18-Month Study of Memory Effects of Curcumin

Summary

This project is designed to study the effects of the dietary supplement curcumin on age-related cognitive impairment. In particular, the study seeks to determine the effects of curcumin on cognitive decline and the amount of abnormal amyloid protein in the brain. Genetic risk will also be studied as a potential predictor of cognitive decline. Subjects will be randomly assigned to one of two treatment groups: either a placebo twice daily or the curcumin supplement (Theracurmin®, containing 90 mg of curcumin). The investigators expect that the volunteers receiving the curcumin supplement will show less evidence of decline after 18 months than those receiving the placebo. The investigators predict that cognitive decline and treatment response will vary according to genetic risk for Alzheimer's. The investigators will study subjects with memory complaints aged 50-90 years. Initially, subjects will undergo a clinical assessment, an MRI and a blood draw to determine genetic risk and to rule out other neurodegenerative disorders linked to memory complaints. Subsequently, subjects will undergo an -(1-{6-\[(2-\[F-18\]fluoroethyl)(methyl)amino\]-2-naphthyl}ethylidene)malononitrile (FDDNP) PET scan and a baseline neuropsychological assessment to confirm a diagnosis of MCI or normal aging. Once enrolled, subjects will begin taking the supplement (either curcumin or a placebo). Some of the initial subjects will be asked to return every three months for regular MRIs. Every 6 months, subjects will also receive neuropsychological assessments. At the conclusion of the study, subjects will be asked to complete a final neuropsychological assessment, MRI scan, PET scan and blood draw. Additional blood will be drawn at baseline and at 18 months and frozen to assess inflammatory markers if cognitive outcomes are positive. FDDNP-PET scans will be used to measure the amount of abnormal amyloid plaque- and tau tangle-proteins in the brain; the MRIs will be used to monitor supplement side effects and measure brain structure; the neuropsychological assessments will monitor rates of cognitive decline; the blood draws will be used to determine genetic risk and to test levels of inflammatory markers.

Timeline

Start

2012-03

Primary completion

2017-04

Completion

2017-04

Publications

• Background Arai T, Ikeda K, Akiyama H, Haga C, Usami M, Sahara N, Iritani S, Mori H. A high incidence of apolipoprotein E epsilon4 allele in middle-aged non-demented subjects with cerebral amyloid beta protein deposits. Acta Neuropathol. 1999 Jan;97(1):82-4. doi: 10.1007/s004010050958.
• Background Beach TG, Honer WG, Hughes LH. Cholinergic fibre loss associated with diffuse plaques in the non-demented elderly: the preclinical stage of Alzheimer's disease? Acta Neuropathol. 1997 Feb;93(2):146-53. doi: 10.1007/s004010050595.
• Background Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239-59. doi: 10.1007/BF00308809.
• Background McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984 Jul;34(7):939-44. doi: 10.1212/wnl.34.7.939.
• Background Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review) [RETIRED]. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001 May 8;56(9):1133-42. doi: 10.1212/wnl.56.9.1133.
• Background Price JL, Morris JC. Tangles and plaques in nondemented aging and "preclinical" Alzheimer's disease. Ann Neurol. 1999 Mar;45(3):358-68. doi: 10.1002/1531-8249(199903)45:33.0.co;2-x.
• Background Reiman EM, Caselli RJ, Yun LS, Chen K, Bandy D, Minoshima S, Thibodeau SN, Osborne D. Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med. 1996 Mar 21;334(12):752-8. doi: 10.1056/NEJM199603213341202.
• Background Shoghi-Jadid K, Small GW, Agdeppa ED, Kepe V, Ercoli LM, Siddarth P, Read S, Satyamurthy N, Petric A, Huang SC, Barrio JR. Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry. 2002 Jan-Feb;10(1):24-35.
• Background Small GW, Ercoli LM, Silverman DH, Huang SC, Komo S, Bookheimer SY, Lavretsky H, Miller K, Siddarth P, Rasgon NL, Mazziotta JC, Saxena S, Wu HM, Mega MS, Cummings JL, Saunders AM, Pericak-Vance MA, Roses AD, Barrio JR, Phelps ME. Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease. Proc Natl Acad Sci U S A. 2000 May 23;97(11):6037-42. doi: 10.1073/pnas.090106797.
• Background Small GW, Mazziotta JC, Collins MT, Baxter LR, Phelps ME, Mandelkern MA, Kaplan A, La Rue A, Adamson CF, Chang L, et al. Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. JAMA. 1995 Mar 22-29;273(12):942-7.
• Background [No authors listed] Consensus report of the Working Group on:
• Background Small GW, Rabins PV, Barry PP, Buckholtz NS, DeKosky ST, Ferris SH, Finkel SI, Gwyther LP, Khachaturian ZS, Lebowitz BD, McRae TD, Morris JC, Oakley F, Schneider LS, Streim JE, Sunderland T, Teri LA, Tune LE. Diagnosis and treatment of Alzheimer disease and related disorders. Consensus statement of the American Association for Geriatric Psychiatry, the Alzheimer's Association, and the American Geriatrics Society. JAMA. 1997 Oct 22-29;278(16):1363-71.
• Background Salloway S, Sperling R, Gilman S, Fox NC, Blennow K, Raskind M, Sabbagh M, Honig LS, Doody R, van Dyck CH, Mulnard R, Barakos J, Gregg KM, Liu E, Lieberburg I, Schenk D, Black R, Grundman M; Bapineuzumab 201 Clinical Trial Investigators. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology. 2009 Dec 15;73(24):2061-70. doi: 10.1212/WNL.0b013e3181c67808. Epub 2009 Nov 18.

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Indications