Table 3. Summary table of cognitive function results grouped as per National Institute for Aging-Alzheimer’s Association (NIA-AA)(3) criteria.
| NIA-AA cognitive domain | Study | Intervention | Cognitive function measure used | Intervention group and control group results | Between group difference |
|---|---|---|---|---|---|
| Memory | Horie et al., 2016(37) | Nutrition counselling and energy restriction v. standard care | RAVLT (delayed recall) | Intervention (mean change 0·7, 95% CI –0·9, 2·3); control (mean change 1·7, 95% CI 0·1, 3·3) | ‡ |
| RAVLT (total learning) | Intervention (mean change 3·3, 95% CI –1·3, 7·9); control (mean change 2·0, 95% CI – 2·6, 6·7 | ‡ | |||
| Digit span backward | Intervention (0·2, 95% CI –0·8,1·2,); control (0·1, 95% CI –0·9, 1·1) | ‡ | |||
| Trail making test, part B | Intervention (mean change –8·6, 95% CI –71·6, 54·5); control (mean change 5·1, 95% CI –58·3, 68·6) | ‡ | |||
| Lee et al. (2013)(27) | Fish oil supplementation with concentrated DHA + EPA v. placebo | RAVLT (delayed recall) | Intervention (baseline mean score 6·7, 95% CI 4·897, 8·442 – 12 months mean score 8·1, 95% CI 6·645, 9·462); control (baseline mean score 6·1, 95% CI 4·431, 7·860 – 12 months(mean score 5·0, 95% CI 3·587, 6·312) | * | |
| Visual reproduction I | Intervention (baseline mean score 20·0, 95% CI 15·234, 24·820 – 12 months mean score 29·2, 95% CI 25·207, 33·269); control(baseline mean score 21·0, 95% CI 16·394, 25·666 – 12 months mean score 23·1, 95% CI 19·154, 26·952) | * | |||
| Visual reproduction II | Intervention (baseline mean score 13·3, 95% CI 8·297, 18·362 – 12 months mean score 20·8, 95% CI 15·564, 26·110); control (baseline mean score 12·6, 95% CI 7·710, 17·445 – 12 months mean score 18·0, 95% CI 12·943, 23·143) | ‡ | |||
| Digit symbol substitution | Intervention (baseline mean score 5·5, 95% CI 3·723, 7·218 – 12 months mean score 5·5, 95% CI 3·723, 7·218); control (baseline mean score 4·9, 95% CI 3·254, 6·634 – 12 months 4·9, 95% CI 3·254, 6·634) | ‡ | |||
| Memory cognitive Z-score | Intervention (mean change 0·96 (sd 0·76)***); control (mean change 0·16, (sd 0·59)) | * | |||
| Petersen et al. (2005)(31) |
2000 IU vitamin E, 10mg donepezil or placebo | Memory Z score (ADAS recall scores and New York University recall scores) | Intervention (6 months, Z score –0·10, sd 0·48; 36 months Z score – 0·31, sd 0·59); control (6 months, Z score –0·17, sd 0·47; 36 months Z score –0·28, sd 0·62) | ‡ | |
| Ma et al. (2016)(24) | Oral folic acid (400 μg/d) v.conventional treatment | Digit span | Intervention (baseline mean score 9·27 (sd 3·11) – 6 months mean score 13·05 (sd 3·07); control (baseline mean score 8·87 (sd 2·70) – 6 months mean score 9·75 (sd 3·14) | * | |
| De Jager et al. (2012)(25) | 0·8mg folic acid, 0·5mg vitamin B12 and 20mg vitamin B6 v. placebo | HVLT-R (subgroup analyses, with baseline tHcy levels) | The odds of correctly remembering a word from the list of twelve in the HVLT test were 69 % greater for a person in the high tHcy group if they were taking B vitamins than if they were taking placebo (OR = 1·69) | * | |
| CERAD (subgroup analyses, with baseline tHcy levels) | The average number of words was 9·4 % greater at follow up in those on B vitamin treatment in the high tHcy group, compared with the placebo (OR = 0·09) | * | |||
| Bayer-Carter et al. (2011)(38) | High fat/high GI diet v. low fat/low GI diet | Brief visuospatial memory test | aMCI low diet baseline mean score 7·39 (sem 0·71) – week 4 mean score 8·31 (sem 0·62); aMCI high diet baseline mean score 8·27 (sem 0·66) – week 4 mean score 8·40 (sem 0·58); healthy controls high diet baseline mean score 9·89 (sem 0·85) – week 4 mean score 9·56 (sem 0·74); healthy controls low diet baseline mean score of 8·27 (sem 0·77) – week 4 mean score 9·82 (sem 0·67) |
‡ | |
| Story recall | aMCI low diet baseline mean score 18·48 (sem 1·43) – week 4 mean score 21·46 (sem 1·70); aMCI high diet baseline mean score 20·37 (sem 1·31) – week 4 mean score 22·30 (sem 1·59); healthy controls high diet baseline mean score 22·69 (sem 1·7 4) – week 4 mean score 23 19 (sem 2·04); healthy controls low diet baseline mean score 21·09 (sem 1·55) – week 4 mean score 19·90 (sem 1·95) | ‡ | |||
| Word list | aMCI low diet baseline mean score 11·62 (sem 0·76) – week 4 mean score 11·77 (sem 0·80), aMCI high diet baseline mean score 11·33 (sem 0·71); healthy controls low diet baseline mean score 13·27 (sem 0·93) – week 4 mean score 13·27 (sem 0·96), healthy controls high diet baseline mean score 12·79 (sem 0·92) – week 4 mean score 13·67 (sem 0·95) | – | |||
| Krikorian et al. (2012)(12) | High carbohydrate v. a very low carbohydrate | Trail making test, part B | Intervention (pre-intervention mean score 79·2s v. post intervention mean score 82·9s, F1,20= 0·46, P= 0·50); control (no detail) | – | |
| V-PAL | Intervention (pre-intervention mean score 11·8s v. post intervention mean score 14·6 s, F1,20= 6·45, P= 0·01); control (no detail) | ‡ | |||
| Krikorian et al. (2010)(35) | Concord grape juice supplementation v. placebo | CVLT learning | Intervention mean change 3·4; control mean change 0·0; ANCOVA analysis intervention v. control F1,8= 5·55, P= 0·04, Cohen’s f= 0·28 | * | |
| CVLT recall | Intervention mean change 1·2; control mean change −0·4; ANCOVA analysis intervention v. control P= 0·10; Cohen’s f= 0·35 | ‡ | |||
| Spatial paired associate learning task | Intervention mean change 1·7; control mean change −0·4; ANCOVA analysis intervention v. control P= 0·12; Cohen’s f= 0·67 | ‡ | |||
| Krikorian et al. (2010)(36) | Wild blueberry juice supplementation v. placebo | V-PAL | Intervention (baseline mean score 9·3 v. week 12 mean score 13·2†); control (no detail); ANCOVA analysis intervention v. control F1,13 = 5·58 | * | |
| CVLT | Intervention (baseline mean score 7·2 v. week 12 mean score 9·6†); control (no detail); ANCOVA analysis intervention v. control F1,13 = 2·27 | ‡ | |||
| Krikorian et al. (2010)(32) | Chromium picolinate supplementation v. placebo | CVLT learning | Intervention v. control mean score at 12 weeks (46·8 v. 45·8) Intrusion errors intervention v. control at 12 weeks (0·20 v. 1·27); F1,23 = 6·48; Cohen’s f= 0·51 |
‡ * |
|
| CVLT delay recall | Intervention v. control mean score at 12 weeks (9·4 v. 8·4) Intrusion errors intervention v. control at 12 weeks (0·98 v. 2·3), F1,23 = 3·35, Cohen’s f= 0·35 |
‡ |
|||
| CVLT long delay recall | Intervention v. Control mean score at 12 weeks (9·3 v. 9·5) Intrusion errors intervention v. control at 12 weeks (0·98 v. 2·3), F1,23 = 3·35, Cohen’s f= 0·35 |
‡ |
|||
| CVLT recognition memory | Intervention v. control mean score at 12 weeks (14·4 v. 14·2) Intrusion errors intervention v. control at 12 weeks (0·88 v. 2·2), F1,23 = 2·94, Cohen’s f= 0·34 |
‡ |
|||
| Desideri et al. (2012)(34) | 990mg HF v. IF v. LF cocoa flavanols per day | Verbal fluency | HF (mean change 8·0 (sd 5·3) words per 60 s***); IF (mean change 5·1 (sd 3·1) words per 60 s***), LF (mean change 1·2 (sd 2·7) words per 60 s†) | * | |
| Bo et al. (2017)(28) | 480mg of DHA + 720mg of EPA daily v. placebo | Working memory | Intervention mean difference 3·32 (sd 3·45); control mean difference 1·38 (sd 2·66) | * | |
| Recognition memory | Intervention: mean change 1·55 (sd 3·96); control mean change 1·98 (sd 3·13) | ‡ | |||
| Soininen et al. (2017)(33) | Souvenaid, a 125 ml once–a–day drink v. control | NTB memory Z score | Intervention mean change at 24 months, 0·003 (sd 0·569); control mean change at 24 months –0·130 (sd 0·619) | ‡ | |
| Zhang et al. (2017)(30) | 2g/d DHA v. placebo | Information test | Intervention mean score 12·28 (sd 3·56); control mean score 10·82 (sd 2·62) | * | |
| Digit span | Intervention mean score 13·44 (sd 3·66); control mean score 10·25 (sd 3·42) | * | |||
| Phillips et al. (2015)(29) | 625mg EPA + 600mg DHA v. placebo | Immediate verbal memory | Intervention mean score (month 1, 19·42 (sd 3·49) – month 4, 17·46 (sd 4·52)); control mean score (month 1, 20·50 (sd 4·31) – month 4, 19·38 (sd4·65)) | – | |
| Delayed verbal memory | Intervention mean score (month 1, 4·85 (sd 2·91) – month 4, 4·34 (sd 2·74)); control mean score (month 1, 5·23 (sd 2·63) – month 4, 4·65 (sd 2·79)) | ‡ | |||
| Recognition verbal memory | Intervention mean score (month 1, 8·92 (sd 2·06) – month 4, 8·38 (sd 2·30)); control mean score (month 1, 9·00 (sd 2·80) – month 4, 8·00 (sd 2·55)) | – | |||
| Visual memory | Intervention mean score (month 1, 11·58 (sd 2·19) – month 4, 12·77 (sd 2·67); control mean score (month 1, 11·50 (sd 2·60) – month 4, 11·85 (sd 1·95)) | ‡ | |||
| Executive function | Lee et al. (2013)(27) | Fish oil supplementation with concentrated DHA + EPA v. placebo | Digit symbol substitution | Intervention (baseline mean score 5·5, 95% CI 3·723, 7·218 – 12 months mean score 5·5,95% CI 3·723, 7·218); control (baseline mean score 4·9, 95% CI 3·254, 6·634 – 12 months mean score 4·9, 95% CI 3·254, 6·634) | – |
| CDT | Intervention (baseline mean score 7·3, 95% CI 6·810, 7·880 – 12 months mean score 7·8, 95% CI 7·142, 8·477); control (baseline mean score 7·5, 95% CI 6·935, 7·969 – 12 months mean score 7·8, 95% CI 7·145, 8·436) | ‡ | |||
| Executive function Z score (cumulative score of all tests used) | Intervention (mean change 0·52 (sd 0·869)†); control (mean change –0·238 (0·683)) | ‡ | |||
| Petersen et al. (2005)(31) | 2000 IU vitamin E, 10mg donepezil or placebo | Executive function Z score (digits backwards test, symbol digit modalities test and number – cancellation test) | Intervention (6 months Z score 0·11, sd 0·41§ – 36 months Z score – 0·19, sd 0·48); control (6 months Z score 0·04, sd 0·42 –36 months Z score –0·19, sd 0·53) | ‡ | |
| Horie et al.(2016)(37) | Nutrition counselling and energy restriction v. standard care | Trail making test, part B | Intervention (mean change –8·6, 95% CI –71·6, 54·5); control (mean change 5·1, 95% CI –58·3, 68·6) | ‡ | |
| Phonemic fluency | Intervention (mean change 0·1, 95% CI –0·5, 5·1); control (mean change 2·0, 95% CI –3·1, 7·1) | ‡ | |||
| Semantic fluency | Intervention (mean change 1·1, 95% CI –1·4, 3·6); control (mean change 1·9, 95% CI –0·6, 4·4) | ‡ | |||
| Modified Wisconsin Card SortingTest | Intervention (mean change 0·4, 95% CI –0·3, 1·0); control (mean change 0·7, 95% CI –0·1, 1·4) | ‡ | |||
| Krikorian et al. (2012)(12) | High carbohydrate diet v. very low carbohydrate | Trail making test, part B | Intervention (pre-intervention mean score 79·2s v. post intervention mean score 82·9 s, F1,20 = 0·46); control (no detail) | ‡ | |
| Bayer-Carter et al. (2011)(38) | High fat/high GI diet v. low fat/low GI diet | Trail making test, part B Stroop colour word test Verbal fluency |
The authors did not include these data in their published paper, merely stating no diet related changes in the text | ‡ | |
| De Jager et al. (2012)(25) | 0·8mg folic acid, 0·5mg vitamin B12 and 20mg vitamin B6 v. placebo | CLOX (subgroup analyses, with baseline tHcy levels) | The odds of a correctly drawn item from CLOX1, after controlling for confounders (CLOX2 at follow-up, CLOX1 at baseline, age,education, ApoE ε4 status and sex), was 30 % greater in those receiving B-vitamins in comparison to placebo (OR = 0·26) | * | |
| Desideri et al. (2012)(34) | 990mg HF v. IF v. LF cocoa flavanols per day | Trail making test, part B | HF (mean change –29·2 (sd 8·0) s***), IF (mean change –22·8 (sd 5·1) s***) LF (mean change 3·8 (sd 16·3) s) | * | |
| Soininen et al. (2017)(33) | Souvenaid, a 125 ml once-a-day drink v. control | NTB executive function Z score | Intervention mean change at 24 months –0·145 (sd 0·445); control mean change at 24 months –0·039 (sd 0·506) | ‡ | |
| Phillips et al.(2015)(29) | 625mg EPA + 600mg DHA v. placebo | CLOX2 | Intervention mean score (month 1, 14·08 (sd 0·89) – month 4, 14·08 (sd 14·08)); control mean score (month 1, 14·38 (sd 0·75) – month 4, 14·27 (sd 0·67)) | ‡ | |
| Attention | Horie et al. (2016)(37) | Nutrition counselling and energy restriction v. standard care | Digit span forward | Intervention (mean change –0·4, 95% CI –1·1, 0·3); control (mean change 0·1, 95% CI –0·6, 0·9) | ‡ |
| Digit span backward | Intervention (mean change 0·2, 95% CI –0·8, 1·2); control (mean change 0·1, 95% CI –0·9, 1·1) | ‡ | |||
| Trail making test, part A | Intervention (mean change –6·1 95% CI –22·6, 10·4); control (mean change –0·7, 95% CI –17·3, 15·9) | ‡ | |||
| Lee et al. (2013)(27) | Fish oil supplementation with concentrated DHA + EPA v. placebo | CDT | Intervention (baseline mean score 7·3, 95% CI 6·810, 7·880 – 12 months mean score 7·8, 95% CI 7·142, 8·477); control (baseline mean score 7·5, 95% CI 6·935, 7·969 – 12 months mean score 7·8, 95% CI 7·145, 8·436) | ‡ | |
| Digit span forward test | Intervention (baseline mean score 8·0, 95% CI 6·99, 9·04 – 12 months mean score 9·6, 95% CI 8·437, 10·749); control (baseline mean score 8·5, 95% CI 7·554, 9·529 – 12 months mean score 8·0, 95% CI 6·877, 9·113) | * | |||
| Attention Z score | Intervention (mean change 0·52 (sd 0·869)†); control (mean change –0·238 (0·683)) | ‡ | |||
| Desideri et al. (2012)(34) | 990mg HF v. IF v. LF cocoa flavanols per day | Trail making test, part A | HF (mean change –14·3 (sd 4·2) s***), IF (mean change –8·8 (sd 3·4) s***), LF (mean change 1·1 (sd 13·0) s) | * | |
| Zhang et al. (2017)(30) | 2 g/d DHA v. placebo | Digit span | Intervention mean score 13·44 (sd 3·66); control mean score 10·25 (sd 3·42) | * | |
| Philips et al. (2015)(29) | 625mg EPA + 600mg DHA v. placebo | Basic attention | Intervention mean score (month 1, 6·38 (sd 1·47) – month 4, 6·54 (sd 1·33); control mean score (month 1, 6·65 (1·36) – month 4, 6·77 (sd 1·31)) | ‡ | |
| Language | Horie et al. (2016)(37) | Nutrition counselling and energy restriction v. standard care | Semantic fluency | Intervention (mean change 1·1, 95% CI –1·4, 3·6); control (mean change 1·9, 95% CI –0·6, 4·4) | ‡ |
| Phonemic fluency | Intervention (mean change 0·1, 95% CI –0·5, 5·1); control (mean change 2·0, 95% CI –3·1, 7·1) | ‡ | |||
| Petersen et al. (2005)(31) | 2000 IU vitamin E, 10mg donepezil or placebo | Language Z score (Boston naming test and category fluency test) | Intervention (6 months Z score 0·07, sd 0·23§ – 36 months Z score – 0·10, sd 0·35); control (6 months Z score 0·03, sd 0·23 – 36 months –0·08, sd 0·33) | ‡ | |
| VS | Lee et al. (2013)(27) | Fish oil supplementation with concentrated DHA + EPA v. placebo | Matrix reasoning block design test | Intervention (baseline mean score 7·6, 95% CI 6·37, 8·75 – 12 months mean score 7·1, 95% CI 6·27, 7·96); control (baseline mean score 7·3, 95% CI 6·16, 8·45 – 12 months mean score 7·9, 95% CI 7·07, 8·71) | ‡ |
| VS Z score | Intervention (mean change 0·17 (sd 0·84)); control (mean change 0·04 (sd 0·60)) | ‡ | |||
| Petersen et al. (2005)(31) | 2000 IU vitamin E, 10mg donepezil or placebo | VS Z score (CDT) | Intervention (6 month Z score 0·03, sd 0·34 – 36 months Z score – 0·12, sd 0·37); control (6 month Z score –0·01, sd 0·34 – 36 months Z score –0·11, sd 0·39) | ‡ | |
| Ma et al. (2016)(24) | Folic acid (400 μg/d) v. control | Block design test | Intervention (baseline mean score 9·77 (sd 5·41) – 6 months mean score 13·28 (sd 4·21)); control (baseline mean score 9·93 (sd 2·273) – 6 months mean score 11·33 (sd 3·11)) | * | |
| Zhang et al. (2017)(30) | 2mg DHA v. placebo | Block design test | Intervention (baseline mean score 10·25 (sd 5·30 – 12 months mean score 11·19 (sd 4·07); control (baseline mean score 9·63 (sd 2·46) – 12 months mean score 10·43 (sd 3·51)) | ‡ |
RAVLT, Rey Auditory Verbal Learning Test; HVLT-R, Hopkins Verbal Learning Test – Revised; tHcy, total homocysteine; GI, glycaemic index; aMCI, amnesic mild cognitive impairment; V-PAL, Verbal Paired Associates Learning; CVLT, California Verbal Learning Test; CDT, clock drawing test; NTB, neuropsychological test battery; CLOX, executive clock drawing task.
*
Statistically significant difference (P≤ 0·05) between intervention and control groups at study completion.
†
Statistically significant difference P≤ 0·05 within group.
‡
No statistically significant difference between intervention and control at study completion.
§
Statistically significant difference between intervention and control at stated time-point.
***
Statistically significant difference P≤ 0·001 within group.