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

No interaction between tDCS current strength and baseline performance: a conceptual replication

Several recent studies have reported non-linear effects of transcranial direct current stimulation (tDCS), which has been attributed to an interaction between the stimulation parameters (e.g., current strength, duration) and the neural state of the cortex being stimulated (e.g., indexed by baseline performance ability, age) (see Fertonani and Miniussi, 2016). We have recently described one such non-linear interaction between current strength and baseline performance on a visuospatial attention (landmark) task (Benwell et al., 2015). In this previous study, we induced a small overall rightward shift of spatial attention across 38 participants using bi-hemispheric tDCS applied for 20 min (concurrent left posterior parietal (P5) anode and right posterior parietal (P6) cathode) relative to a sham protocol. Importantly, this shift in bias was driven by a state-dependent interaction between current intensity and the discrimination sensitivity of the participant at baseline (pre-stimulation) for the landmark task. Individuals with high discrimination sensitivity (HDS) shifted rightward in response to low- (1 mA) but not high-intensity (2 mA) tDCS, whereas individuals with low discrimination sensitivity (LDS) shifted rightward with high- but not low-intensity stimulation. However, in Benwell et al. (2015) current strength was applied as a between-groups factor, where half of the participants received 1 mA and half received 2 mA tDCS, thus we were unable to compare high and low-intensity tDCS directly within each individual. Here we aimed to replicate these findings using a within-group design. Thirty young adults received 15 min of 1 and 2 mA tDCS, and a sham protocol, each on different days, to test the concept of an interaction between baseline performance and current strength. We found no overall rightward shift of spatial attention with either current strength, and no interaction between performance and current strength. These results provide further evidence of low replicability of non-invasive brain stimulation protocols, and the need for further attempts to replicate the key experimental findings within this field

No Interaction between tDCS Current Strength and Baseline Performance:A Conceptual Replication

Several recent studies have reported non-linear effects of transcranial direct current stimulation (tDCS), which has been attributed to an interaction between the stimulation parameters (e.g., current strength, duration) and the neural state of the cortex being stimulated (e.g., indexed by baseline performance ability, age) (see Fertonani and Miniussi, 2016). We have recently described one such non-linear interaction between current strength and baseline performance on a visuospatial attention (landmark) task (Benwell et al., 2015). In this previous study, we induced a small overall rightward shift of spatial attention across 38 participants using bi-hemispheric tDCS applied for 20 min (concurrent left posterior parietal (P5) anode and right posterior parietal (P6) cathode) relative to a sham protocol. Importantly, this shift in bias was driven by a state-dependent interaction between current intensity and the discrimination sensitivity of the participant at baseline (pre-stimulation) for the landmark task. Individuals with high discrimination sensitivity (HDS) shifted rightward in response to low- (1 mA) but not high-intensity (2 mA) tDCS, whereas individuals with low discrimination sensitivity (LDS) shifted rightward with high- but not low-intensity stimulation. However, in Benwell et al. (2015) current strength was applied as a between-groups factor, where half of the participants received 1 mA and half received 2 mA tDCS, thus we were unable to compare high and low-intensity tDCS directly within each individual. Here we aimed to replicate these findings using a within-group design. Thirty young adults received 15 min of 1 and 2 mA tDCS, and a sham protocol, each on different days, to test the concept of an interaction between baseline performance and current strength. We found no overall rightward shift of spatial attention with either current strength, and no interaction between performance and current strength. These results provide further evidence of low replicability of non-invasive brain stimulation protocols, and the need for further attempts to replicate the key experimental findings within this field

Effect of an 18-Month Meditation Training on Regional Brain Volume and Perfusion in Older Adults: The Age-Well Randomized Clinical Trial.

peer reviewedImportance: No lifestyle-based randomized clinical trial directly targets psychoaffective risk factors of dementia. Meditation practices recently emerged as a promising mental training exercise to foster brain health and reduce dementia risk. Objective: To investigate the effects of meditation training on brain integrity in older adults. Design, Setting, and Participants: Age-Well was a randomized, controlled superiority trial with blinded end point assessment. Community-dwelling cognitively unimpaired adults 65 years and older were enrolled between November 24, 2016, and March 5, 2018, in France. Participants were randomly assigned (1:1:1) to (1) an 18-month meditation-based training, (2) a structurally matched non-native language (English) training, or (3) no intervention arm. Analysis took place between December 2020 and October 2021. Interventions: Meditation and non-native language training included 2-hour weekly group sessions, practice of 20 minutes or longer daily at home, and 1-day intensive practices. Main Outcomes and Measures: Primary outcomes included volume and perfusion of anterior cingulate cortex (ACC) and insula. Main secondary outcomes included a global composite score capturing metacognitive, prosocial, and self-regulatory capacities and constituent subscores. Results: Among 137 participants (mean [SD] age, 69.4 [3.8] years; 83 [60.6%] female; 54 [39.4%] male) assigned to the meditation (n = 45), non-native language training (n = 46), or no intervention (n = 46) groups, all but 1 completed the trial. There were no differences in volume changes of ACC (0.01 [98.75% CI, -0.02 to 0.05]; P = .36) or insula (0.01 [98.75% CI, -0.02 to 0.03]; P = .58) between meditation and no intervention or non-native language training groups, respectively. Differences in perfusion changes did not reach statistical significance for meditation compared with no intervention in ACC (0.02 [98.75% CI, -0.01 to 0.05]; P = .06) or compared with non-native language training in insula (0.02 [98.75% CI, -0.01 to 0.05]; P = .09). Meditation was superior to non-native language training on 18-month changes in a global composite score capturing attention regulation, socioemotional, and self-knowledge capacities (Cohen d, 0.52 [95% CI, 0.19-0.85]; P = .002). Conclusions and Relevance: The study findings confirm the feasibility of meditation and non-native language training in elderly individuals, with high adherence and very low attrition. Findings also show positive behavioral effects of meditation that were not reflected on volume, and not significantly on perfusion, of target brain areas. Trial Registration: ClinicalTrials.gov Identifier: NCT02977819

Liens entre le style de vie et les marqueurs cérébraux et cognitifs du vieillissement et de la maladie d'Alzheimer : influence des facteurs de risque cardiovasculaire, du génotype APOE4, et effet d'une intervention de méditation

Lifestyle factors are amongst the main modifiable risk factors for Alzheimer’s disease (AD) and are linked to brain and cognitive integrity in cognitively unimpaired older adults. However, the underlying mechanisms and whether and how other risk and protective factors are linked to/or influence lifestyle variables are not clear. The objective of this thesis was to better understand how cardiovascular risk factors, AD genetic predisposition (APOE4 genotype), and meditation training could mediate, modulate or influence the association between lifestyle and brain and cognitive markers of aging and AD. Our results demonstrate that insulin levels and body mass index mediate the association between physical activity and gray matter volume, while for cerebral glucose metabolism physical activity could act through more direct mechanisms. We also evidence a complex interaction between lifestyle factors and APOE4 genotype on brain/cognitive integrity. More specifically, we show that cognitive activity and adherence to the Mediterranean diet are associated with brain integrity and cognition in APOE4 carriers, helping them to better cope with (resilience) and resist to (resistance) brain alterations, respectively. Conversely, physical activity is associated with greater brain integrity in APOE4 non-carriers only. Finally, we show that an 18-month meditation training could induce an increase in physical activity in older adults, which might in turn be associated with greater cognition. Our results suggest that lifestyle factors are associated with cognitive/brain integrity through different mechanisms. Taking into account their interplay with other risk factors may help designing personalized lifestyle-based strategies to prevent age- or disease-related brain and cognitive decline in older adults.Les facteurs de style de vie font partie des principaux facteurs de risque modifiables de la maladie d’Alzheimer (MA) et sont associés à l’intégrité cognitive et cérébrale chez les sujets âgés cognitivement sains. Toutefois, les mécanismes sous-tendant ces liens ainsi que ‘si’ et ‘comment’ d’autres facteurs de risque et de protection pourraient être liés au style de vie ou l’influencer, restent mal compris. L'objectif de cette thèse était de mieux comprendre comment les facteurs de risque cardiovasculaire, la prédisposition génétique à la MA (génotype APOE4), et un entraînement à la méditation, pourraient médier, moduler ou influencer l'association entre le style de vie et les marqueurs cérébraux et cognitifs du vieillissement et de la MA. Nos résultats montrent que, si l'insuline et l'indice de masse corporelle médient l'association entre l'activité physique et le volume de substance grise, l'association avec le métabolisme cérébral du glucose agit possiblement par le biais de mécanismes plus directs. Nous avons également montré des interactions complexes entre style de vie et génotype APOE4. Plus précisément, l'activité cognitive et le régime méditerranéen semblent permettre aux porteurs de l'APOE4 de mieux faire face (résilience) et mieux résister (résistance) aux altérations cérébrales, respectivement ; tandis que l’activité physique semble particulièrement bénéfique aux non-porteurs de l’APOE4. En outre, un entraînement à la méditation de 18 mois pourrait permettre d’augmenter l'activité physique chez les séniors et pourrait, par ailleurs, être associée à une meilleure préservation cognitive. Nos résultats suggèrent que les facteurs de style de vie sont associés à l'intégrité cognitive et cérébrale par différents mécanismes. La prise en compte de leur interaction avec d'autres facteurs de risque pourrait aider à concevoir des stratégies personnalisées afin de prévenir le déclin cérébral et cognitif lié à l'âge ou à la maladie chez les personnes âgées

Liens entre le style de vie et les marqueurs cérébraux et cognitifs du vieillissement et de la maladie d'Alzheimer : influence des facteurs de risque cardiovasculaire, du génotype APOE4, et effet d'une intervention de méditation

Les facteurs de style de vie font partie des principaux facteurs de risque modifiables de la maladie d’Alzheimer (MA) et sont associés à l’intégrité cognitive et cérébrale chez les sujets âgés cognitivement sains. Toutefois, les mécanismes sous-tendant ces liens ainsi que ‘si’ et ‘comment’ d’autres facteurs de risque et de protection pourraient être liés au style de vie ou l’influencer, restent mal compris. L'objectif de cette thèse était de mieux comprendre comment les facteurs de risque cardiovasculaire, la prédisposition génétique à la MA (génotype APOE4), et un entraînement à la méditation, pourraient médier, moduler ou influencer l'association entre le style de vie et les marqueurs cérébraux et cognitifs du vieillissement et de la MA. Nos résultats montrent que, si l'insuline et l'indice de masse corporelle médient l'association entre l'activité physique et le volume de substance grise, l'association avec le métabolisme cérébral du glucose agit possiblement par le biais de mécanismes plus directs. Nous avons également montré des interactions complexes entre style de vie et génotype APOE4. Plus précisément, l'activité cognitive et le régime méditerranéen semblent permettre aux porteurs de l'APOE4 de mieux faire face (résilience) et mieux résister (résistance) aux altérations cérébrales, respectivement ; tandis que l’activité physique semble particulièrement bénéfique aux non-porteurs de l’APOE4. En outre, un entraînement à la méditation de 18 mois pourrait permettre d’augmenter l'activité physique chez les séniors et pourrait, par ailleurs, être associée à une meilleure préservation cognitive. Nos résultats suggèrent que les facteurs de style de vie sont associés à l'intégrité cognitive et cérébrale par différents mécanismes. La prise en compte de leur interaction avec d'autres facteurs de risque pourrait aider à concevoir des stratégies personnalisées afin de prévenir le déclin cérébral et cognitif lié à l'âge ou à la maladie chez les personnes âgées.Lifestyle factors are amongst the main modifiable risk factors for Alzheimer’s disease (AD) and are linked to brain and cognitive integrity in cognitively unimpaired older adults. However, the underlying mechanisms and whether and how other risk and protective factors are linked to/or influence lifestyle variables are not clear. The objective of this thesis was to better understand how cardiovascular risk factors, AD genetic predisposition (APOE4 genotype), and meditation training could mediate, modulate or influence the association between lifestyle and brain and cognitive markers of aging and AD. Our results demonstrate that insulin levels and body mass index mediate the association between physical activity and gray matter volume, while for cerebral glucose metabolism physical activity could act through more direct mechanisms. We also evidence a complex interaction between lifestyle factors and APOE4 genotype on brain/cognitive integrity. More specifically, we show that cognitive activity and adherence to the Mediterranean diet are associated with brain integrity and cognition in APOE4 carriers, helping them to better cope with (resilience) and resist to (resistance) brain alterations, respectively. Conversely, physical activity is associated with greater brain integrity in APOE4 non-carriers only. Finally, we show that an 18-month meditation training could induce an increase in physical activity in older adults, which might in turn be associated with greater cognition. Our results suggest that lifestyle factors are associated with cognitive/brain integrity through different mechanisms. Taking into account their interplay with other risk factors may help designing personalized lifestyle-based strategies to prevent age- or disease-related brain and cognitive decline in older adults

Liens entre le style de vie et les marqueurs cérébraux et cognitifs du vieillissement et de la maladie d'Alzheimer : influence des facteurs de risque cardiovasculaire, du génotype APOE4, et effet d'une intervention de méditation

Lifestyle factors are amongst the main modifiable risk factors for Alzheimer’s disease (AD) and are linked to brain and cognitive integrity in cognitively unimpaired older adults. However, the underlying mechanisms and whether and how other risk and protective factors are linked to/or influence lifestyle variables are not clear. The objective of this thesis was to better understand how cardiovascular risk factors, AD genetic predisposition (APOE4 genotype), and meditation training could mediate, modulate or influence the association between lifestyle and brain and cognitive markers of aging and AD. Our results demonstrate that insulin levels and body mass index mediate the association between physical activity and gray matter volume, while for cerebral glucose metabolism physical activity could act through more direct mechanisms. We also evidence a complex interaction between lifestyle factors and APOE4 genotype on brain/cognitive integrity. More specifically, we show that cognitive activity and adherence to the Mediterranean diet are associated with brain integrity and cognition in APOE4 carriers, helping them to better cope with (resilience) and resist to (resistance) brain alterations, respectively. Conversely, physical activity is associated with greater brain integrity in APOE4 non-carriers only. Finally, we show that an 18-month meditation training could induce an increase in physical activity in older adults, which might in turn be associated with greater cognition. Our results suggest that lifestyle factors are associated with cognitive/brain integrity through different mechanisms. Taking into account their interplay with other risk factors may help designing personalized lifestyle-based strategies to prevent age- or disease-related brain and cognitive decline in older adults.Les facteurs de style de vie font partie des principaux facteurs de risque modifiables de la maladie d’Alzheimer (MA) et sont associés à l’intégrité cognitive et cérébrale chez les sujets âgés cognitivement sains. Toutefois, les mécanismes sous-tendant ces liens ainsi que ‘si’ et ‘comment’ d’autres facteurs de risque et de protection pourraient être liés au style de vie ou l’influencer, restent mal compris. L'objectif de cette thèse était de mieux comprendre comment les facteurs de risque cardiovasculaire, la prédisposition génétique à la MA (génotype APOE4), et un entraînement à la méditation, pourraient médier, moduler ou influencer l'association entre le style de vie et les marqueurs cérébraux et cognitifs du vieillissement et de la MA. Nos résultats montrent que, si l'insuline et l'indice de masse corporelle médient l'association entre l'activité physique et le volume de substance grise, l'association avec le métabolisme cérébral du glucose agit possiblement par le biais de mécanismes plus directs. Nous avons également montré des interactions complexes entre style de vie et génotype APOE4. Plus précisément, l'activité cognitive et le régime méditerranéen semblent permettre aux porteurs de l'APOE4 de mieux faire face (résilience) et mieux résister (résistance) aux altérations cérébrales, respectivement ; tandis que l’activité physique semble particulièrement bénéfique aux non-porteurs de l’APOE4. En outre, un entraînement à la méditation de 18 mois pourrait permettre d’augmenter l'activité physique chez les séniors et pourrait, par ailleurs, être associée à une meilleure préservation cognitive. Nos résultats suggèrent que les facteurs de style de vie sont associés à l'intégrité cognitive et cérébrale par différents mécanismes. La prise en compte de leur interaction avec d'autres facteurs de risque pourrait aider à concevoir des stratégies personnalisées afin de prévenir le déclin cérébral et cognitif lié à l'âge ou à la maladie chez les personnes âgées

Enforcement of Policies Against Illicit Trade in Tobacco Products in Italy

-

Medial Temporal Lobe Subregional Atrophy in Aging and Alzheimer's Disease: A Longitudinal Study

International audienceMedial temporal lobe (MTL) atrophy is a key feature of Alzheimer's disease (AD), however, it also occurs in typical aging. To enhance the clinical utility of this biomarker, we need to better understand the differential effects of age and AD by encompassing the full AD-continuum from cognitively unimpaired (CU) to dementia, including all MTL subregions with up-to-date approaches and using longitudinal designs to assess atrophy more sensitively. Age-related trajectories were estimated using the best-fitted polynomials in 209 CU adults (aged 19–85). Changes related to AD were investigated among amyloid-negative (Aβ−) ( n = 46) and amyloid-positive (Aβ+) ( n = 14) CU, Aβ+ patients with mild cognitive impairment (MCI) ( n = 33) and AD ( n = 31). Nineteen MCI-to-AD converters were also compared with 34 non-converters. Relationships with cognitive functioning were evaluated in 63 Aβ+ MCI and AD patients. All participants were followed up to 47 months. MTL subregions, namely, the anterior and posterior hippocampus (aHPC/pHPC), entorhinal cortex (ERC), Brodmann areas (BA) 35 and 36 [as perirhinal cortex (PRC) substructures], and parahippocampal cortex (PHC), were segmented from a T1-weighted MRI using a new longitudinal pipeline (LASHiS). Statistical analyses were performed using mixed models. Adult lifespan models highlighted both linear (PRC, BA35, BA36, PHC) and nonlinear (HPC, aHPC, pHPC, ERC) trajectories. Group comparisons showed reduced baseline volumes and steeper volume declines over time for most of the MTL subregions in Aβ+ MCI and AD patients compared to Aβ− CU, but no differences between Aβ− and Aβ+ CU or between Aβ+ MCI and AD patients (except in ERC). Over time, MCI-to-AD converters exhibited a greater volume decline than non-converters in HPC, aHPC, and pHPC. Most of the MTL subregions were related to episodic memory performances but not to executive functioning or speed processing. Overall, these results emphasize the benefits of studying MTL subregions to distinguish age-related changes from AD. Interestingly, MTL subregions are unequally vulnerable to aging, and those displaying non-linear age-trajectories, while not damaged in preclinical AD (Aβ+ CU), were particularly affected from the prodromal stage (Aβ+ MCI). This volume decline in hippocampal substructures might also provide information regarding the conversion from MCI to AD-dementia. All together, these findings provide new insights into MTL alterations, which are crucial for AD-biomarkers definition

The role of deconditioning in the end stage renal disease (ESRD) myopathy: physical exercise improves altered resting muscle oxygen consumption.

Background: Skeletal muscle dysfunction and poor exercise tolerance are hallmarks of end-stage renal disease (ESRD). Noninvasively measured (near-infrared spectroscopy, NIRS) resting muscle oxygen consumption (rmVO 2 ) is a biomarker of muscle dysfunction, which can be applied to study the severity and the reversibility of ESRD myopathy. We tested the hypothesis that deconditioning is a relevant factor in ESRD myopathy. Methods: The whole dialysis population (n = 59) of two of the eight centers participating into the EXCITE study (ClinicalTrials.gov NCT01255969), a randomized trial evaluating the effect of a home-based exercise program on the functional capacity of these patients was studied. Thirty-one patients were in the active arm (exercise group) and 28 in the control arm (no intervention). Normative data for rmVO 2 were obtained from a group of 19 healthy subjects. Results: rmVO 2 was twice higher (p < 0.001) in ESRDs patients (0.083 ± 0.034 ml/100 g/min) than in healthy subjects (0.041 ± 0.020 ml/100 g/min) indicating substantial skeletal muscle dysfunction in ESRD. rmVO 2 correlated with resting heart rate (r = 0.34, p = 0.009) but was independent of age, dialysis vintage, biochemical, vascular and nutrition parameters. After the 6-month exercise program, rmVO 2 reduced to 0.064 ± 0.024 ml/100 g/min (–23%, p < 0.001) in the exercise group indicating that skeletal muscle dysfunction is largely reversible but remained identical in the control group (0.082 ± 0.032 to 0.082 ± 0.031 ml/100 g/min). Conclusion: Deconditioning has a major role in ESRD myopathy. rmVO 2 is a marker of physical deconditioning and has the potential for monitoring re-conditioning programs based on physical exercise in the ESRD population