Table 4. Study characteristics .
Serial Threes and Sevens and the virtual Morris Water Maze are used for cognitive performance exams; the Profile of Mood States is used for mood assessment. Biocurcuma, Theracurmin, CurQfen®️, and Curcumin C3 Complex are all synthetic copyrighted brands of curcumin. A positron emission tomography radiotracer is used for tracking neurofibrillary tangles and amyloid aggregates in the brain [15]. Cohen's d effect size measures the difference between group means.
sICAM: soluble intercellular adhesion molecule; c-Reactive Protein: carbohydrate capsule of the pneumococcus capsule reactive protein; SD: standard deviation; MoCA: Montreal Cognitive Assessment; P: probability value; FDDNP: 2-(1-{6-[(2-[fluorine-18]fluoroethyl)(methyl)amino]-2-naphthyl}-ethylidene)malononitrile; PET: positron emission tomography; BMI: body mass index; DHA: docosahexaenoic acid; EPA: eicosapentaenoic acid; CVR: cerebrovascular reactivity; WM: working memory; R: correlation coefficient; GSK-3β: glycogen synthase kinase-3β; IAPP: islet amyloid polypeptide; HOMA2-IR: homeostasis model assessment of insulin resistance; CGM: CurQfen®️-curcumin; USC: unformulated standard curcumin; MMSE: Mini-Mental State Exam; GI: gastrointestinal; η²: ratio of variance; CICI: chemotherapy-induced cognitive impairment; ∆ median: statistical variability from median; Z: z-score or statistical variability from the mean
| Author and year of publication | Population characteristics | Intervention studied | Number of patients | Study design | Results | Conclusion |
| Disilvestro et al. (2012) [12] | Healthy middle-aged adults (men and “post menopause women”) 40-60 years old | Lipidated curcumin extract (80 mg/day) | 38 (19 curcumin and 19 placebo) | four-week randomized and placebo-controlled trial | Curcumin had statistically significant results in plasma and salivary levels as follows: lower beta-amyloid protein, lower triglyceride, lower sICAM, lower alanine aminotransferase, lower amylase, higher myeloperoxidase without higher CRP, higher catalase, higher nitric oxide, and higher radical scavenging | Lipid preparation of curcumin can lead to health-promoting effects in healthy middle-aged adults |
| Cox et al. (2020) [13] | Healthy older people aged 50-80 years (mean=68.1, SD=6.34) | Longvida®️ curcumin (400 mg daily containing 80 mg curcumin) | 80 (40 curcumin and 40 placebo) | 12-week double-blind, placebo-controlled, and partial replication study | Curcumin was associated with statistically significant results in cognitive performance and serum levels as below: improved WM at 12 weeks (Serial Threes and Sevens, and virtual Morris Water Maze), lower fatigue at four and 12 weeks (Profile of Mood States), lower mood-related confusion at four weeks, and higher glucose | Longvida®️ preparations of curcumin improve WM and mood in healthy older adults. The improvements in hippocampal functional domains hold promise for alleviating cognitive decline in similar populations |
| Rainey-Smith et al. (2016) [14] | Healthy older adults 40-90 years old with no cerebrovascular disease or cognitive impairment | 1500 mg/day Biocurcuma™️ | 96 (160 initially enrolled) | 12-month randomized, placebo-controlled, and double-blind study | Curcumin was associated with statistically significant results in time to treatment for the MoCA (P<0.050). At six months, cognitive function declined in the placebo group, but not in the curcumin group. No other differences were detected | The study suggests curcumin can potentially prevent cognitive decline, but more research is needed to investigate changes in cognitive measures in conjunction with serum biomarkers |
| Small et al. (2018) [15] | Non-demented adults with normal brain aging or mild cognitive impairment age 50-90 years old | Bioavailable form of curcumin (Theracurmin®️ containing 90 mg of curcumin twice daily) | 40 (21 curcumin and 19 placebo) | 18-month randomized, double-blind, and placebo-controlled trial | Curcumin in the form of Theracurmin®️ was associated with statistically significant results in improved verbal memory (p=0.002), improved visual memory (p=0.006), improved attention (p<0.0001), and decreased FDDNP binding in the amygdala (p=0.04) and hypothalamus (p=0.02) as observed on PET | The results suggest daily curcumin in the form of Theracurmin®️ can improve memory and attention in non-demented adults. The coinciding FDDNP-PET results correlate these functional benefits with decreases in the neurodegenerative proteins amyloid and tau in brain areas controlling emotions and recall |
| Kuszewski et al. (2020) [16] | Overweight or obese (BMI 25-40 kg/m2) middle-aged and older adults (50-80 years) | Fish oil (2000 mg/d docosahexaenoic acid (DHA)+400 mg/d eicosapentaenoic acid (EPA), curcumin (160 mg/d), and combination | 152 (134 completed) | 16-week double-blind, and placebo-controlled intervention trial | The following statistically significant findings were observed: isolated curcumin caused improvement in CVR in a WM test and improved performance in a verbal memory test for males only, isolated fish oil caused improved CVR for processing speed tests in males only, and combining fish oil with curcumin did not add benefits | Improvements in processing speed following fish-oil consumption and memory following curcumin consumption in 50-80 years old males may correlate with improved circulatory function or CVR. Sex differences need more investigation |
| Lee et al. (2014) [17] | Pre-diabetic adults (BMI 18.5-30 kg/m2 and fasting glucose 100-125 mg/dL), age 60 and older | Turmeric (1 g), cinnamon (2 g), or both (1 g turmeric+2 g cinnamon) | 48 | Double-blind metabolic study | Curcumin in the form of dietary turmeric was associated with statistically significant results compared to cinnamon as follows: WM increased from 2.6 to 2.9 out of 3.0 (p=0.05); WM was inversely related to insulin resistance (R of 34.5% and p<0.01), not with serum biomarkers. WM responses to turmeric had significant beta-coefficients for turmeric, BMI, and insulin/glucose area under the curve | Consumption of turmeric with white bread improves WM regardless of body fat, glycemia, insulin, or biomarkers. Findings suggest turmeric may benefit the cognitive performance of adults with pre-diabetes |
| Thota et al. (2020) [18] | Adults with high risk of type 2 diabetes mellitus age 30-70 years | Curcumin (180 mg/day) | 29 (15 placebo and 14 curcumin) | 12-week randomized, double-blind, and placebo-controlled study | Curcumin is associated with statistically significant reductions in the following serum biomarker levels: GSK-3β (−2.4±0.4 ng/mL, p=0.00001) as compared to placebo (p=0.0068 ), IAPP (−2.0±0.7 ng/mL, p=0.01) as compared to placebo (p=0.0163), and HOMA2-IR (p=0.0142) compared to placebo (p=0.9747) | Curcumin significantly reduces serum levels of insulin resistance-biomarkers GSK-3β and IAPP, suggesting curcumin can decrease risk of type 2 diabetes and Alzheimer’s dementia |
| Das et al. (2023) [19] | Cognitively impaired adults aged 55-75 years with MMSE scores (14-24, all values inclusive) | CGM (400 mg x 2/day), USC complex with 95% purity, and placebo | 48 (16 per group) | Six-month randomized, double-blinded, placebo-controlled, and 3-arm, 3-sequence comparative study | Curcumin in the form of CGM compared to placebo and USC was associated with statistically significant results as follows: improved MMSE scores, improved Geriatric Locomotive Function Scale Scores, and improved serum biomarkers (brain-derived neurotrophic factor, beta-amyloid 42, tau protein, Interleukin 6, and tumor necrosis factor-α) | Curcumin in the form of CGM significantly hindered the development of Alzheimer’s disease, as observed in improved cognitive and locomotive functions as well as serum biomarkers. The bioavailable form of CGM is more effective than USC and the placebo |
| Ringman et al. (2012) [20] | Adults aged greater than 49 years with mild to moderate as well as probable, Alzheimer’s disease (MMSE scores 17-29), have a mean age of 73.5 years and mean MMSE score of 22.5 | Curcumin C3 Complex®️ (2 g/day or 4 g/day) | 36 | 24-week randomized, double-blind, and placebo-controlled study with a 24-week open-label extension | Curcumin as Curcumin C3 Complex®️ was associated with no difference in clinical measures or serum biomarker measures compared to placebo [20]. Serum levels of curcumin were low (7.32 ng/mL), and there were insignificantly lower serum hematocrit and increased serum glucose associated with curcumin [20]. One subject (8%) in the placebo group withdrew due to worse memory, and five of twenty-four subjects (21%) withdrew in the curcumin group due to gastrointestinal (GI) side effects | Curcumin was well-tolerated despite the GI side effects [20]. No clinical or biochemical efficacy of Curcumin C3 Complex®️ was found in Alzheimer's disease [20]. The lack of efficacy may be attributed to the limited bioavailability of the compound as suggested by preliminary data |
| Alimadadi et al. (2022) [21] | Major depressive disorder patients aged 18-55 years with normal literacy | Curcumin (500 mg twice daily) plus sertraline vs. placebo plus sertraline | 120 (60 curcumin and 60 control) | 12-week double-blind and randomized clinical trial | Curcumin compared to placebo was associated with statistically significant (P<0.001) results as follows: cognitive improvement in forwarding and backward digit span (η²=0.286 and η²=0.390), Trial Making Test-A and B (η²=0.161 and η²=0.026), verbal fluency task: letter and category (η²=0.105 and η²=0.128), Tower of London (η²=0.211), and inflammatory markers: interleukin 6 and 1β (η²=0.121 and η²=0.097) | Curcumin significantly enhanced cognitive performance and attenuated serum inflammatory markers for major depressive disorder patients, suggesting curcumin is a potential adjuvant treatment for depression |
| Putri Laksmidewi et al. (2024) [22] | Cooperative patients with cervical cancer treated with carboplatin-pacitaxel chemotherapy at risk of CICI; treatment group mean age 46.74 (SD: 10.67) and placebo mean age 50.46 (SD: 7.02) | Curcumin extract (240 to 400 mg intermittently) | 78 (39 curcumin and 39 placebo) | 24-week double-blind, randomized, and placebo-controlled trial | Curcumin compared to placebo was associated with statistically significant improvements in cognitive function as follows: Stroop test (∆ median 8.57 vs. 2.46; Z −4.503 vs. −1.762; p<0.0001 vs. 0.078) and MoCA-Ina (∆ mean 1.53 vs. 0.72; Z −2.99 vs. −2.05; p<0.003 vs. 0.04) [22]. No difference between groups was observed for drop-out, mortality, or adverse drug response | Curcumin extract administered intermittently with dose escalation significantly improved cognitive function in patients with CICI as compared to placebo, and it has a good safety profile |
| Ng et al. (2022) [23] | Community-dwelling adults in Singapore age 55 years and older (mean age 65.9 and SD 7.4) | Curcumin-rich curry consumption (frequency: never/rarely, occasionally, often, and very often) | 2751 | 4.5-year longitudinal observational study | Curcumin in the form of curry consumption was associated with statistically significant and higher scores on the following neurocognitive tests as listed: Digit Span-Backward with higher scores in the "very often" and "often" groups, Verbal Fluency (Animals) with higher scores in the "very often" group, and Block Design with higher scores in the "occasional," "often,” and "very often" groups. Cohen’s d-effect size ranged from 0.130 to 0.186 for the significant differences observed. | Consumption of dietary curcumin was significantly associated with higher attention, short-term WM, visual-spatial constructional ability, language, and executive function among older adults in the community of Singapore. The findings suggest curcumin may directly and indirectly offer neuroprotective benefits, through metabolic, antiplatelet, and cardioprotective mechanisms |