Efficacy of curcumin for age-associated cognitive decline: a narrative review of preclinical and clinical studies

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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Correspondence to Marjana Rahman Sarker.

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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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Keywords

  • Curcumin
  • Cognition
  • Aging