Table 2 Summary of characteristics for studies involving older adults with subjective cognitive impairment

Ban et al. 2018 Korea [20]

To examine the efficacy and safety of oral administration of Tremella fuciformis in individuals with subjective cognitive impairment

Community dwelling adults (65F:10 M) with subjective cognitive complaints aged m = 53.83 (± 5.5) years, range 40–65 years with 26F:4 M in the HD group and 26F:4 M in the LD group and 13F:2 M in the placebo group

MMSE (≥ 25), clinical dementia rating scale ≤ 0.5

Randomised, double-blind placebo control trial, outcomes at 0 and 8 weeks

Tremella fuciformis (species of fungus)

1) HD = 1200 mg daily (2 capsules, 3 × per day)

2) LD = 600 mg daily (2 capsules, 3 × per day)

3) Matched placebo (2 capsules, 3 × per day) N.R = placebo ingredients

8 weeks

Immediate recall from the pattern recognition memory task and the spatial span task (CANTAB), executive function (WCST)

Cognition: improvement in short-term memory and executive function in both HD and LD groups compared to placebo with a significant improvement in the HD group compared to placebo alone

Retention/adherence: 69/75 participants completed the study: HD 93.3%, LD 90% and placebo 93.3%, with a > 90% adherence rate in all groups

Adverse events: no serious AE’s were reported and no participants withdrew due to AE’s

Barbhaiya et al., 2008 India [21]

To evaluate the clinical efficacy, safety and tolerability of BacoMind® on impaired memory in elderly individuals

Adults with memory complaints for 1 year with no major cognitive deficits (AAMI) aged m = 64.98 (± 9.37) years, range 50–75 years with 23F:42 M

MMSE (≥ 24)

Randomised, double-blind placebo control trial, outcomes at 0, 12 and 24 weeks

BacoMind® (standardised extract of Bacopa monnieri with bioactive constituents) 1 × 450-mg capsule daily

Matched placebo 1 × capsule daily, N.R = ingredients in placebo, only states ‘matched without actives’

12-week intervention period then a 12-week withdrawal period

Digit Span Forward and Backward (WAIS), Digit Cancellation Test, Serial Subtraction Test, list learning (RAVLT) immediate and delayed recall, passages (WMS-1) immediate and delayed recall, paired associates—similar and dissimilar pairs—immediate and delayed recall, visual retention 1 (based on designs), visual retention 2 (based on pictures), digit symbol (WAIS)

Cognition: significant group × time interaction (improvement) for intervention c.f. placebo in: digit span backward, list learning delayed recall, paired associates dissimilar delayed recall and visual retention

Retention/adherence: 59/65 completed the study with 15 then excluded as outliers, participants taking ≥ 85% of medication were considered compliant

Adverse events: no serious, mild or moderate adverse events reported by participants

Brautigam et al., 1998 The Netherlands [22]

To determine the efficacy and tolerance of two dosages of an alcohol/water extract of Ginkgo biloba versus placebo in the elderly with memory and/or concentration complaints

Elderly adults with self-reported memory and/or concentration complaints m = 68.96 (± 7.77) years, range 55–86 years with 31 males and 46 females in a high-dose group, 50F:32 M in a low-dose group and 47F:35 M in the placebo group

MMSE (≥ 20) and memory loss of known origin

Randomised, double-blind placebo control trial, outcomes at 0, 6, 12 and 24 weeks

Ginkgo biloba alcohol/water extract (composition: Ginkgo biloba leaf, folium, ethanol, flavone glycosides)

1) High dose (40 drops, 1.9 ml undiluted 3 × daily)

2) Low dose (40 drops (1.9 ml extract with placebo 3 × daily)

3) Placebo (40 drops, 1.9 ml 3 × daily) (water-soluble chlorophyll powder dissolved in an alcohol/water mixture, (water insoluble chlorophyll was dissolved in alcohol) both solutions were mixed together, taste and colour of all 3 dosages similar

4 weeks washout then 24 weeks treatment

EMCT (measuring attention and concentration), Benton test of visual retention-revised (short-term visual memory), Rey test parts 1 and 2 (short-term verbal memory and learning, long-term memory)

Cognition: no significant between-group improvements across time on the EMCT or Rey 1 and 2 tests. Within-group, Benton test scores increased in all 3 groups with the largest increase in the low-dose group

Retention/adherence: total withdrawals from high dose group = 15, low dose = 14 and placebo = 15 (total retention rate of 81.7%) with an adherence rate of 93.98%

Adverse events: 25 participants withdrew due to AEs including but not limited to gastro-intestinal complaints, dizziness, headache and sleepiness (across all groups)

Cicero et al., 2016 Italy [26]

To evaluate the effects of a rational assemblage of nutraceuticals on cognitive functions in a sample of 30 elderly subjects

30 older adults (m = 66 (± 3) years of age) (N.R = range, sex), with self-perceived cognitive decline

MMSE (20–27), self-perceived cognitive decline without a known diagnosis of cognitive decline or dementia

Randomised, double-blind placebo control trial, outcomes at 0 and 8 weeks

Combination of Bacopa monnieri dry extract 320 mg, l-Teanina 100 mg, Crocus sativus 30 mg, vitamin B6 9.5 mg, Biotine 450 mcg, folic acid 400 mcg, vitamin B12 33 mcg, vitamin D 25 mcg, copper 2 mg, capsule form and 1 per day

Matched placebo, 1 × capsule per day, N.R = placebo ingredients

8 weeks

MMSE

Cognition: improvement in MMSE score in the active group

Retention/adherence: no withdrawals from the trial, with 95% adherence in the active group and 90% in the placebo group

Adverse events: one reported aftertaste after active product intake

Herrlinger et al., 2018 USA [28]

To investigate the effects of supplementation with a spearmint extract on cognitive performance, sleep and mood in individuals with AAMI

Adults with AAMI (based on the National Institute of Mental Health criteria) aged m = 59.4 (± 0.6) years, range 50–70 years with 30 participants in each group (placebo, 600 mg spearmint and 900 mg spearmint), (overall 30 M:60F)

MMSE (≥ 24), MAC-Q (≥ 25), WMS (≤ 29 on VPA-1) and WMS (≤ 9 on VPA-2)

Randomised, double-blind placebo control trial, outcomes at 0, 45 and 90 days (average on each day) (participants arrived on testing day fasting from product/food and were assessed 15 min prior to ingestion of intervention or placebo, then 30 min and 2, 4 and 6 h after ingestion. Average of scores across testing day equiv. to the overall score for that day)

1) 600 mg spearmint extract (Mentha spicata L.)/day (2 × capsules total)

2) 900 mg spearmint extract (Mentha spicata L.)/day (2 × capsules total)

3) Placebo capsules contained microcrystalline cellulose/day (2 × capsules total), N.R = if matched on taste, appearance and smell

90 days

CDR − with 11 tasks investigating attention and information processing, episodic and working memory, executive function and tracking (motor control)

Cognition: 900 mg spearmint group significantly improved in working memory and spatial working memory accuracy

Retention/adherence: 3 participants withdrew (1 from the placebo group and 2 from the 600 mg group due to adverse events with a 98.1% (placebo), 99.1% (600 mg) and 100% (900 mg) adherence

Adverse events: three participants reported AE’s: knee pain, myalgia, headache, worsening of oily scalp, cystic acne and heartburn. All deemed ‘not related’ with the exception of heartburn in both the placebo and 600 mg intervention groups

Macpherson et al., 2012 Australia [38]

To investigate the effects of 16-week supplementation of a multivitamin and herbal formula on cognition in community-dwelling, elderly women

Women reporting subjective memory complaints multivitamin group (m = 71.9 (± 4.8) years, placebo group (m = 70.3 (± 4.3) years, range 64–82 years with 28 participants in each group

MMSE (≥ 24), memory questionnaire to screen for SMCs and medical exam with a medical practitioner to determine whether participants were in good health

Randomised, double-blind placebo control trial, outcomes at 0 and 16 weeks

Swisse Women’s Ultivite 50 + ™ tablet (combination formula with 46 ingredients, with the largest quantities being from Silybum marianum dry fruit (St. Mary’s thistle), Ginkgo biloba and Vitis vinifera dry seed (grape seed), 1 tablet each day with breakfast. Placebo tablet matched on appearance of intervention, contained starch and 2 mg of riboflavin (vitamin B2), 1 tablet taken with breakfast

16 weeks

Swinburne University computerised cognitive assessment battery (SUCCAB) and CVLT-2 (word list learning)

Cognition: spatial working memory reaction time improved significantly for the intervention group, across time, compared to placebo

Retention/adherence: 51/56 completed the study. Adherence was an average of 97%, with participants < 80% excluded from the trial (only 1/56 non-compliant)

Adverse events = 1 participant from intervention experienced nausea and vomiting, and one in placebo developed a mild rash, both participants withdrew from study

Neri et al., 1995 Italy [33]

To determine the influence of treatment (intervention) on two major domains of well-being and their interrelationships (psychological well-being—affection and cognitive functioning and perceived quality of life)

Older adults (m = 60.45 (± 3.9) years, range 51–65 years) with AAMI, 21F:9 M in the intervention group and 21F:9 M in the placebo group

MMSE (≥ 24)

Randomised, double-blind placebo control trial, outcomes at 15 days, 3, 6 and 9 months (only first and last session analyses conducted)

Standardised ginseng extract G115 (N.R = dose) (from the root of Panax ginseng), dimethylaminoethanol bitartrate, minerals and vitamins (not specified)—two capsules daily (one after breakfast, one after lunch). Placebo ‘identical’ to study drug—two capsules daily (one after breakfast, one after lunch), N.R = placebo ingredients

9 months

RMT − (memory index, acquisition recall and deferred memory)

Cognition: memory index significantly increased in the treatment group compared to placebo at the endpoint

Retention/adherence: no withdrawals reported in the study with a 92% adherence rate as an average across the duration of the study (reported at 3-month intervals)

Adverse events: none reported by participants

Raghav et al., 2006 India [35]

To study the efficacy of SBME in subjects with AAMI

Forty adults with AAMI, range 55–70 years, N.R = mean age (± SD), (3F:37 M) with 20 participants in each group

MMSE (≤ 24) and WMS Logical Memory (< 6)^a

Randomised, double-blind placebo control trial, outcomes at 0, 4, 8, 12 and 16 weeks

125 mg of SBME twice a day, N.R = type of administration. Placebo twice daily, N.R = administration, ingredients

12 weeks, then following 4 weeks of a placebo period

Mental control, logical memory, digit forward, digit backward, visual reproduction and paired associate learning (WMS)

Cognition: mental control (12 weeks), logical memory (4 weeks, 8 weeks and 12 weeks), digit forward (12 weeks) and paired associated learning (8 and 12 weeks) significantly improved at each of the time points listed during the intervention period

Retention/adherence: 87.5% retention (2 participants in the placebo group and 1 in the SBME group withdrew), N.R = adherence

Adverse events: 1 patient withdrew due to maculopapular rashes in the intervention group

Zhu et al., 2016 China [37]

To evaluate the safety and effectiveness of short-term administration of BrainPower Advanced, a multi-ingredient dietary supplement on SMCs in older adults

Community volunteers with SMCs aged m = 67.1 (± 10.5) years, range 47.28–88.43 years including 33F:14 M in the intervention group and 34F:17 M in the placebo group (ages and participant numbers calculated after withdrawals)

No reports of hypomnesis, forgetfulness, memory loss or impaired attention/concentration as determined by a standard medical questionnaire, constructed and validated for a Chinese population, participants scoring 1 (no SC or occasional slight SC) or 2 (slight/mild SC) were combined as ‘slight SC group’, 3 (moderate severe), 4 (severe) and 5 (very severe) were categorised as ‘severe SC group’, N.R = name of questionnaire

Randomised, double-blind placebo control trial, outcomes at 0 and 12 weeks

BrainPower Advanced (Phosphatidylserine, Catharanthus roseus, Huperzia serrata (whole plant), Ginkgo biloba, vitamin B6, vitamin B12, l-tyrosine, l-pyroglutamic acid, green tea extract (Camellia sinensis leaf), acetyl-l-carnitine, cola nut extract (kola nitida), choline bitartrate, l-glutamine, l-phenylalanine and l-cysteine) (2 capsules with meals daily

Matched placebo, mainly containing flour, N.R = specific dose measurements for active and placebo (states 2 capsules with meals p/day) or additional placebo ingredients

12 weeks

Visual/auditory memory, abstracting and memory recall

Cognition: no significant between group improvements across time. Within group, both intervention and placebo outcomes improved across time—audio/visual memory, abstracting ability and memory retrieval (except memory retrieval for placebo)

Retention/adherence: 98/101 participants completed the study, N.R = adherence

Adverse events: 2 adverse event reports with withdrawal of participants due to gastrointestinal upset, N.R = which group they withdrew from