A summary of the evidence and evaluation of the effectiveness of nonpharmacological interventions for mild cognitive impairment

AMSTAR 2	Wu and Sun 2017⁴⁰	Hardman et al. 2016⁴¹	Liu et al. 2016⁴²	Panzaetal.2015⁴³	van de Rest et al. 2015⁴⁴	Li et al. 2014⁴⁵	Singh et al. 2014⁴⁶
Q1	√	√	√	√	√	√	√
Q2	×	×	×	×	×	×	√
Q3	×	×	×	×	×	×	×
Q4	≠	√	≠	≠	≠	≠	√
Q5	√	×	√	×	√	√	√
Q6	√	×	√	×	√	√	√
Q7	√		√	√	√	√	√
Q8	√	√	√	√	√	√	√
Q9	√	×	×	×	×	√	√
Q10	×	×	×	×	×	×	×
Q11	√	—	√	—	—	√	√
Q12	√	—	√	—	—	√	√
Q13	√	√	√	×	√	√	√
Q14	√	√	√	×	√	√	√
Q15	√	—	√	—	—	√	√
Q16	√	√	×	√	√	√	√
Systematically evaluate the overall quality level	moderate	low	low	very low	low	moderate	moderate

Assessment of the methodological quality of systematic reviews (SRs) of exercise interventions.

AMSTAR 2	Wang et al. 2019¹⁶	Loprinzi et al. 2019"	Song et al. 2018¹⁸	Lam et al. 2019⁹	Barreto et al. 2018²⁰	Cammisuli et al. 2017²¹	Zheng et al. 2017²²	Guure et al. 2017²³	Quan et al. 2016²⁴	Zheng et al. 2016²⁵	Cai and Abrahamson 2015 ²⁶	Ströhle et al. 2015²⁷	Wang et al. 2014²⁸	Öhman et al. 2014²⁹
Q1	√	√	√	√	√	√	√	√	√	√	√	√	√	√
Q2	×	×	×	×	√	×	×	×	×	√	×	√	×	×
Q3	×	×	×	×	×	×	×	×	×	×	×	×	×	×
Q4	√			√	√	√				√	√	√		√
Q5	√	√	√	√	√	√			√	√	×	√	√	√
Q6	√	√	√	×	√	√	√	√	√	√	×	√	√	√
Q7	√	√	√	√	×	√	×	×	√	√	√	√	√	√
Q8	√	√	√	√	√	√	√	×	√	√	√	√	√	√
Q9	√	√	√	√	√	√	×	√	√	√	×	√	√	√
Q10	×	×	×	×	×	×	×	×	×	×	×	×	×	×
Q11	√	√	√	√	—	—	—	—	√	√	—	√	√	—
Q12	√	√	√	√	—	—	—	—	×	√	—	√	√	—
Q13	√	√	√	√					√	√		√	√
Q14	√	×	√	√					√	√		√	√
Q15	√	√	√	√	–	–	–	–	√	√	–	√	√	–
Q16	√	√	×	√			×		√	√	×	√	√
Systematically the overall quality evaluate level	moderate	moderate	moderate	moderate	moderate	moderate	low	low	moderate	moderate	very low	moderate	moderate	moderate

A summary of the characteristics of systematic reviews (SRs) of acupuncture and detailed characteristics derived from the full data abstraction.

Articles	Study (sample size)	Intervention	Control	Treatment time	Frequency	Key findings	Safety
Deng and Wang 2017³⁶	5 (568)	Acupuncture	Nimodipine	8 weeks	30 min/time	MMSE (3RCT): MD=0.99, [0.71-1.28], P<0.01	3 RCT reported the safety of acupuncture, 2 RCT adverse reactions may occur in the area of acupuncture, 1 RCT may appear megrim; another 1 RCT mention of gastrointestinal reactions and minor headaches in the nimodipine group
		Acupuncture	Nimodipine	8 weeks	3 times/week	Picture cognition (2RCT): MD = 2.12, [1.48-2.75], P<0.01
		Acupuncture + Nimodipine	Nimodipine	8 weeks	30 min/time 3 times/week	MMSE (2RCT): MD = 1.09, [0.29-1.89], P<0.01
Shuai et al.2016³⁷	18 (1095)	Acupuncture + medicine (Nimodipine, Duxil, Donepezil, Aniracetam)	Single medication (Nimodipine, Duxil, Donepezil, Aniracetam)	4-24 weeks	30-50 min/time	MMSE(12RCT): MD = 1.73, [1.28-2.18], P<0.00001	4 RCT reported security, 3 RCT mentioned bleeding reaction, 1RCT mention that intervention group and control group all vomiting
Shuai et al.2016³⁷	18 (1095)			4-24 weeks	4-6 times/week	ADL (6RCT): MD=5.63, [4.40-6.87],P<0.001
Mai and Zheng 2015³⁸	5 (565)	electric scalp acupuncture	Nimodipine	8 weeks	30 min/time 6 times/week	MMSE(3RCT): MD = 1.33, [0.85-1.82], P<0.0001	3 RCT mention causing headaches dizziness, bleeding, motion sickness, Subcutaneous ecchymosis, 1 RCT report no reaction, 1RCT unreported
Mai and Zheng 2015³⁸	5 (565)	cluster needling of scalp acupuncture + cognitive training	cognitive training	8 weeks	30 min/time 6 times/week	MoCA(2RCT): MD = 2.12, [0.78-3.47], P = 0.0002
Hu et al. 2014³⁹	14 (1052)	Acupuncture + Nimodipine	Nimodipine	8-9weeks	30 min/time 3-4 times/week	MMSE(6RCT): MD = 1.19, [0.67-1.70], P<0.00001	5/14 RCT reported security, there were 240 cases in the acupuncture group, reported a total of 6 cases of fainting during acupunctures ecchymosis and 3 cases of fainting during acupuncture
Hu et al. 2014³⁹	14 (1052)	Acupuncture + Aricept	Aricept	4-6weeks	30 min/time 6 times/week	MMSE (2RCT): MD=0.70, [0.24-1.17], P =0.003

Basic characteristics of the included guideline.

Study	Nation	Development organization	Published, updated times	Guideline type	References	Recommendation	Grade
AAN, 2017²	America	American Academy of Neurology	2017 (update)	clinical practice guideline	103	In patients with MCI, treatment with exercise training for 6 months is likely to improve cognitive function^10,11	moderate confidence
						There is insufficient evidence to support or refute the use of any individual cognitive intervention ¹²	very low confidence
						When various cognitive interventions are considered as a group, for patients with MCI, cognitive interventions may improve select measures of cognitive function ¹²	low confidence
						In patients with MCI, there is insufficient evidence to support or refute the use of homocysteine lowering therapies in patients with MCI ¹³	very low confidence
						In patients with MCI, use of vitamin E 2,000 IU daily is possibly ineffective for reducing progression to AD ¹⁴	low confidence
						In patients with MCI, combined use of oral vitamin E 300 mg and vitamin C 400 mg daily over 12 months is of uncertain efficacy ¹⁵	very low confidence

A summary of the characteristics of SRs analyzing cognitive interventions and detailed characteristics obtained from the full data abstraction.

Articles	Study (sample size)	Intervention groups	Control groups	Time	Frequency	Outcome	Main conclusions
Wang 2019³⁰	21 (1470)	cognitive Intervention	blank controls/conventional therapy	—	—	MoCA	Cognitive intervention can effectively improve MCI cognitive function
Zhao et al. 2018³¹	11 (1069)	cognitive training	conventional health education	4-48 weeks	—	MMSE, ADL, MoCA	Cognitive training can effectively improve MCI cognitive function
Yang et al. 2017³²	27 (2177)	memory training/rehabilitation is conducted individually or in groups	blank controls/conventional therapy	4-9 weeks	30-120 min/time, 3-36 times (70%<10 times)	learning, memory function, immediate response, delayed response, overall cognitive function	Memory training has medium to high benefits for learning, memory, subjective memory, moderate benefits for delayed response and global cognitive function, low benefit for immediate reaction and no obvious effect for recognition
Le et al. 2017³³	13(692)	conventional therapy + computerized cognitive function training	conventional therapy + conventional cognitive function training	3-12weeks	30-45 min/time, 5-7 times/week	immediate effects, different cognitive domains (memory, orientation, attention)	Short-term computerized cognitive training can improve patients' cognitive function; computerized cognitive function training was better than control group in terms of directional ability and attention improvement in different cognitive domains
Chandler et al. 2016³⁴	6 (224)	computerized cognitive function training	conventional therapy /conventional cognitive function training	2-36 weeks an average of 25.5 h (6-130h)	—	memory function	Computerized cognitive training could not improve MCI memory function.
Hill et al. 2016³⁵	17 (686)	computerized cognitive training	blank controls/conventional therapy	4h +	—	global cognition, verbal fluency, working memory, attention	Computer cognitive function training can improve MCI patients' global cognition, and it has significant effects on different cognitive domains (language learning, language memory, working memory, attention)

Assessment of the methodological quality of systematic reviews (SRs) examining cognitive interventions.

AMSTAR 2	Wang 2019³⁰	Zhao et al. 2018³¹	Yang et al. 2017³²	Le et al. 2017³³	Chandler et al. 2016³⁴	Hill et al. 2016³⁵
Q1	√	√	√	√	√	√
Q2	×	×	×	×	√	√
Q3	×	×	×	×	×	×
Q4	≠	≠	√	√	≠	√
Q5	√	√	√	√	√	√
Q6	√	√	√	√	√	√
Q7	√	√	√	√	√	√
Q8	≠	√	√	√	√	√
Q9	√	√	√	√	√	√
Q10	×	×	×	×	×	×
Q11	√	×	——	√	——	√
Q12	×	×	——	×	——	√
Q13	×	×	√	×	√	√
Q14	×	×	√	√	√	√
Q15	×	×	——	√	——	√
Q16	×	×	×	×	√	√
Systematically evaluate the overall quality level	very low	very low	low	low	moderate	moderate

Assessment of the methodological quality of systematic reviews (SRs) evaluating acupuncture.

AMSTAR 2	Deng and Wang 2017³⁶	Shuai et al. 2016³⁷	Mai and Zheng 2015³⁸	Hu et al. 2014³⁹
Q1	√	√	√	√
Q2	×	×	×	×
Q3	×	×	×	×
Q4	√	≠	≠	√
Q5	√	×	×	×
Q6	√	√	√	√
Q7	√	√	√	√
Q8	√	√	√	√
Q9	√	√	√	√
Q10	×	×	×	×
Q11	√	√	√	√
Q12	×	×	×	×
Q13	√	×	×	×
Q14	√	√	√	√
Q15	√	√	√	√
Q16	√	√	×	×
Systematically evaluate the overall quality level	moderate	low	low	low

Summary of the characteristics of systematic reviews (SRs) assessing exercise interventions and detailed characteristics obtained from the full data abstraction.

Articles	Study (sample size)	Research design type	Intervention group/(exposure section)	Intervention frequency/time	Control group (unexposed group)	Outcome	Main conclusions
Wang et al. 2019¹⁶	18 (1364)	RCT	aerobic exercise, resistance exercise, mind-body exercise	30-90 min/time; 1-5 times/week; 6-12 weeks	health education/placebo	MMSE, MoCA, ADAS-Cog	Four exercise types all had significant benefits compared to the control, and resistance exercises outperformed mind-body exercises.
Loprinzi et al. 2019"	6 (355)	RCT	exercise intervention	30-50 min/time; 2-4 times/week; 2-6 months	regular exercise	short term memory, long term memory	Exercise may help to improve MCI memory function
Song et al. 2018¹⁸	13 (956)	RCT	aerobic exercise, resistance exercise, multi-mode exercise	30-60 min/time; 1-4 times/week; 3-12 months	regular exercise/placebo	global cognitive function, memory (short term memory, long term memory), executive function	Physical exercise can improve global cognitive function, but there was no significant effect on short-term memory, long-term memory, executive function
Lam et al. 2018¹⁹	43 (3988)	RCT	aerobic exercise (slow walking)	60 min/time; 2-3 times/week	regular exercise	physical functions (BMI/strength/flexibility/stride/balance, walking endurance)	Aerobic exercise can improve physical function (strength/flexibility/stride/balance)
Barreto et al. 2018²⁰	5 (2878)	RCT	aerobics, Tai Chi	12/24 months	regular exercise	MMSE	Exercise intervention could not improve MCI cognitive function and reduce the risk of MCI
Cammisuli et al. 2017²¹	9 (768)	RCT	aerobic exercise (slow walking, handball)	30-60 min; 2-4 times/week; 6-26 weeks	regular exercise/placebo	global cognitive function (MMSE, ADAS-Cog, MoCA)	Aerobic exercise can improve MCI cognitive function
Zheng et al. 2017²²	3 (455)	RCT	Tai Chi	24 style of Tai Chi (30 min, 3 times/week), Yang style of Tai Chi (60 min, 2 times/week), Dao style of Tai Chi (90 min, 2 times/week)	regular exercise	memory	Tai chi can improve MCI cognitive function
Guure et al. 2017²³	45 (117410)	prospective study	physical exercise	more than once a week	—	—	Physical exercise has positive benefits for improving MCI and AD
Quan et al. 2016²⁴	17 (24089)	prospective study	slow walking	—	—	—	Slow walking can improve cognitive function
Zheng et al. 2016²⁵	11 (1497)	RCT	aerobic exercises (Tai Chi, walking, jogging)	30-90 min/day; 1-5 times/week; 3-12 months	regular exercise	global cognitive function (MMSE, ADAS-Cog, MoCA), attention, executive function, memory (short- term, long- term memory)	Aerobic exercise can improve MMSE, MoCA, short-term memory and long-term memory, has no significant effect on ADAS-cog, attention and executive function
Cai and Abrahamson 2015²⁶	13 (1171)	RCT	aerobic exercise (walking, Tai Chi)	10 weeks-6/12 months	regular exercise	global cognitive function (MMSE, ADAS-Cog), attention, execution and memory function	Aerobic exercise has an ameliorative effect on MMSE, memory, endurance, attention and executive function
Ströhle et al. 2015²⁷	5 (22689)	RCT	western medicine + exercise therapy	6-12 months	western medicine + regular exercise/western medicine treatment	global cognitive function (ADAS-Cog, MMSE)	Exercise interventions can improve MCI cognitive function
Wang et al. 2014²⁸	9 (795)	RCT	aerobic exercise (Tai Chi, walking, stretching)	6 weeks-12 months	regular exercise	global cognitive function (ADAS-Cog, MMSE) attention, executive function, memory (short-term, long-term memory)	Exercise interventions can improve MCI cognitive function
Öhman et al. 2014²⁹	22 (1699)	RCT	physical exercise, walking	6 weeks-12 months	regular exercise/blank control	global cognitive function, executive function, long-term memory, attention	Exercise interventions can improve MCI global cognitive function, executive function, long-term memory and attention

A summary of the characteristics of systematic reviews (SRs) analyzing dietary interventions and detailed characteristics obtained from the full data abstraction.

Articles	Study (sample size)	Exposure group/ intervention group	Unexposed group/ control group	Design	Results
Wu and Sun 2017⁴⁰	9 (34168)	Mediterranean diet	unexposed group	cohort studies	High adherence to the Mediterranean diet can delay cognitive function decline, reduce the risk of AD
Hardman et al. 2016⁴¹	18 (59928)	Mediterranean diet	unexposed group	cohort, longitudinal studies, RCT	High Mediterranean adherence diet towards can delay cognitive decline and reduce the risk of AD
Liu et al. 2016⁴²	11 (29155)	coffee	unexposed group	cohort studies	Moderate coffee intake can delay cognitive decline and reduce the risk of MCI/AD
Panza et al. 2015⁴³	28 (56384)	coffee	unexposed group	cross-sectional, longitudinal studies, case control	Moderate coffee intake can delay cognitive decline and reduce the risk of MCI/AD
Van de Rest et al. 2015⁴⁴	26 (84481)	Mediterranean diet	unexposed group	cross-longitudinal sectional studies, RCT	Higher Mediterranean adherence diet towards can delay cognitive decline and reduce the risk of AD
Li et al. 2014⁴⁵	5 (900)	Vitamin B	placebo	RCT	Vitamin B intake had no significant effect on MCI global cognitive function, executive function and attention
Singh et al. 2014⁴⁶	5 (3636)	Mediterranean diet	unexposed group	Cohort studies	Higher adherence towards Mediterranean diet can delay cognitive decline and reduce the risk of AD

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A summary of the evidence and evaluation of the effectiveness of nonpharmacological interventions for mild cognitive impairment

Article Category: Original article

Published Online: Dec 31, 2019

Page range: 301 - 316

Received: Apr 22, 2019

Accepted: Jul 05, 2019

DOI: https://doi.org/10.2478/FON-2019-0038

Keywords
nonpharmacological intervention, mild cognitive impairment, systematic review methodology, evidence evaluation, evidence synthesis

© 2019 Zi-Meng Li et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Figure 1

Figure 2

Assessment of the methodological quality of systematic reviews (SRs) evaluating dietary interventions.

Assessment of the methodological quality of systematic reviews (SRs) of exercise interventions.

A summary of the characteristics of systematic reviews (SRs) of acupuncture and detailed characteristics derived from the full data abstraction.

Basic characteristics of the included guideline.

A summary of the characteristics of SRs analyzing cognitive interventions and detailed characteristics obtained from the full data abstraction.

Assessment of the methodological quality of systematic reviews (SRs) examining cognitive interventions.

Assessment of the methodological quality of systematic reviews (SRs) evaluating acupuncture.

Summary of the characteristics of systematic reviews (SRs) assessing exercise interventions and detailed characteristics obtained from the full data abstraction.

A summary of the characteristics of systematic reviews (SRs) analyzing dietary interventions and detailed characteristics obtained from the full data abstraction.

A summary of the evidence and evaluation of the effectiveness of nonpharmacological interventions for mild cognitive impairment

Article Category: Original article

Published Online: Dec 31, 2019

Page range: 301 - 316

Received: Apr 22, 2019

Accepted: Jul 05, 2019

DOI: https://doi.org/10.2478/FON-2019-0038

Keywordsnonpharmacological intervention, mild cognitive impairment, systematic review methodology, evidence evaluation, evidence synthesis

© 2019 Zi-Meng Li et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Figure 1

Figure 2

Assessment of the methodological quality of systematic reviews (SRs) evaluating dietary interventions.

Assessment of the methodological quality of systematic reviews (SRs) of exercise interventions.

A summary of the characteristics of systematic reviews (SRs) of acupuncture and detailed characteristics derived from the full data abstraction.

Basic characteristics of the included guideline.

A summary of the characteristics of SRs analyzing cognitive interventions and detailed characteristics obtained from the full data abstraction.

Assessment of the methodological quality of systematic reviews (SRs) examining cognitive interventions.

Assessment of the methodological quality of systematic reviews (SRs) evaluating acupuncture.

Summary of the characteristics of systematic reviews (SRs) assessing exercise interventions and detailed characteristics obtained from the full data abstraction.

A summary of the characteristics of systematic reviews (SRs) analyzing dietary interventions and detailed characteristics obtained from the full data abstraction.

Keywords
nonpharmacological intervention, mild cognitive impairment, systematic review methodology, evidence evaluation, evidence synthesis