Effect of a Multidomain Intervention Plus Turmeric on the Prevention of Cognitive Decline in People Over 55 Years of Age With Insulin Resistance.

NCT07284316 | Active Not Recruiting Phase 2

• 1 other identifier: R-2024-785-058
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Introduction: The Insulin resistance itself has been recognized as an independent risk factor for dementia development. Insulin plays an important role in the regulation of muscle function and the processes of learning and memory. Insulin resistance is associated with increased inflammation and oxidative stress. These processes are involved in the pathophysiology of neurodegenerative diseases. Thus, reducing IR could have implications for improving metabolism, muscle, and cognitive function. Methods and analysis. The investigators will conduct a randomized, double-blind, placebo-controlled clinical trial in which a multidomain program, including an aerobic and cognitive exercise program, will be evaluated. The latter is an exercise program conducted on a checkered mat and will be randomized to participants receiving turmeric plus black pepper or placebo. Participants are affiliated with the Mexican Social Security Institute (IMSS) and are between 55 and 74 years old. The program will last for 24 weeks; after 52 weeks, it will be repeated. The outcomes that the investigators will evaluate are: global cognitive function, specific cognitive function, and the investigators will evaluate serum markers of inflammation, oxidative stress, and GSK-3beta levels. The effect of the interventions on each variable will be analyzed by ANOVA, and a multivariate analysis study with multiple linear regression will be conducted. Ethics and dissemination of the study: the study was approved by the IMSS National Ethics and Research Committee all participants provided written informed consent prior to their participation.

Conditions

Cognitive Decline; Subjective Cognitive Impairment; Insulin Resistance

Keywords

Subjective cognitive decline; Insulin resistance; Elderly; Multidomain intervention

Outcome Measures

Primary Outcomes (4)

• Improving insulin resistance by 5%.

  The investigadors will measure various parameters of insulin resistance such as glycated hemoglobin, insulin resistance index, and we will measure the improvement of these parameters.

  12, 24 y 52 weeks

• General Cognitive funtion

  General cognitive function assessed by the Montreal Cognitive Assessment (MoCA) test on a scale of 0-30 points. Scores are interpreted as follows: \>26 indicates no dementia, 18-26 mild cognitive impairment, 6-10 moderate dementia.

  Time Frame: 0, 24 and 52 weeks

• Specific domains of cognitive function

  Measured through composite scores: Executive function/mental flexibility will be measured with the Trail Making Tests, Part A and Part B. The results for both TMT-A and TMT-B are reported as the number of seconds required to complete a task. Processing speed (using the Digit Symbol Substitution Test) will be measured as the total correct number-symbol matches achieved in 90 seconds. Verbal learning and memory will be assessed through Rey's Auditory Verbal Learning Test (RAVLT), that consists of documenting the number of words remembered from a list of 15 words presented in two separate moments; this test allows evaluation of the RAVLT-Immediate and RAVLT-Percent Forgetting. Verbal fluency (semantic, animal naming, and phonemic) will be measured by using the Controlled Oral Word Association Test and assessed through the total number of words identified by category and letter.

  0, 24, 52 weeks

• Oxidative stress.

  The investigators will measure several parameters of oxidative stress, including 4-hydroxynonenal (4OH-N), malonaldehyde (MDA), quinones, and glutathione system activity.

  0, 12. 24. 52 weeks.

Secondary Outcomes (3)

• Usual walking and dual-task gait

  0 and 52 weeks

• Quality of life as measured by SF-12

  0 and 52 weeks

• Cardiovascular biomarkers and endothelial function: MCP-1, ICAM VCAM and Selectin

  0 and 52weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

500mg capsule grenadine every 12 hours. Measurement of insulin resistance, global cognitive function (subjective and objective), specific cognitive function (executive function/mental flexibility, verbal learning and memory, and verbal fluency), motor function (gait speed, grip strength, balance, and rising from a chair); reduction of biomarkers of inflammation (IL-6, TNF-α, IL-10), endothelial dysfunction (ICAM-1, E-selectin, VCAM-1), and oxidative stress (MDA, GSH) in people aged 55-70 years with insulin resistance; as well as the post-intervention effect at 28 weeks.

Other: Control: Placebo. 500mg gelatin in capsules 2 times a day

Turmeric extract intervention

EXPERIMENTAL

Multidomain program (MeMo-Health-Cog-4) with 500 mg/day of turmeric plus 5 mg of black pepper for 24 weeks against a multidomain program (MeMo-Health-Cog-4) with a placebo for the improvement of insulin resistance, global cognitive function (subjective and objective), specific cognitive function (executive function/mental flexibility, verbal learning and memory, and verbal fluency), motor function (gait speed, grip strength, balance, and rising from a chair); reduction of biomarkers of inflammation (IL-6, TNF-α, IL-10), endothelial dysfunction (ICAM-1, E-selectin, VCAM-1), and oxidative stress (MDA, GSH) in people aged 55-70 years with insulin resistance; as well as the post-intervention effect at 28 weeks.

Dietary Supplement: Turmeric extract

Interventions

Turmeric extract DIETARY_SUPPLEMENT

The intervention group includes aerobic exercise and cognitive exercise (grid mat), nutritional guidance, a healthy aging program, turmeric capsules, and black pepper

Turmeric extract intervention

Control: Placebo. 500mg gelatin in capsules 2 times a day OTHER

The control group includes an aerobic exercise program and cognitive exercise (grid mat with various patterns of complexity, applied by a health professional), nutritional guidance, and healthy aging program, plus a placebo.

Placebo

Eligibility Criteria

• Age: 55 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. With 55-70 years of age.
• \. They have self-reported cognitive concerns (ie, have answered "yes" to the question: "Do you feel like your memory or thinking skills have gotten worse recently?").
• \. The participant has insulin resistance measured with HOMA IR index \> 2.5.
• \. They demonstrate functional independence in activities of daily living and instrumental activities of daily living.
• \. They have symptoms or signs of underlying cognitive dysfunction without a diagnosis of dementia (ie, confirmed by a review of their health records and a Mini Mental State Exam \[MMSE\] score\> 24).
• \. If the participant are a woman, one year after having gone through menopause.

You may not qualify if:

• \. With depression (score\> 15 according to the Center for Epidemiological Studies Depression Scale - Revised \[CESD-R\]).
• \. With clinically significant neurological or psychiatric disorders (eg, Parkinson's, schizophrenia).
• \. With a recent severe cardiovascular event (eg, myocardial infarction, stroke).
• \. With a major orthopedic condition (eg, severe osteoarthritis).
• \. With blood pressure that is unsafe for exercise (ie,\> 180/100 mmHg or \<100/60 mmHg).
• \. With a severe visual or auditory impairment.
• \. With an unwillingness to adhere to the intervention schedules.
• \. Patients with active cancer, who are undergoing chemotherapy, radiotherapy, or other treatments aimed at eradicating cancer and who have been undergoing treatment during the last year.
• \. Elimination: participants with incomplete data and who have not complied with the intervention by 80%.

Sponsors & Collaborators

• Instituto Mexicano del Seguro Social: lead

Study Sites (1)

Centro Medico Nacional Siglo XXI, unidad de investigación en epidemiología y servicio de salud.

Mexico City, Cuauhtémoc, 06720, Mexico

Location

Related Publications (89)

• Hixson JE, Vernier DT. Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res. 1990 Mar;31(3):545-8.

  PMID: 2341813 BACKGROUND

• Raulin AC, Doss SV, Trottier ZA, Ikezu TC, Bu G, Liu CC. ApoE in Alzheimer's disease: pathophysiology and therapeutic strategies. Mol Neurodegener. 2022 Nov 8;17(1):72. doi: 10.1186/s13024-022-00574-4.

  PMID: 36348357 BACKGROUND

• Custodia A, Aramburu-Nunez M, Rodriguez-Arrizabalaga M, Pias-Peleteiro JM, Vazquez-Vazquez L, Camino-Castineiras J, Aldrey JM, Castillo J, Ouro A, Sobrino T, Romaus-Sanjurjo D. Biomarkers Assessing Endothelial Dysfunction in Alzheimer's Disease. Cells. 2023 Mar 22;12(6):962. doi: 10.3390/cells12060962.

  PMID: 36980302 BACKGROUND

• Johnson FK, Peyton KJ, Liu XM, Azam MA, Shebib AR, Johnson RA, Durante W. Arginase promotes endothelial dysfunction and hypertension in obese rats. Obesity (Silver Spring). 2015 Feb;23(2):383-90. doi: 10.1002/oby.20969. Epub 2014 Dec 31.

  PMID: 25557182 BACKGROUND

• Gieseg SP, Simpson JA, Charlton TS, Duncan MW, Dean RT. Protein-bound 3,4-dihydroxyphenylalanine is a major reductant formed during hydroxyl radical damage to proteins. Biochemistry. 1993 May 11;32(18):4780-6. doi: 10.1021/bi00069a012.

  PMID: 8387814 BACKGROUND

• Dean RT, Gieseg S, Davies MJ. Reactive species and their accumulation on radical-damaged proteins. Trends Biochem Sci. 1993 Nov;18(11):437-41. doi: 10.1016/0968-0004(93)90145-d.

  PMID: 8291091 BACKGROUND

• Garcia-Blanco A, Baquero M, Vento M, Gil E, Bataller L, Chafer-Pericas C. Potential oxidative stress biomarkers of mild cognitive impairment due to Alzheimer disease. J Neurol Sci. 2017 Feb 15;373:295-302. doi: 10.1016/j.jns.2017.01.020. Epub 2017 Jan 7.

  PMID: 28131209 BACKGROUND

• Mandal PK, Saharan S, Khan SA, James M. Apps for Dementia Screening: A Cost-effective and Portable Solution. J Alzheimers Dis. 2015;47(4):869-72. doi: 10.3233/JAD-150255. No abstract available.

  PMID: 26401765 BACKGROUND

• Malek-Ahmadi M, Small BJ, Raj A. The diagnostic value of controlled oral word association test-FAS and category fluency in single-domain amnestic mild cognitive impairment. Dement Geriatr Cogn Disord. 2011;32(4):235-40. doi: 10.1159/000334525. Epub 2011 Dec 8.

  PMID: 22156335 BACKGROUND

• Moradi E, Hallikainen I, Hanninen T, Tohka J; Alzheimer's Disease Neuroimaging Initiative. Rey's Auditory Verbal Learning Test scores can be predicted from whole brain MRI in Alzheimer's disease. Neuroimage Clin. 2016 Dec 18;13:415-427. doi: 10.1016/j.nicl.2016.12.011. eCollection 2017.

  PMID: 28116234 BACKGROUND

• Rosano C, Perera S, Inzitari M, Newman AB, Longstreth WT, Studenski S. Digit Symbol Substitution test and future clinical and subclinical disorders of cognition, mobility and mood in older adults. Age Ageing. 2016 Sep;45(5):688-95. doi: 10.1093/ageing/afw116. Epub 2016 Jul 4.

  PMID: 27496932 BACKGROUND

• Gaudino EA, Geisler MW, Squires NK. Construct validity in the Trail Making Test: what makes Part B harder? J Clin Exp Neuropsychol. 1995 Aug;17(4):529-35. doi: 10.1080/01688639508405143.

  PMID: 7593473 BACKGROUND

• Aguilar-Navarro SG, Mimenza-Alvarado AJ, Palacios-Garcia AA, Samudio-Cruz A, Gutierrez-Gutierrez LA, Avila-Funes JA. Validity and Reliability of the Spanish Version of the Montreal Cognitive Assessment (MoCA) for the Detection of Cognitive Impairment in Mexico. Rev Colomb Psiquiatr (Engl Ed). 2018 Oct-Dec;47(4):237-243. doi: 10.1016/j.rcp.2017.05.003. Epub 2017 Jul 29. English, Spanish.

  PMID: 30286846 BACKGROUND

• Saghaei M. Random allocation software for parallel group randomized trials. BMC Med Res Methodol. 2004 Nov 9;4:26. doi: 10.1186/1471-2288-4-26.

  PMID: 15535880 BACKGROUND

• Kohout FJ, Berkman LF, Evans DA, Cornoni-Huntley J. Two shorter forms of the CES-D (Center for Epidemiological Studies Depression) depression symptoms index. J Aging Health. 1993 May;5(2):179-93. doi: 10.1177/089826439300500202.

  PMID: 10125443 BACKGROUND

• Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98. doi: 10.1016/0022-3956(75)90026-6. No abstract available.

  PMID: 1202204 BACKGROUND

• Kelly ME, Loughrey D, Lawlor BA, Robertson IH, Walsh C, Brennan S. The impact of cognitive training and mental stimulation on cognitive and everyday functioning of healthy older adults: a systematic review and meta-analysis. Ageing Res Rev. 2014 May;15:28-43. doi: 10.1016/j.arr.2014.02.004. Epub 2014 Mar 4.

  PMID: 24607830 BACKGROUND

• Willis SL, Tennstedt SL, Marsiske M, Ball K, Elias J, Koepke KM, Morris JN, Rebok GW, Unverzagt FW, Stoddard AM, Wright E; ACTIVE Study Group. Long-term effects of cognitive training on everyday functional outcomes in older adults. JAMA. 2006 Dec 20;296(23):2805-14. doi: 10.1001/jama.296.23.2805.

  PMID: 17179457 BACKGROUND

• Licastro F, Pedrini S, Caputo L, Annoni G, Davis LJ, Ferri C, Casadei V, Grimaldi LM. Increased plasma levels of interleukin-1, interleukin-6 and alpha-1-antichymotrypsin in patients with Alzheimer's disease: peripheral inflammation or signals from the brain? J Neuroimmunol. 2000 Feb 1;103(1):97-102. doi: 10.1016/s0165-5728(99)00226-x.

  PMID: 10674995 BACKGROUND

• Lyra E Silva NM, Goncalves RA, Pascoal TA, Lima-Filho RAS, Resende EPF, Vieira ELM, Teixeira AL, de Souza LC, Peny JA, Fortuna JTS, Furigo IC, Hashiguchi D, Miya-Coreixas VS, Clarke JR, Abisambra JF, Longo BM, Donato J Jr, Fraser PE, Rosa-Neto P, Caramelli P, Ferreira ST, De Felice FG. Pro-inflammatory interleukin-6 signaling links cognitive impairments and peripheral metabolic alterations in Alzheimer's disease. Transl Psychiatry. 2021 Apr 28;11(1):251. doi: 10.1038/s41398-021-01349-z.

  PMID: 33911072 BACKGROUND

• Windham BG, Simpson BN, Lirette S, Bridges J, Bielak L, Peyser PA, Kullo I, Turner S, Griswold ME, Mosley TH. Associations between inflammation and cognitive function in African Americans and European Americans. J Am Geriatr Soc. 2014 Dec;62(12):2303-10. doi: 10.1111/jgs.13165.

  PMID: 25516026 BACKGROUND

• Xing YW, Liu KZ. Azithromycin inhibited oxidative stress and apoptosis of high glucose-induced podocytes by inhibiting STAT1 pathway. Drug Dev Res. 2021 Nov;82(7):990-998. doi: 10.1002/ddr.21801. Epub 2021 Mar 2.

  PMID: 33655586 BACKGROUND

• Markesbery WR. Oxidative stress hypothesis in Alzheimer's disease. Free Radic Biol Med. 1997;23(1):134-47. doi: 10.1016/s0891-5849(96)00629-6.

  PMID: 9165306 BACKGROUND

• Gill DP, Gregory MA, Zou G, Liu-Ambrose T, Shigematsu R, Hachinski V, Fitzgerald C, Petrella RJ. The Healthy Mind, Healthy Mobility Trial: A Novel Exercise Program for Older Adults. Med Sci Sports Exerc. 2016 Feb;48(2):297-306. doi: 10.1249/MSS.0000000000000758.

  PMID: 26285025 BACKGROUND

• Abner EL, Kryscio RJ, Caban-Holt AM, Schmitt FA. Baseline subjective memory complaints associate with increased risk of incident dementia: the PREADVISE trial. J Prev Alzheimers Dis. 2015 Mar;2(1):11-16. doi: 10.14283/jpad.2015.37.

  PMID: 26180776 BACKGROUND

• Wang X, Ji X. Sample Size Estimation in Clinical Research: From Randomized Controlled Trials to Observational Studies. Chest. 2020 Jul;158(1S):S12-S20. doi: 10.1016/j.chest.2020.03.010.

  PMID: 32658647 BACKGROUND

• Zhong B. How to calculate sample size in randomized controlled trial? J Thorac Dis. 2009 Dec;1(1):51-4.

  PMID: 22263004 BACKGROUND

• Camacho-Ruiz J, V A, Rendon-Macias ME, Bernabe-Garcia M, Gonzalez-Bautista E, Manuel-Apolinar L, Basurto-Acevedo L, Orihuela-Rodriguez O, M Ruiz-Batalla J, Rojas-Rubio B, Olivares-Santos RA, Paredes-Manjarrez C, Sanchez-Arenas R. [Cognitive function groups in older people and risk factors]. Rev Med Inst Mex Seguro Soc. 2024 May 6;62(3):1-11. doi: 10.5281/zenodo.10998801. Spanish.

  PMID: 39528344 BACKGROUND

• Mimenza-Alvarado A, Aguilar-Navarro SG, Yeverino-Castro S, Mendoza-Franco C, Avila-Funes JA, Roman GC. Neuroimaging Characteristics of Small-Vessel Disease in Older Adults with Normal Cognition, Mild Cognitive Impairment, and Alzheimer Disease. Dement Geriatr Cogn Dis Extra. 2018 May 16;8(2):199-206. doi: 10.1159/000488705. eCollection 2018 May-Aug.

  PMID: 29928288 BACKGROUND

• Zahedipour F, Hosseini SA, Sathyapalan T, Majeed M, Jamialahmadi T, Al-Rasadi K, Banach M, Sahebkar A. Potential effects of curcumin in the treatment of COVID-19 infection. Phytother Res. 2020 Nov;34(11):2911-2920. doi: 10.1002/ptr.6738. Epub 2020 Jun 23.

  PMID: 32430996 BACKGROUND

• Hoppe JB, Haag M, Whalley BJ, Salbego CG, Cimarosti H. Curcumin protects organotypic hippocampal slice cultures from Abeta1-42-induced synaptic toxicity. Toxicol In Vitro. 2013 Dec;27(8):2325-30. doi: 10.1016/j.tiv.2013.10.002. Epub 2013 Oct 14.

  PMID: 24134851 BACKGROUND

• Khandia R, Viswanathan N, Singhal S, Alqahtani T, Almikhlafi MA, Simonov AN, Ashraf GM. Ameliorative Effects of Phytomedicines on Alzheimer's Patients. Curr Alzheimer Res. 2022;19(6):420-439. doi: 10.2174/1567205019666220610155608.

  PMID: 35692129 BACKGROUND

• Berry A, Collacchi B, Masella R, Vari R, Cirulli F. Curcuma Longa, the "Golden Spice" to Counteract Neuroinflammaging and Cognitive Decline-What Have We Learned and What Needs to Be Done. Nutrients. 2021 Apr 30;13(5):1519. doi: 10.3390/nu13051519.

  PMID: 33946356 BACKGROUND

• Randino R, Grimaldi M, Persico M, De Santis A, Cini E, Cabri W, Riva A, D'Errico G, Fattorusso C, D'Ursi AM, Rodriquez M. Investigating the Neuroprotective Effects of Turmeric Extract: Structural Interactions of beta-Amyloid Peptide with Single Curcuminoids. Sci Rep. 2016 Dec 22;6:38846. doi: 10.1038/srep38846.

  PMID: 28004737 BACKGROUND

• Chainoglou E, Hadjipavlou-Litina D. Curcumin in Health and Diseases: Alzheimer's Disease and Curcumin Analogues, Derivatives, and Hybrids. Int J Mol Sci. 2020 Mar 13;21(6):1975. doi: 10.3390/ijms21061975.

  PMID: 32183162 BACKGROUND

• Kocaadam B, Sanlier N. Curcumin, an active component of turmeric (Curcuma longa), and its effects on health. Crit Rev Food Sci Nutr. 2017 Sep 2;57(13):2889-2895. doi: 10.1080/10408398.2015.1077195.

  PMID: 26528921 BACKGROUND

• Thota RN, Rosato JI, Dias CB, Burrows TL, Martins RN, Garg ML. Dietary Supplementation with Curcumin Reduce Circulating Levels of Glycogen Synthase Kinase-3beta and Islet Amyloid Polypeptide in Adults with High Risk of Type 2 Diabetes and Alzheimer's Disease. Nutrients. 2020 Apr 9;12(4):1032. doi: 10.3390/nu12041032.

  PMID: 32283762 BACKGROUND

• Hewlings SJ, Kalman DS. Curcumin: A Review of Its Effects on Human Health. Foods. 2017 Oct 22;6(10):92. doi: 10.3390/foods6100092.

  PMID: 29065496 BACKGROUND

• Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007 Nov-Dec;4(6):807-18. doi: 10.1021/mp700113r. Epub 2007 Nov 14.

  PMID: 17999464 BACKGROUND

• Ryu EK, Choe YS, Lee KH, Choi Y, Kim BT. Curcumin and dehydrozingerone derivatives: synthesis, radiolabeling, and evaluation for beta-amyloid plaque imaging. J Med Chem. 2006 Oct 5;49(20):6111-9. doi: 10.1021/jm0607193.

  PMID: 17004725 BACKGROUND

• Murakami M, Ikeda Y, Nakagawa Y, Tsuji A, Kitagishi Y, Matsuda S. Special bioactive compounds and functional foods may exhibit neuroprotective effects in patients with dementia (Review). Biomed Rep. 2020 Aug;13(2):1. doi: 10.3892/br.2020.1310. Epub 2020 Jun 2.

  PMID: 32509304 BACKGROUND

• Ferrari CK. Functional foods and physical activities in health promotion of aging people. Maturitas. 2007 Dec 20;58(4):327-39. doi: 10.1016/j.maturitas.2007.09.011. Epub 2007 Nov 5.

  PMID: 17980978 BACKGROUND

• Janelidze S, Mattsson N, Stomrud E, Lindberg O, Palmqvist S, Zetterberg H, Blennow K, Hansson O. CSF biomarkers of neuroinflammation and cerebrovascular dysfunction in early Alzheimer disease. Neurology. 2018 Aug 28;91(9):e867-e877. doi: 10.1212/WNL.0000000000006082. Epub 2018 Jul 27.

  PMID: 30054439 BACKGROUND

• Qiu S, Cai X, Liu J, Yang B, Zugel M, Steinacker JM, Sun Z, Schumann U. Association between circulating cell adhesion molecules and risk of type 2 diabetes: A meta-analysis. Atherosclerosis. 2019 Aug;287:147-154. doi: 10.1016/j.atherosclerosis.2019.06.908. Epub 2019 Jun 20.

  PMID: 31280040 BACKGROUND

• Meigs JB, Hu FB, Rifai N, Manson JE. Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA. 2004 Apr 28;291(16):1978-86. doi: 10.1001/jama.291.16.1978.

  PMID: 15113816 BACKGROUND

• Toledo JB, Arnold SE, Raible K, Brettschneider J, Xie SX, Grossman M, Monsell SE, Kukull WA, Trojanowski JQ. Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer's Coordinating Centre. Brain. 2013 Sep;136(Pt 9):2697-706. doi: 10.1093/brain/awt188. Epub 2013 Jul 10.

  PMID: 23842566 BACKGROUND

• Pedersen BK. Physical activity and muscle-brain crosstalk. Nat Rev Endocrinol. 2019 Jul;15(7):383-392. doi: 10.1038/s41574-019-0174-x.

  PMID: 30837717 BACKGROUND

• Tumminia A, Vinciguerra F, Parisi M, Frittitta L. Type 2 Diabetes Mellitus and Alzheimer's Disease: Role of Insulin Signalling and Therapeutic Implications. Int J Mol Sci. 2018 Oct 24;19(11):3306. doi: 10.3390/ijms19113306.

  PMID: 30355995 BACKGROUND

• Hoppe JB, Coradini K, Frozza RL, Oliveira CM, Meneghetti AB, Bernardi A, Pires ES, Beck RC, Salbego CG. Free and nanoencapsulated curcumin suppress beta-amyloid-induced cognitive impairments in rats: involvement of BDNF and Akt/GSK-3beta signaling pathway. Neurobiol Learn Mem. 2013 Nov;106:134-44. doi: 10.1016/j.nlm.2013.08.001. Epub 2013 Aug 14.

  PMID: 23954730 BACKGROUND

• Liang LL, He MF, Zhou PP, Pan SK, Liu DW, Liu ZS. GSK3beta: A ray of hope for the treatment of diabetic kidney disease. FASEB J. 2024 Feb 15;38(3):e23458. doi: 10.1096/fj.202302160R.

  PMID: 38315453 BACKGROUND

• Wang YJ, Ren QG, Gong WG, Wu D, Tang X, Li XL, Wu FF, Bai F, Xu L, Zhang ZJ. Escitalopram attenuates beta-amyloid-induced tau hyperphosphorylation in primary hippocampal neurons through the 5-HT1A receptor mediated Akt/GSK-3beta pathway. Oncotarget. 2016 Mar 22;7(12):13328-39. doi: 10.18632/oncotarget.7798.

  PMID: 26950279 BACKGROUND

• Li X, Jope RS. Is glycogen synthase kinase-3 a central modulator in mood regulation? Neuropsychopharmacology. 2010 Oct;35(11):2143-54. doi: 10.1038/npp.2010.105. Epub 2010 Jul 28.

  PMID: 20668436 BACKGROUND

• Jia YR, Guo ZQ, Guo Q, Wang XC. Glycogen Synthase Kinase-3beta, NLRP3 Inflammasome, and Alzheimer's Disease. Curr Med Sci. 2023 Oct;43(5):847-854. doi: 10.1007/s11596-023-2788-4. Epub 2023 Sep 18.

  PMID: 37721665 BACKGROUND

• Rafii MS, Aisen PS. Detection and treatment of Alzheimer's disease in its preclinical stage. Nat Aging. 2023 May;3(5):520-531. doi: 10.1038/s43587-023-00410-4. Epub 2023 May 18.

  PMID: 37202518 BACKGROUND

• Mandal PK, Saharan S, Tripathi M, Murari G. Brain glutathione levels--a novel biomarker for mild cognitive impairment and Alzheimer's disease. Biol Psychiatry. 2015 Nov 15;78(10):702-10. doi: 10.1016/j.biopsych.2015.04.005. Epub 2015 Apr 14.

  PMID: 26003861 BACKGROUND

• Bradley-Whitman MA, Lovell MA. Biomarkers of lipid peroxidation in Alzheimer disease (AD): an update. Arch Toxicol. 2015 Jul;89(7):1035-44. doi: 10.1007/s00204-015-1517-6. Epub 2015 Apr 18.

  PMID: 25895140 BACKGROUND

• Gigase FAJ, Smith E, Collins B, Moore K, Snijders GJLJ, Katz D, Bergink V, Perez-Rodriquez MM, De Witte LD. The association between inflammatory markers in blood and cerebrospinal fluid: a systematic review and meta-analysis. Mol Psychiatry. 2023 Apr;28(4):1502-1515. doi: 10.1038/s41380-023-01976-6. Epub 2023 Apr 13.

  PMID: 37055513 BACKGROUND

• Albar NY, Hassaballa H, Shikh H, Albar Y, Ibrahim AS, Mousa AH, Alshanberi AM, Elgebaly A, Bahbah EI. The interaction between insulin resistance and Alzheimer's disease: a review article. Postgrad Med. 2024 May;136(4):377-395. doi: 10.1080/00325481.2024.2360887. Epub 2024 Jun 4.

  PMID: 38804907 BACKGROUND

• Sedzikowska A, Szablewski L. Insulin and Insulin Resistance in Alzheimer's Disease. Int J Mol Sci. 2021 Sep 15;22(18):9987. doi: 10.3390/ijms22189987.

  PMID: 34576151 BACKGROUND

• Leng F, Edison P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat Rev Neurol. 2021 Mar;17(3):157-172. doi: 10.1038/s41582-020-00435-y. Epub 2020 Dec 14.

  PMID: 33318676 BACKGROUND

• Li H, Ren J, Li Y, Wu Q, Wei J. Oxidative stress: The nexus of obesity and cognitive dysfunction in diabetes. Front Endocrinol (Lausanne). 2023 Apr 3;14:1134025. doi: 10.3389/fendo.2023.1134025. eCollection 2023.

  PMID: 37077347 BACKGROUND

• Arellano-Campos O, Gomez-Velasco DV, Bello-Chavolla OY, Cruz-Bautista I, Melgarejo-Hernandez MA, Munoz-Hernandez L, Guillen LE, Garduno-Garcia JJ, Alvirde U, Ono-Yoshikawa Y, Choza-Romero R, Sauque-Reyna L, Garay-Sevilla ME, Malacara-Hernandez JM, Tusie-Luna MT, Gutierrez-Robledo LM, Gomez-Perez FJ, Rojas R, Aguilar-Salinas CA. Development and validation of a predictive model for incident type 2 diabetes in middle-aged Mexican adults: the metabolic syndrome cohort. BMC Endocr Disord. 2019 Apr 28;19(1):41. doi: 10.1186/s12902-019-0361-8.

  PMID: 31030672 BACKGROUND

• Rojas R, Aguilar-Salinas CA, Jimenez-Corona A, Shamah-Levy T, Rauda J, Avila-Burgos L, Villalpando S, Ponce EL. Metabolic syndrome in Mexican adults: results from the National Health and Nutrition Survey 2006. Salud Publica Mex. 2010;52 Suppl 1:S11-8. doi: 10.1590/s0036-36342010000700004.

  PMID: 20585723 BACKGROUND

• Gastaldelli A. Measuring and estimating insulin resistance in clinical and research settings. Obesity (Silver Spring). 2022 Aug;30(8):1549-1563. doi: 10.1002/oby.23503.

  PMID: 35894085 BACKGROUND

• Haeusler RA, McGraw TE, Accili D. Biochemical and cellular properties of insulin receptor signalling. Nat Rev Mol Cell Biol. 2018 Jan;19(1):31-44. doi: 10.1038/nrm.2017.89. Epub 2017 Oct 4.

  PMID: 28974775 BACKGROUND

• Rodriguez-Colman MJ, Dansen TB, Burgering BMT. FOXO transcription factors as mediators of stress adaptation. Nat Rev Mol Cell Biol. 2024 Jan;25(1):46-64. doi: 10.1038/s41580-023-00649-0. Epub 2023 Sep 14.

  PMID: 37710009 BACKGROUND

• Lennicke C, Cocheme HM. Redox metabolism: ROS as specific molecular regulators of cell signaling and function. Mol Cell. 2021 Sep 16;81(18):3691-3707. doi: 10.1016/j.molcel.2021.08.018.

  PMID: 34547234 BACKGROUND

• James DE, Stockli J, Birnbaum MJ. The aetiology and molecular landscape of insulin resistance. Nat Rev Mol Cell Biol. 2021 Nov;22(11):751-771. doi: 10.1038/s41580-021-00390-6. Epub 2021 Jul 20.

  PMID: 34285405 BACKGROUND

• Yang Q, Vijayakumar A, Kahn BB. Metabolites as regulators of insulin sensitivity and metabolism. Nat Rev Mol Cell Biol. 2018 Oct;19(10):654-672. doi: 10.1038/s41580-018-0044-8.

  PMID: 30104701 BACKGROUND

• DeFronzo RA, Ferrannini E, Groop L, Henry RR, Herman WH, Holst JJ, Hu FB, Kahn CR, Raz I, Shulman GI, Simonson DC, Testa MA, Weiss R. Type 2 diabetes mellitus. Nat Rev Dis Primers. 2015 Jul 23;1:15019. doi: 10.1038/nrdp.2015.19.

  PMID: 27189025 BACKGROUND

• Biessels GJ, Despa F. Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications. Nat Rev Endocrinol. 2018 Oct;14(10):591-604. doi: 10.1038/s41574-018-0048-7.

  PMID: 30022099 BACKGROUND

• Shigematsu R, Okura T, Nakagaichi M, Tanaka K, Sakai T, Kitazumi S, Rantanen T. Square-stepping exercise and fall risk factors in older adults: a single-blind, randomized controlled trial. J Gerontol A Biol Sci Med Sci. 2008 Jan;63(1):76-82. doi: 10.1093/gerona/63.1.76.

  PMID: 18245764 BACKGROUND

• Shigematsu R, Okura T. A novel exercise for improving lower-extremity functional fitness in the elderly. Aging Clin Exp Res. 2006 Jun;18(3):242-8. doi: 10.1007/BF03324655.

  PMID: 16804371 BACKGROUND

• Sanchez-Arenas R, Doubova SV, Bernabe-Garcia M, Gregory MA, Mejia-Alonso LA, Orihuela-Rodriguez O, Paredes-Manjarrez C, Colin-Martinez T, Mujica-Morales I, Grijalva-Otero I, Basurto-Acevedo L, Manuel-Apolinar L, Cuadros-Moreno J, Bernal-Diaz A, Shigematsu R. Double-task exercise programmes to strengthen cognitive and vascular health in older adults at risk of cognitive decline: protocol for a randomised clinical trial. BMJ Open. 2020 Dec 30;10(12):e039723. doi: 10.1136/bmjopen-2020-039723.

  PMID: 33380479 BACKGROUND

• Wahl D, Cavalier AN, LaRocca TJ. Novel Strategies for Healthy Brain Aging. Exerc Sport Sci Rev. 2021 Apr 1;49(2):115-125. doi: 10.1249/JES.0000000000000242.

  PMID: 33739944 BACKGROUND

• Stillman CM, Esteban-Cornejo I, Brown B, Bender CM, Erickson KI. Effects of Exercise on Brain and Cognition Across Age Groups and Health States. Trends Neurosci. 2020 Jul;43(7):533-543. doi: 10.1016/j.tins.2020.04.010. Epub 2020 May 11.

  PMID: 32409017 BACKGROUND

• Piercy KL, Troiano RP, Ballard RM, Carlson SA, Fulton JE, Galuska DA, George SM, Olson RD. The Physical Activity Guidelines for Americans. JAMA. 2018 Nov 20;320(19):2020-2028. doi: 10.1001/jama.2018.14854.

  PMID: 30418471 BACKGROUND

• Ross R, Chaput JP, Giangregorio LM, Janssen I, Saunders TJ, Kho ME, Poitras VJ, Tomasone JR, El-Kotob R, McLaughlin EC, Duggan M, Carrier J, Carson V, Chastin SF, Latimer-Cheung AE, Chulak-Bozzer T, Faulkner G, Flood SM, Gazendam MK, Healy GN, Katzmarzyk PT, Kennedy W, Lane KN, Lorbergs A, Maclaren K, Marr S, Powell KE, Rhodes RE, Ross-White A, Welsh F, Willumsen J, Tremblay MS. Canadian 24-Hour Movement Guidelines for Adults aged 18-64 years and Adults aged 65 years or older: an integration of physical activity, sedentary behaviour, and sleep. Appl Physiol Nutr Metab. 2020 Oct;45(10 (Suppl. 2)):S57-S102. doi: 10.1139/apnm-2020-0467.

  PMID: 33054332 BACKGROUND

• Boa Sorte Silva NC, Gregory MA, Gill DP, Petrella RJ. Multiple-modality exercise and mind-motor training to improve cardiovascular health and fitness in older adults at risk for cognitive impairment: A randomized controlled trial. Arch Gerontol Geriatr. 2017 Jan-Feb;68:149-160. doi: 10.1016/j.archger.2016.10.009. Epub 2016 Oct 24.

  PMID: 27810663 BACKGROUND

• Boa Sorte Silva NC, Gill DP, Gregory MA, Bocti J, Petrella RJ. Multiple-modality exercise and mind-motor training to improve mobility in older adults: A randomized controlled trial. Exp Gerontol. 2018 Mar;103:17-26. doi: 10.1016/j.exger.2017.12.011. Epub 2017 Dec 17.

  PMID: 29262308 BACKGROUND

• Andrieu S, Coley N, Lovestone S, Aisen PS, Vellas B. Prevention of sporadic Alzheimer's disease: lessons learned from clinical trials and future directions. Lancet Neurol. 2015 Sep;14(9):926-944. doi: 10.1016/S1474-4422(15)00153-2. Epub 2015 Jul 23.

  PMID: 26213339 BACKGROUND

• Jessen F, Amariglio RE, Buckley RF, van der Flier WM, Han Y, Molinuevo JL, Rabin L, Rentz DM, Rodriguez-Gomez O, Saykin AJ, Sikkes SAM, Smart CM, Wolfsgruber S, Wagner M. The characterisation of subjective cognitive decline. Lancet Neurol. 2020 Mar;19(3):271-278. doi: 10.1016/S1474-4422(19)30368-0. Epub 2020 Jan 17.

  PMID: 31958406 BACKGROUND

• Dubois B, Hampel H, Feldman HH, Scheltens P, Aisen P, Andrieu S, Bakardjian H, Benali H, Bertram L, Blennow K, Broich K, Cavedo E, Crutch S, Dartigues JF, Duyckaerts C, Epelbaum S, Frisoni GB, Gauthier S, Genthon R, Gouw AA, Habert MO, Holtzman DM, Kivipelto M, Lista S, Molinuevo JL, O'Bryant SE, Rabinovici GD, Rowe C, Salloway S, Schneider LS, Sperling R, Teichmann M, Carrillo MC, Cummings J, Jack CR Jr; Proceedings of the Meeting of the International Working Group (IWG) and the American Alzheimer's Association on "The Preclinical State of AD"; July 23, 2015; Washington DC, USA. Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria. Alzheimers Dement. 2016 Mar;12(3):292-323. doi: 10.1016/j.jalz.2016.02.002.

  PMID: 27012484 BACKGROUND

• Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR Jr, Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Carrillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):280-92. doi: 10.1016/j.jalz.2011.03.003. Epub 2011 Apr 21.

  PMID: 21514248 BACKGROUND

• Frisoni GB, Altomare D, Ribaldi F, Villain N, Brayne C, Mukadam N, Abramowicz M, Barkhof F, Berthier M, Bieler-Aeschlimann M, Blennow K, Brioschi Guevara A, Carrera E, Chetelat G, Csajka C, Demonet JF, Dodich A, Garibotto V, Georges J, Hurst S, Jessen F, Kivipelto M, Llewellyn DJ, McWhirter L, Milne R, Minguillon C, Miniussi C, Molinuevo JL, Nilsson PM, Noyce A, Ranson JM, Grau-Rivera O, Schott JM, Solomon A, Stephen R, van der Flier W, van Duijn C, Vellas B, Visser LNC, Cummings JL, Scheltens P, Ritchie C, Dubois B. Dementia prevention in memory clinics: recommendations from the European task force for brain health services. Lancet Reg Health Eur. 2023 Jan 31;26:100576. doi: 10.1016/j.lanepe.2022.100576. eCollection 2023 Mar.

  PMID: 36895446 BACKGROUND

• Ribeiro F, Teixeira-Santos AC, Caramelli P, Leist AK. Prevalence of dementia in Latin America and Caribbean countries: Systematic review and meta-analyses exploring age, sex, rurality, and education as possible determinants. Ageing Res Rev. 2022 Nov;81:101703. doi: 10.1016/j.arr.2022.101703. Epub 2022 Aug 3.

  PMID: 35931410 BACKGROUND

• Mukadam N, Sommerlad A, Huntley J, Livingston G. Population attributable fractions for risk factors for dementia in low-income and middle-income countries: an analysis using cross-sectional survey data. Lancet Glob Health. 2019 May;7(5):e596-e603. doi: 10.1016/S2214-109X(19)30074-9.

  PMID: 31000129 BACKGROUND

• Ganguli M, Albanese E, Seshadri S, Bennett DA, Lyketsos C, Kukull WA, Skoog I, Hendrie HC. Population Neuroscience: Dementia Epidemiology Serving Precision Medicine and Population Health. Alzheimer Dis Assoc Disord. 2018 Jan-Mar;32(1):1-9. doi: 10.1097/WAD.0000000000000237.

  PMID: 29319603 BACKGROUND

• Altomare D, Molinuevo JL, Ritchie C, Ribaldi F, Carrera E, Dubois B, Jessen F, McWhirter L, Scheltens P, van der Flier WM, Vellas B, Demonet JF, Frisoni GB; European Task Force for Brain Health Services. Brain Health Services: organization, structure, and challenges for implementation. A user manual for Brain Health Services-part 1 of 6. Alzheimers Res Ther. 2021 Oct 11;13(1):168. doi: 10.1186/s13195-021-00827-2.

  PMID: 34635163 BACKGROUND

MeSH Terms

Conditions

Cognitive Dysfunction; Insulin Resistance

Interventions

turmeric extract; Gelatin

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Scleroproteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Svetlana Dubrovna, PhD

  Instituto Mexicano del Seguro Social

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The researchers will use key-labeled bottles to designate placebo vs turmeric; the participants, doctors, and staff do not know which group each bottle corresponds to. Only two people from the research team know which group each bottle corresponds to.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research

Model Details: To compare the efficacy of a multidomain program (MeMo-Health-Cog-4) with 500 mg/day of turmeric plus 5 mg of black pepper for 24 weeks against a multidomain program (MeMo-Health-Cog-4) with a placebo for the improvement of insulin resistance, global cognitive function (subjective and objective), specific cognitive function (executive function/mental flexibility, verbal learning and memory, and verbal fluency), motor function (gait speed, grip strength, balance, and rising from a chair); reduction of biomarkers of inflammation (IL-6, TNF-alpha, IL-10), endothelial dysfunction (ICAM-1, E-selectin, VCAM-1), and oxidative stress (MDA, GSH) in people aged 55-70 years with insulin resistance; as well as the post-intervention effect at 28 weeks.

Study Record Dates

• First Submitted: February 18, 2025
• First Posted: December 16, 2025
• Study Start: February 20, 2025
• Primary Completion (Estimated): February 15, 2027
• Study Completion (Estimated): February 15, 2027
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)