Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial

Small, Gary W.; Siddarth, Prabha; Li, Zhaoping; Miller, Karen J.; Ercoli, Linda; Emerson, Natacha D.; Martinez, Jacqueline; Wong, Koon-Pong; Liu, Jie; Merrill, David A.; Chen, Stephen T.; Henning, Susanne M.; Satyamurthy, Nagichettiar; Huang, Sung-Cheng; Heber, David; Barrio, Jorge R.

doi:10.1016/j.jagp.2017.10.010

Title: Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial

Journal Article · Thu Mar 01 00:00:00 EST 2018 · The American Journal of Geriatric Psychiatry

DOI:https://doi.org/10.1016/j.jagp.2017.10.010· OSTI ID:1437762

Small, Gary W.; Siddarth, Prabha; Li, Zhaoping; Miller, Karen J.; Ercoli, Linda; Emerson, Natacha D.; Martinez, Jacqueline; Wong, Koon-Pong; Liu, Jie; Merrill, David A.; Chen, Stephen T.; Henning, Susanne M.; Satyamurthy, Nagichettiar; Huang, Sung-Cheng; Heber, David; Barrio, Jorge R.

Because curcumin's anti-inflammatory properties may protect the brain from neurodegeneration, we studied its effect on memory in non-demented adults and explored its impact on brain amyloid and tau accumulation using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile positron emission tomography (FDDNP-PET). Forty subjects (age 51–84 years) were randomized to a bioavailable form of curcumin (Theracurmin® containing 90 mg of curcumin twice daily [N = 21]) or placebo (N = 19) for 18 months. Primary outcomes were verbal (Buschke Selective Reminding Test [SRT]) and visual (Brief Visual Memory Test-Revised [BVMT-R]) memory, and attention (Trail Making A) was a secondary outcome. FDDNP-PET signals (15 curcumin, 15 placebo) were determined in amygdala, hypothalamus, medial and lateral temporal, posterior cingulate, parietal, frontal, and motor (reference) regions. Mixed effects general linear models controlling for age and education, and effect sizes (ES; Cohen's d) were estimated. SRT Consistent Long-Term Retrieval improved with curcumin (ES = 0.63, p = 0.002) but not with placebo (ES = 0.06, p = 0.8; between-group: ES = 0.68, p = 0.05). Curcumin also improved SRT Total (ES = 0.53, p = 0.002), visual memory (BVMT-R Recall: ES = 0.50, p = 0.01; BVMT-R Delay: ES = 0.51, p = 0.006), and attention (ES = 0.96, p < 0.0001) compared with placebo (ES = 0.28, p = 0.1; between-group: ES = 0.67, p = 0.04). FDDNP binding decreased significantly in the amygdala with curcumin (ES = -0.41, p = 0.04) compared with placebo (ES = 0.08, p = 0.6; between-group: ES = 0.48, p = 0.07). In the hypothalamus, FDDNP binding did not change with curcumin (ES = -0.30, p = 0.2), but increased with placebo (ES = 0.26, p = 0.05; between-group: ES = 0.55, p = 0.02). Daily oral Theracurmin may lead to improved memory and attention in non-demented adults. The FDDNP-PET findings suggest that symptom benefits are associated with decreases in amyloid and tau accumulation in brain regions modulating mood and memory.

View Journal Article

Cite

Export

Save

Research Organization:: Univ. of California, Los Angeles, CA (United States)

Sponsoring Organization:: USDOE; National Inst. of Health (NIH) (United States)

Grant/Contract Number:: FC03-87ER60615; P01-AG025831; AG13308; P50 AG 16570; MH/AG58156; MH52453; AG10123; M01-RR00865

OSTI ID:: 1437762

Alternate ID(s):: OSTI ID: 1505140

Journal Information:: The American Journal of Geriatric Psychiatry, Journal Name: The American Journal of Geriatric Psychiatry Vol. 26 Journal Issue: 3; ISSN 1064-7481

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

Citation Metrics:

Cited by: 150 works

Citation information provided by
Web of Science

References (58)

Neuropathological stageing of Alzheimer-related changes Braak, H.; Braak, E. Acta Neuropathologica, Vol. 82, Issue 4 https://doi.org/10.1007/BF00308809	journal	September 1991
Six-Month Randomized, Placebo-Controlled, Double-Blind, Pilot Clinical Trial of Curcumin in Patients With Alzheimer Disease Baum, Larry; Lam, Christopher Wai Kei; Cheung, Stanley Kwok-Kuen Journal of Clinical Psychopharmacology, Vol. 28, Issue 1 https://doi.org/10.1097/jcp.0b013e318160862c	journal	January 2008
Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population Cox, Katherine HM; Pipingas, Andrew; Scholey, Andrew B. Journal of Psychopharmacology, Vol. 29, Issue 5 https://doi.org/10.1177/0269881114552744	journal	October 2014
Polyphenols in dementia: From molecular basis to clinical trials Molino, Silvia; Dossena, Maurizia; Buonocore, Daniela Life Sciences, Vol. 161 https://doi.org/10.1016/j.lfs.2016.07.021	journal	September 2016
Localization of Neurofibrillary Tangles and Beta-Amyloid Plaques in the Brains of Living Patients With Alzheimer Disease Shoghi-Jadid, Kooresh; Small, Gary W.; Agdeppa, Eric D. The American Journal of Geriatric Psychiatry, Vol. 10, Issue 1 https://doi.org/10.1097/00019442-200201000-00004	journal	January 2002
What cognitive abilities are involved in trail-making performance? Salthouse, Timothy A. Intelligence, Vol. 39, Issue 4 https://doi.org/10.1016/j.intell.2011.03.001	journal	July 2011
Distribution Volume Ratios without Blood Sampling from Graphical Analysis of PET Data Logan, Jean; Fowler, Joanna S.; Volkow, Nora D. Journal of Cerebral Blood Flow & Metabolism, Vol. 16, Issue 5 https://doi.org/10.1097/00004647-199609000-00008	journal	September 1996
Mild cognitive impairment as a diagnostic entity Petersen, R. C. Journal of Internal Medicine, Vol. 256, Issue 3 https://doi.org/10.1111/j.1365-2796.2004.01388.x	journal	September 2004
Innovative Preparation of Curcumin for Improved Oral Bioavailability Sasaki, Hiroki; Sunagawa, Yoichi; Takahashi, Kenji Biological & Pharmaceutical Bulletin, Vol. 34, Issue 5 https://doi.org/10.1248/bpb.34.660	journal	January 2011
Depression and Anxiety Symptoms Are Associated With Cerebral FDDNP-PET Binding in Middle-Aged and Older Nondemented Adults Lavretsky, Helen; Siddarth, Prabha; Kepe, Vladimir The American Journal of Geriatric Psychiatry, Vol. 17, Issue 6 https://doi.org/10.1097/JGP.0b013e3181953b82	journal	June 2009
High-Yield, Automated Radiosynthesis of 2-(1-{6-[(2-[18F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([18F]FDDNP) Ready for Animal or Human Administration Liu, Jie; Kepe, Vladimir; Žabjek, Alenka Molecular Imaging and Biology, Vol. 9, Issue 1 https://doi.org/10.1007/s11307-006-0061-4	journal	October 2006
Enhancement of transport of curcumin to brain in mice by poly(n-butylcyanoacrylate) nanoparticle Sun, Min; Gao, Yan; Guo, Chenyu Journal of Nanoparticle Research, Vol. 12, Issue 8 https://doi.org/10.1007/s11051-010-9907-4	journal	April 2010
Curcumin attenuates memory deficits and the impairment of cholinergic and purinergic signaling in rats chronically exposed to cadmium: Effects of Curcumin on Memory and on Enzymatic Signaling da Costa, Pauline; Gonçalves, Jamile F.; Baldissarelli, Jucimara Environmental Toxicology, Vol. 32, Issue 1 https://doi.org/10.1002/tox.22213	journal	November 2015
Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer’s disease Goozee, K. G.; Shah, T. M.; Sohrabi, H. R. British Journal of Nutrition, Vol. 115, Issue 3 https://doi.org/10.1017/S0007114515004687	journal	December 2015
Practice parameter: Diagnosis of dementia (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology Knopman, D. S.; DeKosky, S. T.; Cummings, J. L. Neurology, Vol. 56, Issue 9 https://doi.org/10.1212/WNL.56.9.1143	journal	May 2001
Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder Haapakoski, Rita; Mathieu, Julia; Ebmeier, Klaus P. Brain, Behavior, and Immunity, Vol. 49 https://doi.org/10.1016/j.bbi.2015.06.001	journal	October 2015
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 Sperling, Reisa A.; Aisen, Paul S.; Beckett, Laurel A. Alzheimer's & Dementia, Vol. 7, Issue 3 https://doi.org/10.1016/j.jalz.2011.03.003	journal	May 2011
Towards a Pharmacophore for Amyloid Landau, Meytal; Sawaya, Michael R.; Faull, Kym F. PLoS Biology, Vol. 9, Issue 6 https://doi.org/10.1371/journal.pbio.1001080	journal	June 2011
Efficacy and Safety of Curcumin in Major Depressive Disorder: A Randomized Controlled Trial: CURCUMIN IN MAJOR DEPRESSIVE DISORDER Sanmukhani, Jayesh; Satodia, Vimal; Trivedi, Jaladhi Phytotherapy Research, Vol. 28, Issue 4 https://doi.org/10.1002/ptr.5025	journal	July 2013
Curcumin induces changes in expression of genes involved in cholesterol homeostasis Peschel, Dieter; Koerting, Ramona; Nass, Norbert The Journal of Nutritional Biochemistry, Vol. 18, Issue 2 https://doi.org/10.1016/j.jnutbio.2006.03.007	journal	February 2007
An Inventory for Measuring Depression Beck, A. T. Archives of General Psychiatry, Vol. 4, Issue 6 https://doi.org/10.1001/archpsyc.1961.01710120031004	journal	June 1961
Safety and Pharmacokinetics of a Solid Lipid Curcumin Particle Formulation in Osteosarcoma Patients and Healthy Volunteers Gota, Vikram S.; Maru, Girish B.; Soni, Tejal G. Journal of Agricultural and Food Chemistry, Vol. 58, Issue 4 https://doi.org/10.1021/jf9024807	journal	February 2010
Revision of the Brief Visuospatial Memory Test: Studies of normal performance, reliability, and validity. Benedict, Ralph H. B.; Schretlen, David; Groninger, Lowell Psychological Assessment, Vol. 8, Issue 2 https://doi.org/10.1037/1040-3590.8.2.145	journal	January 1996
Influence of Cognitive Status, Age, and APOE-4 Genetic Risk on Brain FDDNP Positron-Emission Tomography Imaging in Persons Without Dementia Small, Gary W.; Siddarth, Prabha; Burggren, Alison C. Archives of General Psychiatry, Vol. 66, Issue 1 https://doi.org/10.1001/archgenpsychiatry.2008.516	journal	January 2009
Hypothalamic pathology in Alzheimer's disease Saper, Clifford B.; German, Dwight C. Neuroscience Letters, Vol. 74, Issue 3 https://doi.org/10.1016/0304-3940(87)90325-9	journal	March 1987
Protein Binding in Patients With Late-Life Depression Kumar, Anand Archives of General Psychiatry, Vol. 68, Issue 11 https://doi.org/10.1001/archgenpsychiatry.2011.122	journal	November 2011
Education delays accelerated decline on a memory test in persons who develop dementia Hall, C. B.; Derby, C.; LeValley, A. Neurology, Vol. 69, Issue 17 https://doi.org/10.1212/01.wnl.0000278163.82636.30	journal	October 2007
Curry Consumption and Cognitive Function in the Elderly Ng, Tze-Pin; Chiam, Peak-Chiang; Lee, Theresa American Journal of Epidemiology, Vol. 164, Issue 9 https://doi.org/10.1093/aje/kwj267	journal	July 2006
Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study Ringman, John M.; Frautschy, Sally A.; Teng, Edmond Alzheimer's Research & Therapy, Vol. 4, Issue 5 https://doi.org/10.1186/alzrt146	journal	January 2012
Curcuminoids enhance amyloid-β uptake by macrophages of Alzheimer's disease patients Zhang, Laura; Fiala, Milan; Cashman, John Journal of Alzheimer's Disease, Vol. 10, Issue 1 https://doi.org/10.3233/JAD-2006-10101	journal	September 2006
Role of inflammatory molecules in the Alzheimer's disease progression and diagnosis Bagyinszky, Eva; Giau, Vo Van; Shim, Kyuhwan Journal of the Neurological Sciences, Vol. 376 https://doi.org/10.1016/j.jns.2017.03.031	journal	May 2017
The Memory Functioning Questionnaire for assessment of memory complaints in adulthood and old age. Gilewski, Michael J.; Zelinski, Elizabeth M.; Schaie, K. Warner Psychology and Aging, Vol. 5, Issue 4 https://doi.org/10.1037/0882-7974.5.4.482	journal	December 1990
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 McKhann, G.; Drachman, D.; Folstein, M. Neurology, Vol. 34, Issue 7 https://doi.org/10.1212/WNL.34.7.939	journal	July 1984
PET of Brain Amyloid and Tau in Mild Cognitive Impairment Small, Gary W.; Kepe, Vladimir; Ercoli, Linda M. New England Journal of Medicine, Vol. 355, Issue 25 https://doi.org/10.1056/NEJMoa054625	journal	December 2006
Selective reminding for analysis of memory and learning Buschke, Herman Journal of Verbal Learning and Verbal Behavior, Vol. 12, Issue 5 https://doi.org/10.1016/S0022-5371(73)80034-9	journal	October 1973
Amyloid binding properties of curcumin analogues in Alzheimer’s disease postmortem brain tissue Veldman, Emma R.; Jia, Zhisheng; Halldin, Christer Neuroscience Letters, Vol. 630 https://doi.org/10.1016/j.neulet.2016.07.045	journal	September 2016
Curcumin and cognition: a randomised, placebo-controlled, double-blind study of community-dwelling older adults Rainey-Smith, Stephanie R.; Brown, Belinda M.; Sohrabi, Hamid R. British Journal of Nutrition, Vol. 115, Issue 12 https://doi.org/10.1017/S0007114516001203	journal	April 2016
Comparative Absorption of a Standardized Curcuminoid Mixture and Its Lecithin Formulation Cuomo, John; Appendino, Giovanni; Dern, Adam S. Journal of Natural Products, Vol. 74, Issue 4 https://doi.org/10.1021/np1007262	journal	April 2011
Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study Lopresti, Adrian L.; Drummond, Peter D. Journal of Affective Disorders, Vol. 207 https://doi.org/10.1016/j.jad.2016.09.047	journal	January 2017
Prediction of Cognitive Decline by Positron Emission Tomography of Brain Amyloid and Tau Small, Gary W. Archives of Neurology, Vol. 69, Issue 2 https://doi.org/10.1001/archneurol.2011.559	journal	February 2012
The significance of neuroinflammation in understanding Alzheimer’s disease Eikelenboom, P.; Veerhuis, R.; Scheper, W. Journal of Neural Transmission, Vol. 113, Issue 11 https://doi.org/10.1007/s00702-006-0575-6	journal	October 2006
Recent Developments in Delivery, Bioavailability, Absorption and Metabolism of Curcumin: the Golden Pigment from Golden Spice Prasad, Sahdeo; Tyagi, Amit K.; Aggarwal, Bharat B. Cancer Research and Treatment, Vol. 46, Issue 1 https://doi.org/10.4143/crt.2014.46.1.2	journal	January 2014
Quantitative analysis of [18F]FDDNP PET using subcortical white matter as reference region Wong, Koon-Pong; Wardak, Mirwais; Shao, Weber European Journal of Nuclear Medicine and Molecular Imaging, Vol. 37, Issue 3 https://doi.org/10.1007/s00259-009-1293-8	journal	October 2009
Curcumin as a putative antidepressant Seo, Ho-Jun; Wang, Sheng-Min; Han, Changsu Expert Review of Neurotherapeutics, Vol. 15, Issue 3 https://doi.org/10.1586/14737175.2015.1008457	journal	February 2015
Curcumin Labeling of Neuronal Fibrillar Tau Inclusions in Human Brain Samples Mohorko, Nina; Repovš, Grega; Popović, Mara Journal of Neuropathology & Experimental Neurology, Vol. 69, Issue 4 https://doi.org/10.1097/NEN.0b013e3181d709eb	journal	April 2010
In vitro detection of (S)-naproxen and ibuprofen binding to plaques in the Alzheimer’s brain using the positron emission tomography molecular imaging probe 2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile Agdeppa, E. D.; Kepe, V.; Petri, A. Neuroscience, Vol. 117, Issue 3 https://doi.org/10.1016/S0306-4522(02)00907-7	journal	March 2003
Curcumin inhibits cholesterol uptake in Caco-2 cells by down-regulation of NPC1L1 expression Feng, Dan; Ohlsson, Lena; Duan, Rui-Dong Lipids in Health and Disease, Vol. 9, Issue 1 https://doi.org/10.1186/1476-511X-9-40	journal	January 2010
Curcumin and Dehydrozingerone Derivatives: Synthesis, Radiolabeling, and Evaluation for β-Amyloid Plaque Imaging ^† Ryu, Eun Kyoung; Choe, Yearn Seong; Lee, Kyung-Han Journal of Medicinal Chemistry, Vol. 49, Issue 20 https://doi.org/10.1021/jm0607193	journal	October 2006
Curcumin and Resveratrol in the Management of Cognitive Disorders: What is the Clinical Evidence? Mazzanti, Gabriela; Di Giacomo, Silvia Molecules, Vol. 21, Issue 9 https://doi.org/10.3390/molecules21091243	journal	September 2016
Dose-escalation and pharmacokinetic study of nanoparticle curcumin, a potential anticancer agent with improved bioavailability, in healthy human volunteers Kanai, Masashi; Imaizumi, Atsushi; Otsuka, Yoshihiko Cancer Chemotherapy and Pharmacology, Vol. 69, Issue 1 https://doi.org/10.1007/s00280-011-1673-1	journal	May 2011
Prevalence of dementia in an urban population in Kerala, India Shaji, S.; Bose, Srija; Verghese, Abraham British Journal of Psychiatry, Vol. 186, Issue 2 https://doi.org/10.1192/bjp.186.2.136	journal	February 2005
Retracted: Mechanisms and effects of curcumin on spatial learning and memory improvement in APPswe/PS1dE9 mice Wang, Pengwen; Su, Caixin; Li, Ruisheng Journal of Neuroscience Research, Vol. 92, Issue 2 https://doi.org/10.1002/jnr.23322	journal	November 2013
Clinical development of curcumin in neurodegenerative disease Hu, Shuxin; Maiti, Panchanan; Ma, Qiulan Expert Review of Neurotherapeutics, Vol. 15, Issue 6 https://doi.org/10.1586/14737175.2015.1044981	journal	May 2015
Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer's disease animal models Baum, Larry; Ng, Alex Journal of Alzheimer's Disease, Vol. 6, Issue 4 https://doi.org/10.3233/JAD-2004-6403	journal	August 2004
L-deprenyl in Alzheimer's disease: Cognitive and behavioral effects Freedman, M.; Rewilak, D.; Xerri, T. Neurology, Vol. 50, Issue 3 https://doi.org/10.1212/WNL.50.3.660	journal	March 1998
Tangles and plaques in nondemented aging and ?preclinical? Alzheimer's disease Price, Joseph L.; Morris, John C. Annals of Neurology, Vol. 45, Issue 3 https://doi.org/10.1002/1531-8249(199903)45:3<358::AID-ANA12>3.0.CO;2-X	journal	March 1999
Neuropsychological tests for predicting cognitive decline in older adults Baerresen, Kimberly M.; Miller, Karen J.; Hanson, Eric R. Neurodegenerative Disease Management, Vol. 5, Issue 3 https://doi.org/10.2217/nmt.15.7	journal	June 2015
Normative data for the Montreal Cognitive Assessment (MoCA) in a population-based sample Rossetti, H. C.; Lacritz, L. H.; Cullum, C. M. Neurology, Vol. 77, Issue 13 https://doi.org/10.1212/WNL.0b013e318230208a	journal	September 2011

Figures / Tables (6)

Similar Records

Longer TOMM40 poly-T variants associated with higher FDDNP-PET medial temporal tau and amyloid binding

Journal Article · Wed Dec 05 00:00:00 EST 2018 · PLoS ONE · OSTI ID:1437762

Siddarth, Prabha; Burggren, Alison C.; Merrill, David A.; +4 more

In Vivo Brain Plaque and Tangle Burden Mediates the Association Between Diastolic Blood Pressure and Cognitive Functioning in Nondemented Adults

Journal Article · Fri Sep 15 00:00:00 EDT 2017 · The American Journal of Geriatric Psychiatry · OSTI ID:1437762

Roussotte, Florence F.; Siddarth, Prabha; Merrill, David A.; +6 more

Quantitative analysis of [¹⁸F]FDDNP PET using subcortical white matter as reference region

Journal Article · Sat Oct 31 00:00:00 EDT 2009 · European Journal of Nuclear Medicine and Molecular Imaging · OSTI ID:1437762

Wong, Koon-Pong; Wardak, Mirwais; Shao, Weber; +7 more

Related Subjects

60 APPLIED LIFE SCIENCES
bioavailable curcumin
normal aging
memory
cognition
positron emission tomography

Title: Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial

Citation Formats

References (58)

Figures / Tables (6)

Similar Records

Related Subjects