Effect of cognitive reserve on the association between slow wave sleep and cognition in community-dwelling older adults

Sleep, especially slow wave sleep (SWS), is essential for cognitive functioning and is reduced in aging. The impact of sleep quality on cognition is variable, especially in aging. Cognitive reserve (CR) may be an important modulator of these effects. We aimed at investigating this question to better identify individuals in whom sleep disturbances might have greater behavioral consequences. Polysomnography and neuropsychological assessments were performed in 135 cognitively intact older adults (mean age ± SD: 69.4 ± 3.8y) from the Age-Well randomized controlled trial (baseline data). Two measures of cognitive engagement throughout life were used as CR proxies. Linear regression analyses were performed between the proportion of SWS, and executive function and episodic memory composite scores. Then, interaction analyses between SWS and CR proxies on cognition were conducted to assess the possible impact of CR on these links. SWS was positively associated with episodic memory, but not with executive function. CR proxies modulated the associations between SWS and both executive and episodic memory performance. Specifically, individuals with higher CR were able to maintain cognitive performance despite low amounts of SWS. This study provides the first evidence that CR may protect against the deleterious effects of age-related sleep changes on cognition

Patient‐reported outcomes after 3‐dimensional conformal, intensity‐modulated, or proton beam radiotherapy for localized prostate cancer

BACKGROUND: Recent studies have suggested differing toxicity patterns for patients with prostate cancer who receive treatment with 3‐dimensional conformal radiotherapy (3DCRT), intensity‐modulated radiotherapy (IMRT), or proton beam therapy (PBT). METHODS: The authors reviewed patient‐reported outcomes data collected prospectively using validated instruments that assessed bowel and urinary quality of life (QOL) for patients with localized prostate cancer who received 3DCRT (n = 123), IMRT (n = 153) or PBT (n = 95). Clinically meaningful differences in mean QOL scores were defined as those exceeding half the standard deviation of the baseline mean value. Changes from baseline were compared within groups at the first post‐treatment follow‐up (2‐3 months from the start of treatment) and at 12 months and 24 months. RESULTS: At the first post‐treatment follow‐up, patients who received 3DCRT and IMRT, but not those who received PBT, reported a clinically meaningful decrement in bowel QOL. At 12 months and 24 months, all 3 cohorts reported clinically meaningful decrements in bowel QOL. Patients who received IMRT reported clinically meaningful decrements in the domains of urinary irritation/obstruction and incontinence at the first post‐treatment follow‐up. At 12 months, patients who received PBT, but not those who received IMRT or 3DCRT, reported a clinically meaningful decrement in the urinary irritation/obstruction domain. At 24 months, none of the 3 cohorts reported clinically meaningful changes in urinary QOL. CONCLUSIONS: Patients who received 3DCRT, IMRT, or PBT reported distinct patterns of treatment‐related QOL. Although the timing of toxicity varied between the cohorts, patients reported similar modest QOL decrements in the bowel domain and minimal QOL decrements in the urinary domains at 24 months. Prospective randomized trials are needed to further examine these differences. Cancer 2013. © 2013 American Cancer Society. Prostate cancer patients who receive 3‐dimensional conformal radiotherapy, intensity‐modulated radiotherapy, or proton beam therapy report distinct patterns of treatment‐related quality of life. Although the timing of toxicity varies between cohorts, patients report similar modest quality‐of‐life decrements in the bowel domain and minimal QOL decrements in the urinary domains at 24 months.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97476/1/27956_ftp.pd

Effects of Meditation Training and Non-Native Language Training on Cognition in Older Adults: A Secondary Analysis of a Randomized Clinical Trial

IMPORTANCE: Nonpharmacological interventions are a potential strategy to maintain or promote cognitive functioning in older adults. OBJECTIVE: To investigate the effects of 18 months' meditation training and 18 months' non-native language training on cognition in older adults. DESIGN, SETTING, AND PARTICIPANTS: This study was a secondary analysis of the Age-Well trial, an 18-month, observer-masked, randomized clinical trial with 3 parallel arms. Eligible participants were community-dwelling adults aged 65 years and older residing in Caen, France. Participants were enrolled from November 24, 2016, to March 5, 2018, and randomly assigned (1:1:1) to meditation training, non-native language (English) training, or no intervention arms. Final follow-up was completed on February 6, 2020. Data were analyzed between December 2021 and November 2022. INTERVENTIONS: The 18-month meditation and non-native language training interventions were structurally equivalent and included 2-hour weekly group sessions, daily home practice of 20 minutes or longer, and 1 day of more intensive home practice. The no intervention group was instructed not to change their habits and to continue living as usual. MAIN OUTCOMES AND MEASURES: Cognition (a prespecified secondary outcome of the Age-Well trial) was assessed preintervention and postintervention via the Preclinical Alzheimer Cognitive Composite 5 (PACC5), and composites assessing episodic memory, executive function, and attention. RESULTS: Among 137 randomized participants, 2 were excluded for not meeting eligibility criteria, leaving 135 (mean [SD] age, 69.3 [3.8] years; 83 female [61%]) eligible for analysis. One participant among the remaining 135 did not complete the trial. In adjusted mixed effects models, no interaction effects were observed between visit and group for PACC5 (F2,131.39 = 2.58; P = .08), episodic memory (F2,131.60 = 2.34; P = .10), executive function (F2,131.26 = 0.89; P = .41), or attention (F2,131.20 = 0.34; P = .79). Results remained substantively unchanged across sensitivity and exploratory analyses. CONCLUSIONS AND RELEVANCE: In this secondary analysis of an 18-month randomized trial, meditation and non-native language training did not confer salutary cognitive effects. Although further analyses are needed to explore the effects of these interventions on other relevant outcomes related to aging and well-being, these findings did not support the use of these interventions for enhancing cognition in cognitively healthy older adults. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02977819

Effects of a mindfulness-based versus a health self-management intervention on objective cognitive performance in older adults with subjective cognitive decline (SCD): a secondary analysis of the SCD-Well randomized controlled trial.

peer reviewedBACKGROUND: Older individuals with subjective cognitive decline (SCD) perceive that their cognition has declined but do not show objective impairment on neuropsychological tests. Individuals with SCD are at elevated risk of objective cognitive decline and incident dementia. Non-pharmacological interventions (including mindfulness-based and health self-management approaches) are a potential strategy to maintain or improve cognition in SCD, which may ultimately reduce dementia risk. METHODS: This study utilized data from the SCD-Well randomized controlled trial. One hundred forty-seven older adults with SCD (MAge = 72.7 years; 64% female) were recruited from memory clinics in four European countries and randomized to one of two group-based, 8-week interventions: a Caring Mindfulness-based Approach for Seniors (CMBAS) or a health self-management program (HSMP). Participants were assessed at baseline, post-intervention (week 8), and at 6-month follow-up (week 24) using a range of cognitive tests. From these tests, three composites were derived-an "abridged" Preclinical Alzheimer's Cognitive Composite 5 (PACC5Abridged), an attention composite, and an executive function composite. Both per-protocol and intention-to-treat analyses were performed. Linear mixed models evaluated the change in outcomes between and within arms and adjusted for covariates and cognitive retest effects. Sensitivity models repeated the per-protocol analyses for participants who attended ≥ 4 intervention sessions. RESULTS: Across all cognitive composites, there were no significant time-by-trial arm interactions and no measurable cognitive retest effects; sensitivity analyses supported these results. Improvements, however, were observed within both trial arms on the PACC5Abridged from baseline to follow-up (Δ [95% confidence interval]: CMBAS = 0.34 [0.19, 0.48]; HSMP = 0.30 [0.15, 0.44]). There was weaker evidence of an improvement in attention but no effects on executive function. CONCLUSIONS: Two non-pharmacological interventions conferred small, non-differing improvements to a global cognitive composite sensitive to amyloid-beta-related decline. There was weaker evidence of an effect on attention, and no evidence of an effect on executive function. Importantly, observed improvements were maintained beyond the end of the interventions. Improving cognition is an important step toward dementia prevention, and future research is needed to delineate the mechanisms of action of these interventions and to utilize clinical endpoints (i.e., progression to mild cognitive impairment or dementia). TRIAL REGISTRATION: ClinicalTrials.gov, NCT03005652

Brain Phenotype of Transgenic Mice Overexpressing Cystathionine β-Synthase

The cystathionine β-synthase (CBS) gene, located on human chromosome 21q22.3, is a good candidate for playing a role in the Down Syndrome (DS) cognitive profile: it is overexpressed in the brain of individuals with DS, and it encodes a key enzyme of sulfur-containing amino acid (SAA) metabolism, a pathway important for several brain physiological processes.Here, we have studied the neural consequences of CBS overexpression in a transgenic mouse line (60.4P102D1) expressing the human CBS gene under the control of its endogenous regulatory regions. These mice displayed a ∼2-fold increase in total CBS proteins in different brain areas and a ∼1.3-fold increase in CBS activity in the cerebellum and the hippocampus. No major disturbance of SAA metabolism was observed, and the transgenic mice showed normal behavior in the rotarod and passive avoidance tests. However, we found that hippocampal synaptic plasticity is facilitated in the 60.4P102D1 line.We demonstrate that CBS overexpression has functional consequences on hippocampal neuronal networks. These results shed new light on the function of the CBS gene, and raise the interesting possibility that CBS overexpression might have an advantageous effect on some cognitive functions in DS

Involvment of both calcium influx and calcium mobilization in growth hormone-induced (CA2+)i increases in Chinese hamster ovary cells

International audienc

Roles of extracellular and cytoplasmic domains of the prolactin receptor in signal transduction to milk protein genes

International audienc

Development of a constitutively active mutant form of the prolactin receptor, a member of the cytokine receptor family

International audienc