Table 2.
Study (support source) | Inclusion criteria | Treatment | n | Control | n | Duration | Measures on which control and intervention groups differed significantly; post-intervention mean (sd) and statistical comparisons | Validity (answers to questions 1–5 in method) | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Intervention | Control | 1 | 2 | 3 | 4 | 5 | |||||||||
Baker17 (Gov, USA) | aMCI*; sedentary adults | 1 hour, individual, high intensity aerobic exercise, 4 days a week | 23 | Stretching control | 19 | 6 months | DSST | n/a | n/a | F=4·18; P=·05 | n | y | n | y | n |
Verbal fluency | n/a | n/a | F=4·87; P=·04 | ||||||||||||
Trail making test B | n/a | n/a | F=4.58; P=.04 | ||||||||||||
Busse26 (not stated) | MCI*; sedentary adults | 1 hour, twice a week of resistance training | 14 | No treatment | 17 | 9 months | Rivermead memory behavioural test | 18.9 | 15.33 | ANOVA (group/time): p=0.021 | y | n | y | y | n |
$De Jager30(Gov, UK; Charities) | Aged 70+; MCI* | 0·8mg folic acid, 0·5mg vitamin B12 and 20mg vitamin B6 | 110 | Placebo | 113 | 2 years | CDT correctly performed | Low H1: 13.5(1.7) High H: 12.6(1.9) |
Low H: 13.0(1.7) High H: 12.3(2.4) |
OR=1·3, p=0·015 | y | y | y | y | n |
Ferris52 (Forest research institute) | Aged 50–79; MMSE 27+; AAMI diagnosis** | Memantine 20mg | 30 | placebo | 30 | 3 months | Cogscreen symbol digit accuracy | n/a | n/a | F=2.86, 0.05 | y | y | y | y | y |
Finn55 (LumosityInc.) | Aged 60+; MCI diagnosis, MMSE<24 | 30 computerised cognitive training sessions, each with 4–5 exercises | 12 | Waitlist | 13 | 8 weeks | Visual sustained attention (CANTAB) | 0.90 (0.05) | 0.79 (0.13) | F=11·95, p=0·004 | y | y | n | y | n |
Forlenza59(Gov, Brazil; Charities) | aged 60+; Mayo clinic aMCI criteria | Lithium | 21 | Placebo | 20 | 1 year | n | y | n | y | n | ||||
Fu36 (Peking University; Gov, China) | MCI*, MMSE 24–27; no ChEI | Wuzi Yanzong granules 4·5g sachet as a drink, twice a day | 18 | Placebo | 18 | 3 months | Memory quotient | 15·83 (17·54) | 5·17 (13·5) | p<0·05 | n | y | y | y | n |
Koontz22(Janssen) | MCI*, MMSE >25 | Galantamine titrated to 12mg bd | 8 | Placebo | 11 | 16 weeks | Problem solving (CANTAB) | 8·3 (1·89) | 7·0 (1·41) | p=0·023 | n | y | n | y | n |
Pattern recognition memory | 2449 (807) | 2239(690) | p=0·001 | ||||||||||||
Krikorian32(Welch food) | SuMC & CDR “mild” | grape juice 444–621ml/d | 5 | Placebo | 7 | 12 weeks | CVLT | 38.6 | 33.2 | F= 5·55; P=0·04 | n | y | y | y | n |
Luijpen39(Gov, Netherland) | MCI*, living in care home | TENS 30 minutes a day 5 days a week for 6 weeks | 17 | Placebo | 17 | 6 weeks | GDS | 7.35 (3.22) | 11.82 (6.79) | F= 4·35 p= 0·02 | y | y | y | y | n |
GARS | 39.35 (10.14) | 45.41 (13.71) | F=3·90, p=0·03 | ||||||||||||
Mowla43(none stated) | MCI* and HDS <10 | Fluoxetine titrated to 20mg | 23 | Placebo | 21 | 8 weeks | MMSE | 27.0 (1.5) | 24.1 ±1.5 | MWU, p=0.003 | n | y | n | y | n |
Immediate memory (WMS) | 10.8(4.9) | 7.62 (4.7) | MWU p=0.015 | ||||||||||||
Delayed memory (WMS) | 9.28(5.1) | 5.95(4.3) | MWU p=0.008 | ||||||||||||
Park33 (LG) | aged 40–75; GLDS 2/3; MMSE 21–26; SuMC | green tea extract and L-theanine | 45 | Placebo | 46 | 16 weeks | n | y | y | y | n | ||||
Pelton27 | Aged 50+, depression or memory clinic out-patients; SuMC, NPT >1SD below normal; MMSE>19; no ADL impairment | Antidepressant + donepezil | 12 | Antidepressant + placebo | 9 | 12 weeks | Buschke Selective Reminding Test immediate recall | 37.8 (10.9) | 39.0 (12.0) | ANOVA: F=3.0, p=0.05 | y | y | y | y | n |
Rapp46(none stated) | MCI* | 6, weekly 2 hour groups, psycho-education, memory skills & homework | 9 | Given manual | 10 | 6 weeks | n | y | n | y | n | ||||
Rondanelli40(none stated) | MCI*, MMSE 24+ | Nutritional supplement (see text) | 11 | Placebo | 14 | 12 weeks | MMSE | −2·07c | 1·01c | p=0·0011 | y | y | y | y | n |
Rozzini47 (not stated) | Aged 63–78, MCI*, living independently, GDS<5 | Neuropsychological training + ChEI | 15 | ChEI | 22 | 9 months | Short story recall | 11.0 (3.5) | 8.3 (3.5) | t=2·3, p=0·03 | n | y | n | y | n |
ChEI | 22 | No treatment | |||||||||||||
Scherder41 (Gov, Netherlands) | MCI* and abbreviated MMSE score of 7+ | Half hour assisted walk, 3× a day/6 weeks | 15 | Half had additional social visit | 15 | 6 weeks | category fluency | 24.80 (11.37) | 20.27 (9.51) | F=5·02; p=0·02 | n | y | n | y | n |
hand and face exercises, same duration | 13 | category fluency | 25.69 (8.14) | 20.27 (9.51) | F=3·27; p=0·04 | ||||||||||
Trail making | 273.15 (139.85) | 253.73 (150.03) | F=5·03; p=0·02 | ||||||||||||
Sinn34 (Gov, Australia; Novasel) | MMSE 22+, SuMC, normal daily functioning | EPA-rich fish oil | 17 | Vegetable oil | 15 | 6 months | GDS | n/a | n/a | LMM: t=2·2, p=0·04 | n | y | y | y | n |
DHA-rich fish oil | 18 | n/a | n/a | LMM: t=2·6, p<0·01 | |||||||||||
Letter fluency | n/a | n/a | LMM: t=2·1, p=0·04 | ||||||||||||
Suzuki42 (Gov, Japan) | Aged 65+, aMCI* | multicomponent exercise group 90mins, 2days/week | 25 | Educational group | 25 | 1 year | MMSE | n/a | n/a | LMM: F=3.4, p=0.04 | y | n | y | y | n |
WMS-LM I | n/a | n/a | LMM: F=3.9, p=0.03 | ||||||||||||
Verbal fluency | n/a | n/a | LMM: F=4.1, p=0.02 | ||||||||||||
Tian37 (Gov, China) | MCI*, SuMC, age 45–70 CDR <1; MMSE 25+ | Ginseng | 30 | Placebo | 15 | 12 weeks | Cognitive score | 5.3c | 6.2c | p<0·05 | n | n | n | n | n |
Verbal subscale | 18·6c | −6·0c | p<0·05 | ||||||||||||
Troyer24 ** | aMCI* | 10× 2 hour relaxation and memory strategy groups | 24 | Waitlist | 24 | 6 months | n | n | y | n | n | ||||
Pelton27 (Gov, USA; Pfizer, Inc. & Esai, Inc.) | aMCI* | 10× 2 hour relaxation and memory strategy groups | 24 | Waitlist | 24 | 6 months | n | n | y | n | n | ||||
Zhou50 (Gov, China) | MCI*; SuMC, MMSE 24–27, aged < 80, HDS<18 | Shenyin oral liquid 10ml bd | 42 | Placebo | 37 | 1 year | CDT | 1·25 (1·13) | 0·26 (1·1) | p<0·001 | n | n | n | y | n |
Picture recognition | 5.15 (4·7) | 0·63 (5·0) | p<0·05 | ||||||||||||
vitamin E tablets 500mg | 38 | 3·68 (6·51) | 0·63(4·99) | p<0·05 |
Summary statistics are given by median split of homocysteine levels; high H indicates value for those scoring above this cut point, Low H for those scoring below
diagnosed according to Petersen criteria 1 ;
Charity, Dejardins Financial & Richter Usher & Vineberg
AAMI diagnosed using Crook criteria;
aMCI=amnestic mild cognitive impairment; AVLT = Rey Auditory Verbal Learning Test; C=mean change rather than mean post-intervention displayed; CANTAB=Cambridge Automated Neuropsychiatric Test Assessment Battery; CDT=Clock drawing test; ChEI= cholinesterase inhibitor; DSST=Digit Symbol Substitution Test EL= eligible for inclusion in this review; CVLT=California verbal learning test; F= MANOVA statistic; GDS=Geriatric Depression Scale; GLDS: Global deterioration scale; GARS=Groninger Activity Restriction Scale; Gov = National government supported funding source; HDS=Hamilton depression score; LG=LG Household & Health Care, Ltd LMM=Linear Mixed Model; M=Mean; MC=Mean change, baseline to follow-up; MD= Mean difference between groups at follow-up; MCI= mild cognitive impairment; MMSE=Minim mental state examination; n/a= not available; NPT= Neuropsychological testing battery; SD=Standard deviation; SuMC=Subjective memory complaint; TCPR=time to correct pattern recognition; OR = odds ratio; WMS=Wechsler Memory Scale III; WMS-LM; Logical Memory subtest of the Wechsler memory scale-revised