In the past decade, experimental studies involving healthy human volunteers have revealed that manipulations of the central serotonin (5-HT) system can produce quite specific changes in cognitive functioning, independent of overt mood changes. Reduced 5-HT turnover is consistently associated with impaired long-term memory functioning. Low 5- HT function may also impair cognitive flexibility and improve focused attention. On the other hand, stimulation of central 5-HT has repeatedly been found to impair performance in a true vigilance task. Currently, there is little evidence for mirrored cognitive changes due to opposite 5-HT manipulations in healthy volunteers. Given the mounting evidence for a role of 5-HT in human cognition, reduced 5-HT function could be directly linked to cognitive disturbances in certain conditions, such as in depression and Alzheimers Disease (AD). There is evidence that stimulating (i.e. normalizing) 5- HT activity in depression may have specific beneficial effects on cognition, independent of a general relief of depressive symptoms, but this premise needs to be confirmed by larger-scale clinical studies. Recently, a potential role of 5-HT in the cognitive symptoms in AD has been identified, but there is insufficient data to evaluate the effects of 5-HT stimulation on cognitive symptoms in AD. It is concluded that serotonin is a potential target for pharmacological cognition enhancement, particularly for restoration of impaired cognitive performance due to 5-HT dysfunction. Further differentiation of the role of 5-HT in normal and disturbed cognition and evaluation of the effects of 5-HT manipulations in various populations is required to establish the full potential of 5-HT drugs as cognition enhancers.

Epicatechin is a monomeric flavanol found in food sources such as tea, apples, berries and cocoa. A number of large-scale epidemiological studies have demonstrated an association between the consumption of these foods and cognitive function, as well as improved blood flow. The aim of this review is to summarise the evidence from intervention studies to clarify the effect of epicatechin on cognition and to consider the role of increased cerebral blood flow as a mechanism for any effects. The effects of epicatechin as consumed in cocoa are, therefore, reviewed here as this represents the only dietary source where it is purported to be the major active component. Our main findings are that a) the positive modulation of tasks that involve memory, executive function and processing speed in older adults; b) the cognitive benefits are more often shown in studies containing more than 50 mg epicatechin/day; and c) all studies with a duration of 28 days or longer in populations >50 years old demonstrate a cognitive improvement. However, as highlighted by this review, it is not currently possible to attribute effects solely to epicatechin without consideration of synergies. In order to overcome this issue, further studies examining the cognitive effects of epicatechin in isolation are required. The role of cerebral blood flow also requires further investigation through simultaneous measurement alongside cognitive function.

Serotonergic hypofunction may underlie at least part of the symptoms that are experienced by women with premenstrual complaints, including memory deficits. In the current study we investigated changes in memory functions in the premenstrual phase compared to the early postmenstrual phase in 16 women with premenstrual complaints. In addition, the effect of an acute serotonergic stimulation by administration of an alpha-lactalbumin protein on premenstrual memory performance was assessed using a double-blind placebo-controlled crossover design. It was found that both short-term and long-term memory for words (30-word learning task) and abstract figures (abstract visual learning task) were mildly impaired in the premenstrual phase. Administration of alpha-lactalbumin during the premenstrual phase could only partially attenuate the memory performance decrements that are seen in the premenstrual phase. Specifically, alphalactalbumin improved long-term memory for abstract figures, but not for words. There were no effects of menstrual phase or alpha-lactalbumin on planning functions (computerized Tower of London). The data suggest that serotonergic hypofunction may play a role in premenstrual memory decline, but serotonergic mechanisms cannot fully account for observed cognitive changes in the premenstrual phase.

The complexity of the carbohydrate structure is associated with post-prandial glucose response and diverse health benefits. The aim of this study was to determine whether, thanks to the usage of minimally invasive glucose monitors, it was possible to evaluate, in a decentralized study setup, the post-prandial glycemic response (PPGR) of α-glucans differing systematically in their degree of polymerization (DP 3 vs. DP 60) and in their linkage structure (dextrin vs. dextran). Ten healthy subjects completed a double-blind, randomized, decentralized crossover trial, testing at home, in real life conditions, four self-prepared test beverages consisting of 25 g α-glucan dissolved in 300 mL water. The incremental area under the curve of the 120 min PPGR (2h-iAUC) was the highest for Dextrin DP 3 (163 ± 27 mmol/L*min), followed by Dextrin DP 60 (−25%, p = 0.208), Dextran DP 60 (−59%, p = 0.002), and non-fully caloric Resistant Dextrin (−68%, p = 0.002). These results show that a fully decentralized crossover study can be successfully used to assess the influence of both polymerization and structure of α-glucans on PPGR.

Background: Fully decentralized self-administered mindfulness interventions show promise for stress reduction, but rigorous evaluations of their feasibility, acceptability, and effectiveness using both self-report and physiological measures remain limited. In Singapore, where mental health concerns rank as the top health care priority (46%), ahead of cancer (38%) and stress-related issues (35%), accessible and scalable interventions are urgently needed to address the significant economic burden of mental health conditions. Objective: This study aimed to evaluate a decentralized, 3-day self-administered mindfulness intervention with minimal supervision, compared with a sham control in Singaporean adults, examining effects on self-reported and physiologically measured stress responses. The inclusion of a sham control condition was intended to disentangle mindfulness-specific effects from demand characteristics and expectation effects, addressing a critical methodological gap in digital mindfulness research. Methods: This was a purely smartphone-based, decentralized pilot trial with no face-to-face components. Participants were recruited using web-based methods and, after providing informed consent, 60 adults were randomized to either a mindfulness intervention or a structurally matched sham control. The daily 10-minute mindfulness sessions guided participants to focus on present-moment breath and body sensations, while the sham control omitted a focus on present-moment awareness. Outcomes were assessed remotely, using self-report questionnaires (State-Trait Anxiety Inventory-6) and physiological data from smartphone-based photoplethysmography (heart rate variability; HRV). The study incorporated three methodological innovations: (1) a structurally equivalent sham control to match expectancy and credibility, (2) remote collection of HRV as an objective physiological biomarker, and (3) full decentralization allowing unsupervised multiplatform delivery. Feasibility was evaluated through recruitment, retention rates, and data quality. Acceptability was assessed through quantitative ratings and qualitative feedback. Results: The study demonstrated excellent feasibility, with near-perfect retention (59/60, 98.3%) and moderate HRV data quality (231/331, 69.8% valid signals). Acceptability ratings were high (mean 4.17, SD 0.53), with comfort/engagement receiving the highest scores (mean 4.27, SD 0.57) on a 5-point scale, exceeding established usability benchmarks for digital health interventions. Qualitative feedback identified technical challenges (HRV instability and device overheating) and scheduling difficulties. While Bayesian analyses did not detect significant group differences in stress reduction (Bayes factor10 [BF10]=0.03) or HRV improvement (BF10=0.2), both groups showed significant stress reductions (BF10=3.01×106), suggesting that observed benefits may stem from nonspecific factors common to both interventions. Conclusions: This study demonstrates (1) the feasibility of conducting fully decentralized mindfulness trials with multimodal assessment, (2) the value of a mixed methods acceptability evaluation, and (3) the identification of key technical and control condition refinements necessary for future trials. By addressing methodological limitations through improved control conditions and objective measures, this study provides a foundation for more rigorous investigation of mindfulness-specific effects. Trial Registration: ClinicalTrials.gov NCT06765889; https://clinicaltrials.gov/study/NCT06765889