. 2022 Aug 10;11(8):1549. doi: 10.3390/antiox11081549

Table 3.

Summary of included studies.

Study	Intervention	Cognitive Variable Measurement Tool and Measurement Frequency (Months)	Results
Catechins/Flavanols
Ide et al. (2016) [12]	-I: 2 g/day green tea (220.2 mg catechins) -C: placebo	-MMSE (Japanese version) -NPQ-I -Laboratory tests (MDA-LDL, TC, LDL, HDL, TG, FPG, HbA1c)	-The levels of MDA-LDL, a marker of oxidative stress, were significantly lower in the green tea group. -No significant changes in the rest of the analytical parameters. -No significant changes in MMSE-J or NPI-Q scores.
Ide et al. (2016) [12]	-I: 2 g/day green tea (220.2 mg catechins) -C: placebo	(0–3-6–9–12 months)
Mastroiacovo et al. (2015) [8]	-I: HF drink (993 mg/day flavanol) -I: IF drink (520 mg/day flavanol) -I: LF drink (48 mg/day flavanol)	-MMSE -TMT A and B -VFT -BP -Laboratory tests (glucose, insulin, TC, LDL, HDL, TG, HOMA-IR index, 8-Iso-PGF)	-Lower response time after the HF and IF drinks in the TMT tests. -Improvement in all treatments in the VFT test, but greater improvement after the HF drink. -Lower SBP and improvement in insulin resistance and fluid peroxidation after drinking HF and IF. -No change in MMSE score or DBP.
Mastroiacovo et al. (2015) [8]		(0–2 months)
Brickman et al. (2014) [20]	-I: High intake (900 mg cocoa flavanols and 138 mg epicatechin daily) + aerobic exercise (1 h/day 4 days/week) -I: High intake + no aerobic exercise -I: Low intake (10 mg cocoa flavanols and 12 mg epicatechin daily) + aerobic exercise (1 h/day 4 days/week) -I: Low intake (10 mg cocoa flavanols and 12 mg epicatechin daily) + no aerobic exercise	-ModBent test -fMRI	-An intervention with high flavanol content has a significant effect on ModBent performance (independent of exercise). Improvement of 630 ms with respect to those of the intervention with low content. -Changes in the ModBent and changes in the CBV images of the dentate gyrus are correlated. -Exercise has no significant effect on ModBent.
Brickman et al. (2014) [20]		(0–3 months)
Desideri et al. (2012) [9]	-I: High intake (990 mg/day flavanols) -I: Intermediate intake (520 mg/day flavanols) -I: Low intake (45 mg/day flavanols)	-MMSE -TMT A and B -VFT -BP -Laboratory tests (glucose, insulin, TC, LDL, HDL, TG, HOMA-IR index, 8-Iso-PGF)	-Lower response time after high intake drinks (−14.3 s and −29.2 s) and intermediate (−8 s and −22.8 s) in the TMT A and B tests, respectively. -Greater improvement in VFT in subjects with high drink intake (+8 words in 60 s) and medium (+5.1 words), and, to a lesser extent, in low intake (+1.2 words). -Lower insulin resistance in high (−1.6 mU/L) and medium (−0.9 mU/L) intake. -Lower glucose levels in high (−0.6 mmol/L) and medium (−0.5 mmol/L) intake. -BP: High intake (SBP −10 mmHg and DBP −4.8 mmHg), medium (SBP −8.2 mmHg and DBP −3.4 mmHg) and, to a lesser extent, low intake (SBP −1.4 mmHg and DBP −0.9 mmHg). -Total plasma levels of 8-iso-PGF2 decrease in high (−99.8 pg/L) and intermediate (−65.8 pg/L) intake. -No change in MMSE score. -No changes in insulin, total cholesterol, LDL, HDL, and triglycerides.
Desideri et al. (2012) [9]		(0–2 months)
Krikorian et al. (2012) [21]	-I: Grape juice (425 mgl/L anthocyanins and 888 mg/L procyanidins) -C: Placebo * Daily dose by weight (6.3–7.8 mL/kg)	-GDS -RAVLT -CVLT -BP -Laboratory tests (glucose, insulin) -Anthropometric parameters (weight, height) -fMRI	-CVLT without changes, but with a tendency to better performance in the placebo group (13.8 vs. 12.4) but fewer errors (7.16 vs. 5.03) and better ability to distinguish the elements learned in the intervention group. -Greater activation in the regions of the hemisphere (fMRI images) of the patients in the group consuming grape juice, in turn being associated with a vascular benefit. -No changes in analytical or anthropometric parameters. -No changes in the GDS.
Krikorian et al. (2012) [21]		(0–4 months)
Lee et al. (2017) [22]	-I: freeze-dried grape powder made from fresh California grapes -C: placebo * 72 g/day, equivalent to 3 standard servings of fresh grapes per day.	-ADAS-Cog -MMSE -HVLT -Benton visual retention test -ROFT Test -Boston Appointments Test -Fluency of FAC letters -Fluency of categories (naming animals) -Stroop test -TMT A and B -WCST -Symbol and digit speed (WAIS-III tasks) -MFQ -HDRS -fMRI	-Improvements in attention/working memory according to the WAIS-III tasks in the intervention group. -Decline in the posterior cingulate and superior posterolateral temporal cortical regions in the placebo group while the intervention group did not observe said decline. -No significant changes in the rest of the tests.
Lee et al. (2017) [22]		(0–6 months)
Lamport et al. (2015) [23]	-High intake: 494 mg/day flavanols -Low intake: 23 mg/day flavanols	-CBF -fMRI	-Better regional cerebral perfusion in the group that consumed the drink with high flavanol intake (in the anterior cingulate cortex and in the parietal lobe regions).
Lamport et al. (2015) [23]		(0–2 h)
Pase et al. (2013) [24]	-I: High intake (500 mg/day cocoa flavanols) -I: Average intake (250 mg/day cocoa flavanols) -C: Placebo	-CDR -Bond-Lader Visual Analogue Scale	-Greater calm and self-rated satisfaction after receiving 30 days of treatment with high dose of flavanols. -Mood did not change with acute treatment. -Cognitive performance did not vary at any of the measurement times.
Pase et al. (2013) [24]		(0–1 h-2.5 h-4 h-30 days)
Resveratrol/Stilbenes
Witte et al. (2014) [25]	-I: 200 mg resveratrol and 320 mg quercetin daily -C: Placebo	-AVLT -PANAS -Freiburger Physical Activity Questionnaire -BP -Laboratory tests (glucose, insulin, TC, LDL, HDL, TG, HbA1c, leptin, BDNF, IGF-1, TNF-, interleukin 6, hs-CRP) -Anthropometric parameters (biomedical impedance, weight, height) -Vascular markers (CMIT)-fMRI	-Better delayed recall and recognition in the subjects of the intervention group. Learning ability significantly improved in both groups, but with a greater difference in the group that ingested resveratrol and quercetin. After the intervention, retention in the subjects was lower. * retention: number of correct words recalled after the fifth trial (maximum 15 words) subtracted from those recalled correctly after the 30 min delay (maximum 15 words). * delayed recall: number of words correctly recalled after the 30 min delay (maximum 15 words). * recognition: number of words correctly recognized minus false positives from a subsequent list of 45 words read aloud that included 15 correct words and 30 new ones (maximum 15). * learning capacity: sum of words correctly recalled during the five immediate learning trials (maximum score: 75 words). -Increased functional connectivity of the hippocampus in the frontal, parietal, and occipital areas. -Decrease in HB1ac (−0.13%) and DBP (−5.2 mmHg), and increase in leptin (+7.5 ng/mL). -No change in physical activity and mood.
Witte et al. (2014) [25]		(0–6+1/2 months)
Anton et al.(2018) [10]	-I: 1000 mg/day of resveratrol -I: 300 mg/day of resveratrol -C: placebo	-COWA. -Word Digits Forward and Backward and Digit Symbol Substitution Test (WAIS-IV tasks) -Eriksen flanking task- HVLT-R. -Change of tasks -TMT A and B	-Better psychomotor speed in the TMT A test in the intervention group with 1000 mg/day of resveratrol compared with 300 mg/day of resveratrol (−10.59 s) and placebo (−8.79 s). -No significant changes in performance on tests of visual attention, working memory, verbal fluency, and semantic memory between treatment groups.
Anton et al.(2018) [10]		(0–3 months)
Moran et al. (2018) [26]	-I: multi-ingredient supplement (omega-3 polyunsaturated fatty acids, vitamin D, 150 mg resveratrol and whey protein) -C: placebo	-TMT A and B -RAVLT -TUG -CFQ -Stroop test (CW version) -COWA -Digits of words forwards and backwards (WAIS-III task)	-In the intervention group there was a shorter response time in the Stroop Test both at 3 and 6 months, compared with the placebo group. -No significant changes in the rest of the tests.
Moran et al. (2018) [26]		(0–3-6 months)
Wong et al.(2016) [27]	-I: 300 mg/day of resveratrol -I: 150 mg/day of resveratrol -I: 75 mg/day of resveratrol -C: placebo	-CVR	-Resveratrol consumption increased CVR in MCA with all 3 doses of resveratrol: mean change from placebo was 13.8 ± 3.5% at intake of 75 mg resveratrol, 8.9 ± 3.5% in the 150 mg resveratrol dose, and 13.7 ± 3.3% in the 300 mg resveratrol dose. -The 75 mg dose was the only effective one in PCA, 13.2 ± 4.5% compared to placebo.
Wong et al.(2016) [27]		(0–45/60 min–90/120 min after treatment). Four separate visits of 7 days were made
Evans et al. (2017) [11]	-I: 150 mg/day of trans-resveratrol (2 capsules of 75 mg) C: placebo	-TMT A and B -RAVLT -Cambridge Semantic Memory Battery -BP and heart rate -TCD -CVR -Double Scope Task -POMS-V2 -CES-D	-Significant improvements in the immediate RAVLT (+4.5 words), in categorical fluency (+3.2 words), and in the camel and cactus test (+2.8 correct answers). These improvements correlate with a 17% CVR increase. -Mood tended to improve in the intervention group but not significantly.
Evans et al. (2017) [11]		(0–3 + 1/2 months)
Kobe et al. (2017) [13]	-I: 200 mg of resveratrol and 350 mg of quercetin daily -C: Placebo 1015 mg/day of olive oil	-RAVLT -PANAS -BDI -STAI X1 -Freiburger physical activity questionnaire -Analytical parameters (glucose, insulin, LDL, HDL, HbA1c and hs-CRP) -Anthropometric parameters (BMI and weight) -fMRI	-No significant differences in memory performance between the intervention group and the placebo group. -HbA1c was significantly reduced (−0.15%) after resveratrol intervention. -Hippocampal volume is preserved, and functional connectivity at rest of the hippocampus improves in the intervention group.
Kobe et al. (2017) [13]		0–6 + 1/2 months

ADAS-COG: Cognitive subscale of the Alzheimer’s Disease Rating Scale; BDI: Beck’s Depression Inventory; BDNF: Brain Derived Neurotrophic Factor; BP: Blood Pressure; CBF: Cerebral Blood Flow; CBV: Cerebral Blood Volume; CDR: Cognitive Drug Research; CES-D: The Center for Epidemiological Studies Depression Scale; CFQ: Cognitive Failures Questionnaire; CMIT: Carotid Intima Media Thickness; COWA: Controlled Oral Word Association Test; CVLT: California Verbal Learning Test-II; CVR: Cerebrovascular Responsiveness; DBP: Diastolic Blood Pressure; fMRI: magnetic resonance imaging; FPG: Fasting Plasma Glucose; GDS: Geriatric Depression Scale; HbA1c: Hemoglobin A1c; HDL: High Density lipoprotein cholesterol; HDRS: Hamilton Depression Rating Scale; HF: High Flavanol; HOMA-IR índice: [insulina sérica en ayunas (mU/L) x glucosa plasmática en ayunas (mmol/L)]/22.5; hs-CRP: High Sensitive C Reactive Protein; HVLT-R: Hopkins Verbal Learning Test-Revised; IF: Intermediate Flavanol; IGF-1: Insulin Like Growth Factor 1; 8-Iso-PGF: 8-iso-prostaglandin F (índice de peroxidación lipídica relacionado con el estrés oxidativo); LDL: Low Density Lipoprotein Cholesterol; LF: Fow Flavanol; MCA: Middle Cerebral Arteries; MDA-LDL: Malondialdehyde-modified Low Density Lipoprotein;MFQ: Memory Function Questionnaire; MMSE: Mini Mental State Examination; MRS: Menopausal Rating Scale; NPI-Q: The Neuropsychiatric Inventory Questionnaire; PANAS: Positive and Negative Affect Schedule; PCA: Posterior Cerebral Arteries; POMS-V2: Profile of Mood States; RAVLT: Rey Auditory Verbal Learning Test; ROFC Test: Rey Ostereith Complex Figure Test; SPB: Systolic Blood Pressure; STAI X1: State Trait Anxiety Inventory; TC: Total Cholesterol; TCD: Transcranial Doppler; TG: triglycerides; TMT A y B: Trail Making Test A y B; TNF-: Tumor Necrosis Factor; TUG: Timed Up and Go; VFT: Verbal Fluency Test; WAIS-IV: Wechsler Adult Intelligence Scale IV; WAIS-III: Wechsler Adult Intelligence Scale III; WCST: Wisconsin Card Sorting Test.