Targeting preclinical stages of Alzheimer’s disease

a clinical trial to assess the efficacy of curcumin using brain biomarkers.

Kathryn G. Goozee, Pratishtha Chatterjee, Hamid R. Sohrabi, Kai Kai Shen, Bethany Ball, Preeti Dave, Candice ManYan, Prita Riana Asih, Kevin Taddei, Ralph Martins

Research output: Contribution to journalMeeting abstract

Abstract

Background: Current pharmacological interventions for Alzheimer’s disease (AD) target its cognitive and behavioural symptoms, but do not impede disease pathogenesis. Furthermore, the lack of efficacy of disease modifying agents is conceivably attributable to administration of interventions too late in the disease process. Consequently, we have identified cognitively normal individuals in the preclinical stage of AD by assessing their brain beta-amyloid (Aβ) load via Positron Emission Tomography (PET), to investigate the therapeutic efficacy of curcumin. Methods: Participants living within independent living units, at the Anglican Retirement Villages (ARV), Sydney Australia, were recruited to establish the McCusker Kerr Anglican Retirement Village Initiative in Ageing Health (McCusker KARVIAH) cohort. All eligible participants were 65-90 years of age, had subjective memory complaints (no dementia), stable health, and considered ‘at risk’ of AD. At baseline participants underwent physical health and lifestyle assessments (exercise, nutrition and sleep), blood draw for biochemical analysis, comprehensive neuropsychological assessment, and neuroimaging (PET using 18F-Florbetaben; 18F-Fluorodeoxyglucose; and magnetic resonance imaging). Following, a double blind placebo controlled, 12 month intervention using oral curcumin (BCM-95™, 1.5mg daily) with scheduled completion due in October, 2016, all participants will be re-assessed for the aforementioned parameters. Results: Thirty-four percent of cohort participants (N=105) PET imaged using ligand 18F-Florbetaben had high amyloid load (defined as neocortical SUVR>1.35). Further within the cohort APOE ε4 carriers (N=24) were observed to have significantly elevated brain amyloid load compared to non- ε4 carriers (N=81; p<0.000). No significant difference was present between high and low amyloid load participants in age, gender and education. The therapeutic efficacy of curcumin will be assessed based on findings obtained at the 6 month (blood chemistry only) and 12 month time points. Conclusions: While the anti-oxidative and anti-inflammatory properties of curcumin have been established from findings reported in in vitro and in vivostudies, its benefits in clinical AD pathology have not been confirmed. Limitations identified in earlier studies, including the low bioavailability of curcumin and the use of interventions too late in the disease process, have been addressed in our study, thus providing the best opportunity to elucidate the full potential of curcumin as a nutraceutical for AD prevention.
Original languageEnglish
Article numberP2-020
Pages (from-to)P616
Number of pages1
JournalAlzheimer's and Dementia
Volume12
Issue number7 Supplement
DOIs
Publication statusPublished - 2016
EventAlzheimer's Association International Conference 2016 - Toronto, Canada
Duration: 22 Jul 201628 Jul 2016

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