Outcomes of the effect of exercise on cognitive function in patients with depression: A meta-analysis

Table 1 PICOS framework for the intervention effect of exercise on cognitive function in patients with depression

PICOS	Content
Population	Patients with depression: Meet any of the diagnostic criteria of the International Classification of Disease and the Diagnostic and Statistical Manual of Mental Disorders
Intervention	Exercise or exercise in addition to the control group intervention
Comparison	Standard treatment, daily activities, and stretching exercises, etc.
Outcome	All indicators related to cognitive function
Study design	Randomized controlled trials

Table 2 Retrieval strategies for each database

Database	Retrieval strategies
Cochrane and PubMed	#1“Exercise”[Mesh] OR “Aerobic exercise” [Title/Abstract] OR “Resistance exercise”[Title/Abstract] OR “High-intensity interval” [Title/Abstract] OR “Yoga” [Title/Abstract] OR “Dance” [Title/Abstract] OR “Taichi” [Title/Abstract] OR “Baduanjin” [Title/Abstract] OR “Wuqinxi” [Title/Abstract] OR “Yijinjing” [Title/Abstract] OR “Walking” [Title/Abstract] OR “Physical and mental exercise” [Title/Abstract]; #2“Depression”[Mesh] OR “Depressive disorder”[Title/Abstract] OR “Depressive symptom” [Title/Abstract] OR “Emotional depression” [Title/Abstract] OR “Depressive neurosis” [Title/Abstract] OR “Endogenous depression” [Title/Abstract] OR “Deurotic depression” [Title/Abstract] OR “Unipolar depression” [Title/Abstract]; #3“Cognition”[Mesh] OR“Cognitive performance”[Title/Abstract] OR“Executive function”[Title/Abstract] OR“Inhibition”[Title/Abstract] OR“Working memory”[Title/Abstract] OR“Shifiting”[Title/Abstract]; #4Randomized controlled trial[Publication Type] OR “Randomized” [Title/Abstract] OR “controlled”[Title/Abstract] OR “Trial” [Title/Abstract]; #5 #1 AND #2 AND #3 AND #4
Embase	#1 “Exercise”[exp] OR “Aerobic exercise”[ab,ti] OR “Resistance exercise”[ab,ti] OR “High-intensity interval” [ab,ti] OR “Yoga” [ab,ti] OR “Dance” [ab,ti] OR “Taichi” [ab,ti] OR “Baduanjin” [ab,ti] OR “Wuqinxi” [ab,ti] OR “Yijinjing” [ab,ti] OR “Walking” [ab,ti] OR “Physical and mental exercise” [ab,ti]; #2 “Depression”[exp] OR “Depressive disorder” [ab,ti] OR “Depressive symptom” [ab,ti] OR “Emotional depression” [ab,ti] OR “Depressive neurosis” [ab,ti] OR “Endogenous depression” [ab,ti] OR “Deurotic depression” [ab,ti] OR “Unipolar depression” [ab,ti]; #3 “Cognition” [exp] OR“Executive function” [ab,ti] OR “Cognitive performance” [ab,ti] OR “Cognitive” [ab,ti] OR “Working memory” [ab,ti] OR “Shifiting” [ab,ti] OR “Inhibition” [ab,ti]; #4 “Randomized controlled trial” [exp] OR “Randomized” [ab,ti] OR “Controlled” [ab,ti] OR “Trial” [ab,ti]; #5 #1 AND #2 AND #3 AND #4
Web of Science	#1 TS = ( “Exercise” OR “Aerobic exercise” OR “Resistance exercise” OR “High-intensity interval” OR “Yoga” OR “Dance” OR “Taichi” OR “Baduanjin” OR “Wuqinxi” OR “Yijinjing” OR “Walking” OR “Physical and mental exercise”); #2 TS = (“Depression” OR “Depressive disorder” OR “Depressive symptom” OR “Emotional depression” OR “Depressive neurosis” OR “Endogenous depression” OR “Deurotic depression” OR “Unipolar depression”); #3 TS = (“Cognition” OR “Cognitive performance” OR “Inhibition” OR “Working memory” OR “Shifiting” OR “Executive function”) #4 TS = ( “Randomized controlled trial” OR “Randomized” OR “Controlled” OR “Trial”); #5 #1 AND #2 AND #3 AND #4
CNKI	(Exercise + Physical education + Taijiquan + Baduanjin + Wuqinxi + Walking + Jogging + Strength Training + Aerobic Exercise) AND (Depression) AND (Memory + Working Memory + Cognition + Executive Function), core journal
Wanfang and China Biomedical	(Exercise OR Physical education OR Taichi OR Baduanjin OR Wuqinxi OR Walking OR Jogging OR Strength training OR Aerobic exercise) and (Depression) and (Memory OR Working memory OR Cognition OR Executive function), core journal

Table 3 Characteristics of the literature included

Ref.	Country	Depression level	Sample size	Age	Intervention		Exercise intensity	Outcome indicators
					Experimental group	Control group
Buschert et al[6]	Germany	Moderate	18/20	47.27 ± 6.84; 47.47 ± 8.47	Aerobic exercise, 30 minutes, 2-3 times/week, 3-4 weeks	Occupational or art therapy	85% HRmax/moderate to high intensity	TAP
Hoffman et al[20]	United States	Mild-moderate	104/49	51.7 ± 7.6	Aerobic exercise, 3 times/week, 16 weeks	Placebo	70%-85% HRR/moderate to high intensity	Digit Span, Stroop, digit symbol subtest
Imboden et al[7]	Switzerland	Moderate-severe	22/20	41.3 ± 9.2; 38.3 ± 13.4	Aerobic exercise, 45 minutes, 3 times/week, 6 weeks	Stretching exercises	60%-75% HRmax/moderate intensity	Go-NoGo, TAP
Khatri et al[21]	United States	Mild-severe	42/42	56.73 ± 6.45	Aerobic exercise, 45 minutes, 3 times/week, 16 weeks	Sertraline	70%-85% HRR/moderate to high intensity	Digit Span, TMT-A/B, stroop, digit symbol
Krogh et al[22]	Denmark	Mild-moderate	47/48/42	41.98 ± 8.7; 38.1 ± 9.0; 36.7 ± 8.7	Aerobics, strength exercises, 90 minutes, 2 times/week, 16 weeks	Relaxation exercises	50%-75% R, 70%-89% HRmax/moderate to high intensity	Digit Span, Subtracting Serial Sevens, TMT-A/B, Digit Symbol
Lavretsky et al[19]	United States	Moderate-severe	36/37	69.1 ± 7; 72 ± 7.4	Tai chi, 120 minutes, 1 times/week, 10 weeks	health education	Low intensity	TMT-A
Olson et al[23]	United States	Moderate	15/15	21.0 ± 1.9; 21.2 ± 2.2	Aerobic exercise, 45 minutes, 3 times/week, 8 weeks	Stretching exercises	40%-65% HRR/moderate intensity	Flanker
Sharma et al[25]	India	Not specified	15/15	31.87 ± 8.78; 31.67 ± 8.46	Yoga in combination with standard treatment, 30 minutes, 3 times/week, 8 weeks	Standard treatment	Low intensity	LCT, TMT-A/B, Digit Span
Zhang et al[26]	China	Mild-severe	20/19	47.2 ± 6.99/54.16 ± 6.09	Taichi, 90 minutes, 2 times/week, 12 weeks	Daily life	Low intensity	Stroop
Krogh et al[18]	Denmark	Mild-moderate	56/59	39.7 ± 11.3; 43.4 ± 11.2	Aerobic exercise, 45 minutes, 3 times/week, 12 weeks	Stretching exercise	65%-80% VO2max/moderate to high intensity	TMT-A/B, troop, Buscher's SRT, RCFT, Digit Span, Subtracting Series Seven, Digit Symbol Test
Krogh et al[27]	Denmark	Mild-moderate	41/38	38.9 ± 11.7; 43.8 ± 12.2	Aerobic exercise, 45 minutes, 3 times/week, 12 weeks	Stretching exercise	80% HRmax/moderate to high intensity	RCFT
Brush et al[24]	United States	Mild-severe	35/31	20.26 ± 2.84; 20.19 ± 1.78	Aerobic exercise, 45 minutes, 3 times/week, 8 weeks	Stretching exercise	40%-65% HRR/moderate intensity	Flanker
Luttenberger et al[17]	Germany	Mild	22/25	42.71 ± 11.88; 44.96 ± 12.08	Indoor climbing, 180 minutes, 1 times/week, 8 weeks	Waiting group	Not specified	Attention Test d2-R
Chan et al[28]	China	Not specified	17/16	47.06 ± 9.54; 45.44 ± 8.25	Zen Martial Arts Medication, 90 minutes, 1 times/week, 10 weeks	Waiting group	Not specified	DVT
Kerr[29]	Lithuania	Moderate	39/13	54.1 ± 18.3; 55.1 ± 16.5	Aerobic exercise combined with medication treatment, strength training combined with medication treatment, 45 minutes, 3 times/week, 4 weeks	Medication treatment	Moderate intensity	Go-NoGo, Simple Reaction Time, Two Choice Reaction Time
Chen et al[30]	China	Remission phase	63/32	30.3 ± 7.5; 32.7 ± 6.5	Aerobic exercise, 30-60 minutes, 3 days/week, 16 weeks	Medication treatment	64%-76% HRmax/moderate intensity	TMT-A/B, CPT, Digit Span
Zheng et al[31]	China	Not specified	30/30	37.5 ± 9.12; 35.17 ± 5.93	Aerobic exercise combined with standard treatment, 60 minutes, 5 days/week, 4 weeks	Standard treatment	Moderate intensity	RBANS

TMT-A/B: The Trail Making Test (part A and B); TAP: Testbat terie zur Aufmerksamkeitsprüfung; Digit Span: Digit Span Subtest from the WAIS-R; Digit Symbol Subtest: Digit Symbol Subtest from the Wechsler Adult Intelligence Scale-Revised; LCT: Letter Cancellation Test; CPT: Continuous Performance Test; Buscher's SRT: Buschke Selective Reminding Test; RCFT: Rey’s Complex Figure Test; DVT: Digit Vigilance Test; RBANS: Repeatable Battery for the Assessment of Neuropsychological Status; HRmax: Maximal Heart Rate; HHR: Heart Rate Reserve; VO₂max: Maximal oxygen uptake; RM: Repetition maximum.

Table 4 Subgroup analysis of the effect of exercise on attention in depression patients

Moderating variables	I2	n	Hedges’s, 95%CI	P value
Exercise type
Aerobic exercise	57.44	16	0.21, 0.03-0.40	0.02
Strength training	53.34	5	0.31, -0.05-0.68	0.09
Mind-body exercise and others	0.0	6	0.13, -0.14-0.40	0.36
Single exercise session duration
30-60 minutes	43.1	21	0.27, 0.11-0.42	0.00
> 60 minutes	0	6	0.03, -0.14-0.20	0.70
Exercise program duration
3-12 weeks	0	17	0.23, 0.06-0.40	0.01
13-16 weeks	67.77	10	0.18, -0.06-0.42	0.15
Exercise frequency
1 day/week	0.32	2	0.30, -0.14-0.73	0.18
2 days/week	0	4	-0.02, -0.20-0.17	0.87
3 days/week	49.48	19	0.27, 0.10-0.44	0.00
2-3 days/week	80.43	2	0.23, -0.91-1.37	0.69
Exercise intensity
Low	0	4	0.02, -0.33-0.37	0.92
Moderate	0	10	0.53, 0.373-0.68	0.00
Moderate-high	0	11	-0.03, -0.16-0.10	0.67
Not specified	0.32	2	0.30, -0.14-0.73	0.18

Table 5 Quality assessment of outcome level

Outcome indicators	RCTs/item	Quality assessment of evidence					Number of events/sample size		Relative effect size	Quality
		Limitations	Inconsistency	Indirectness	Imprecision	Publication bias	Intervention group	Control group
Attention	22	Downgrade 1 level (A)	Downgrade 1 level (B)	No downgrade	No downgrade	No downgrade	877	877	0.21 (0.07, 0.34)	Low
Executive function	16	Downgrade 1 level (A)	Downgrade 1 level (C)	Downgrade 1 level (D)	No downgrade	No downgrade	521	464	0.11 (-0.11, 0.32)	Very low
Information processing speed	13	Downgrade 1 level (A)	Downgrade 1 level (B)	No downgrade	No downgrade	No downgrade	697	647	0.14 (0.04, 0.25)	Low
Memory	27	Downgrade1 level (A)	Downgrade 1 level (B)	No downgrade	No downgrade	No downgrade	1229	1124	0.08 (0.00, 0.16)	Low

RCT: Randomized controlled trial; A: Most studies did not perform allocation concealment and blinding assessment; B: Some studies did not differentiate the severity of depression in patients; C: High heterogeneity between studies; D: The assessment tools for executive function were not finely included.