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Understanding the factors that predict why some individuals perceive to respond more to meditation training than others could impact the development, efficacy, adherence levels, and implementation of meditation-based interventions. We investigated individual-level variables associated with self- and teacher-perceived responsiveness to longer-term meditation training. This study presents a secondary analysis of the Age-Well trial (NCT02977819, 30/11/2016) and includes 90 healthy older adults (65–84 years) that were randomised to an 18-month meditation training or a non-native language (English) training. Responsiveness was measured post-intervention using participants' and teachers' ratings of four psychological domains (connection, positive/negative emotions, meta-awareness) in relation to two contexts (during sessions, in daily life), teachers' perception of overall benefit, and a global composite comprising all self- and teacher-perceived responsiveness measures. Linear regression modelling indicates that, when including baseline variables (sex, education, neuroticism, cognition, expectancy) and engagement (hours of formal practice during intervention), only higher levels of engagement were associated with higher global composite scores (standardised estimate = 0.50, 95% CI: 0.24–0.77, p < 0.001). Global composite scores were not correlated with pre-post changes in well-being. Findings indicate that more time spent practising meditation was related to greater perceived intervention effects. We suggest that future studies closely monitor levels of engagement and map reasons for disengagement. [ABSTRACT FROM AUTHOR]

Background: White matter hyperintensities (WMH) are very frequent in older adults and associated with worse cognitive performance. Little is known about the links between WMH and vascular risk factors, cortical β-amyloid (Aβ) load, and cognition in cognitively unimpaired adults across the entire lifespan, especially in young and middle-aged adults. Methods: One hundred and thirty-seven cognitively unimpaired adults from the community were enrolled (IMAP cohort). Participants underwent (i) a comprehensive neuropsychological assessment of episodic memory, processing speed, working memory, and executive functions; (ii) brain structural T1 and FLAIR MRI scans used for the automatic segmentation of total and regional (frontal, parietal, temporal, occipital, and corpus callosum) WMH; and (iii) a Florbetapir-PET scan to measure cortical Aβ. The relationships of total and regional WMH to age, vascular risk factors, cortical Aβ, and cognition were assessed within the whole sample, but also splitting the sample in two age groups (≤ or > 60 years old). Results: WMH increased with age across the adult lifespan, i.e., even in young and middle-aged adults. Systolic blood pressure, diastolic blood pressure, and glycated hemoglobin were all associated with higher WMH before, but not after, adjusting for age and the other vascular risk factors. Higher frontal, temporal, and occipital WMH were associated with greater Aβ, but this association was no longer significant when adjusting for age and vascular risk factors. Higher total and frontal WMH were associated with worse performance in executive functions, with no interactive effect of the age group. In contrast, there was a significant interaction of the age group on the link between WMH and working memory, which was significant within the subgroup of young/middle-aged adults only. Adding cortical Aβ load in the models did not alter the results, and there was no interaction between WMH and Aβ on cognition. Conclusion: WMH increased with age and were associated with worse executive functions across the adult lifespan and with worse working memory in young/middle-aged adults. Aβ load was weakly associated with WMH and did not change the relationship found between WMH and executive functions. This study argues for the clinical relevance of WMH across the adult lifespan, even in young and middle-aged adults with low WMH. [ABSTRACT FROM AUTHOR]

Over the last ten years, we have conducted research in Alzheimer's disease (AD) using multimodal neuroimaging techniques to improve diagnosis, further our understanding of the pathological mechanisms underlying the disease, and support the development of innovative non-pharmacological preventive strategies. Our works emphasized the interest of hippocampal subfield volumetry in early diagnosis and the need for further development in this field including optimization, standardization, and automatization of the techniques. Also, we conducted several studies in cognitively intact at-risk elderly (e.g., subjective cognitive decline patients and APOE4 carriers) to better identify biomarkers associated with increased risk of developing AD. Regarding the physiopathological mechanisms, specific multimodal neuroimaging techniques allowed us to highlight the relevance of diaschisis, the mismatch between neurodegeneration and local Aβ deposition and the regional variation in the mechanisms underlying structural or functional alterations. Further works integrating other biomarkers known to play a role in the physiopathology of AD (tau, TDP-43, inflammation, etc.) in a longitudinal design would be useful to get a comprehensive understanding of their relative role, sequence, and causal relationships. Our works also highlighted the relevance of functional connectivity in further understanding the specificity of cognitive deficits in AD and how connectivity differentially influences the propagation of the different AD biomarkers. Finally, we conducted several studies on the links between lifestyle factors and neuroimaging biomarkers to unravel mechanisms of reserve. Further efforts are needed to better understand which lifestyle factor, or combination of factors, impact on AD pathology, and when, to help translating our knowledge to training programs that might prevent or delay brain and cognitive changes leading to AD dementia. [ABSTRACT FROM AUTHOR]

Aging is associated with cognitive changes, even in the absence of brain pathology. This study aimed to determine if meditation training, by comparison to active and passive control groups, is linked to changes in the perception of cognitive functioning in older adults. One hundred thirty-four healthy older participants from the Age-Well Randomized Clinical Trial were included: 45 followed a meditation training, 45 a non-native language training and 44 had no intervention. Subjective cognition was assessed at baseline and following the 18-month intervention period. Perception of attentional efficiency was assessed using internal and external Attentional Style Questionnaire (ASQ) subscale scores. Perception of global cognitive capacities was measured via the total score of Cognitive Difficulties Scale (CDS). Deltas ([posttest minus pretest scores]/standard deviation at pretest) were calculated for the analyses. Generalized mixed effects models controlling for age, sex, education and baseline scores revealed that meditation training decreased the vulnerability score toward external distractors measured by the ASQ compared to non-native language training. However, no between-groups differences on ASQ internal or CDS total scores were observed. Results suggest a beneficial effect of meditation practice on perceived management of external distracting information in daily life. Meditation training may cultivate the ability to focus on specific information (e.g., breath) and ignore stimulation from other kinds of stimuli (e.g., noise). [ABSTRACT FROM AUTHOR]

Background: In Alzheimer's disease (AD), pathological changes may arise up to 20 years before the onset of dementia. This pre-dementia window provides a unique opportunity for secondary prevention. However, exposing non-demented subjects to putative therapies requires reliable biomarkers for subject selection, stratification, and monitoring of treatment. Neuroimaging allows the detection of early pathological changes, and longitudinal imaging can assess the effect of interventions on markers of molecular pathology and rates of neurodegeneration. This is of particular importance in pre-dementia AD trials, where clinical outcomes have a limited ability to detect treatment effects within the typical time frame of a clinical trial. We review available evidence for the use of neuroimaging in clinical trials in pre-dementia AD. We appraise currently available imaging markers for subject selection, stratification, outcome measures, and safety in the context of such populations. Main body: Amyloid positron emission tomography (PET) is a validated in-vivo marker of fibrillar amyloid plaques. It is appropriate for inclusion in trials targeting the amyloid pathway, as well as to monitor treatment target engagement. Amyloid PET, however, has limited ability to stage the disease and does not perform well as a prognostic marker within the time frame of a pre-dementia AD trial. Structural magnetic resonance imaging (MRI), providing markers of neurodegeneration, can improve the identification of subjects at risk of imminent decline and hence play a role in subject inclusion. Atrophy rates (either hippocampal or whole brain), which can be reliably derived from structural MRI, are useful in tracking disease progression and have the potential to serve as outcome measures. MRI can also be used to assess comorbid vascular pathology and define homogeneous groups for inclusion or for subject stratification. Finally, MRI also plays an important role in trial safety monitoring, particularly the identification of amyloid-related imaging abnormalities (ARIA). Tau PET to measure neurofibrillary tangle burden is currently under development. Evidence to support the use of advanced MRI markers such as resting-state functional MRI, arterial spin labelling, and diffusion tensor imaging in pre-dementia AD is preliminary and requires further validation. Conclusion: We propose a strategy for longitudinal imaging to track early signs of AD including quantitative amyloid PET and yearly multiparametric MRI. [ABSTRACT FROM AUTHOR]

Psycho-affective states or traits such as stress, depression, anxiety and neuroticism are known to affect sleep, cognition and mental health and well-being in aging populations and to be associated with increased risk for Alzheimer's disease (AD). Mental training for stress reduction and emotional and attentional regulation through meditation practice might help reduce these adverse factors. So far, studies on the impact of meditation practice on brain and cognition in aging are scarce and have limitations but the findings are encouraging, showing a positive effect of meditation training on cognition, especially on attention and memory, and on brain structure and function especially in frontal and limbic structures and insula. In line with this, we showed in a pilot study that gray matter volume and/or glucose metabolism was higher in six older adult expert meditators compared to 67 age-matched controls in the prefrontal, anterior and posterior cingulate cortex, insula and temporo-parietal junction. These preliminary findings are important in the context of reserve and brain maintenance as they suggest that long-term meditation practice might help preserve brain structure and function from progressive age-related decline. Further studies are needed to confirm these results with larger samples and in randomized controlled trials and to investigate the mechanisms underlying these meditation-related effects. The European Commission-funded project Silver Santé Study will address these challenges by studying 316 older adults including 30 expert meditators and 286 meditation-naïve participants (either cognitively normal or with subjective cognitive decline). Two randomized controlled trials will be conducted to assess the effects of 2-month and 18-month meditation, English learning or health education training programs (versus a passive control) on behavioral, sleep, blood sampling and neuroimaging measures. This European research initiative illustrates the progressive awareness of the benefit of such non-pharmacological approaches in the prevention of dementia and the relevance of taking into account the psycho-affective dimension in endeavoring to improve mental health and well-being of older adults. [ABSTRACT FROM AUTHOR]