. Author manuscript; available in PMC: 2019 Aug 3.

Published in final edited form as: Br J Nutr. 2018 Nov 9;120(12):1388–1405. doi: 10.1017/S0007114518002945

Table 2. Overview of study characteristics.

Author, year and location	MCI sample characteristics	Diagnostic criteria for MCI	Intervention	Study duration	Outcome measures
Bayer-Carter et al. (2011)⁽³⁸⁾ (n 49) USA	68·4 years aMCI=29 High=15 Low=14 Healthy controls=20 High=9 Low=11 Lost to follow up=no detail	Petersen (2004)⁽⁸²⁾	Intervention groups: (1) High diet – 45% fat (saturated fat 25%), 35–40% carbohydrate (GI >70) and 15–20% protein (2) Low diet – 25% fat (saturated fat <7%), 55–60% carbohydrate (GI <55) and 15–20% protein Control group: healthy adult control group	4 weeks	Immediate and delayed memory: story recall, word list, brief visuospatial memory test; executive function: trail making test part B, Stroop test, verbal fluency test; motor speed: trail making test part A, Stroop test; AD biomarkers CSF Aβ42, CSF Aβ40, tau protein phosphorylated tau, ApoE
Horie et al. (2016) (n 80)⁽³⁷⁾ Brazil	68·1 years Intervention=40 Control=40 Lost to follow up=5	European Consortium on Alzheimer’s Disease⁽⁸⁰⁾	Intervention group: energetic restriction and counselling with nutritionists (26–28×1 h meetings). Advice-eating a diet rich in fibre, fruits, vegetables, wholegrains and included at least 1 g/kg body weight of protein/d. Recommended energy deficit of approximately 500 kcal/d (2092 kJ/d) (min 1200 kcal/d (5021 kJ/d)) Control group: conventional medical care with consultant geriatrician All participants were advised to engage in physical activity (at least 150 min/week of moderate intensity aerobic activity or walking)⁽³⁵⁾	12 months	Verbal memory: RAVLT delayed recall, total learning and recall recognition; attention: digit span forward, digit span backward, trail making test part A; working memory: digit span backwards, trail making test part; psychomotor processing speed: trail making test part A, trail making test part B; executive function: modified Wisconsin Card Sorting Test, trail making test part B, verbal fluency; language: phonemic verbal fluency, semantic verbal fluency
Krikorian et al. (2012)⁽¹²⁾ (n 23) USA	70·1 years High carbohydrate=11 Low carbohydrate=12 Lost to follow up=0	CDR⁽⁸¹⁾	Intervention groups: high carbohydrate (50% of total energy content) v. a very low carbohydrate group (5–10% total energy content). Intake of protein and fat were allowed to vary and total energy intake was not restricted	6 weeks	Working memory and executive ability: trail making test, part B. Secondary or long term memory: V-PAL test
de Jager et al. (2012)⁽²⁵⁾ (n 266) UK	76·8 years Intervention=133 Control=133 Lost to follow up=43	Petersen criteria (2004)⁽⁸²⁾	Intervention group: 0·8 mg folic acid, 0·5 mg vitamin B₁₂, 20 mg vitamin B₆ (daily) Control group: vitamin-free tablets of similar appearance	2 years	Global cognition: MMSE; episodic memory: HVLT-R; semantic memory: category fluency CERAD; executive function: CLOX; clinical outcome measures: CDR
Ma et al. (2016)⁽²⁴⁾ (n 180) China	65 years Intervention=90 Control=90 Lost to follow up=21	Petersen criteria (2004)⁽⁸²⁾	Intervention group: oral folic acid (400 μg/d). Participants were instructed to supplement with one tablet daily, during or immediately after a meal Control group: conventional medical treatment	6 months	Chinese version of the WAIS-RC-information, similarities, vocabulary, comprehension, arithmetic, digit span, block design, picture completion, digit symbol-coding, object assembly and picture arrangement
DeKosky et al. (2008)⁽²⁶⁾ (total study n 3069, n 482 with MCI) USA	79·1 years Intervention=256 Control=226 Lost to follow up: 195 (total study)	International Working Group on MCI Guidelines⁽⁸³⁾	Intervention group: twice-daily doses of 120 mg G. biloba extract Control group: received an identically appearing placebo	6·1 years	Diagnosis of dementia by DSM-IV criteria, modified MMSE, CDR, ADAS-Cog
Lee et al. (2013) (n 36)⁽²⁷⁾ Malaysia	65·0 years Intervention=18 Control=18 Lost to follow up=1	Petersen criteria (2004)⁽⁸²⁾	Intervention group: 3×1-g soft gelatine capsules each day, each containing 430 mg of DHA and 150 mg of EPA Control group: isoenergetic placebo maize oil (0·6 g linoleic acid)	12 months	Memory: visual reproduction I and II, RAVLT, digit span backward; executive function and attention: clock drawing test, digit span forward; psychomotor speed: digit symbol substitution test; visuospatial skills: matrix reasoning, block design; global cognitive function: MMSE
Petersen et al.(2005)⁽³¹⁾ (total study n 769) USA and Canada	72·9 years Donepezil=253 Vitamin E=257 Placebo=259 Lost to follow up: 230 (total study)	Petersen (1999)⁽⁸⁴⁾	Intervention group: (1) 2000 IU (1·3mg) of vitamin E, placebo donepezil and a multivitamin daily; (2) 10mg of donepezil, placebo vitamin E and a multivitamin daily. The multivitamin contained 15 IU of vitamin E. The initial dose of vitamin E was 1000 IU daily, and the dose was increased to 2000 IU (1000 IU twice daily) after 6 weeks Control group: received a placebo vitamin E, placebo donepezil and a multivitamin daily	3 years	Primary end-point: time to development of possible of probable Alzheimer’s disease; secondary: MMSE, ADAS-Cog, global CDR, CDR-SB, the global deterioration scale neuropsychological battery consisting of: New York University paragraph recall test, symbol digit modalities test, category fluency test, number-cancellation test, Boston naming test, digits-backwards test, clock drawing test, maze tracing task
Desideri et al.(2012)⁽³⁴⁾ (n 90)Italy	71·2 years High=30 Medium=30 Low=30 Lost to follow up: 3 (included in analysis)	Petersen criteria (2004)⁽⁸²⁾	Intervention group: once daily a dairy-based cocoa drink containing cocoa flavanols either at – (1) high flavanol (990mg of flavanols per serving), (2) intermediate flavanol (520 mg of flavanols per serving) and (3) low flavanol (45 mg of flavanols per serving)	8 weeks	MMSE, trail making test A and B, verbal fluency test
Krikorian et al. (2010)⁽³⁵⁾ (n 12) USA	72·8 years Male and female Intervention=5 Control=7 Lost to follow up=0	CDR⁽⁸¹⁾	Intervention group: 100% concord grape juice. A dosing schedule was instituted determined by body weight to maintain daily consumption between 6 and 9ml/kg, a range consistent with other human grape juice trials. Taken daily in equal, divided dosages with the morning, midday and evening meals Control: contained no juice or natural polyphenol	12 weeks	Memory: V-PAL test and CVLT
Krikorian et al. (2010)⁽³²⁾ (n 26) USA	71·0 years Intervention=15 Control=11 Lost to follow up=no detail	CDR⁽⁸¹⁾	Intervention group: chromium picolinate containing 1000 μg elemental Cr Control group: placebo – no details	12 weeks	Memory: CVLT functional MRI scanning
Bo et al. (2017) (n 86)⁽²⁸⁾ China	71·1 years Intervention=42 Control=44 Lost to follow up=22	Petersen criteria (1999)⁽⁸⁴⁾	Intervention group: 625 mg DHA+600 mg EPA (twice daily) Control group: placebo capsules containing olive oil (twice daily)	6 months	Basic cognitive aptitude tests: digit copy, Chinese character comparison, mental arithmetic, Chinese character rotation, recall answer of mental arithmetic, recognition of two-word nouns, and recognition of meaningless figures. These seven sub-items were divided into five sections: perceptual speed, mental arithmetic efficiency, space imagery efficiency, working memory and recognition memory
Soininen et al.(2017)⁽³³⁾ (n 311)Finland	71·0 years Intervention=153 Control=158 Lost to follow up/discontinued=66	Dubois et al.(2007)⁽⁸⁵⁾	Intervention group: medical food Souvenaid, a 125 ml once-a-day drink containing the specific nutrient combination Fortasyn Connect (1200 mg DHA, 300 mg EPA, 106 mg phospholipids, 400 mg choline, 625 mg UMP, 40 mg vitamin E, 80 mg vitamin C, 60 μg Se, 3 μg vitamin B₁₂, 1 mg vitamin B₆, 400 μg folic acid) Control group: 125 ml once-a-day control drink	24 months	Primary end points: composite Z score based on CERAD ten-word list learning immediate recall, CERAD ten-word delayed recall, CERAD ten-word recognition, category fluency and LDST. Memory (CERAD ten-word list learning immediate recall, delayed recall and recognition); executive function (category fluency, Wechsler Memory Scale revised digit span total score, concept shifting test condition C (corrected for the zero trials) and LDST); NTB total (composite Z score based on all sixteen items of the NTB); secondary end points: CDR-SB; brain volumes based on MRI; progression to dementia by DSM-IV Criteria
Zhang et al. (2017) (n 240)⁽³⁰⁾ China	74·5 years Intervention=120 Control=120 Lost to follow up=21	Petersen criteria (2004)⁽⁸²⁾	Intervention group: DHA supplementation (2 g/d) Control group: maize oil	12 months	Chinese version of the WAIS-RC. The WAIS-RC includes eleven sub-tests: information,arithmetic, digit span, block design, picture completion, digit symbol-coding, object assembly and picture arrangement
Phillips et al.(2015)⁽²⁹⁾ (n 57)UK	68·7 years Intervention=29 Control=28 Lost to follow up=2	Petersen criteria (2004)⁽⁸²⁾	Intervention group: 625 mg DHA+600 mg EPA (twice daily) Control group: placebo capsules containing olive oil (twice daily)	4 months	MMSE; Hopkins Learning Test Revised and neuropsychological measures of executive functioning, language, verbal reasoning and visual memory

MCI, mild cognitive impairment; aMCI, amnesic mild cognitive impairment; GI, glycaemic index; AD, Alzheimer’s disease; RAVLT, Rey Auditory Verbal Learning Test; CDR, clinical dementia rating; V-PAL, verbal paired associates learning; MMSE, Mini Mental State Examination; HVLT-R, Hopkins Verbal Learning Test – revised; CERAD, Consortium to Establish a Registry for Alzheimer’s Disease; CLOX, executive clock drawing task; WAIS-RC, Wechsler Adult Intelligence Scale Revised; ADAS-Cog, Alzheimer’s Disease Assessment Scale cognitive assessment; CDR-SB, clinical dementia rating-sum of boxes; CVLT, California Verbal Learning Test; LDST, letter digit substitution test; NTB, neuropsychological test battery.