To investigate the changes in specific domains of cognitive function in older adults reporting subjective memory complaints with a low omega-3 index receiving omega 3 polyunsaturated fatty acid (n-3 PUFA) supplementation or placebo.

Significant research attention has focussed on the identification of nutraceutical agents for the prevention of cognitive decline as a natural means of cog

P73, like Notch, has been implicated in neurodevelopment and in the maintenance of the mature central nervous system. In this study, by the use of reporter-gene assays, we demonstrate that C-promoter binding factor-1 (CBF-1)-dependent gene transcription driven by the Notch-1 intracellular domain (N1^ICD) is potently antagonized by exogenously expressed transactivating (TA) p73 splice variants in SH-SY5Y neuroblastomas and in primary neurones. Time course analysis indicated that the inhibitory effects of TAp73 are direct and are not mediated via the product of a downstream target gene. We found that endogenous TAp73 stabilized by either c-Abl or cisplatin treatment also potently antagonized N1^ICD/CBF-1-dependent gene transcription. Furthermore, western blotting revealed that exogenous TAp73 suppressed endogenous hairy and enhancer of split-1 (HES-1) protein levels and antagonized the increase in HES-1 protein induced by exogenous N1^ICD expression. Evidence of a direct physical interaction between N1^ICD and TAp73α was demonstrated by co-immunoprecipitation. Using Notch deletion constructs, we demonstrate that TAp73α binds the N1^ICD in a region C-terminal of aa 2094. Interestingly, ΔNp73α and TAp73α_R292H also co-purified with N1^ICD, but neither inhibited N1^ICD/CBF-1-dependent transcription. This suggests that an intact transactivation (TA) domain and the ability to bind DNA are necessary for TAp73 to antagonize Notch signalling. Finally we found that TAp73α reversed the N1^ICD-mediated repression of retinoic acid-induced differentiation of SH-SY5Y neuroblastomas, providing functional evidence for an inhibitory effect of TAp73α on notch signalling. Collectively, these findings may have ramifications for neurodevelopment, neurodegeneration and oncogenesis.

Multidomain lifestyle interventions (including combinations of physical exercise, cognitive training and nutritional guidance) are attracting increasing re

Alzheimer's disease (AD) is a neurodegenerative disorder characterised by amyloid-β (Aβ), tau hyperphosphorylation and neurodegeneration. Blood-based biomarkers are emerging as a minimally invasive tool for disease detection and monitoring. This review depicts the relationships between modifiable lifestyle factors (nutrition, physical activity (PA), sleep, alcohol consumption, smoking, and social isolation) and plasma biomarkers of AD: Aβ₄₂, Aβ₄₀, Aβ_42/40, phosphorylated tau, total tau, neurofilament light chain (NfL) and glial fibrillary acidic protein. Limited evidence suggests that better nutrition is associated with favourable AD plasma biomarker profiles and that PA is associated with less plasma NfL and Aβ, whilst poor sleep is associated with elevated plasma Aβ. However, lack of data and inconsistent findings highlight the need for further investigation to substantiate or refute these trends. Moreover, future research should include the analysis of lifestyle on plasma biomarkers according to gender, metabolic health and APOE status. Considering the growing emphasis on modifiable lifestyle factors for preventing and delaying dementia onset further investigation is justified.

Vitamin D deficiency is associated with an increased risk of Alzheimer’s disease and increased beta-amyloid (Aβ) in animals. Hence we sought to investigate the relationship between plasma 25-hydroxyvitamin D (25(OH)D) and cerebral Aβ in older adults with subjective memory complaints. This is a secondary analysis of the Multidomain Alzheimer Preventive Trial. Participants were 178 dementia-free individuals aged 70 years or older with data on plasma 25(OH)D and cerebral Aβ load assessed by [18F]-florbetapir positron emission tomography. Plasma 25(OH)D was measured at study baseline using a commercially available electro-chemiluminescence competitive binding assay. Standard uptake value ratios (SUVRs) were generated using the cerebellum as a reference. Brain regions assessed included the cortex, anterior cingulate, anterior putamen, caudate, hippocampus, medial orbitofrontal cortex, occipital cortex, parietal cortex, pons, posterior cingulate, posterior putamen, precuneus, semioval centre and temporal cortex. Associations were explored using fully adjusted multiple linear regression models. Participants had a mean (SD) age of 76.2 years (4.4) and 59.6% were female. The mean (SD) plasma 25(OH)D level was 22.4 ng/ml (10.8) and the mean (SD) cortical SUVR was 1.2 (0.2). We did not find any cross-sectional associations (p > 0.05) between baseline 25(OH)D levels and Aβ in any of the brain regions studied. These preliminary results suggest that circulating 25(OH)D is not associated with cerebral Aβ in older adults. Further longitudinal studies with the measurement of mid-life vitamin D status are required to explore the relationship between vitamin D and Aβ accrual over time, thereby circumventing the shortfalls of a cross-sectional study.