreements were resolved by a third reviewer.

Data synthesis

Baseline characteristics and cognitive and physical assessments of reports were tabulated (Table 1). Study outcomes were synthesized into three tables: cross-sectional studies that assessed the relationship between cognitive test scores and physical measure (Table 2); dual task studies (Table 3); and interventions that evaluated cognitive and physical outcomes (Table 4).

Table 1.

Baseline characteristics and assessments.

Author (Year)	Study design	Sample (n)	Age	Male Female	FEV₁ (% pred)	Cognitive assessment
Correlation/Regression/Mean comparison studies
Antonelli-Incalzi (2008)	Cross-sectional	High CF COPD (48)	—	38:10	38	Raven’s progressive matrices, phonemic verbal fluency test, Corsi’s block-tapping task, auditory word span, rey auditory 15-word learning test, line cancellation test, copying drawings, immediate visual memory test, sentence construction
		Mid CF COPD (49)		44:5	36
		Low CF COPD (52)		44:8	33
Cleutjens (2018)	Cross-sectional	CI COPD (76)	63	46:30	55	Concept shifting test, letter digit substitution test, SCWT, visual verbal learning task, shortened groninger intelligence test
Cleutjens (2018)	Cross-sectional	CN COPD (107)	64	51:56	54
Cruthirds (2021)	Cross-sectional	COPD (37)	68	17:20	45	TMT-B, SCWT part 3
Dag (2016)	Cross-sectional	CI COPD (16)	65	47:5	51	MMSE
Dag (2016)	Cross-sectional	COPD (36)	60		56	MoCA
Gore (2021)	Cross-sectional	COPD (382)	75	166:216		Immediate word recall, delayed word recall, orientation, semantic verbal fluency test
Grant (1982)	Cross-sectional	COPD (203)	65	160:43		Average impairment rating, Clinician’s global neuropsychological rating
Karpman (2014)	Cross-sectional	COPD (130)	68	77:53	50	DSST
Kaygusuz (2021)	Cross-sectional	COPD (60)	57	58:2	44	MMSE
Ozyemisci-Taskiran (2015)	Retrospective cross-sectional	AECOPD (133)	69	113:20	38	MMSE
Park (2015)	Cross-sectional	COPD (593)	67	382:211	28	TMT
Park (2018)	Longitudinal; secondary analysis	COPD class 1 (109)	67	64:45	28	TMT part B
		COPD class 2 (122)	67	72:50	28
		COPD class 3 (56)	67	32:24	29
		COPD class 4 (20)	68	15:5	30
Park (2020)	Cross-sectional	COPD (34)	69	14:20	44	Stroop interference
Randeep (2019)	Cross-sectional	COPD (50)	65	28:22	—	DSST, TMT, MMSE, MoCA
Roncero (2016)	Cross-sectional	CI COPD (570)	70	463:107	56	MMSE
Roncero (2016)	Cross-sectional	CN COPD (370)	66	299:71	55	MMSE
Schure (2016)	Cross-sectional	TMT-A: Normal (213)	67	175:38	46	TMT-A, TMT-B
		Borderline (44)	68	33:11	44
		Impaired (44)	69	34:10	44
		TMT- B: Normal (213)	67	172:41	46
		Borderline (38)	69	33:5	46
		Impaired (50)	68	37:13	42
Soysal Tomruk (2015)	Cross-sectional	COPD (35)	63	31:4	38	MMSE
Tudorache (2017)	Cross-sectional	COPD (62)	68	62:0	29	MoCA
Yazar (2018)	Cross-sectional	CI COPD (16)	62	13:3	3	MMSE, CDT
Yazar (2018)	Cross-sectional	CN COPD (75)	62	73:2	45	MMSE, CDT
Yohannes (2021)	Cross-sectional	CI COPD (119)	66	64:55	53	MoCA
Yohannes (2021)	Cross-sectional	CN COPD (101)	65	54:47	47	MoCA
Summary for cross-sectional		N = 3962	57-75	70:30%	28-56	—
Dual task studies
Hassan (2020)	Cross-sectional	COPD (15)Healthy (20)	7169	9:69:11	5293	Backwards spelling
Heraud (2018)	Cross-sectional	COPD (25)Healthy (20)	6570	——	48112	Backwards counting by 3
Morlino (2017)	Cross-sectional	COPD (40)Healthy (28)	7170	29:1116:12	50116	Backwards counting by 3
Ozsoy (2021)	Cross-sectional	COPD (35)Healthy (27)	6261	31:423:4	59—	Backwards counting by 3
Van Hove (2021)	Cross-sectional	COPD (21)Healthy (21)	6463	14:7	41	Backwards counting by 3, verbal fluency task
Summary for dual task		N = 136	62-71	61:21%18% NR	41-59	—
Intervention studies
Abumossalam (2021)	RCT	Piracetam (low dose) (42)Piracetam (high dose) (44)Control (no placebo) (40)	585662	36:640:433:7	———	AD8 dementia screening
Adrianopoulos (2021)	Pre-post; 3-weeks inpatient PR	CI COPD (25)CN COPD (35)	6868	16:919:16	4647	MoCA, S-MMSE, T-ICS, ACE-R, visuospatial skills, memory, orientation, attention, language/executive, fluency
Aquino (2016)	Randomized trial; 4-weeks EX	CT group (14)AT group (14)	6569	14:014:0	6869	Attentive matrices test, Raven’s progressive matrices, rey-immediate recall, rey-delayed recall, verbal fluency, drawing test I and II
Bonnevie (2020)	Pre-post; 8-weeks outpatient PR	CI COPD (41)CN COPD (15)	6459	21:205:10	3639	MoCA
Cleutjens (2017)	Cross-sectional; PR	CI COPD (46)CN COPD (87)	62^a	65:68^a	54^a	Visual verbal learning test, groninger intelligence test, letter digit substitution test 60 s, concept shifting test, SCWT card III
Dal Negro (2012)	Rct; 12-weeks	EAA (44)Placebo (44)	7573	32:1229:15	——	MMSE
Emery (1991)	Pre-post; 1-month Outpatient PR	COPD (61)	—	34:27	—	TMT-A, TMT-B, digit symbol (WAIS-R), digit span (WAIS-R), finger tapping (halstead-reitan)
Emery (1994)	Pre-post; 1-month Outpatient PR	Older COPD (13)Mid-aged COPD (14)	6943	10:17 (total)	—-	TMT-A, TMT-B, digit symbol (WAIS-R), digit span (WAIS-R), finger tapping (halstead-reitan)
Emery (1998)	Rct; 10-weeks PR	EXESM (30)ESM (24)Waiting list (25)	656767	15:1510:1412:13	———	TMT-A, TMT-B, digit vigilance, digit symbol (WAIS-R), finger tapping (halstead-reitan), verbal fluency
Etnier (2001)	RCT; 15-months outpatient AT	AT (8)Control (7)	6770	5:36:1	6268	Culture fair intelligence test
Ferrari (2004)	Pre-post; 12weeks home-based PR	COPD (28)	70	20:8	55	MMSE
France (2021)	Pre-post; 6weeks PR	COPD (67)	67	37:30	31	MoCA
Kilic (2021)	Randomized trial; 12-weeks	Home PR (31)Hospital PR (27)	7068	27:425:2	5850	S-MMSE
Kozora (2002)	Non-RCT; 3-weeks PR	COPD PR (30)Untreated COPD (29)Con (21)	666765	15:1513:165:16	4045—	Digit span and digit symbol subtests (WAIS-R), digit vigilance test, TMT, logical memory, visual reproduction and paired associates subtests (WMS-R), clock drawing to command, boston naming Test-15 item, controlled oral word association test, animal naming test
Kozora (2005)	RCT	LVRS (19)Medical therapy (20)Con (39)	656464	14:518:233:6	2524—	Digit span and arithmetic subtests (WAIS-R), logical memory, verbal paired associates, and faces subtests (WMS-R), digit vigilance test, TMT, complex ideational material subtest (boston diagnostic aphasia examination), controlled oral word association test, animal naming test, boston naming Test-15 item, CDT
Lavoie (2019)	RCT; 12-weeks SMBM $\pm$ bronchodilators $\pm$ EX	SMBM + T/O + EX (76)SMBM + T/O (76)SMBM + T (76)SMBM + placebo (76)	65656564	45:3148:2855:2153:23	49504947	MoCA
Liu (2021)	RCT; 12-weeks virtual PR	Virtual PR (50)Routine PR (50)	7475	40:1038:12	3940	MoCA
NOTT (1980)	RCT; minimum 12-months	12-h nocturnal O₂ (102)Continuous O₂ (101)	6665	82:2078:23	3030	Halstead impairment index. Russell-neuringer average impairment index, brain age quotient
Rosenstein (2020)	Randomized trial; 12-weeks EX	CTHI (12)CTVT (12)HIIT (12)	666967	3:96:64:8	606650	MoCA, digit span, digit symbol, and block design subtests (WAIS), TMT, SCWT, semantic verbal fluency, letter verbal fluency, RAVLT, Rey-O complex Figure (copy)
van Beers (2021)	RCT; 12-weeks training WM + 12-weeks Mainten	WM training (33)Sham WM training (31)	6666	13:2016:15	5861	Cambridge neuropsychological test automated battery
Summary for interventional		—	43-75	65:35%	24-69	—

ACE-R: Addenbrooke’s Cognitive Examination-Revised; AECOPD: Acute Exacerbation of COPD; AT: Aerobic Training; CDT: Clock Drawing Test; CI: cognitively impaired; CF: cognitive functioning; CN: cognitively normal; CT: Combined training (Aerobic + Resistance); CTHI: continuous training at high intensity; CTVT: continuous training at the ventilatory threshold; DSST: Digit Symbol Substitution Test; EAA: Essential Amino Acid supplementation; ESM: education and stress management; EXESM: exercise and ESM; HIIT: high-intensity interval training; LVRS: Lung Volume Reduction Surgery; Mainten: Maintenance; MMSE: Mini-Mental State Examination; MoCA: Montreal Cognitive Assessment; mo: month; PR: Pulmonary Rehabilitation; RAVLT: Rey Auditory Verbal Learning Test; SCWT: Stroop Color and Word Test; S-MMSE: Standardized MMSE; T-ICS: Interview for Cognitive Status; SMBM + T/O + Ex: self-management behaviour modification + tiotropium/olodaterol + exercise training; TMT: Trail Making Test; TUG: Timed Up and Go; WAIS: Wechsler Adult Intelligence Scale; WAIS-R: WAIS-Revised; WM: working memory; WMS-R: Wechsler Memory Scale-Revised.

^aValues for total combined group (CI and CN COPD).

Table 2.

Cross-sectional studies showing relationships between cognitive test scores and physical performance.

Author (Year)	Sample	Cognitive measure	Score	Physical measure	Score	Method	Outcomes
Andrianopoulos (2021)	CI COPD	MoCA	$\leq$ 25	mMRC	1.4 (1.0)	Independent t-test	mMRC did not differ between groups (p > 0.05)
Andrianopoulos (2021)	CN COPD	MoCA	$\geq$ 26		1.6 (0.8)	Independent t-test	mMRC did not differ between groups (p > 0.05)
Antonelli-Incalzi (2008)	High CI	NTB	Scores adjusted for age and education	6MWD (m)	293 (88)	1-Way ANOVA with scheffe post hoc test	6MWD (m and %pred did not differ among groups (p = 0.216 and p = 0.762, respectively)
	Mid CI				277 (124)		VAS dyspnea did not differ among groups (p = 0.279)
	Low CI				254 (110)
				6MWD % pred	59.3 (26.0)
					60.0 (26.4)
					56.4 (23.3)
				VAS dyspnea	5.7 (3.1)
					6.0 (3.7)
					6.8 (3.5)
Bonnevie (2020)	CI COPD	MoCA	$<$ 26	6MWD (steps)	148 (103–202)	Mann–Whitney U test; Independent t-test	6MWD (steps and m) are comparable between CI and CN subgroups (p = 0.08; p = 0.39)
	CN COPD		$\geq$ 26		191 (156–246)
				6MWD (m)	377 (117)
					409 (112)
Cleutjens (2018)	CI COPD	NTB		mMRC	2.2 (1.0)	Independent t-test; Chi-squared test	mMRC and 6MWT are similar between CI and CN COPD patients (p = 0.53; p = 0.30; p = 0.14; p = 0.16 as listed respectively)
	CN COPD				2.3 (1.0)
				6MWD (m)	421.8 (112.2)
					439.2 (111.5)
				6MWD % pred	66.1 (16.7)
					69.8 (16.4)
Cruthirds (2021)	COPD	SCWT pt 3	134.7 (6.8)	Leg extension force/kg lean mass (N/kg)	4.9 (0.2)	Pearson’s correlation	SCWT pt 3 and TMT pt B negatively correlated with leg extension force (r = −0.3671, p < 0.05; r = −0.4563, p < 0.05)
Cruthirds (2021)		TMT pt B	80.9 (6.3)			Pearson’s correlation
Dag (2016)	CI COPD	MMSE	$\leq$ 24	6MWD (m)	389.4 (97.5)	Independent t-test; Pearson’s correlation	6MWD not different between groups for MMSE and MoCA scores (p = 0.15, p = 0.14) but correlated with MMSE and MoCA (r = 0.29, p = 0.037, r = 0.39, p = 0.004)
	CN COPD		$>$ 24		441.5 (117.2)
		MoCA	$<$ 21
			$\geq$ 21
Gore (2021)	COPD	DWR	3.88 (1.99)	Gait speed Tandem stance time	0.69 (0.22)	Multivariate linear regression (covariates: IWR, orientation, executive function)	Model 1: Covariates not associated with gait speed
Gore (2021)					24.63 (18.5)		Model 2: DWR associated with tandem stance time ( $β$ = 1.42, 95% CI 0.10–2.74, p = 0.04)
Grant (1982)	COPD	AIR	2.28 (0.78)	Maximum cycle ergometer work		Pearson’s correlation	AIR and CGNR negatively correlated with max cycle work (r = −0.18, p = 0.03; r = −0.23, p = 0.002)
Grant (1982)		CGNR	4.38 (1.12)			Pearson’s correlation
Karpman (2014)	COPD	DSST	—	6MWD (m)	410 (120)	Stepwise multivariate linear regression (covariates: Gait speed, DLCO%pred, FEV1%pred)	DSST weakly associated with 6MWD ( $β$ = 1.2, p = 0.011)
Kaygusuz (2021)	COPD (mMRC <2)	MMSE	26.63 (2.94)	BBS	55.20 (1.62)	Spearman’s correlation; Simple linear regression	MMSE correlated with BBS and mMRC (r = 0.331, p = 0.001; r = −0.446, p < 0.001) and associated with BBS ( $β$ = 0.314, SE = 0.099, 95% CI = 0.117–0.512, p = 0.002)
	COPD (mMRC $\geq$ 2)		25.97 (3.36)		52.97 (4.50)
				mMRC	0.60 (0.49)
					2.97 (0.76)
Park & larson (2015)	COPD	TMT pt A	43.1 (16.0)	6MWD (ft)	1104.0 (307.7)	Pearson’s correlation	TMT pt a negatively correlated with 6MWD and peak work (r = −0.09, p = 0.024; r = −0.12, p = 0.007) and positively with ucsd-sobq (r = 0.09, p = 0.028)
		TMT pt B	99.9 (44.5)	Peak work (W)	36.1 (21.0)		TMT B correlated with UCSD-SOBQ (r = 0.09, p = 0.028)
				UCSD-SOBQ	58.4 (16.6)		TMT B correlated with UCSD-SOBQ (r = 0.09, p = 0.028)
Park (2018)	Class 1	TMT pt B	77.0 (21.5)	6MWD (ft)	1265.4 (295.7)	1-Way ANOVA with bonferroni correction	Class 1 had greater 6MWD than classes 2 and 3 (p = 0.01)
	Class 2		88.3 (19.9)		1139.5 (276.1)		No significant differences among classes for UCSD-SOBQ (p = 0.40)
	Class 3		130.7 (19.5)		1123.2 (308.0)
	Class 4		185.9 (52.2)		1240.5 (229.0)
				UCSD-SOBQ	59.8 (18.5)
					63.0 (19.9)
					64.9 (19.1)
					60.4 (19.2)
Park (2020)	COPD	Stroop interference	61.66 (3.924)	AP mean sway velocity BBS	1.11 (0.073)	Pearson’s correlation; Multiple linear regression (covariates: O₂ therapy, fat mass, diabetic status)	Stroop interference- Correlated with postural balance and negatively with BBS (r = 0.59, p = 0.0002; r = −0.45, p = 0.048)- Associated with CoP ( $β$ = 0.009796, SE = 0.0022, p = 0.0001)
					53.11 (0.55)
Ozyemisci-Taskiran (2015)	CI AECOPD	MMSE	$<$ 24	6MWD (m)	146 (134)	Independent t-test; Pearson $χ$ ²; Test (adjusted for age and education)	6MWD different among unadjusted groups (p = 0.002) but not different among adjusted groups (p = 0.389)
	CN AECOPD		$\geq$ 24		242 (152)
			$<$ Adjusted cutoff		240 (42–360)
			$\geq$ Adjusted cutoff		252 (100.5–355)
Randeep (2019)	COPD	S-MMSE	23.3 (3.3)	6MWD (m)	392.3 (124.856)	Pearson’s correlation	MMSE, MoCA, TMT, and DSST correlated with 6MWD (r = 0.41, p = 0.00; r = 0.30, p = 0.03; r = 0.33, p = 0.02; r = 0.34, p = 0.02)
		MoCA	22.2 (3.6)
		TMT	223 (27)
		DSST	28.4 (2.2)
Roncero (2016)	CI COPD	MMSE	$<$ 27	mMRC	3.1 (0.9)	Independent t-test	CI COPD had higher mMRC scores (p < 0.001)
Roncero (2016)	CN COPD		$\geq$ 27		2.6 (0.9)	Independent t-test	CI COPD had higher mMRC scores (p < 0.001)
Schure (2016)	TMT A CN	TMT A	Z-score $>$ −1.0	mMRC	1.8 (1.1)	One-way ANOVA; Multivariable regression (covariates: Age, sex, living arrangements, FEV % pred, home oxygen use, mMRC, hospitalization in past year, BMI, charlson comorbidity Index)	mMRC and 6 MWD differed in TMT part B subgroups (p = 0.05 and (p = 0.03, respectively)
	TMT A CB	TMT B			2.2 (1.1)		Grip strength differed in both TMT a and TMT B subgroups (p = 0.002; p = 0.02); Borderline impaired TMT A showed significant association with grip strength ( $β$ = -2.9, 95% CI -5.5, −0.4, p < 0.05). Borderline and impaired TMT B showed significant association with grip strength ( $β$ = -3.0, 95% CI -5.7, −0.3, p < 0.05; $β$ = -2.5 95% CI -2.5, −0.0, p < 0.01, respectively)
	TMT A CI		Z-score −1.0 to −1.5		2.1 (1.2)
	TMT B CN				1.8 (1.1)
	TMT B CB		Z-score $<$ −1.5		2.0 (1.1)
	TMT B CI				2.2 (1.2)
				6MWD (ft)	1122 (375)
					1025 (328)
					976 (377)
					1113.3 (361.2)
					1065.4 (346.9)
					987.7 (421.1)
				Grip strength (kg)	33.6 (9.4)
					29.1 (8.9)
					29.4 (9.8)
					33.3 (9.8)
					30.2 (7.6)
					29.6 (9.2)
Soysal Tomruk (2015)	Hypoxemic COPD	MMSE	23.9 (3.3)	Placement dexterity (min)	2.1 (0.3)	Pearson’s correlation	MMSE negatively correlated with placement and turning dexterity (r = −0.411, p = 0.0015; r = 0.418, p = 0.013)
Soysal Tomruk (2015)				Turning dexterity (min)	2.3 (0.3)	Pearson’s correlation
Tudorache (2017)	COPD	MoCA	21.50 (20–24)	6MWD (m)	360 (315–400)	Spearman’s Correlation	MoCA not correlated with 6MWD (r = 0.131, NS)
Yazar (2018)	CI COPD	MMSE	$\leq$ 24	6MWD (m)	285.94 (136.921)	Independent t-test; Pearson’s correlation	6MWD different between groups (p = 0.018) but mMRC similar
	CN COPD		$>$ 24		358.89 (103.696)		6MWD correlated with MMSE and CDT (r = 0.294, p = 0.005; r = 0.258, p = 0.014) but not mMRC
	COPD	CDT	4.14 (1.3)	MMRC	2.06 (1.526)
					1.53 (1.057)
Yohannes (2021)	CI COPD	MoCA	[18,26)	6MWD	1134 (842, 1356)	Independent t-test	6MWD and mMRC did not significantly differ among subgroups (p = 0.102; p = 0.392, respectively)
	CN COPD		$\geq$ 26		1198 (983, 1420)
		mMRC		mMRC	3 (2, 4)
					3 (1, 4)

6MWD: 6-min walk distance; AIR: average impairment rating; AP: anteroposterior; BBS: berg balance scale; CGNR: clinician’s global neuropsychologic Rating; CoP: center of pressure; DLCO: diffusing capacity for carbon monoxide; DWR: delayed word recall; IWR: immediate word recall; mMRC: modified medical research council dyspnea scale; NS: non-significant; NTB: neuropsychological testing battery; UCSD-SOBQ: The University of California, San Diego shortness of breath questionnaire; VAS: visual analogue scale.

Table 3.

Dual task studies—performance of COPD patients relative to healthy controls (Con).

Author (Year)	Cognitive screening (COPD vs control)	Motor task	Single task	Between group p-value	Dual task	Between group p-value	Main outcomes
Hassan (2020)	MoCA	PPW velocity	Lower	0.005	Lower	0.025	COPD exhibited decreased gait velocity in both single and dual tasks (+ backwards spelling) compared to Con
	24.2 vs 26.1	FPW velocity	Lower	0.001	Lower	0.035
	p = 0.032
Heraud (2018)	No screening	Gait speed	Lower	NS	Lower	NS	COPD patients exhibit increased stride time variability during dual task (+ counting backwards by 3) compared to Con
Heraud (2018)		Stride time variability	Lower	NS	Higher	<0.001
Morlino (2017)	MMSE	TUG test	Higher	<0.05	Higher	<0.05	COPD patients exhibit longer TUG test time for single and dual tasks (+ counting backwards by 3) compared to Con
	26.7 vs 28.3
	p < 0.025
Ozsoy (2020)	No screening	TUG test	Higher	NS	Higher	NS	COPD did not differ in the TUG test and knee extension muscle force production in single and dual tasks (+ counting backwards by 3) compared to Con
Ozsoy (2020)		Knee extensor force	Lower	NS	Lower	NS
Van hove (2021)^a	No screening	DOT	Higher	NS	Higher^b	<0.05	COPD patients exhibit greater balance-related deficits single and dual tasks (+ counting backwards by 3 or verbal fluency task) compared to Con
					Higher^c	<0.05
		Area	Higher	<0.05	Higher	<0.05
					Higher	<0.05
		ML RoM	Higher	<0.05	Higher	<0.05
					Higher	NS
		AP RoM	Higher	NS	Higher	<0.05
					Higher	NS
		ML SD	Higher	<0.05	Higher	NS
					Higher	NS
		AP SD	Higher	NS	Higher	<0.05
					Higher	NS	No correlation was found between cognitive function (verbal fluency or backwards counting) and postural control
		ML speed	Higher	<0.05	Higher	<0.05
					Higher	<0.05
		AP speed	Higher	<0.05	Higher	<0.05
					Higher	<0.05
		TMV	Higher	<0.05	Higher	<0.05
					Higher	<0.05

Area: area of the 95% prediction ellipse; healthy controls: Con; DOT: total displacement of sway; ML: medial-lateral; RoM: Range of motion; PPW: preferred paced walk; FPW: fast paced walk; SD: CoP standard deviation; TMV: trajectory mean velocity; TUG: timed-up-and-go test.

^aResults from eyes closed condition only shown.

^bResults for counting backwards dual task condition.

^cResults for verbal fluency dual task condition.

Table 4.

Interventions showing within subject changes in cognition and physical performance.

Author (Year)	Sample	Cognitive measure	Result (Δ mean (SD))	Pre-post p-value	Physical measure	Result	Pre-post p-value	NS measures^a
Pulmonary rehabilitation
Andrianopoulos (2021)	CI COPD	S-MMSE	0.7 (1.1)	<0.05	6MWD (m)	25 (59)	<0.05	Cognitive measures: Orientation, attention
	CN COPD		0.5 (1.2)	<0.05		46 (48)	<0.05
		T-ICS	1.1 (1.9)	<0.05	6MWD%pred	3.6 (9.3)	NS
			1.1 (1.7)	<0.05		7.1 (7.3)	<0.05
		ACE-R	4.4 (4.6)	<0.05	CET 75%WRpeak (s)	140 (142)	<0.05
			1.8 (2.9)	<0.05		117 (166)	<0.05
		Visuospatial skills	7.5 (14.4)	<0.05
			0.4 (12.9)	NS
		Memory	6.0 (9.3)	<0.05
			4.2 (5.8)	<0.05
		Language/executive	2.1 (5.9)	NS
			1.9 (3.4)	<0.05
		Fluency	8.3 (16.0)	<0.05
			0.9 (9.5)	NS
Bonnevie (2020)	CI COPD	MoCA	1.0	<0.01	6MST	34	<0.01
	CN COPD			0.37		27	0.03
					6MWD (m)	28	0.10
						34	0.08
Cleutjens (2017)	CI COPD				6MWD (m)	21.7 (47.2)	0.003
	CN COPD					15.7 (57.8)	0.013
					mMRC	−0.6 (1.3)	0.013
						−0.4 (0.9)	<0.001
Emery (1991) and Emery (1994)^b	Male/Female	TMT part A	−2.17/-4.02	NS	VO₂max (ml/min)	140.7/67.1	<0.001	Cognitive measures: Digit span forward, digit span backward, tapping non-dominant hand
	Middle/Old		−6.76/-8.06	<0.05		212.9/65.54	NS
		TMT part B	−33.9/-40.4	<0.001	Power (W)	11.7/8.54	<0.001
			−39.1/-55.2	<0.05		20.2/7.32	<0.05/NS
		Digit symbol	5.62/6.61	<0.001	Laps (in 12 min)	2.05/2.43	<0.05
			11.19/6.82	<0.05/<0.01		3.71/1.36	<0.001/<0.05
		Tapping dominant hand	2.05/3.61	<0.05
			4.98/3.1	NS
Emery (1998)	EXESM	Verbal fluency	5.3	<0.001	Work (kp-m)	11.3	<0.01	Cognitive measures: Digit vigilance, tapping dominant hand, tapping non-dominant hand, TMT part A, TMT part B, digit symbol
	ESM		−0.2	NS		1.8	NS
	WL		0.4	NS		−1.0	NS
					VO₂max (mL/kg/min)	2.0	<0.01
						−3.0	NS
						−0.3	NS
Ferrari (2004)	Home PR	MMSE			Max work (W)VO₂max	↑↑	<0.05<0.05
France (2021)	COPD	MoCA	0.6 (2.8)	NS	SPPB	↑	<0.001
	CI COPD		1.6 (2.4)	0.004
	CN COPD		−0.8 (2.)	0.276
Kilic (2021)	Home PR	S-MMSE	0.48	0.001	6MWD (m)	14.48	0.005
Kilic (2021)	Hospital PR		0.77	0.001		68.22	<0.001
Kozora (2002)	PR COPD	Digit vigilance	−31.3	CI 0.004	6MWD (ft)	266	<0.001	Digit span, digit symbol, TMT part B, visual retention, verbal pairs, BNT-SF, letter fluency, semantic fluency
	COPD-no PR		−17.6	NS		43	<0.001
	Con		−30.7	NS
		Story retention	11.1	CI 0.006
			10.0	NS
			9.0	NS
		Clock score	0.4	CI 0.06
			−0.4	NS
			0.4	NS
Liu (2021)	Virtual PR Control	MoCA	↑↔	<0.05	6MWD (m)	↑↑
Aerobic and resistance training
Aquino (2016)	CT	Attentive matrices	2.43	<0.01	VO₂max (mL/kg/min)	4.78		Cognitive measures: Rey-IR, drawing test I
	AT		3.15	<0.01		5.01
		Rey-DR	1.35	<0.01		11.72
			0.64	<0.05	Quadricep strength kg	11.07
		Raven test	1.72	<0.01		4.43
			0.64	<0.05		2.85
		Verbal fluency	5.0	<0.01	Arms strength kg
			4.0	<0.01
		Drawing test II	5.71	<0.01
			3.21	<0.05
Etnier (2001) 3-months exercise phase	COPD	CFIT	4.93	<0.001	6MWD (ft)	207	<0.001	—
					VO₂max	0.94	<0.01
Maintenance phase(3–18 months)					(mL/kg/min)
	Long term exercise	CFIT	2.5	NS	6MWD (ft)	40.38	NS
	No exercise		−0.14	NS		−75.85	NS
					VO₂max	−0.84	<0.01
					(mL/kg/min)	−1.75	<0.01
Rosenstein (2020)
12-weeks intervention phase	CTHI	WAIS digit span	2.4	0.830^c	Endurance time (s)	30.92	<0.001	Medium to small effect sizes during intervention phase: TMT part A, TMT part B, SCWT, semantic and letter verbal fluency, RAVLT (total 1–5), RAVLT (list B), RAVLT (immediate recall), RAVLT (delayed recall), WAIS block design, WAIS digit symbol coding
	CTVT		−1.0	−0.310		33.26	<0.001
	HIIT		1.5	0.423		36.28	<0.001
		Rey-O complex Figure (copy)	2.0	0.963
			2.9	0.659
			0	0.015
Maintenance phase (week 12 to year 1)	CTHI		1.7	0.932
	CTVT	MoCA	−0.3	-
	HIIT		1.1	-
			−0.04	0.111
		SCWT (part 4-3)	−0.58	−0.391
			0.49	0.849
Working memory (WM) training
van Beers (2021)								Cognitive measures: Motor orientation task, paired associates learning, stop-signal task, delayed match-to-sample, spatial working memory Physical measures: 6MWD, accelerometry activity count
12-weeks intervention phase	WM training
	Sham training
12-weeks maintenance phase
	WM training	5-Choice movement time (RTI)	↓	0.016
	Sham training		↔	0.303

6MST: 6-min stepper test; BNT-SF: Boston Naming Test-Short Form; CET: cycle-endurance test; CFIT: Culture Fair Intelligence Test; DR: delayed recall; ESWT: endurance shuttle walk test; IR: immediate recall; MT: medical therapy; PEmax: maximal expiratory pressure; PImax: maximal inspiratory pressure; RTI: Reaction Time Task; SPPB: Short Physical Performance Battery; SNIP: sniff nasal inspiratory pressure; WL: waiting list. Some of the abbreviations are shown for Table 1.

^aData from the same study.

^bEffect sizes reported instead of p-values.

^cNon-significant pre-to-post measures for all study groups.

Results

The PRISMA diagram (Figure 1) summarizes the screening results.³² The initial and second searches yielded 10,045 and 1207 articles, respectively. The number of duplicates removed was 3619. Screening resulted in 133 full-text articles to be screened for eligibility and 44 articles met the inclusion criteria.^10,33–75 Studies were excluded due to lack of a relationship between cognition and physical outcomes (n = 84); regression models utilizing cognition as an outcome rather than an explanatory variable (n = 2); drug intervention studies that evaluated pre- and post-cognitive outcomes to assess safety (n = 2); and a study that evaluated cognitive but not physical outcomes after rehabilitation.

Of the 31 studies evaluated using the modified Downs and Black checklist (see Supplementary Appendix), quality assessment scores ranged from 43.8% to 87.5%, with a mean of 65.5%. All 31 studies scored points for: stating the study hypothesis or study aim(s); clearly delineating study outcomes; clearly describing the main findings; using appropriate statistical tests; and using valid and reliable study measures. Studies demonstrated poor external validity and internal validity (confounding) with a combined mean percentage of 14.6% and 32.3%, respectively. The 31 studies had a mean score of 74.2% for internal validity (bias), with no studies receiving points for blinding outcome measures.

Of the 13 studies evaluated using the full Downs and Black checklist, quality assessment scores ranged from 46.4% to 89.3%, with a mean of 60.7%. These studies scored high for internal validity (bias) with a mean of 83.5%. The studies demonstrated poor external validity with a mean of 12.8%. Only two of the 13 studies demonstrated sufficient statistical power.

Baseline characteristics of study participants and cognitive assessment used are summarized in Table 1. Regarding the type of cognitive assessment used in the cross-sectional and longitudinal (non-intervention) studies, three studies used a comprehensive neuropsychological testing battery, seven studies used the Mini-Mental State Examination (MMSE), four studies used the Montreal Cognitive Assessment (MoCA) test, and nine studies used a combination of the Stroop Test, Trail Making Test (TMT), Digit Symbol Substitution Test (DSST), clock-drawing test (CDT), a verbal fluency test, and word recall. For the dual task studies, one applied backwards spelling, four used backwards subtraction by threes, and one of these four also applied a verbal fluency task. Among the intervention studies, 10 utilized neuropsychological testing batteries, nine utilized either the MoCA or MMSE, one used the Culture Fair Intelligence Test, and one used the AD8 dementia screening tool.

The relationship between cognitive test scores and physical performance are summarized in Table 2.

Cognition and exercise capacity

Inconsistent findings were reported for the relationship between 6MWD and stratification of subgroups using cognitive screening tools (MoCA or MMSE) or a comprehensive neuropsychological testing battery. Observational studies did not identify a difference in 6MWD in cognitively impaired (CI) and cognitively normal (CN) subgroups.^38,42,75 Two cross-sectional studies^62,74 identified a difference in 6MWD between CI and CN subgroups when stratified by the MMSE, with the CI group having a lower mean 6MWD. However, this relationship was negated in one report after adjusting for age and education.⁶² Of note, cross-sectional studies identified significant weak-to-moderate correlations between cognitive screening tools and 6MWD,^42,66,74 while another study did not find an association between the MoCA and 6MWD.⁷¹ When using a comprehensive neuropsychological testing battery, cross-sectional studies did not identify a difference in 6MWD between CI and CN individuals.^36,40

Other cognitive tests used to evaluate relationships with 6MWD also showed mixed results. A longitudinal study organized patients into low or high baseline TMT part B (higher scores indicate greater impairment for TMT A and B) scores (measure of executive function) and reported varying improvements in their cognitive test scores over 3 years, with those improving having higher baseline 6MWD.⁶⁴ A cross-sectional study found differences in 6MWD when stratifying COPD patients by TMT part A scores (measure of psychomotor speed) but not according to TMT part B scores; COPD patients with impaired TMT part A had lower 6MWD than patients categorized with a normal TMT part A score.⁶⁹ Moreover, TMT part A but not TMT part B was found to have a weak inverse correlation with 6MWD.⁶⁵ Another cross-sectional study found a weak correlation between TMT and 6MWD.⁶⁶ Two cross-sectional studies found the DSST, a measure of psychomotor speed, to be weakly associated⁵³ and weakly correlated with 6MWD.⁶⁶ The CDT, a measure of memory, attention, and visuospatial abilities had a weak correlation with 6MWD.⁷⁴

Regarding gait speed, in a cross-sectional study using multivariate linear regression, all covariates, which included delayed word recall, immediate word recall, measurement of orientation or executive function, were not significant.⁵⁰

Regarding cycle ergometry, Average Impairment Rating, a global index of impairment (higher score indicates greater CI), and an independent global rating by clinicians, demonstrated a weak negative correlation with maximum work.¹⁰ TMT part A was also reported to have a weak negative correlation with maximum work, while the relationship with TMT part B was not significant.⁶⁵

The Stroop-Color Word Test (SCWT), a measure of executive function and cognitive flexibility, and TMT part B, were both found to have a moderate inverse correlation with leg extension force.⁴¹

Cognition and dyspnea

Categorizing COPD patients into CI and CN subgroups according to cognitive test scores had mixed results regarding Modified Medical Research Council (mMRC) Dyspnea scores. Higher mMRC Dyspnea scores were found in CI COPD when stratifying by MMSE⁶⁷ and TMT part B,⁶⁹ while MoCA,^35,75 a comprehensive neuropsychological testing battery,⁴⁰ and TMT part A⁶⁹ stratification showed no significant differences.

Regarding other measures of dyspnea, categorizing subgroups based on a comprehensive neuropsychological battery, one cross-sectional study did not identify a difference in their Visual Analogue Scale (VAS) dyspnea scores.³⁶ Categorizing patients into high or low TMT part B baseline scores with varying trajectories of cognitive improvement, did not find a significant difference between their University of California, San Diego Shortness of Breath Questionnaire (UCSD-SOBQ) scores⁶⁴; with TMT part B being weakly correlated with the UCSD-SOBQ, while TMT part A was not.⁶⁵

Cognition and balance

An investigation of postural and functional balance through center-of-pressure displacement and Berg Balance Scale (BBS), respectively, found moderate correlations with Stroop interference.⁶³ Multiple linear regression modelling showed associations with Stroop interference score and center-of-pressure, adjusted for other covariates (see Table 2).⁶³ In a younger COPD cohort (mean of 57 years), the MMSE was weakly correlated with BBS, and MMSE was associated with BBS through simple linear regression.⁵⁴ Moreover, another cross-sectional study using multivariate linear regression, found an association between delayed word recall and tandem stance time.⁵⁰

Cognition and hand function

In COPD patients categorized by TMT part A and TMT part B scores, grip strength was significantly higher in CN individuals.⁶⁹ Additionally, through multivariable regression, borderline impaired TMT part A scores and borderline impaired and impaired TMT part B scores were independently associated with decreased grip strength (Table 2).⁶⁹ Along with handgrip strength, cognition measured through MMSE had a moderate negative correlation with placement and turning dexterity in a hypoxemic cohort, with the dexterity correlation not being different in those with mild and moderate hypoxemia.⁷⁰

Dual tasking in COPD patients compared to healthy controls

In one study, COPD patients exhibited decreased walking velocity during both single and dual task (walking and backwards spelling) conditions compared to healthy controls,⁵¹ while another study did not report differences in gait speed in both task conditions, but did find greater stride time variability for COPD patients during dual tasking (walking and backwards counting by 3).⁵² Mixed results were also found for the Timed Up and Go (TUG) test, whereby one study reported COPD patients having a longer TUG completion time in both single and dual tasks relative to healthy controls,⁶⁰ while the other did not report a difference in single and dual task conditions for the TUG test and knee extension muscle force.⁶¹ Both studies utilized backwards counting as their cognitive task paradigm.^60,61 Regarding balance assessed through CoP displacement during dual tasking, COPD patients exhibited greater balance deficits in both single and dual tasks relative to healthy controls.⁷³

Effects of interventions on cognitive outcomes in COPD patients

Pulmonary rehabilitation (PR) resulted in variable improvements among the studies assessing specific cognitive domains.^{35,44–46,57} PR showed improvements in global cognition,^{35,38,49,55,59} attention and processing speed,^44,45,57 executive function,^35,44–46 visuospatial skills,^35,57 and language ability.⁵⁷ Among the five PR studies showing improvements in global cognition,^{35,38,49,55,59} two studies demonstrated improvements only in CI COPD patients.^38,49 All PR interventions resulted in significant improvements in physical outcomes,^{35,38,39,44–46,48,49,55,57,59} with three studies^35,38,39 reporting no difference in 6MWD post-rehabilitation between CI and CN COPD patients, while investigation³⁸ reported CN COPD patients having significantly greater post-rehabilitation 6-min stepper test (6MST) scores than CI COPD patients. Studies evaluating whether cognition is associated with PR physical improvements showed mixed results.^38,48 Improvements in MoCA scores were not associated with changes in exercise capacity as measured by 6MWD and 6MST in hospital-based PR,³⁸ while baseline MMSE scores were significantly correlated with improvements in maximum cycling effort (watts) (r = 0.46, p < 0.05) and VO₂max (r = 0.41, p < 0.05) in home-based PR.⁴⁸

Exercise interventions had variable cognitive outcomes.^37,47,68 Endurance training was shown to improve fluid intelligence,^37,47 global cognition,⁶⁸ visuospatial abilities,^37,68 working memory,⁶⁸ attention,³⁷ delayed recall,³⁷ and executive function.³⁷ Combined aerobic and resistance training resulted in greater improvements in delayed recall, fluid intelligence, and visuospatial abilities compared to aerobic training alone.³⁷

Working memory (WM) training versus sham WM training was also studied.⁷² WM refers to the short-term memory that is required to do things in the moment. Although WM span increased over 24 weeks in the intervention group, this was not reflected in improvements in cognitive test scores.⁷² Moreover, physical capacity as measured by 6MWT and Short Physical Performance Battery (SPPB) showed no improvements.⁷²

Other interventions such as behavioral modification,⁵⁸ lung volume reduction surgery,⁵⁶ oxygen (O₂) therapy,³³ amino acid⁴³ and piracetam supplementation³⁴ resulted in cognitive improvements. Moreover, all these therapies also improved physical outcomes except O₂ supplementation.^{33,34,43,56,58}

Discussion

COPD, 6MWD, and balance

Our findings indicate that CI and CN COPD patients have comparable 6MWT scores,^36,38,42,75 with studies finding no association between cognitive impairment and 6MWD.^40,62 These findings are corroborated by the low-order correlation between global^42,74 and domain-specific^65,74 cognitive test scores and 6MWD. Similarly, dyspnea scores were comparable between CI and CN COPD patients,^{35,36,40,64,74,75} with low,⁶⁵ moderate,⁵⁴ and non-significant correlations found.⁷⁴ Importantly, lower cognitive test scores were associated with impairments in balance parameters.^50,54,63

Of clinical importance, a recent meta-analysis found that COPD patients had greater deficits in their balance compared to healthy controls.⁷⁶ Nonetheless, while shorter 6MWDs are correlated with impairments in balance function,^77–79 and a 6MWD <300 m being a predictor for balance impairments as measured by the BBS and TUG,⁸⁰ the reviewed studies indicate no difference in 6MWDs between CI and CN COPD patients. Given the importance of balance in daily activities, further exploration of interventions to improve the relationship between CI and falls are required.

Potential mechanisms underlying cognitive-physical relationship

As depicted from the results, COPD patients who display decreased cognitive capacity are more likely to exhibit impairments in balance and hand function, rather than functional exercise capacity or physical conditioning as measured by the 6MWT. Our results do not reflect a lack of relationship with 6MWD, but that the relationship with cognition and 6MWD is less pronounced. One plausible mechanism is the increased cortical sensorimotor connectivity demonstrated while standing versus walking.⁸¹ This heightened cortical connectivity suggests greater attention is needed for balance and postural control, while walking may depend more on spinal neural networks.⁸¹ COPD patients exhibit reduced white matter integrity and impairments in gray matter functional connectivity⁸²; thus, CI COPD patients may lack the cortical resources to sustain adequate balance.

A regression model investigating cognitive-balance relationships demonstrated an association between better delayed word recall and increased tandem stance time.⁵⁰ The 10-word list used for delayed recall is often utilized to detect mild CI by assessing hippocampal and entorhinal cortical functions.⁸³ Poor delayed recall is associated with hippocampal^84,85 and entorhinal atrophy.^86,87 Importantly, hippocampal atrophy and its association with CI has been reported in COPD.⁸⁸ The hippocampus and entorhinal cortex receive input from the vestibular system.⁸⁹ Notably, hippocampal and entorhinal atrophy is associated with impaired vestibular function, a system important for maintaining balance.⁹⁰

Additionally, another regression model depicted poorer TMT scores (worse executive function) associated with weaker handgrip strength.⁶⁹ The prefrontal cortex (PFC) facilitates executive function,⁹¹ and PFC impairments can lead to worse motor planning and recruitment, and thereby reduced strength.^92,93

Dual tasking

Similarly, cognitive-motor dual tasking induced static balance deficits in COPD patients.⁷³ Balance⁷⁶ and postural control^94,95 are often impaired in COPD. While several factors have been implicated in balance impairments, such as age,^96,97 dyspnea,⁹⁸ inspiratory muscle weakness,⁹⁹ and lower limb muscle strength,⁹⁸ the influence of cognition has not been investigated as thoroughly. Although, a cognitive screening test was not conducted in the dual task study by Van Hove et al.,⁷³ COPD patients had lower verbal fluency task scores than healthy controls.

Impairments when performing a concurrent task may arise due to processing constraints within the brain, such as the PFC. In a single-cell recording study in monkeys, dual tasking resulted in concurrent activation of the same lateral PFC region suggesting cognitive capacity limitations.¹⁰⁰ Related to limitations in capacity, Hassan et al.⁵¹ observed that COPD patients did not increase dorsolateral PFC oxygenated hemoglobin (O₂Hb) from single to dual tasks, while healthy individuals did increase O₂Hb. Therefore, this observed ceiling effect in neural activity may be pivotal to the constraints in simultaneous processing. In addition to limited cognitive capacity, impairment has been reflected by reduced PFC automaticity (decrease in O₂Hb seen in tasks requiring less executive function) during single and dual task walking in COPD and older adults, respectively.^101,102

Pulmonary Rehabilitation

In this review, the predominant intervention to facilitate cognitive-physical improvements was PR. All PR studies found significant improvements in cognition. However, of the four studies^35,38,49,57 assessing differences in PR outcomes between CI and CN COPD patients, three^38,49,57 found cognitive improvements only in CI COPD patients. Thus, the efficacy of PR cognitive improvement may also, among other factors, rely on baseline cognition.

Notably, the physical improvements that arise from PR seem to be independent from baseline cognition, as all studies specifically evaluating PR in CI COPD patients note an improvement in physical performance.^35,38,39,49 Although, Ferrari et al.⁴⁸ did find a moderate correlation between baseline MMSE scores and improvements in exercise capacity in a minimally supervised home PR setting. While compliance was assessed, potential CI may have influenced proper completion of the training sessions in a minimally supervised setting, hence the moderate correlation between MMSE scores and exercise capacity. Furthermore, Cleutjens et al.³⁹ found that CI COPD patients had an increased rate of PR dropout compared to CN COPD patients.

Nonetheless, despite the potential risk for PR dropouts, physical improvements were observed in CI COPD, with the 6MWT being the most frequent treatment outcome. While this scoping review identified balance as a potential factor that is impaired in CI COPD patients, most PR studies included in our review did not conduct balance assessments. Of interest, a report that examined physical outcomes but not cognition before and after PR in COPD patients, found that the small improvement in BBS were not related to improvements of 6MWD.¹⁰³ Thus, including balance outcomes, along with usual exercise capacity measures, may be warranted, especially in CI COPD patients.

Aerobic and resistance training

An interesting finding regarding exercise is the enhanced cognitive benefits found in combining aerobic and resistance training versus aerobic training alone in COPD patients.³⁷ This approach is corroborated by studies of those with stroke¹⁰⁴ and dementia,¹⁰⁵ as well as a meta-analysis of healthy individuals that showed a larger effect size of combined aerobic-resistance training than aerobic training alone.¹⁰⁶

Working memory training

Cognitive training, specifically WM training, has been recently investigated in COPD patients. While van Beers et al.⁷² found an improvement in WM trained task, the improvements did not generalize to overall cognitive improvements as measured by the Cambridge Neuropsychological Test Automated Battery. Additionally, secondary outcomes measuring exercise capacity showed no improvements. A previous study investigating cognitive training in hypoxemic COPD also found no cognitive improvements relative to the control group (no cognitive training).¹⁰⁷ A review investigating cognitive training also affirms that, while cognitive training can improve the specific trained task, there may be a lack of generalizability.¹⁰⁸

Limitations

There are some limitations in this scoping review. To develop a broader descriptive scope of the differences between CI and CN COPD patients, results from independent t-tests, Mann-Whitney U tests, and correlation coefficients were included. While these results help characterize the relationship between cognition and physical performance, they cannot delineate the underlying mechanisms. Secondly, there was a large degree of heterogeneity in study designs and outcomes that prevented a meta-analysis of the interventions. Moreover, the low statistical power in many of these interventions precludes conclusions of actual treatment effects. Regarding dual task studies, the comparator groups were healthy individuals rather than CN COPD patients, thus the impact CI has on dual tasking cannot be stated. Importantly, most of the data was collected from cross-sectional studies, thus determining the causality between cognition and physical performance is not possible.

Conclusions and future directions

Limited cognitive capacity in COPD was more likely to be associated with impairments in balance, hand function, and dual tasking rather than exercise capacity. Due to the inherent limitations in study design and statistical analysis, causal mechanisms cannot be determined. Pulmonary rehabilitation was the most common treatment, which resulted in variable cognitive improvements. Given the increased incidence of falls in COPD,¹⁰⁹ and the possible relationship between cognitive impairment and balance deficits, future interventions may incorporate balance assessment in COPD patients that present with cognitive decline and impairment.

Supplemental Material

Supplemental Material - Impact of cognitive capacity on physical performance in chronic obstructive pulmonary disease patients: A scoping review

Supplemental Material for Impact of cognitive capacity on physical performance in chronic obstructive pulmonary disease patients: A scoping review by Peter Rassam, Eli M. Pazzianotto-Forti, Umi Matsumura, Ani Orchanian-Cheff, Saina Aliabadi, Manjiri Kulkarni, Rachel L. Fat Fur, Antenor Rodrigues, Daniel Langer, Dmitry Rozenberg and W Darlene Reid in Chronic Respiratory Disease

Footnotes

Authors’ contributions

PR, DR and WDR conceived and designed the study. AO-C performed the data base searches. PR, EF, UM, SA, MK, RLFF screened eligibility of titles and abstracts and PR, EF, UM, SA, MK screened for full text exclusion and abstracted data including the quality assessment for the included articles. PR wrote the initial manuscript and WDR contributed to the writing of the manuscript. PR revised the manuscript. All authors read and approved the final manuscript.

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 authors disclosed funding support from the RAMP Trust fund, Canadian Institutes of Health Research (PCS 183427), Canadian Institute of Health Research Operating Grant (PJM 179846). Dmitry Rozenberg receives research support from the Sandra Faire and Ivan Fecan Professorship in Rehabilitation Medicine.

ORCID iDs

Peter Rassam

Eli Maria Pazzianotto-Forti

Ani Orchanian-Cheff

Daniel Langer

Dmitry Rozenberg

W Darlene Reid

Supplemental Material

Supplemental material for this article is available online.

References

Szalontai

Gemes

Furak

, et al. Chronic obstructive pulmonary disease: epidemiology, biomarkers, and paving the way to lung cancer. J Clin Med 2021; 10: 2889. DOI: 10.3390/jcm10132889

Adeloye

Song

Zhu

, et al. Global, regional, and national prevalence of, and risk factors for, chronic obstructive pulmonary disease (COPD) in 2019: a systematic review and modelling analysis. Lancet Respir Med 2022; 10: 447–458. DOI: 10.1016/S2213-2600(21)00511-7

WHO . The top 10 causes of death. https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death, 2020.

Laveneziana

Guenette

Webb

, et al. New physiological insights into dyspnea and exercise intolerance in chronic obstructive pulmonary disease patients. Expert Rev Respir Med 2012; 6: 651–662. DOI: 10.1586/ers.12.70

Casanova

Cote

Marin

, et al. Distance and oxygen desaturation during the 6-min walk test as predictors of long-term mortality in patients with COPD. Chest 2008; 134: 746–752. DOI: 10.1378/chest.08-0520

Cote

Pinto-Plata

Kasprzyk

, et al. The 6-min walk distance, peak oxygen uptake, and mortality in COPD. Chest 2007; 132: 1778–1785. DOI: 10.1378/chest.07-2050

Waschki

Kirsten

Holz

, et al. Physical activity is the strongest predictor of all-cause mortality in patients with COPD: a prospective cohort study. Chest 2011; 140: 331–342. DOI: 10.1378/chest.10-2521

Cleutjens

FAHM

Janssen

DJA

Ponds

RWHM

, et al. COgnitive-pulmonary disease. Biomed Res Int 2014; 2014(697825): 697825. DOI: 10.1155/2014/697825

Andrianopoulos

Gloeckl

Vogiatzis

, et al.

Cognitive impairment in COPD: should cognitive evaluation be part of respiratory assessment?

Breathe (Sheff) 2017; 13: e1–e9. DOI: 10.1183/20734735.001417

10.

Grant

Heaton

McSweeny

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

11.

Cleutjens

Franssen

Spruit

, et al. Domain-specific cognitive impairment in patients with COPD and control subjects. Int J Chron Obstruct Pulmon Dis 2017; 12: 1–11. DOI: 10.2147/COPD.S119633

12.

Dodd

. Lung disease as a determinant of cognitive decline and dementia. Alzheimers Res Ther 2015; 7(32): 32. DOI: 10.1186/s13195-015-0116-3

13.

Schou

Ostergaard

Rasmussen

, et al. Cognitive dysfunction in patients with chronic obstructive pulmonary disease–a systematic review. Respir Med 2012; 106: 1071–1081. DOI: 10.1016/j.rmed.2012.03.013

14.

Torres-Sanchez

Rodriguez-Alzueta

Cabrera-Martos

, et al. Cognitive impairment in COPD: a systematic review. J Bras Pneumol 2015; 41: 182–190. DOI: 10.1590/S1806-37132015000004424

15.

Leone

Feys

Moumdjian

, et al. Cognitive-motor dual-task interference: a systematic review of neural correlates. Neurosci Biobehav Rev 2017; 75: 348–360. DOI: 10.1016/j.neubiorev.2017.01.010

16.

Pashler

. Dual-task interference in simple tasks: data and theory. Psychol Bull 1994; 116: 220–244. DOI: 10.1037/0033-2909.116.2.220

17.

Tombu

Jolicoeur

. Testing the predictions of the central capacity sharing model. J Exp Psychol Hum Percept Perform 2005; 31: 790–802. DOI: 10.1037/0096-1523.31.4.790

18.

Tombu

Jolicoeur

. A central capacity sharing model of dual-task performance. J Exp Psychol Hum Percept Perform 2003; 29: 3–18. DOI: 10.1037//0096-1523.29.1.3

19.

Zimprich

Martin

. Can longitudinal changes in processing speed explain longitudinal age changes in fluid intelligence? Psychol Aging 2002; 17: 690–695. DOI: 10.1037/0882-7974.17.4.690

20.

Bishnoi

Hernandez

. Dual task walking costs in older adults with mild cognitive impairment: a systematic review and meta-analysis. Aging Ment Health 2021; 25: 1618–1629. DOI: 10.1080/13607863.2020.1802576

21.

Chan

JSY

Yan

. Mild cognitive impairment affects motor control and skill learning. Rev Neurosci 2016; 27: 197–217. DOI: 10.1515/revneuro-2015-0020

22.

O'Donnell

Milne

James

, et al. Dyspnea in COPD: new mechanistic insights and management implications. Adv Ther 2020; 37: 41–60. DOI: 10.1007/s12325-019-01128-9

23.

Davenport

Vovk

. Cortical and subcortical central neural pathways in respiratory sensations. Respir Physiol Neurobiol 2009; 167: 72–86. DOI: 10.1016/j.resp.2008.10.001

24.

von Leupoldt

Farre

. The load of dyspnoea on brain and legs. Eur Respir J 2020; 56: 2001096. DOI: 10.1183/13993003.01096-2020

25.

Dodd

Getov

Jones

. Cognitive function in COPD. Eur Respir J 2010; 35: 913–922. DOI: 10.1183/09031936.00125109

26.

Sorond

Cruz-Almeida

Clark

, et al. Aging, the central nervous system, and mobility in older adults: neural mechanisms of mobility impairment. J Gerontol A Biol Sci Med Sci 2015; 70: 1526–1532. DOI: 10.1093/gerona/glv130

27.

Arksey

O’Malley

. Scoping studies: towards a methodological framework. International Journal of Social Research Methodology 2005; 8: 19–32. DOI: 10.1080/1364557032000119616

28.

Levac

Colquhoun

O'Brien

. Scoping studies: advancing the methodology. Implement Sci 2010; 5(69): 69. DOI: 10.1186/1748-5908-5-69

29.

Colquhoun

Levac

O'Brien

, et al. Scoping reviews: time for clarity in definition, methods, and reporting. J Clin Epidemiol 2014; 67: 1291–1294. DOI: 10.1016/j.jclinepi.2014.03.013

30.

Tanaka

Basoudan

Melo

, et al. Deoxygenation of inspiratory muscles during cycling, hyperpnoea and loaded breathing in health and disease: a systematic review. Clin Physiol Funct Imaging 2018; 38: 554–565. DOI: 10.1111/cpf.12473

31.

Downs

Black

. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health 1998; 52: 377–384. DOI: 10.1136/jech.52.6.377

32.

Page

McKenzie

Bossuyt

, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372: n71. DOI: 10.1136/bmj.n71

33.

Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease . Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen Therapy Trial Group. Ann Intern Med 1980; 93: 391–398. DOI: 10.7326/0003-4819-93-3-391

34.

Abumossalam

Sheta

Ahmed

, et al. Extra pulmonary boosting in chronic obstructive pulmonary disease: leverage of piracetam as an adjunctive therapy on respiratory and neuropsychiatric functions in patients with chronic obstructure pulmonary disease. The Egyptian Journal of Chest Diseases and Tuberculosis 2021; 70: 60–70. DOI: 10.4103/ejcdt.ejcdt._112_20

35.

Andrianopoulos

Gloeckl

Schneeberger

, et al. Benefits of pulmonary rehabilitation in COPD patients with mild cognitive impairment - A pilot study. Respir Med 2021; 185(106478): 106478. DOI: 10.1016/j.rmed.2021.106478

36.

Antonelli-Incalzi

Corsonello

Trojano

, et al. Correlation between cognitive impairment and dependence in hypoxemic COPD. J Clin Exp Neuropsychol 2008; 30: 141–150. DOI: 10.1080/13803390701287390

37.

Aquino

Iuliano

di Cagno

, et al. Effects of combined training vs aerobic training on cognitive functions in COPD: a randomized controlled trial. Int J Chron Obstruct Pulmon Dis 2016; 11: 711–718. DOI: 10.2147/COPD.S96663

38.

Bonnevie

Medrinal

Combret

, et al. Mid-term effects of pulmonary rehabilitation on cognitive function in people with severe chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2020; 15: 1111–1121. DOI: 10.2147/COPD.S249409

39.

Cleutjens

FAHM

Spruit

Ponds

RWHM

, et al. The impact of cognitive impairment on efficacy of pulmonary rehabilitation in patients with COPD. J Am Med Dir Assoc 2017; 18: 420–426. DOI: 10.1016/j.jamda.2016.11.016

40.

Cleutjens

FAHM

Spruit

Ponds

RWHM

, et al. Cognitive impairment and clinical characteristics in patients with chronic obstructive pulmonary disease. Chron Respir Dis 2018; 15: 91–102. DOI: 10.1177/1479972317709651

41.

Cruthirds

van der Meij

Wierzchowska-McNew

, et al. Presence or absence of skeletal muscle dysfunction in chronic obstructive pulmonary disease is associated with distinct phenotypes. Arch Bronconeumol (Engl Ed) 2021; 57: 264–272. DOI: 10.1016/j.arbres.2019.12.034

42.

Dag

Bulcun

Turkel

, et al. Factors influencing cognitive function in subjects with COPD. Respir Care 2016; 61: 1044–1050. DOI: 10.4187/respcare.04403

43.

Dal Negro

TestA

Aquilani

, et al. Essential amino acid supplementation in patients with severe COPD: a step towards home rehabilitation. Monaldi Arch Chest Dis 2012; 77: 67–75. DOI: 10.4081/monaldi.2012.154

44.

Emery

. Effects of age on physiological and psychological functioning among COPD patients in an exercise program. J Aging Health 1994; 6: 3–16. DOI: 10.1177/089826439400600101

45.

Emery

Leatherman

Burker

, et al. Psychological outcomes of a pulmonary rehabilitation program. Chest 1991; 100: 613–617. DOI: 10.1378/chest.100.3.613

46.

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: 232–240. DOI: 10.1037//0278-6133.17.3.232

47.

Etnier

Berry

. Fluid intelligence in an older COPD sample after short- or long-term exercise. Med Sci Sports Exerc 2001; 33: 1620–1628. DOI: 10.1097/00005768-200110000-00002

48.

Ferrari

Vangelista

Vedovi

, et al. Minimally supervised home rehabilitation improves exercise capacity and health status in patients with COPD. Am J Phys Med Rehabil 2004; 83: 337–343. DOI: 10.1097/01.phm.0000124437.92263.ba

49.

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): 20201121. DOI: 10.1016/j.rmed.2020.106249

50.

Gore

Blackwood

Ziccardi

. Associations between cognitive function, balance, and gait speed in community-dwelling older adults with copd. J Geriatr Phys Ther 2021: 20210729. DOI: 10.1519/JPT.0000000000000323

51.

Hassan

Campos

Kasawara

, et al. Changes in oxyhemoglobin concentration in the prefrontal cortex during cognitive-motor dual tasks in people with chronic obstructive pulmonary disease. COPD 2020; 17: 289–296. DOI: 10.1080/15412555.2020.1767561

52.

Heraud

Alexandre

Gueugnon

, et al. Impact of chronic obstructive pulmonary disease on cognitive and motor performances in dual-task walking. COPD 2018; 15: 277–282. DOI: 10.1080/15412555.2018.1469607

53.

Karpman

DePew

LeBrasseur

, et al. Determinants of gait speed in COPD. Chest 2014; 146: 104–110. DOI: 10.1378/chest.13-2017

54.

Kaygusuz

Oral Tapan

Tapan

, et al. Balance impairment and cognitive dysfunction in patients with chronic obstructive pulmonary disease under 65 years. Clin Respir J 2022; 16: 200–207. DOI: 10.1111/crj.13469

55.

Kilic

Cicek

Avci

. Comparing the effects of self-management and hospital-based pulmonary rehabilitation programs in COPD patients. Niger J Clin Pract 2021; 24: 362–368. DOI: 10.4103/njcp.njcp._165_20

56.

Kozora

Emery

Ellison

, et al. Improved neurobehavioral functioning in emphysema patients following lung volume reduction surgery compared with medical therapy. Chest 2005; 128: 2653–2663. DOI: 10.1378/chest.128.4.2653

57.

Kozora

Tran

Make

. Neurobehavioral improvement after brief rehabilitation in patients with chronic obstructive pulmonary disease. J Cardiopulm Rehabil 2002; 22: 426–430. DOI: 10.1097/00008483-200211000-00008

58.

Lavoie

Sedeno

Hamilton

, et al. Behavioural interventions targeting physical activity improve psychocognitive outcomes in COPD. ERJ Open Res 2019; 5: 00013.02019. DOI: 10.1183/23120541.00013-2019

59.

Liu

Yang

Wang

, et al. Study on adjuvant medication for patients with mild cognitive impairment based on vr technology and health education. Contrast Media Mol Imaging 2021; 2021(1187704): 1187704. DOI: 10.1155/2021/1187704

60.

Morlino

Balbi

Guglielmetti

, et al. Gait abnormalities of COPD are not directly related to respiratory function. Gait Posture 2017; 58: 352–357. DOI: 10.1016/j.gaitpost.2017.08.020

61.

Ozsoy

Kararti

, et al. Cognitive and motor performances in dual task in patients with chronic obstructive pulmonary disease: a comparative study. Ir J Med Sci 2021; 190: 723–730. DOI: 10.1007/s11845-020-02357-6

62.

Ozyemisci-Taskiran

Bozkurt

Kokturk

, et al.

Is there any association between cognitive status and functional capacity during exacerbation of chronic obstructive pulmonary disease?

Chron Respir Dis 2015; 12: 247–255. DOI: 10.1177/1479972315589748

63.

Park

Deutz

NEP

Cruthirds

, et al. Risk factors for postural and functional balance impairment in patients with chronic obstructive pulmonary disease. J Clin Med 2020; 9: 609. DOI: 10.3390/jcm9020609

64.

Park

. Trajectories of change in cognitive function in people with chronic obstructive pulmonary disease. J Clin Nurs 2018; 27: 1529–1542. DOI: 10.1111/jocn.14285

65.

Park

Larson

. Cognitive function as measured by trail making test in patients with COPD. West J Nurs Res 2015; 37: 236–256. DOI: 10.1177/0193945914530520

66.

Randeep

Archana

Malay

, et al. Cognitive domain impaired in COPD patients and its correlation with exercise capacity in COPD patients. Research Journal of Pharmaceutical, Biological and Chemical Sciences 2019; 10: 1132–1137.

67.

Roncero

Campuzano

Quintano

, et al. Cognitive status among patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2016; 11: 543–551. DOI: 10.2147/COPD.S100850

68.

Rosenstein

Smyrnova

Rizk

, et al. Short- and long-term changes in cognitive function after exercise-based rehabilitation in people with COPD: a pilot study. Canadian Journal of Respiratory, Critical Care, and Sleep Medicine 2021; 5: 300–309. DOI: 10.1080/24745332.2020.1790060

69.

Schure

Borson

Nguyen

, et al. Associations of cognition with physical functioning and health-related quality of life among COPD patients. Respir Med 2016; 114: 46–52. DOI: 10.1016/j.rmed.2016.03.005

70.

Soysal Tomruk

Ozalevli

Dizdar

, et al. Determination of the relationship between cognitive function and hand dexterity in patients with chronic obstructive pulmonary disease (COPD): a cross-sectional study. Physiother Theory Pract 2015; 31: 313–317. DOI: 10.3109/09593985.2015.1004768

71.

Tudorache

Fildan

Frandes

, et al. Aging and extrapulmonary effects of chronic obstructive pulmonary disease. Clin Interv Aging 2017; 12: 1281–1287. DOI: 10.2147/CIA.S145002

72.

van Beers

Mount

Houben

, et al. Working memory training efficacy in COPD: the randomised, double-blind, placebo-controlled Cogtrain trial. ERJ Open Res 2021; 7: 00475.02021. DOI: 10.1183/23120541.00475-2021

73.

Van Hove

Cebolla

Andrianopoulos

, et al. The influence of cognitive load on static balance in chronic obstructive pulmonary disease patients. Clin Respir J 2021; 15: 351–357. DOI: 10.1111/crj.13307

74.

Yazar

Aydin

Gunluoglu

, et al. Clinical effects of cognitive impairment in patients with chronic obstructive pulmonary disease. Chron Respir Dis 2018; 15: 306–314. DOI: 10.1177/1479972317743757

75.

Yohannes

N Eakin

Holbrook

, et al. Association of mild cognitive impairment and characteristic of COPD and overall health status in a cohort study. Expert Rev Respir Med 2021; 15: 153–159. DOI: 10.1080/17476348.2021.1838278

76.

Loughran

Atkinson

Beauchamp

, et al. Balance impairment in individuals with COPD: a systematic review with meta-analysis. Thorax 2020; 75: 539–546. DOI: 10.1136/thoraxjnl-2019-213608

77.

de Castro

Ribeiro

Mesquita

, et al. Static and functional balance in individuals with COPD: comparison with healthy controls and differences according to sex and disease severity. Respir Care 2016; 61: 1488–1496. DOI: 10.4187/respcare.04749

78.

Iwakura

Okura

Shibata

, et al. Relationship between balance and physical activity measured by an activity monitor in elderly COPD patients. Int J Chron Obstruct Pulmon Dis 2016; 11: 1505–1514. DOI: 10.2147/COPD.S107936

79.

Ozalevli

Ilgin

Narin

, et al. Association between disease-related factors and balance and falls among the elderly with COPD: a cross-sectional study. Aging Clin Exp Res 2011; 23: 372–377. DOI: 10.1007/BF03325235

80.

Liwsrisakun

Pothirat

Chaiwong

, et al. Exercise Performance as a Predictor for Balance Impairment in COPD Patients. Medicina (Kaunas) 2019; 55: 171. DOI: 10.3390/medicina55050171

81.

Lau

Gwin

Ferris

. Walking reduces sensorimotor network connectivity compared to standing. J Neuroeng Rehabil 2014; 11(14): 14. DOI: 10.1186/1743-0003-11-14

82.

Dodd

Chung

van den Broek

, et al. Brain structure and function in chronic obstructive pulmonary disease: a multimodal cranial magnetic resonance imaging study. Am J Respir Crit Care Med 2012; 186: 240–245. DOI: 10.1164/rccm.201202-0355OC

83.

Shankle

Romney

Hara

, et al. Methods to improve the detection of mild cognitive impairment. Proc Natl Acad Sci U S A 2005; 102: 4919–4924. DOI: 10.1073/pnas.0501157102

84.

Huang

Zhou

Liu

, et al. High fall risk associated with memory deficit and brain lobes atrophy among elderly with amnestic mild cognitive impairment and mild alzheimer's disease. Front Neurosci 2022; 16(896437): 896437. DOI: 10.3389/fnins.2022.896437

85.

Kilpatrick

Murrie

Cook

, et al. Degree of left hippocampal atrophy correlates with severity of neuropsychological deficits. Seizure 1997; 6: 213–218. DOI: 10.1016/s1059-1311(97)80008-8

86.

Rodrigue

Raz

. Shrinkage of the entorhinal cortex over five years predicts memory performance in healthy adults. J Neurosci 2004; 24: 956–963. DOI: 10.1523/JNEUROSCI.4166-03.2004

87.

Saloner

Casaletto

Marx

, et al. Performance on a 1-week delayed recall task is associated with medial temporal lobe structures in neurologically normal older adults. Clin Neuropsychol 2018; 32: 456–467. DOI: 10.1080/13854046.2017.1370134

88.

Fei

. The unique alterations of hippocampus and cognitive impairment in chronic obstructive pulmonary disease. Respir Res 2013; 14(140): 140. DOI: 10.1186/1465-9921-14-140

89.

Hitier

Besnard

Smith

. Vestibular pathways involved in cognition. Front Integr Neurosci 2014; 8(59): 59. DOI: 10.3389/fnint.2014.00059

90.

Jacob

Tward

Resnick

, et al. Vestibular function and cortical and sub-cortical alterations in an aging population. Heliyon 2020; 6: e04728. DOI: 10.1016/j.heliyon.2020.e04728

91.

Koechlin

Summerfield

. An information theoretical approach to prefrontal executive function. Trends Cogn Sci 2007; 11: 229–235. DOI: 10.1016/j.tics.2007.04.005

92.

McGrath

Vincent

Hackney

, et al. The longitudinal associations of handgrip strength and cognitive function in aging Americans. J Am Med Dir Assoc 2020; 21: 634–639. DOI: 10.1016/j.jamda.2019.08.032

93.

Kwon

Yoon

. Sarcopenia: neurological point of view. J Bone Metab 2017; 24: 83–89. DOI: 10.11005/jbm.2017.24.2.83

94.

Porto

Castro

AAM

Schmidt

VGS

, et al. Postural control in chronic obstructive pulmonary disease: a systematic review. Int J Chron Obstruct Pulmon Dis 2015; 10: 1233–1239. DOI: 10.2147/COPD.S63955

95.

Roig

Eng

Macintyre

, et al. Postural control is impaired in people with COPD: an observational study. Physiother Can 2011; 63: 423–431. DOI: 10.3138/ptc.2010-32

96.

Alsubheen

Beauchamp

Ellerton

, et al. Age and sex differences in balance outcomes among individuals with chronic obstructive pulmonary disease (COPD) at risk of falls. COPD 2022; 19: 166–173. DOI: 10.1080/15412555.2022.2038120

97.

Boffino

Pereira

ACAC

Coelho

, et al. Age and disease have a distinct influence on postural balance of patients with COPD. COPD 2019; 16: 246–253. DOI: 10.1080/15412555.2019.1634683

98.

Oliveira

Lee

McGinley

, et al. Balance and falls in acute exacerbation of chronic obstructive pulmonary disease: a prospective study. COPD 2017; 14: 518–525. DOI: 10.1080/15412555.2017.1342232

99.

Janssens

Brumagne

McConnell

, et al. Proprioceptive changes impair balance control in individuals with chronic obstructive pulmonary disease. PLoS One 2013; 8: e57949. DOI: 10.1371/journal.pone.0057949

100.

Watanabe

Funahashi

. Neural mechanisms of dual-task interference and cognitive capacity limitation in the prefrontal cortex. Nat Neurosci 2014; 17: 601–611. DOI: 10.1038/nn.3667

101.

Hassan

Bonetti

Kasawara

, et al. Decreased automaticity contributes to dual task decrements in older compared to younger adults. Eur J Appl Physiol 2022; 122: 965–974.

102.

Hassan

Bonetti

Kasawara

, et al. Loss of neural automaticity contributes to slower walking in COPD patients. Cells 2022; 11: 1606.

103.

Beauchamp

O'Hoski

Goldstein

, et al. Effect of pulmonary rehabilitation on balance in persons with chronic obstructive pulmonary disease. Arch Phys Med Rehabil 2010; 91: 1460–1465. DOI: 10.1016/j.apmr.2010.06.021

104.

Marzolini

McIlroy

, et al. The effects of an aerobic and resistance exercise training program on cognition following stroke. Neurorehabil Neural Repair 2013; 27: 392–402. DOI: 10.1177/1545968312465192

105.

Bossers

WJR

van der Woude

LHV

Boersma

, et al. A 9-week aerobic and strength training program improves cognitive and motor function in patients with dementia: a randomized, controlled trial. Am J Geriatr Psychiatry 2015; 23: 1106–1116. DOI: 10.1016/j.jagp.2014.12.191

106.

Colcombe

Kramer

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

107.

Incalzi

Corsonello

Trojano

, et al. Cognitive training is ineffective in hypoxemic COPD: a six-month randomized controlled trial. Rejuvenation Res 2008; 11: 239–250. DOI: 10.1089/rej.2007.0607

108.

Sala

Gobet

. Cognitive training does not enhance general cognition. Trends Cogn Sci 2019; 23: 9–20. DOI: 10.1016/j.tics.2018.10.004

109.

Roig

Eng

MacIntyre

, et al. Falls in people with chronic obstructive pulmonary disease: an observational cohort study. Respir Med 2011; 105: 461–469. DOI: 10.1016/j.rmed.2010.08.015

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.52 MB