Background
Methods
Search strategy
Inclusion and exclusion criteria
Selection of studies and data extraction
First Author (Year) Country | Participants | Baseline levels of serum Hcy a (µmol/L) | Characteristics of Participants | Intervention | Treatment Duration | ||
---|---|---|---|---|---|---|---|
N(IG/CG) ITT | Mean Age a (years) (IG/CG) | Male (n/%) (IG/CG) | |||||
Fei Ma (2019) China [28] | 120 MCI patients aged ≥ 65 years with no terminal illness or mental disorders, recruited from communities | 20.6 ± 2.2 | 60/60 | 69.2 ± 2.5/ 68.5 ± 3.9 | 21(35.0)/ 22(36.7) | folic acid 800 µg and vitamin B12 25 µg/day | 6 months |
Kwok Timothy (2019) China [29] | 279 MCI outpatients aged ≥ 65 years | 13.8 ± 3.2 | 138/141 | 76.9 ± 5.4/ 78.0 ± 5.3 | 87(63.1)/ 79(56.1) | folic acid 400 µg and vitamin B12 500 µg/day | 24 months |
Fei Ma (2017) China [30] | 180 MCI patients aged ≥ 65 years with no terminal illness or mental disorders, recruited from communities | 12.9 ± 4.4 | 90/90 | 74.8 ± 2.8/ 74.6 ± 3.2 | 39(43.3)/ 38(42.2) | folic acid 400 µg/day | 24 months |
Kwok Timothy (2017) China [34] | 271 diabetic non-demented outpatients aged ≥ 70 years | 16.8 ± 5.7 | 137/134 | 74.7 ± 4.0/ 75.8 ± 4.2 | 82(59.9)/ 76(56.7) | vitamin B12 1000 µg/day | 27 months |
Cheng D (2016) China [35] | 104 elderly volunteers aged ≥ 55 years, recruited from communities or nursing homes | 20.0 ± 5.6 | 57/47 | 74.3 ± 9.6/ 72.5 ± 7.0 | 27(47.4)/ 23(48.9) | folic acid 800 µg, vitamin B6 10 mg and vitamin B12 25 µg/day | 14 weeks |
Dangour AD (2015) United Kingdom [36] | 201 healthy volunteers aged ≥ 75 years | 16.1 ± 4.3 | 99/102 | 79.9 ± 3.5/ 80.1 ± 3.7 | 46(46.5)/ 23(48.9) | vitamin B12 1 mg/day | 12 months |
van der Zwaluw NL (2014) Netherlands [37] | 856 elderly participants aged ≥ 65 years with no dementia | 14.2 ± 2.5 | 425/431 | 72.6 ± 5.7/ 72.6 ± 5.8 | 244(57.0)/ 255(59.0) | folic acid 400 µg and vitamin B12 500 µg/day | 24 months |
Hankey GJ (2013) Australia [26] | 2214 patients with stroke or transient ischemic attack, MMSE ≥ 24 | 14.3 ± 8.5 | 1110/1104 | 63.6 ± 11.8 b | 1491(67.3) | folic acid 2 mg, vitamin B6 25 mg and vitamin B12 500 µg/day | 3.4 years |
Walker JG (2012) Australia [38] | 900 elderly adults aged 60 ~ 74 years, recruited from communities | 9.7 ± 2.7 | 447/453 | 65.9 ± 4.3/ 66.0 ± 4.2 | 181(40.5)/ 177(39.1) | folic acid 400 µg and vitamin B12 100 µg/day | 24 months |
de Jager CA (2012) United Kingdom [39] | 266 MCI patients aged ≥ 70 years | 11.5 ± 4.5 | 133/133 | 76.8 ± 5.1/ 76.7 ± 4.8 | 40(36.4)/ 40(35.4) | folic acid 0.8 mg, vitamin B12 0.5 mg and vitamin B6 20 mg/day | 24 months |
Ford AH (2010) Australia [40] | 299 community-dwelling elderly men aged ≥ 75 years with hypertension | 13.6 ± 5.3 | 150/149 | 79.3 ± 2.8/ 78.7 ± 2.7 | 150(100)/ 149(100) | folic acid 2 mg, vitamin B12 0.4 mg and vitamin B6 25 mg/day | 24 months |
van Uffelen JG (2008) Netherlands [41] | 179 MCI patients aged 70 ~ 80 years, recruited from communities | NR | 90/89 | 75.4 ± 2.8/ 74.9 ± 3.0 | 44(56.4)/ 41(55.4) | folic acid 5 mg, vitamin B12 0.4 mg and vitamin B6 50 mg/day | 12 months |
Durga J (2007) Netherlands [42] | 819 men and post-menopausal women aged 50 ~ 70 years | 12.9 ± 2.4 | 406/413 | 60 ± 5/ 60 ± 6 | 294(72)/ 292(70) | folic acid 0.8 mg/day | 3 years |
McMahon JA (2006) New Zealand [43] | 276 healthy participants aged ≥ 65 years | 16.6 ± 4.9 | 138/138 | 73.6 ± 5.8/ 73.4 ± 5.7 | 80(63.0)/ 61(48.4) | folic acid 1 mg, vitamin B12 0.5 mg and vitamin B6 10 mg/day | 2 years |
Eussen SJ (2006) Netherlands [44] | 131 elderly people aged ≥ 70 years with mild vitamin B12 deficiency | 15.2 ± 5.1 | 66/65 | 83 ± 6/ 82 ± 5 | 49(74.2)/ 51(78.5) | folic acid 0.4 mg, vitamin B12 1 mg/day | 6 months |
Stott DJ (2005) United Kingdom [45] | 47 elderly people aged ≥ 65 years with ischemic vascular disease | 16.7 ± 6.5 | 23/24 | 72.6 ± 6.4/ 72.8 ± 5.4 | 12(52.2)/ 14(58.3) | folic acid 2.5 mg, vitamin B12 0.5 mg and vitamin B6 25 mg/day | 3 months |
Lewerin C (2005) Sweden [46] | 195 community-dwelling participants | 17.2 ± 5.2 | 126/69 | 75.7 ± 4.7/ 75.6 ± 4.0 | 48(38.1)/ 30(43.5) | folic acid 0.8 mg, vitamin B12 0.5 mg and vitamin B6 3 mg/day | 4 months |
Hvas AM (2004) Denmark [47] | 140 elderly people with plasma methylmalonic acid 0.40 ~ 2.00µmol/L | 13.2 c | 70/70 | 75/74 c | 20(28.6)/ 22(31.4) | vitamin B12 1 mg/week | 1 month |
Garcia A (2004) Canada [48] | 24 community-dwelling participants aged ≥ 65 years, with an increased plasma methylmalonic acid and MMSE ≥ 24 | 12.2 ± 4.0 | 12/12 | 76/76 c | 5(22.7) b | vitamin B12 1 mg/month | 6 months |
Janet Bryan (2002) Australis [49] | 40 healthy older women aged 65 ~ 92 years, who did not smoke, were not pregnant or lactating | NR | 19/21 | 74.1 ± 5.75 b | 0(0)/ 0(0) | folic acid 750 µg/day | 5 weeks |
Fioravanti M (1998) Italy [50] | 30 elderly patients aged 70 ~ 90 years, with memory complaints, MMSE score 16 ~ 24 and serum folate < 3 ng/ml, recruited from homes or communities | NR | 16/14 | 80.3 ± 5.8/ 80.2 ± 5.5 | 4(25)/ 1(7.1) | folic acid 15 mg/day | 2 months |
Quality assessment
Definitions of outcome measures
Statistical Analysis
Results
Overall search findings
Characteristics of included studies
Quality assessment of included studies (risk of bias)
Outcome evaluation
Global cognitive function
Outcome measures | Subgroup | The Num of studies | Pooled estimate [SMD/MD (95 %CI)] | P value | I2(%) | Test for subgroup differences | |
---|---|---|---|---|---|---|---|
global cognitive function | Treatment duration | ≤ 12 months | 7 | 0.35(-0.15, 0.84) | P = 0.17 | 87 | P = 0.67 |
> 12 months | 8 | 0.23(0.07, 0.40) | P = 0.006 | 91 | |||
participants | MCI patients | 5 | 0.82(0.20, 1.45) | P = 0.01 | 95 | P = 0.03* | |
EAWCI | 10 | 0.13(0.03, 0.23) | P = 0.01 | 66 | |||
information processing speed | Treatment duration | ≤ 12 months | 5 | -0.19(-0.38, 0.01) | P = 0.06 | 39 | P = 0.007* |
> 12 months | 4 | 0.16(0.01, 0.31) | P = 0.04 | 64 | |||
participants | MCI patients | 1 | 0.04(-0.28, 0.36) | P = 0.79 | NA | P = 0.89 | |
EAWCI | 9 | 0.07(-0.13, 0.27) | P = 0.50 | 81 | |||
episodic memory | Treatment duration | ≤ 12 months | 7 | -0.09(-0.27, 0.09) | P = 0.34 | 40 | P = 0.09 |
> 12 months | 6 | 0.08(0.02, 0.13) | P = 0.01 | 0 | |||
participants | MCI patients | 4 | 0.42(-0.24, 1.08) | P = 0.21 | 94 | P = 0.26 | |
EAWCI | 11 | 0.04(-0.04, 0.12) | P = 0.34 | 28 | |||
executive function | Treatment duration | ≤ 12 months | 4 | 0.01(-0.14, 0.17) | P = 0.87 | 0 | P = 0.21 |
> 12 months | 5 | -0.29(-0.75, 0.16) | P = 0.20 | 96 | |||
participants | MCI patients | 3 | -0.33(-0.81, 0.15) | P = 0.18 | 89 | P = 0.59 | |
EAWCI | 8 | -0.17(-0.51, 0.17) | P = 0.34 | 94 | |||
Hcy | Treatment duration | ≤ 12 months | 7 | -4.77(-6.28, -3.27) | P < 0.01 | 78 | P = 0.68 |
> 12 months | 5 | -4.41(-5.27, -3.54) | P < 0.01 | 82 | |||
participants | MCI patients | 3 | -5.45(-6.51, -4.39) | P < 0.01 | 81 | P = 0.05 | |
EAWCI | 8 | -4.13(-4.93, -3.32) | P < 0.01 | 65 |