The association of sleep and cortical thickness in mild cognitive impairment.

We investigated whether device-measured sleep parameters are associated with cortical thickness in older adults with probable mild cognitive impairment (MCI). We performed a cross-sectional, exploratory analysis of sleep and structural MRI data. Sleep data were collected with MotionWatch8© actigraphy over 7 days. We computed average and variability for sleep duration, sleep efficiency, and fragmentation index. T1-weighted MRI scans were used to measure cortical thickness in FreeSurfer. We employed surface-based analysis to determine the association between sleep measures and cortical thickness, adjusting for age, sex, Montreal Cognitive Assessment (MoCA) score, and sleep medication use. Our sample included 113 participants (age = 73.1 [5.7], female = 72 [63.7 %]). Higher fragmentation index variability predicted lower cortical thickness in the left superior frontal gyrus (cluster size = 970.9 mm2, cluster-wise p = 0.017, cortical thickness range = 2.1 mm2 to 3.0 mm2), adjusting for age, sex, MoCA, and sleep medication. Our results suggest that higher variability in sleep fragmentation, an indicator of irregular sleep pattern, is linked to lower cortical thickness. Future longitudinal studies are needed to determine the directionality of these associations.

Effect of a Multimodal Lifestyle Intervention on Sleep and Cognitive Function in Older Adults with Probable Mild Cognitive Impairment and Poor Sleep: A Randomized Clinical Trial.

BACKGROUND: Poor sleep is common among older adults with mild cognitive impairment (MCI) and may contribute to further cognitive decline. Whether multimodal lifestyle intervention that combines bright light therapy (BLT), physical activity (PA), and good sleep hygiene can improve sleep in older adults with MCI and poor sleep is unknown. OBJECTIVE: To assess the effect of a multimodal lifestyle intervention on sleep in older adults with probable MCI and poor sleep. METHODS: This was a 24-week proof-of-concept randomized trial of 96 community-dwelling older adults aged 65-85 years with probable MCI (<26/30 on the Montreal Cognitive Assessment) and poor sleep (>5 on the Pittsburgh Sleep Quality Index [PSQI]). Participants were allocated to either a multimodal lifestyle intervention (INT); or 2) education + attentional control (CON). INT participants received four once-weekly general sleep hygiene education classes, followed by 20-weeks of: 1) individually-timed BLT; and 2) individually-tailored PA promotion. Our primary outcome was sleep efficiency measured using the MotionWatch8© (MW8). Secondary outcomes were MW8-measured sleep duration, fragmentation index, wake-after-sleep-onset, latency, and PSQI-measured subjective sleep quality. RESULTS: There were no significant between-group differences in MW8 measured sleep efficiency at 24-weeks (estimated mean difference [INT -CON]: 1.18%; 95% CI [-0.99, 3.34]), or any other objective-estimate of sleep. However, INT participants reported significantly better subjective sleep quality at 24-weeks (estimated mean difference: -1.39; 95% CI [-2.72, -0.06]) compared to CON. CONCLUSION: Among individuals with probable MCI and poor sleep, a multimodal lifestyle intervention improves subjective sleep quality, but not objectively estimated sleep.

Can we improve cognitive function among adults with osteoarthritis by increasing moderate-to-vigorous physical activity and reducing sedentary behaviour? Secondary analysis of the MONITOR-OA study.

BACKGROUND: Preliminary evidence suggests osteoarthritis is a risk factor for cognitive decline. One potential reason is 87% of adults with osteoarthritis are inactive, and low moderate-to-vigorous physical activity and high sedentary behaviour are each risk factors for cognitive decline. Thus, we investigated whether a community-based intervention to increase moderate-to-vigorous physical activity and reduce sedentary behaviour could improve cognitive function among adults with osteoarthritis. METHODS: This was a secondary analysis of a six month, proof-of-concept randomized controlled trial of a community-based, technology-enabled counselling program to increase moderate-to-vigorous physical activity and reduce sedentary behaviour among adults with knee osteoarthritis. The Immediate Intervention (n = 30) received a Fitbit® Flex™ and four bi-weekly activity counselling sessions; the Delayed Intervention (n = 31) received the same intervention two months later. We assessed episodic memory and working memory using the National Institutes of Health Toolbox Cognition Battery. Between-group differences (Immediate Intervention vs. Delayed Intervention) in cognitive performance were evaluated following the primary intervention (i.e., Baseline - 2 Months) using intention-to-treat. RESULTS: The intervention did not significantly improve cognitive function; however, we estimated small average improvements in episodic memory for the Immediate Intervention vs. Delayed Intervention (estimated mean difference: 1.27; 95% CI [- 9.27, 11.81]; d = 0.10). CONCLUSION: This small study did not show that a short activity promotion intervention improved cognitive health among adults with osteoarthritis. However, the effects of increased moderate-to-vigorous physical activity and reduced sedentary behaviour are likely to be small and thus we recommend subsequent studies use larger sample sizes and measure changes in cognitive function over longer intervals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Protocol Registration System: NCT02315664 ; registered 12 December, 2014; https://clinicaltrials.gov/ct2/show/NCT02315664?cond=NCT02315664&rank=1.

Buying time: a proof-of-concept randomized controlled trial to improve sleep quality and cognitive function among older adults with mild cognitive impairment.

BACKGROUND: Current evidence suggests that good quality sleep is associated with preserved cognitive function and reduced dementia risk in older adults. Sleep complaints are especially common among older adults with mild cognitive impairment (MCI), and this may contribute to their increased risk for progression to dementia. Thus, improving their sleep may be important for maintaining their cognitive health. Chronotherapy is a set of intervention strategies that can improve sleep quality through strengthening the entrainment of the biological clock to the solar light-dark cycle, and includes strategies such as (1) bright light therapy (BLT); (2) physical activity (PA); and (3) good sleep hygiene. Of these strategies, BLT is the most potent and is based on providing individualized timing to entrain circadian rhythms. Thus, a personalized chronotherapy intervention of individually timed BLT and individually tailored PA promotion, in conjunction with general sleep hygiene education may promote older adult sleep quality. We therefore aim to carry out a proof-of-concept randomized controlled trial (RCT) to examine the efficacy of such a personalized chronotherapy intervention to improve sleep quality among older adults with MCI. METHODS/DESIGN: This was a 24-week RCT of a personalized chronotherapy intervention aimed to primarily improve sleep quality as measured by the MotionWatch8©. Participants in the personalized chronotherapy group (INT) will receive four once-weekly, general sleep hygiene education classes, followed by 20 weeks of (1) individually timed BLT and (2) bi-weekly, individually tailored PA counseling phone calls in conjunction with receiving a consumer-available PA tracker-the Fitbit® Flex™. Ninety-six adults (aged 65-85 years) classified as having MCI (i.e., Mini-Mental State Exam (MMSE) ≥ 24; Montreal Cognitive Assessment (MoCA) ≤ 26; without dementia or significant functional impairment) will be randomized to either INT or a waitlist control group (CON). DISCUSSION: The results of this trial will help determine if a personalized chronotherapy intervention that includes individually timed BLT and individually tailored PA promotion, along with general sleep hygiene education can promote sleep quality among older adults at increased risk for dementia. Our results will help inform best practices for promoting sleep quality among older adults with MCI. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02926157 . Registered on 6 October 2016.

Genetic and epigenetic inactivation of T-cadherin in human hepatocellular carcinoma cells.

T-cadherin is an atypical cadherin and growing evidence has indicated that T-cadherin exerts tumor-suppressive effects on cancers of epithelial cell type and also causes positive effects on tumor angiogenesis. Human hepatocellular carcinoma (HCC) is a hypervascular tumor and T-cadherin has been shown to be overexpressed in intratumoral endothelial cells of HCCs. However, the expression status and functions of T-cadherin in hepatocytes or HCC cells remain unclear. Here, we demonstrated that T-cadherin was underexpressed in HCC cells (26.5%, 13/49 cases), but was frequently (77.6%, 38/49) overexpressed in intratumoral endothelial cells immunohistochemically. Semiquantitative RT-PCR analysis also showed that the T-cadherin gene was underexpressed in 7 of 11 HCC cell lines. Loss of heterozygosity analysis revealed that 32-38% of the 42 human HCC samples had allelic losses at this locus. Upon pharmacological treatment with demethylating agent 5-aza-2'-deoxycytidine or histone deacetylase inhibitor trichostatin A, T-cadherin promoter hypermethylation and/or histone deacetylation was frequently observed in HCC samples and cell lines. Functionally, enforced expression of T-cadherin induced G(2)/M cell cycle arrest, reduced cell proliferation in low serum medium, suppressed anchorage-independent growth in soft agar and increased sensitivity to TNFalpha-mediated apoptosis in HCC cells. Intriguingly, we found that T-cadherin significantly suppressed the activity of c-Jun, a crucial oncoprotein constitutively activated in HCC cells. To conclude, T-cadherin was differentially expressed in human HCCs. The underexpression of T-cadherin in HCC cells suggests it may be another critical event in addition to T-cadherin-mediated angiogenesis during HCC development.

Metallothionein gene expression in zebrafish embryo-larvae and ZFL cell-line exposed to heavy metal ions.

The aim of this study is to investigate the induction of zebrafish metallothionein (zMT) gene expression following the administration of different metal ions using in vivo and in vitro models. The zebrafish embryo-larvae were used for the in vivo study, and MT gene expression was studied during the development from fertilization (8hpf) to embryo-larval stage using real-time PCR. The LC50 values and zMT mRNA levels were also measured in embryo-larvae exposed to various metal ions. The general trend of 24 h LC50 values as determined is Cu2+ < Hg2+ < Cd2+ << Zn2+. However, Hg2+ was found to be the most potent metal inducer with the highest level of zMT mRNA induction (40-50 folds) in 8hpf embryo-larvae, followed by Cd2+ (approximately 20 folds); Cu2+ and Zn2+ only gave approximately 5 fold of induction. In the in vitro study of ZFL cell-line, Cd2+ is the most potent inducer of zMT mRNA (up to 250 folds), Cu2+ and Zn2+ gave similar potency of approximately 50-100 folds, and Hg2+ gave approximately 40-50 folds of zMT mRNA levels over the control group.

Metal uptake in zebrafish embryo-larvae exposed to metal-contaminated sediments.

Heavy metal contamination in coastal and estuarine regions of inner Tolo Harbour, as well as some river and nullah areas, is one of the major water-pollution issues in Hong Kong. Zebrafish (Danio rerio) embryo-larvae was used to study metal uptake from coastal sediments collected from Fo Tan River (industrial area, Sha Tin), Tai Po River (residential area, Tai Po) and Wu Kai Sa (rural area, Tolo Harbour). Exposure experiments (7-days) were carried out using different concentrations (0.1%, 0.5%, 1% and 0% as control) of sediments that were added to aquaria containing fertilized zebrafish eggs until they hatched to become larvae. Uptake of heavy metals (Cd, Cu, Pb and Zn) was determined in whole embryo-larvae following exposure. Significant levels of Cd, Cu, Pb and Zn were detected in the embryo-larvae exposed to sediments from Tai Po River. However, significant levels of only Cd and Cu were found in embryo-larvae exposed to sediments from Fo Tan River.