Curcumin derived from turmeric is well documented for its anti-carcinogenic, antioxidant and anti-inflammatory properties. Recent studies show that curcumin also possesses neuroprotective and cognitive-enhancing properties that may help delay or prevent neurodegenerative diseases, including Alzheimer’s disease (AD). Currently, clinical diagnosis of AD is onerous, and it is primarily based on the exclusion of other causes of dementia. In addition, phase III clinical trials of potential treatments have mostly failed, leaving disease-modifying interventions elusive. AD can be characterised neuropathologically by the deposition of extracellularβamyloid (Aβ) plaques and intracellular accumulation of tau-containing neurofibrillary tangles. Disruptions in Aβmetabolism/clearance contribute to AD pathogenesis.In vitrostudies have shown that Aβmetabolism is altered by curcumin, and animal studies report that curcumin may influence brain function and the development of dementia, because of its antioxidant and anti-inflammatory properties, as well as its ability to influence Aβmetabolism. However, clinical studies of curcumin have revealed limited effects to date, most likely because of curcumin’s relatively low solubility and bioavailability, and because of selection of cohorts with diagnosed AD, in whom there is already major neuropathology. However, the fresh approach of targeting early AD pathology (by treating healthy, pre-clinical and mild cognitive impairment-stage cohorts) combined with new curcumin formulations that increase bioavailability is renewing optimism concerning curcumin-based therapy. The aim of this paper is to review the current evidence supporting an association between curcumin and modulation of AD pathology, includingin vitroandin vivostudies. We also review the use of curcumin in emerging retinal imaging technology, as a fluorochrome for AD diagnostics.

Curcumin therapy in animals has produced positive cognitive and behavioural outcomes; results of human trials, however, have been inconsistent. In this study, we report the results of a 12-month, randomised, placebo-controlled, double-blind study that investigated the ability of a curcumin formulation to prevent cognitive decline in a population of community-dwelling older adults. Individuals (n 96) ingested either placebo or 1500 mg/d Biocurcumax^TM for 12 months. A battery of clinical and cognitive measures was administered at baseline and at the 6-month and 12-month follow-up assessments. A significant time×treatment group interaction was observed for the Montreal Cognitive Assessment (repeated-measures analysis; time×treatment; F=3·85, P<0·05). Subsequent analysis revealed that this association was driven by a decline in function of the placebo group at 6 months that was not observed in the curcumin treatment group. No differences were observed between the groups for all other clinical and cognitive measures. Our findings suggest that further longitudinal assessment is required to investigate changes in cognitive outcome measures, ideally in conjunction with biological markers of neurodegeneration.

Western countries are experiencing aging populations and increased longevity; thus, the incidence of dementia and Alzheimer’s disease (AD) in these countries is projected to soar. In the absence of a therapeutic drug, non-pharmacological preventative approaches are being investigated. One of these approaches is regular participation in physical activity or exercise. This paper reviews studies that have explored the relationship between physical activity and cognitive function, cognitive decline, AD/dementia risk and AD-associated biomarkers and processes. There is now strong evidence that links regular physical activity or exercise to higher cognitive function, decreased cognitive decline and reduced risk of AD or dementia. Nevertheless, these associations require further investigation, more specifically with interventional studies that include long follow-up periods. In particular, relatively little is known about the underlying mechanism(s) of the associations between physical activity and AD neuropathology; clearly this is an area in need of further research, particularly in human populations. Although benefits of physical activity or exercise are clearly recognised, there is a need to clarify how much physical activity provides the greatest benefit and also whether people of different genotypes require tailored exercise regimes.

Objective: Biomarkers for Alzheimer disease (AD) can detect the disease pathology in asymptomatic subjects and individuals with mild cognitive impairment (MCI), but their cognitive prognosis remains uncertain. We aimed to determine the prognostic value of β‐amyloid imaging, alone and in combination with memory performance, hippocampal atrophy, and apolipoprotein E ε4 status in nondemented, older individuals.Methods: A total of 183 healthy individuals (age = 72.0 ± 7.26 years) and 87 participants with MCI (age = 73.7 ± 8.27) in the Australian Imaging, Biomarkers, and Lifestyle study of ageing were studied. Clinical reclassification was performed after 3 years, blind to biomarker findings. β‐Amyloid imaging was considered positive if the ¹¹C‐Pittsburgh compound B cortical to reference ratio was ≥1.5.Results: Thirteen percent of healthy persons progressed (15 to MCI, 8 to dementia), and 59% of the MCI cohort progressed to probable AD. Multivariate analysis showed β‐amyloid imaging as the single variable most strongly associated with progression. Of combinations, subtle memory impairment (Z score = −0.5 to −1.5) with a positive amyloid scan was most strongly associated with progression in healthy individuals (odds ratio [OR] = 16, 95% confidence interval [CI] = 3.7–68; positive predictive value [PPV] = 50%, 95% CI = 19–81; negative predictive value [NPV] = 94%, 95% CI = 88–98). Almost all amnestic MCI subjects (Z score ≤ −1.5) with a positive amyloid scan developed AD (OR = ∞; PPV = 86%, 95% CI = 72–95; NPV = 100%, 95% CI = 80–100). Hippocampal atrophy and ε4 status did not add further predictive value.Interpretation: Subtle memory impairment with a positive β‐amyloid scan identifies healthy individuals at high risk for MCI or AD. Clearly amnestic patients with a positive amyloid scan have prodromal AD and a poor prognosis for dementia within 3 years. Ann Neurol 2013;74:905–913