Table 4.

Study outcomes and results summary

References	Outcomes measured	Cognitive domain						Mood, depression, or anxiety	Main results
		Sensation	Perception	Motor skills and construction	Memory	Executive functioning	Language or verbal skills
Haskell-Ramsay et al (2017)16	Memory (immediate and delayed word recall, numeric working memory, word recognition, picture recognition) Attention (simple reaction time, choice reaction time, digit vigilance) Subjective mood (calm, content, alert)	×	✓	×	✓	×	×	✓	Acute results (20 min): improved perception (reaction time on a composite attention measure) (P = 0.047) No effect on memory outcomes Improved mood (increased calm ratings) (P = 0.046) No significant correlations between change in mood ratings and composite cognitive scores were observed.
Bell et al (2020)17	Language or verbal skills (auditory verbal learning test, serial subtraction 3 s and 7 s, the Modified Attention Network Test) Motor skills (simple and complex finger tapping and the switching task) Memory (retention of words over different time-lapses) Executive function (switching task) Subjective mood Mental fatigue	×	✓	✓	✓	✓	×	✓	Overall, outcomes showed no significant effects of treatment for acute and chronic analysis Acute analysis (4–6 h): Improved executive function (faster responses for switching tasks) (P < 0.01) relative to placebo at 2 h and 4 h Improved attention (faster scores in Modified Attention Network Test) (P < 0.001), but this result was also seen in the placebo group Chronic analysis (3 mo): Improved motor skills (finger tapping) (P < 0.05) whereby performance decreased between weeks 6 and 12 for the placebo (P < 0.05) Mood overall was not improved
Calapai et al (2017)18	Memory, attention, and language (Mini-Mental State Examination) Depression (Beck Depression Inventory) Anxiety and Mood (Hamilton Anxiety Rating Scale) Repeatable Battery for the Assessment of Neuropsychological Status	×	✓	×	✓	×	✓	✓	Chronic analysis (3 mo): Improvements relative to placebo and baseline data Improvement in memory, attention, and language (Mini-Mental State Examination scores improvement, P < 0.0001) Improved Repeatable Battery for the Assessment of Neuropsychological Status (P < 0.001), attention (P < 0.001), language (P < 0.05), immediate and delayed memory (both P < 0.0001) Improvement in depression and anxiety. Scores of Beck Depression Inventory (P < 0.0001) and Hamilton Anxiety Rating Scale (P < 0.05) reduced
Lamport et al (2016)19	Language or verbal skills and memory (visual verbal learning test, immediate recall–verbal memory, visual spatial learning test immediate recall–nonverbal spatial memory, Rey Auditory Verbal Learning Test) Executive function (rapid visual information processing, Tower of Hanoi) Motor skills and construction (psychomotor skill, grooved pegboard, driving performance.) Subjective mood, stress, anxiety (100-mm visual analog scales with questions, Perceived Stress Scale, short State–Trait Anxiety Inventory)	×	×	✓	✓	✓	×	✓	Chronic analysis (3 mo): Improvements relative to placebo and to baseline data Improvement in immediate spatial memory and driving performance relative to placebo (P < 0.05). Visual spatial learning test immediate recall showed a significant main effect of condition recall higher after the intervention (no P-value presented). Improvement in executive function (completion time was faster after the intervention) (P < 0.01). Driving performance was more accurate and better scores were recorded for the intervention group (P < 0.05). Alertness and concentration were significantly higher for participants in the intervention group (P < 0.05). There were no improvements in subjective mood, stress, or anxiety.
Krikorian et al (2010)20	Memory and language or verbal skills (verbal learning, retention, nonverbal memory by using The California Verbal Learning Test) Mood and depressive symptoms (Geriatric Depression Scale)	×	×	×	✓	×	✓	✓	Chronic analysis (3 mo): Improvements relative to placebo and to baseline data Improved verbal learning. Significant effect (P = 0.04) for item acquisition across learning trials on the California Verbal Learning Test No significant effect on depressive symptoms, mood, or enhancement of verbal and spatial recall memory
Krikorian et al (2012)21	Memory and language or verbal skills (Montreal Cognitive Assessment and Rey Auditory Verbal Learning Test, the California Verbal Learning Test-II) Mood and depressive symptoms (Geriatric Depression Scale) Brain activation during working memory tests, mood	×	×	×	✓	×	✓	✓	Chronic analysis (4 mo): Enhanced neurocognitive functions (significant effect for right middle frontal cortex, P = 0.05, and marginally significant effect for right superior parietal cortex P = 0.07), indicating greater activation in the grape group compared with the placebo group Reduced semantic interference on memory tasks, but no other effect on memory and language or verbal skills No effect on mood
Bensalem et al (2019)22	Memory (visuospatial learning and episodic memory test, episodic verbal recall memory using the VRM free recall test, working memory, verbal recall memory)	×	✓	×	✓	×	×	×	Chronic analysis (6 mo): improvements relative to placebo and to baseline data No significant difference was observed between intervention and placebo groups in verbal recall and working memory. However, there was improved verbal episodic and recognition memory performance (P = 0.006). There was improved cognitive and memory performance compared with baseline scores, but not compared with the placebo group.
Lee et al (2017)23	Memory (Hopkins Verbal Learning Test-Revised, Benton Visual Retention Test, Rey–Osterreith Complex Figure Test delayed, visuospatial–Rey–Osterreith Complex figure test copy, attention and working memory WAIS-III Letter–Number Sequencing) Language or verbal skills (Boston Naming Test, Letter Fluency FAC, Category Fluency, Estimated Verbal IQ Wechsler Test of Adult Reading) Executive function (Stroop Interference, Trail Making Test–Part B, Wisconsin Card Sorting Test-64, Speed of information Processing, WAIS-III Digital Symbol, WAIS-III Symbol speed) Depression and anxiety (Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale) Neuroimaging tests	×	×	×	97	✓	✓	✓	Chronic analysis (6 mo): Analysis relative to baseline data. No differences between the groups presented in the paper There were no significant changes among any of the measured outcomes (P > 0.05) Decline in the metabolism of the right posterior cingulate cortex (P = 0.01) and left superior posterolateral temporal cortex (P = 0.04) in the placebo group. These regions are known to be significantly affected in the early stages of Alzheimer’s disease, and the decline was seen in the placebo group, but not the active grape formulation group. This would suggest a beneficial effect on the intervention group.