Positive Effect of Cognitive Reserve on Episodic Memory, Executive and Attentional Functions Taking Into Account Amyloid-Beta, Tau, and Apolipoprotein E Status

peer reviewedStudies exploring the simultaneous influence of several physiological and environmental factors on domain-specific cognition in late middle-age remain scarce. Therefore, our objective was to determine the respective contribution of modifiable risk/protective factors (cognitive reserve and allostatic load) on specific cognitive domains (episodic memory, executive functions, and attention), taking into account non-modifiable factors [sex, age, and genetic risk for Alzheimer’s disease (AD)] and AD-related biomarker amount (amyloid-beta and tau/neuroinflammation) in a healthy late-middle-aged population. One hundred and one healthy participants (59.4 ± 5 years; 68 women) were evaluated for episodic memory, executive and attentional functioning via neuropsychological test battery. Cognitive reserve was determined by the National Adult Reading Test. The allostatic load consisted of measures of lipid metabolism and sympathetic nervous system functioning. The amyloid-beta level was assessed using positron emission tomography in all participants, whereas tau/neuroinflammation positron emission tomography scans and apolipoprotein E genotype were available for 58 participants. Higher cognitive reserve was the main correlate of better cognitive performance across all domains. Moreover, age was negatively associated with attentional functioning, whereas sex was a significant predictor for episodic memory, with women having better performance than men. Finally, our results did not show clear significant associations between performance over any cognitive domain and apolipoprotein E genotype and AD biomarkers. This suggests that domain-specific cognition in late healthy midlife is mainly determined by a combination of modifiable (cognitive reserve) and non-modifiable factors (sex and age) rather than by AD biomarkers and genetic risk for AD.Cognitive Fitness in Aging stud

Heterogeneity in the links between sleep arousals, amyloid-beta and cognition

peer reviewedBACKGROUND. Tight relationships between sleep quality, cognition and amyloid-beta (Aβ) accumulation, a hallmark of Alzheimer’s disease (AD) neuropathology, emerge in the literature. Sleep arousals become more prevalent with ageing and are considered to reflect poorer sleep quality. Yet, heterogeneity in arousals has been suggested while their associations with Aβ and cognition are not established. METHODS. We recorded undisturbed night-time sleep with EEG in 101 healthy individuals in late midlife (50-70y), devoid of cognitive and sleep disorders. We classified spontaneous arousals according to their association with muscular tone increase (M+/M-) and sleep stage transition (T+/T-). We assessed cortical Aβ burden over earliest affected regions via PET imaging, and cognition via extensive neuropsychological testing. RESULTS. Arousal types differed in their oscillatory composition in theta and beta EEG bands. Furthermore, T+M- arousals, which interrupt sleep continuity, were positively linked to Aβ burden (p=.0053, R²β*=0.08). By contrast, more prevalent T-M+ arousals, upholding sleep continuity, were associated with lower Aβ burden (p=.0003, R²β*=0.13), and better cognition, particularly over the attentional domain (p<.05, R²β*≥0.04). CONCLUSION. Contrasting with what is commonly accepted, we provide empirical evidence that arousals are diverse and differently associated with early AD-related neuropathology and cognition. This suggests that sleep arousals, and their coalescence with other brain oscillations during sleep, may actively contribute to the beneficial functions of sleep. This warrants re-evaluation of age-related sleep changes and suggests that spontaneous arousals could constitute a marker of favourable brain and cognitive health trajectories

Cognitive efficiency in late midlife is linked to lifestyle characteristics and allostatic load

We investigated whether cognitive fitness in late midlife is associated with physiological and psychological factors linked to increased risk of age-related cognitive decline. Eighty-one healthy late middle-aged participants (mean age: 59.4 y; range: 50-69 y) were included. Cognitive fitness consisted of a composite score known to be sensitive to early subtle cognitive change. Lifestyle factors (referenced below as cognitive reserve factors; CRF) and affective state were determined through questionnaires, and sleep-wake quality was also assessed through actimetry. Allostatic load (AL) was determined through a large range of objective health measures. Generalized linear mixed models, controlling for sex and age, revealed that higher cognitive reserve and lower allostatic load are related to better cognitive efficiency. Crystallized intelligence, sympathetic nervous system functioning and lipid metabolism were the only sub-fields of CRF and AL to be significantly associated with cognition. These results show that previous lifestyle characteristics and current physiological status are simultaneously explaining variability in cognitive abilities in late midlife. Results further encourage early multimodal prevention programs acting on both of these modifiable factors to preserve cognition during the aging process

ENIGMA-Sleep:Challenges, opportunities, and the road map

Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across individual sites. Recently, we have launched the ENIGMA-Sleep working group with the collaboration of several institutes from 15 countries to perform large-scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population-based healthy individuals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA-Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine

Risk and Protective Factors for Cognitive Performance in Late Midlife

Introduction. Cognitive performance undergoes alterations already from middle adulthood, alterations which accelerate in later life, and may lead to dementia, such as Alzheimer’s Disease (AD) (Ferreira et al., 2015; Harada et al., 2013; Jack et al., 2018a). But the presence and extent of these cognitive changes are highly variable across cognitive domains and between individuals (Nyberg et al., 2012). Several risk and protective factors were suggested to explain this variability in age-related cognitive change, including modifiable factors (e.g., cognitive reserve, affective state, allostatic load, sleep quality), non-modifiable factors (sex, age, genetic predisposition), AD biomarkers (amyloid-beta, tau), and subjective cognitive decline (SCD) (Benedict et al., 2015; Da Silva et al., 2013; Hanseeuw et al., 2019; Jessen et al., 2020; Karlamangla et al., 2014; Livingston et al., 2017a; McFall et al., 2019; Salvato, 2015; Stern et al., 2018). However, most of the previous studies included only a handful of risk and protective factors, and rarely studied them together. Moreover, these factors were less often studied in late midlife (50-69 years), a time window associated with the first AD-related manifestations (Coupé et al., 2019).Objectives. Our main objective was to increase the theoretical and empirical knowledge about risk and protective factors for cognitive performance in late midlife. Specifically, we had three more specific objectives: (1) identify modifiable factors explaining the variability in global cognition in this age group; (2) verify if specific cognitive domains such as episodic memory, executive function and attention are related to modifiable and non-modifiable risk and protective factors; (3) investigate if subjective cognitive complaints are related to objective cognitive capacities, subclinical affective state, and amyloid-beta level, when they are considered together.Materials and Methods. We have recruited 101 healthy and cognitively normal individuals aged between 50 and 69 years, among which 68 women. We have realized extensive phenotyping of the participants, which included neuropsychological assessment, collection of blood and urinary samples for estimation of physiological measures and genotyping, structural Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET) for estimation of AD-related biomarkers (the proteins amyloid-beta and tau), actigraphy for rest-activity cycle evaluation, as well as self-assessment questionnaires for daily activities and lifestyle, affective state, and sleep quality. Results. Our results revealed that higher cognitive reserve and lower allostatic load are related to better global cognitive efficiency. Among the sub-factors of cognitive reserve, crystallized intelligence was the only one significantly related to global cognition, whereas among the sub-factors of allostatic load, only sympathetic nervous system functioning and lipid metabolism were related to global cognition. Moreover, higher cognitive reserve was the main correlate of better cognitive performance in episodic memory, and executive and attentional functioning. In addition, age was negatively associated with attentional functioning, whereas sex was a significant predictor for episodic memory, with women having better performance than men. Finally, we have demonstrated that higher level of cognitive complaints was significantly associated with lower episodic memory performance, worse affective state, and higher accumulation of amyloid-beta. Conclusion. The present results indicate that cognitive performance in late middle-aged population are associated with risk and protective factors. A combination of modifiable (cognitive reserve and allostatic load), non-modifiable (sex and age) factors, the presence of amyloid-beta burden, and cognitive complaints seem to predict global cognition and/or certain specific aspects related of cognitive functioning in late middle-aged population. While these results provide new interesting insights, we have confirmed only a part of our hypotheses. Future studies aiming to investigate risk and protective factors for cognitive performance should consider wider age range, differentially defined inclusion criteria, more comprehensive longitudinal assessment, and better refined measures, especially concerning sleep quality and the choice of PET radiotracer with higher specificity for tau

Increased cortical excitability and reduced brain response propagation during attentional lapses

Modern lifestyle curtails sleep and increases nighttime work and leisure activities. This has a deleterious impact on vigilance and attention, exacerbating chances of committing attentional lapses, with potential dramatic outcomes. A full characterization of the brain mechanisms associated with lapses is still lacking. Here, we investigated the brain signature of attentional lapses and assessed whether cortical excitability and brain response propagation were modified during lapses and whether these modifications changed with aging. We compared electroencephalogram (EEG) responses to transcranial magnetic stimulation (TMS) during lapse and no-lapse periods while performing a continuous attentional/vigilance task at night, after usual bedtime. Data were collected in healthy younger (N=12; 18-30 y) and older individuals (N=12; 50- 70 y) of both sexes. Amplitude and slope of the first component of the TMS-Evoked Potential (TEP) and Response Scattering (ReSc) were used to assess cortical excitability and brain response propagation, respectively. In line with our predictions, TEP during lapses was characterized by larger amplitude and slope. We further found that ReSc over the cortical surface was lower during lapses. Importantly, cortical excitability increase and response propagation decrease during lapse did not significantly differ between age groups. These results demonstrate that attentional lapses are associated with transient increase of excitability, and decrease in response propagation and effective connectivity. This pattern is similar to what is observed during sleep, suggesting that lapses reflect a sleep-like phenomenon. These findings could contribute to develop models aimed to predicting and preventing lapses in real life situations

Increased cortical excitability but stable effective connectivity index during attentional lapses.

Modern lifestyle curtails sleep and increases night-time work and leisure activities. This has a deleterious impact on vigilance and attention, exacerbating chances of committing attentional lapses, with potential dramatic outcomes. Here, we investigated the brain signature of attentional lapses and assessed whether cortical excitability and brain response propagation were modified during lapses and whether these modifications changed with aging. We compared electroencephalogram (EEG) responses to transcranial magnetic stimulation (TMS) during lapse and no-lapse periods while performing a continuous attentional/vigilance task at night, after usual bedtime. Data were collected in healthy younger (N=12; 18-30 y) and older individuals (N=12; 50-70 y) of both sexes. The amplitude and slope of the first component of the TMS-Evoked Potential (TEP) were larger during lapses. In contrast, TMS response scattering over the cortical surface, as well as EEG response complexity, did not significantly vary between lapse and no-lapse periods. Importantly, despite qualitative differences, age did not significantly affect any of the TMS-EEG measures. These results demonstrate that attentional lapses are associated with a transient increase of cortical excitability. This initial change is not associated with detectable changes in subsequent effective connectivity - as indexed by response propagation - and are not markedly different between younger and older adults. These findings could contribute to develop models aimed to predicting and preventing lapses in real life situations

Cortical excitability transiently increases during attentional lapses - HBP

peer reviewedIntroduction/Motivation: Cortical excitability is modulated both by conscious states, sleep homeostasis and circadian rhythm, following a nonlinear dynamic across the day1,2. It is low during wakefulness and REM sleep, where subjects experience phenomenological states, and high in conditions such as NREM sleep and Disorders of Consciousness (DoC), where there is inappropriate or absent processing of external stimuli3,4. Cortical excitability increases across the day, peaking at night after habitual sleep time where behavioral impairments such as attentional lapses are more common. Previous researches demonstrated that, at night, lack of vigilance is connected with lower frontoparietal effective connectivity5. However, no study has investigated whether there is a transient increase of cortical excitability during attentional lapses per se. This would be in line with the idea that the brain is less efficient to engage in the ongoing task, acting similarly to an “unconscious state”. To test this hypothesis, we compared cortical excitability during normal awakening and attentional lapses. Methods: Data included in this analysis were retrospectively selected among 3 different studies including repeated assessment of cortical excitability using Transcranial Magnetic Stimulation (TMS) of the superior frontal gyrus coupled to high-density Electroencephalography (hdEEG). This region was selected because it is sensitive to sleep pressure1 and has been implicated both for motor and cognitive tasks6. To increase the likelihood of attention lapses, data was selected among nighttime sessions. Attention lapses were detected based on the performance to a continuous Compensatory Tracking Task (CTT) completed simultaneously to TMS-EEG recording. Volunteers with at least 25 lapses were included to reach a total sample of 26 healthy individuals in 2 age groups (young, N= 13, 18-30 y; old, N = 13, 50-69 y). As previously published1, cortical excitability was inferred from amplitude and slope of the first component of the TMS-evoked EEG potential (TEP; 0–30 ms post-TMS, Figure 1). Latencies of the negative and positive peaks of this evoked potential were also extracted. Statistics were run on SAS 9.4 with a Generalized Linear Mixed Model (GLMM) (for more details, description of Table 1). Results and Discussion: Cortical excitability showed a strong change from no-lapse to attention lapse. In particular, there was a significant increase of amplitude, with a smaller latency of the negative component and a bigger latency of the positive one, leading to an increase in slope (for more details, Table 1). These results suggest that there is a transient increase of cortical excitability during vigilance lapses pointing to an alteration of the brain function that could be similar to what is observed when sleep need is high compared to well-rested condition, or during states of altered consciousness (e.g. sleep). These results could constitute an epiphenomenon of the likelihood of transitions of conscious states or rather a sheer marker of errors. Alternatively, they could reflect a local sleep phenomenon over the target area. Future researches should validate the extent of this description and fathom its molecular mechanisms

Effort during prolonged wakefulness is associated with performance to attentional and executive tasks but not with cortical excitability in late-middle-aged healthy individuals.

peer reviewedOBJECTIVE: Sleep loss negatively affects brain function with repercussion not only on objective measures of performance but also on many subjective dimensions, including effort perceived for the completion of cognitive processes. This may be particularly important in aging, which is accompanied by important changes in sleep and wakefulness regulation. We aimed to determine whether subjectively perceived effort covaried with cognitive performance in healthy late-middle-aged individuals. METHOD: We assessed effort and performance to cognitive tasks in 99 healthy adults (66 women; 50-70 years) during a 20-hr wake extension protocol, following 7 days of regular sleep and wake times and a baseline night of sleep in the laboratory. We further explored links with cortical excitability using transcranial magnetic stimulation coupled to electroencephalography. RESULTS: Perceived effort increased during wake extension and was highly correlated to subjective metrics of sleepiness, fatigue, and motivation, but not to variations in cortical excitability. Moreover, effort increase was associated with decreased performance to some cognitive tasks (psychomotor vigilance and two-back working memory task). Importantly, effort variations during wakefulness extension decreased from age 50 to 70 years, while more effort is associated with worse performance in older individuals. CONCLUSION: In healthy late-middle-aged individuals, more effort is perceived to perform cognitive tasks, but it is not sufficient to overcome the performance decline brought by lack of sleep. Entry in the seventh decade may stand as a turning point in the daily variations of perceived effort and its link with cognition. (PsycInfo Database Record (c) 2022 APA, all rights reserved)