Heart rate and breathing effects on attention and memory (HeartBEAM): study protocol for a randomized controlled trial in older adults.

BACKGROUND: In healthy people, the "fight-or-flight" sympathetic system is counterbalanced by the "rest-and-digest" parasympathetic system. As we grow older, the parasympathetic system declines as the sympathetic system becomes hyperactive. In our prior heart rate variability biofeedback and emotion regulation (HRV-ER) clinical trial, we found that increasing parasympathetic activity through daily practice of slow-paced breathing significantly decreased plasma amyloid-ß (Aß) in healthy younger and older adults. In healthy adults, higher plasma Aß is associated with greater risk of Alzheimer's disease (AD). Our primary goal of this trial is to reproduce and extend our initial findings regarding effects of slow-paced breathing on Aß. Our secondary objectives are to examine the effects of daily slow-paced breathing on brain structure and the rate of learning. METHODS: Adults aged 50-70 have been randomized to practice one of two breathing protocols twice daily for 9 weeks: (1) "slow-paced breathing condition" involving daily cognitive training followed by slow-paced breathing designed to maximize heart rate oscillations or (2) "random-paced breathing condition" involving daily cognitive training followed by random-paced breathing to avoid increasing heart rate oscillations. The primary outcomes are plasma Aß40 and Aß42 levels and plasma Aß42/40 ratio. The secondary outcomes are brain perivascular space volume, hippocampal volume, and learning rates measured by cognitive training performance. Other pre-registered outcomes include plasma pTau-181/tTau ratio and urine Aß42. Recruitment began in January 2023. Interventions are ongoing and will be completed by the end of 2023. DISCUSSION: Our HRV-ER trial was groundbreaking in demonstrating that a behavioral intervention can reduce plasma Aß levels relative to a randomized control group. We aim to reproduce these findings while testing effects on brain clearance pathways and cognition. TRIAL REGISTRATION: ClinicalTrials.gov NCT05602220. Registered on January 12, 2023.

Transfer of learning: Analysis of dose-response functions from a large-scale, online, cognitive training dataset.

Fundamental to the efficacy of cognitive training (CT) is its dose. Here we used the power and breadth afforded by a large dataset to measure precisely dose-response (D-R) functions for CT and to examine the generality of their magnitude and form. The present observational study involved 107,000 users of Lumosity, a commercial program comprising computer games designed to provide CT over the internet. In addition to training with Lumosity games, these users took an online battery of cognitive assessments (NeuroCognitive Performance Test, NCPT) on two or more occasions separated by at least 10 weeks. Changes in performance on the NCPT between the first and second assessments were examined as a function of the amount of intervening gameplay. The resulting D-R functions were obtained both for overall performance on the NCPT and performance on its eight subtests. Also examined were differences between D-R functions from demographic groups defined by age, gender, and education. Monotonically increasing D-R functions, well fit by an exponential approach to an asymptote, were found consistently for overall performance on the NCPT, performance on seven of the eight subtests, and at each level of age, education, and gender. By examining how individual parameters of the D-R functions varied across subtests and groups, it was possible to measure separately changes in the effects on NCPT performance of 1) transfer from CT and 2) direct practice due to repeated testing. The impact of both transfer and direct practice varied across subtests. In contrast, while the effects of direct practice diminished with age, those of transfer remained constant. Besides its implications for CT by older adults, this latter finding suggests that direct practice and transfer do not involve identical learning processes, with transfer being limited to learning processes that remain constant across the adult lifespan.

A massive dataset of the NeuroCognitive Performance Test, a web-based cognitive assessment.

We present a dataset of approximately 5.5 million subtest scores from over 750,000 adults who completed the NeuroCognitive Performance Test (NCPT; Lumos Labs, Inc.), a validated, self-administered cognitive test accessed via web browser. The dataset includes assessment scores from eight test batteries consisting of 5-11 subtests that collectively span several cognitive domains including working memory, visual attention, and abstract reasoning. In addition to the raw scores and normative data from each subtest, the dataset includes basic demographic information from each participant (age, gender, and educational background). The scale and diversity of the dataset provides an unprecedented opportunity for researchers to investigate population-level variability in cognitive abilities and their relation to demographic factors. To facilitate reuse of this dataset by other researchers, we provide a Python module that supports several common preprocessing steps.

Perceptions of Brain Training: Public Expectations of Cognitive Benefits From Popular Activities.

Many popular activities are thought by the general public to improve cognitive function. Such expectations can influence how often people engage in these activities, as well as the scientific evaluation of their putative cognitive benefits, e.g., via placebo effects. Here, we gathered survey data about the public's perceptions of nine different activities commonly thought to be cognitively stimulating, including "brain-training" games. Information was collected about the degree to which participants thought each activity was beneficial for improving cognitive function and how often they engaged in each activity. The patterns of correlation between ratings reveal details about the perception of cognitive benefits and its relation to engagement. They suggest that participants varied with respect to an overarching perception of the entire set of activities, which were perceived also as divided into three clusters. Frequency of engagement and perceived cognitive benefits were positively correlated across participants for each activity considered individually. But, when the activities were compared, the magnitude of their perceived benefits was not a good predictor of their frequency of engagement (and vice versa). Though small, there were systematic demographic differences. Women were more optimistic than men about cognitive benefits. Individual participants differed in the range of their ratings of benefit across activities, and these ranges were greater for younger than older participants, suggesting that perceptions of benefit are more differentiated among the young. Besides contributing to a better understanding of public expectations of cognitive benefits, the findings of this study are relevant to the critical evaluation of such benefits. Our survey can be viewed as providing an interface between expectations held by the general public and the design of studies examining the efficacy of cognitive training. The type of information it provides could be used in the selection of activities performed by an active control group, so that control activities match the treatment intervention as closely as possible with respect to such expectations.

Computerized Cognitive Training by Healthy Older and Younger Adults: Age Comparisons of Overall Efficacy and Selective Effects on Cognition.

Among the non-pharmacological methods under development for maintaining cognitive function across the lifespan is computerized cognitive training (CCT). There has been considerable interest in using CCT to slow or remediate age-related cognitive decline, both normal and pathological. Toward these ends, it would be useful to know how the effects of CCT on cognitive function vary over the course of normal cognitive aging. Are there changes in either 1) the overall efficacy of CCT or 2) which cognitive faculties are affected? To address these two questions, we reanalyzed results from a large online study by Hardy et al. (1) of 4,715 adults between 18 and 80 that examined effects of CCT on both a neuropsychological test battery and self-reported ratings of cognition and affect in daily living. Combined across all participants, Hardy et al. found greater improvement on both types of assessment following 10 weeks of CCT with the commercial program Lumosity, as compared to practice with a control activity involving computerized crossword puzzles. The present study compared the size of these effects on the older (50-80) and younger (18-49) participants. To address the question of overall efficacy, we examined CCT effects (treatment minus control) on overall performance of the test battery and mean rating. No significant difference on either measure was found between the two age cohorts. To address the question of whether the same magnitude of overall effects on both age cohorts was due to equivalent effects on the same set of underlying cognitive functions, we examined the patterns of CCT effects across individual subtests and rated items. These patterns did not differ significantly between the two age cohorts. Our findings suggest that benefits from CCT can occur to a similar degree and in a similar way across an extended part of the adult lifespan. Moreover, the overall effects of CCT delivered over the internet were of the same small to medium size as those typically found in the lab or clinic. Besides improving access and reducing the cost of CCT for older adults, delivery over the internet makes long-term training more practicable, which could potentially yield larger benefits.

Reliability and validity of the NeuroCognitive Performance Test, a web-based neuropsychological assessment.

The NeuroCognitive Performance Test (NCPT) is a brief, repeatable, web-based cognitive assessment platform that measures performance across several cognitive domains. The NCPT platform is modular and includes 18 subtests that can be arranged into customized batteries. Here we present normative data from a sample of 130,140 healthy volunteers for an NCPT battery consisting of 8 subtests. Participants took the NCPT remotely and without supervision. Factor structure and effects of age, education, and gender were evaluated with this normative dataset. Test-retest reliability was evaluated in a subset of participants who took the battery again an average of 78.8 days later. The eight NCPT subtests group into 4 putative cognitive domains, have adequate to good test-retest reliability, and are sensitive to expected age- and education-related cognitive effects. Concurrent validity to standard neuropsychological tests was demonstrated in 73 healthy volunteers. In an exploratory analysis the NCPT battery could differentiate those who self-reported Mild Cognitive Impairment or Alzheimer's disease from matched healthy controls. Overall these results demonstrate the reliability and validity of the NCPT battery as a measure of cognitive performance and support the feasibility of web-based, unsupervised testing, with potential utility in clinical and research settings.