Abstract
Processes such as aberrant redox signaling and chronic low-grade systemic inflammation have been reported to modulate age-associated pathologies such as cognitive impairment. Curcumin, the primary therapeutic component of the Indian spice, Turmeric (Curcuma longa), has long been known for its strong anti-inflammatory and antioxidant activity attributable to its unique molecular structure. Recently, an interest in this polyphenol as a cognitive therapeutic for the elderly has emerged. The purpose of this paper is to critically review preclinical and clinical studies that have evaluated the efficacy of curcumin in ameliorating and preventing age-associated cognitive decline and address the translational progress of preclinical to clinical efficacy. PubMed, semantic scholar, and Google scholar searches were used for preclinical studies; and clinicaltrials.gov, the Australian and New Zealand clinical trials registry, and PubMed search were used to select relevant completed clinical studies. Results from preclinical studies consistently demonstrate curcumin and its analogues to be efficacious for various aspects of cognitive impairment and processes that contribute to age-associated cognitive impairment. Results of published clinical studies, while mixed, continue to show promise for curcumin’s use as a therapeutic for cognitive decline but overall remain inconclusive at this time. Both in vitro and in vivo studies have found that curcumin can significantly decrease oxidative stress, systemic inflammation, and obstruct pathways that activate transcription factors that augment these processes. Future clinical studies would benefit from including evaluation of peripheral and cerebrospinal fluid biomarkers of dementia and behavioral markers of cognitive decline, as well as targeting the appropriate population.
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Abbreviations
- AD:
-
Alzheimer’s disease
- ADAS-Cog:
-
Alzheimer’s Disease Assessment Scale-cognitive subscale
- ADL:
-
Activities of daily living
- AGE:
-
Advanced glycation end products
- APP:
-
Amyloid precursor protein
- AREs:
-
Antioxidant response elements
- Aβ:
-
Amyloid beta
- BDMC:
-
Bisdemethoxycurcumin
- BDNF:
-
Brain-derived neurotrophic factor
- CA:
-
Cornu Ammonis (hippocampal subfield)
- CAMKII:
-
Calcium/calmodulin-dependent kinase II
- CNS:
-
Central nervous system
- cAMP:
-
Cyclic AMP
- CREB:
-
Cyclic AMP-responsive element-binding protein
- CRP:
-
C-reactive protein
- DMC:
-
Demethoxycurcumin
- DSM:
-
Diagnostic and statistical manual of mental disorders
- GCLc:
-
Glutamate cysteine ligase catalytic subunit
- GFAP:
-
Glial fibrillary acidic protein
- GSH:
-
Reduced glutathione
- GSSG:
-
Oxidized glutathione
- Hcy:
-
Homocysteine
- Iba1:
-
Ionized calcium binding adaptor molecule 1
- IKKβ:
-
Inhibitor of nuclear factor kappa-B kinase subunit B
- IL-1β:
-
Interleukin 1 beta
- IL-6:
-
Interleukin 6
- iNOS:
-
Inducible nitric oxide synthase
- IP:
-
Intraperitoneal
- KEAP1:
-
Kelch-like ECH-associated protein 1
- LPS:
-
Lipopolysaccharide
- LTP:
-
Long-term potentiation
- MCI:
-
Mild cognitive impairment
- MDA:
-
Malondialdehyde
- MMSE:
-
Mini Mental Status Exam
- MoCA:
-
Montreal Cognition Assessment
- mTOR:
-
Mammalian target of rapamycin
- MWM:
-
Morris water maze
- NF-κB:
-
Nuclear factor kappa-light-chain-enhancer of activated B cells
- NMDAR:
-
p-N-methyl-d-aspartate receptor
- NO:
-
Nitric oxide
- NOL:
-
Novel object location
- NPI:
-
Neuropsychiatric Inventory
- NRF2:
-
Nuclear factor (erythroid-derived 2)-like 2
- OH:
-
Hydroxyl
- PD:
-
Parkinson’s disease
- PI3K:
-
Phosphoinositide 3-kinase
- PS1 & 2:
-
Presenilin 1 and 2
- ROS:
-
Reactive oxygen species
- SAMP8:
-
Senescence accelerated mouse–Prone 8
- SAMR1:
-
Senescence resistant
- SH:
-
Sulfhydryl
- SOD:
-
Superoxide dismutase
- STZ:
-
Streptozotocin
- TNF-α:
-
Tumor necrosis factor alpha
- TrkB:
-
Tropomycin receptor kinase B
- Tx:
-
Treatment
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Sarker, M.R., Franks, S.F. Efficacy of curcumin for age-associated cognitive decline: a narrative review of preclinical and clinical studies. GeroScience 40, 73–95 (2018). https://doi.org/10.1007/s11357-018-0017-z
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DOI: https://doi.org/10.1007/s11357-018-0017-z