A Subtype Perspective on Cognitive Trajectories in Healthy Aging.

Cognitive aging is a complex and dynamic process characterized by changes due to genetics and environmental factors, including lifestyle choices and environmental exposure, which contribute to the heterogeneity observed in cognitive outcomes. This heterogeneity is particularly pronounced among older adults, with some individuals maintaining stable cognitive function while others experience complex, non-linear changes, making it difficult to identify meaningful decline accurately. Current research methods range from population-level modeling to individual-specific assessments. In this work, we review these methodologies and propose that population subtyping should be considered as a viable alternative. This approach relies on early individual-specific detection methods that can lead to an improved understanding of changes in individual cognitive trajectories. The improved understanding of cognitive trajectories through population subtyping can lead to the identification of meaningful changes and the determination of timely, effective interventions. This approach can aid in informing policy decisions and in developing targeted interventions that promote cognitive health, ultimately contributing to a more personalized understanding of the aging process within society and reducing the burden on healthcare systems.

Neuroimaging and machine learning for studying the pathways from mild cognitive impairment to alzheimer's disease: a systematic review.

BACKGROUND: This systematic review synthesizes the most recent neuroimaging procedures and machine learning approaches for the prediction of conversion from mild cognitive impairment to Alzheimer's disease dementia. METHODS: We systematically searched PubMed, SCOPUS, and Web of Science databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) systematic review guidelines. RESULTS: Our search returned 2572 articles, 56 of which met the criteria for inclusion in the final selection. The multimodality framework and deep learning techniques showed potential for predicting the conversion of MCI to AD dementia. CONCLUSION: Findings of this systematic review identified that the possibility of using neuroimaging data processed by advanced learning algorithms is promising for the prediction of AD progression. We also provided a detailed description of the challenges that researchers are faced along with future research directions. The protocol has been registered in the International Prospective Register of Systematic Reviews- CRD42019133402 and published in the Systematic Reviews journal.

Predictors of the rate of cognitive decline in older adults using machine learning.

BACKGROUND: The longitudinal rates of cognitive decline among aging populations are heterogeneous. Few studies have investigated the possibility of implementing prognostic models to predict cognitive changes with the combination of categorical and continuous data from multiple domains. OBJECTIVE: Implement a multivariate robust model to predict longitudinal cognitive changes over 12 years among older adults and to identify the most significant predictors of cognitive changes using machine learning techniques. METHOD: In total, data of 2733 participants aged 50-85 years from the English Longitudinal Study of Ageing are included. Two categories of cognitive changes were determined including minor cognitive decliners (2361 participants, 86.4%) and major cognitive decliners (372 participants, 13.6%) over 12 years from wave 2 (2004-2005) to wave 8 (2016-2017). Machine learning methods were used to implement the predictive models and to identify the predictors of cognitive decline using 43 baseline features from seven domains including sociodemographic, social engagement, health, physical functioning, psychological, health-related behaviors, and baseline cognitive tests. RESULTS: The model predicted future major cognitive decliners from those with the minor cognitive decline with a relatively high performance. The overall AUC, sensitivity, and specificity of prediction were 72.84%, 78.23%, and 67.41%, respectively. Furthermore, the top 7 ranked features with an important role in predicting major vs minor cognitive decliners included age, employment status, socioeconomic status, self-rated memory changes, immediate word recall, the feeling of loneliness, and vigorous physical activity. In contrast, the five least important baseline features consisted of smoking, instrumental activities of daily living, eye disease, life satisfaction, and cardiovascular disease. CONCLUSION: The present study indicated the possibility of identifying individuals at high risk of future major cognitive decline as well as potential risk/protective factors of cognitive decline among older adults. The findings could assist in improving the effective interventions to delay cognitive decline among aging populations.

Does cognitive aging follow an orchid and dandelion phenomenon?

Cognitive reserve reflects the brain's intrinsic adaptive capacity against the neurodegenerative effects of aging. The maintenance or enhancement of the brain's cognitive reserve plays a crucial role in mitigating the severity of pathologies associated with aging. A new movement, social prescribing, which focuses on prescribing lifestyle activities as a treatment for patients, is growing in popularity as a solution against aging pathologies. However, few studies have demonstrated a clear impact of lifestyle activities on individual cognitive health, outside of floor and ceiling effects. Understanding who benefits from which lifestyle factors remains unclear. Here, we investigated the potential effects of lifestyle activities on individuals' cognitive health from more than 3,530 older adults using a stratification method and advanced analysis technique. Our stratification methods allowed us to observe a new result: older adults who had relatively average cognitive scores were not impacted by lifestyle factors. By comparison, older adults with very high or very low cognitive scores were highly impacted by lifestyle factors. These findings expand the orchid and dandelion theory to the aging field, regarding the biological sensitivity of individuals to harmful and protective environmental effects. Our discoveries demonstrate the role of individual differences in the aging process and its importance for social prescribing programs.

The Challenges Toward Real-world Implementation of Digital Health Design Approaches: Narrative Review.

BACKGROUND: Digital health represents an important strategy in the future of health care delivery. Over the past decade, mobile health has accelerated the agency of health care users. Despite prevailing excitement about the potential of digital health, questions remain on efficacy, uptake, usability, and patient outcome. This challenge is confounded by 2 industries, digital and health, which have vastly different approaches to research, design, testing, and implementation. In this regard, there is a need to examine prevailing design approaches, weigh their benefits and challenges toward implementation, and recommend a path forward that synthesizes the needs of this complex stakeholder group. OBJECTIVE: In this review, we aimed to study prominent digital health intervention design approaches that mediate the digital health space. In doing so, we sought to examine the origins, perceived benefits, contrasting nuances, challenges, and typical use-case scenarios of each methodology. METHODS: A narrative review of digital health design approaches was performed between September 2020 and April 2021 by referencing keywords such as "digital health design," "mHealth design," "e-Health design," "agile health," and "agile healthcare." The studies selected after screening were those that discussed the design and implementation of digital health design approaches. A total of 120 studies were selected for full-text review, of which 62 (51.6%) were selected for inclusion in this review. RESULTS: A review identifying the 5 overarching digital health design approaches was compiled: user-centered design, person-based design, human-centered design, patient-centered design, and patient-led design. The findings were synthesized in a narrative structure discussing the origins, advantages, disadvantages, challenges, and potential use-case scenarios. CONCLUSIONS: Digital health is experiencing the growing pains of rapid expansion. Currently, numerous design approaches are being implemented to harmonize the needs of a complex stakeholder group. Whether the end user is positioned as a person, patient, or user, the challenge to synthesize the constraints and affordances of both digital design and health care, built equally around user satisfaction and clinical efficacy, remains paramount. Further research that works toward a transdisciplinarity in digital health may help break down friction in this field. Until digital health is viewed as a hybridized industry with unique requirements rather than one with competing interests, the nuances that each design approach posits will be difficult to realize in a real-world context. We encourage the collaboration of digital and health experts within hybrid design teams, through all stages of intervention design, to create a better digital health culture and design ethos.

Healthy memory aging - the benefits of regular daily activities increase with age.

As the number of older adults increases, so does the pressure on health care systems due to age-related disorders. Attempts to reduce cognitive decline have focused on individual interventions such as exercise or diet, with limited success. This study adopted a different approach by investigating the impact of combined daily activities on memory decline. We used data from the National Institute of Aging's Health and Retirement Study to explore two new questions: does combining activities affect memory decline, and if yes, does this impact change across the lifespan? We created a new machine learning model using 33 daily activities and involving 3210 participants. Our results showed that the effect of combined activities on memory decline was stronger than any individual activity's impact. Moreover, this effect increased with age, whereas the importance of historical factors such as education, and baseline memory decreased. The present findings point out the importance of selecting multiple, diverse activities for older adults as they age. These results could have a significant impact on aging health policies promoting new programs such as social prescribing.

Moderate-Intensity Physical Activity, Music and Art Activities Preserved Cognitive Health in Older Adults: An Argument for Social Prescribing Solution.

Introduction: Rates of dementia are projected to increase over the coming years as global populations age. Without a treatment to slow the progression of dementia, many health policies are focusing on preventing dementia by slowing the rate of cognitive decline with age. However, it is unclear which lifestyle changes in old age meaningfully reduce the rate of cognitive decline associated with aging. Objectives: Use existing, multi-year longitudinal health data to determine if engagement in a variety of different lifestyle activities can slow the rate of cognitive decline as older adults age. Method: Data from the English Longitudinal Study of Aging was analyzed using a quasi-experimental, efficient matched-pair design inspired by the clinical trial methodology. Changes in short-term memory scores were assessed over a multi-year interval for groups who undertook one of 11 different lifestyle activities, compared to control groups matched across confounding socioeconomic and lifestyle factors. Results: Two factors, moderate-intensity physical activity and learning activities, resulted in significant positive impact on cognitive function. Conclusion: Our analysis brings cognitive benefit arguments in favor of two lifestyle activities, moderate-intensity physical activity and learning activities, while rejecting other factors advanced by the literature such as vigorous-intensity physical activity. Those findings justify and encourage the development of new lifestyle health programs by health authorities and bring forward the new health system solution, social prescribing.

Neuroimaging and analytical methods for studying the pathways from mild cognitive impairment to Alzheimer's disease: protocol for a rapid systematic review.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder commonly associated with deficits of cognition and changes in behavior. Mild cognitive impairment (MCI) is the prodromal stage of AD that is defined by slight cognitive decline. Not all with MCI progress to AD dementia. Thus, the accurate prediction of progression to Alzheimer's, particularly in the stage of MCI could potentially offer developing treatments to delay or prevent the transition process. The objective of the present study is to investigate the most recent neuroimaging procedures in the domain of prediction of transition from MCI to AD dementia for clinical applications and to systematically discuss the machine learning techniques used for the prediction of MCI conversion. METHODS: Electronic databases including PubMed, SCOPUS, and Web of Science will be searched from January 1, 2017, to the date of search commencement to provide a rapid review of the most recent studies that have investigated the prediction of conversion from MCI to Alzheimer's using neuroimaging modalities in randomized trial or observational studies. Two reviewers will screen full texts of included papers using predefined eligibility criteria. Studies will be included if addressed research on AD dementia and MCI, explained the results in a way that would be able to report the performance measures such as the accuracy, sensitivity, and specificity. Only studies addressed Alzheimer's type of dementia and its early-stage MCI using neuroimaging modalities will be included. We will exclude other forms of dementia such as vascular dementia, frontotemporal dementia, and Parkinson's disease. The risk of bias in individual studies will be appraised using an appropriate tool. If feasible, we will conduct a random effects meta-analysis. Sensitivity analyses will be conducted to explore the potential sources of heterogeneity. DISCUSSION: The information gathered in our study will establish the extent of the evidence underlying the prediction of conversion to AD dementia from its early stage and will provide a rigorous and updated synthesis of neuroimaging modalities allied with the data analysis techniques used to measure the brain changes during the conversion process. SYSTEMATIC REVIEW REGISTRATION: PROSPERO,CRD42019133402.

Performance comparison of linear and non-linear feature selection methods for the analysis of large survey datasets.

Large survey databases for aging-related analysis are often examined to discover key factors that affect a dependent variable of interest. Typically, this analysis is performed with methods assuming linear dependencies between variables. Such assumptions however do not hold in many cases, wherein data are linked by way of non-linear dependencies. This in turn requires applications of analytic methods, which are more accurate in identifying potentially non-linear dependencies. Here, we objectively compared the feature selection performance of several frequently-used linear selection methods and three non-linear selection methods in the context of large survey data. These methods were assessed using both synthetic and real-world datasets, wherein relationships between the features and dependent variables were known in advance. In contrast to linear methods, we found that the non-linear methods offered better overall feature selection performance than linear methods in all usage conditions. Moreover, the performance of the non-linear methods was more stable, being unaffected by the inclusion or exclusion of variables from the datasets. These properties make non-linear feature selection methods a potentially preferable tool for both hypothesis-driven and exploratory analyses for aging-related datasets.

Salience drives overt selection of two equally relevant visual targets.

In the present study, we investigated whether salience determines the sequence of selection when participants search for two equally relevant visual targets. To do this, attentional selection was tracked overtly as observers inspected two items of differing physical salience: one a highly salient color singleton, and the other a less salient shape singleton. Participants were instructed to make natural eye movements in order to determine whether two line segments contained within the two singletons were oriented in the same or in different directions. Because both singleton items were task-relevant, participants had no reason to inspect one item before the other. As expected, observers fixated both targets on the majority of trials. Critically, saccades to the color singleton preceded saccades to the less salient shape singleton on the majority of trials. This demonstrates that the order of attentional object selection is largely determined by stimulus salience when task relevance is equated.

Do Lifestyle Activities Protect Against Cognitive Decline in Aging? A Review.

The number of patients suffering from dementia is expected to more than triple by the year 2040, and this represents a major challenge to publicly-funded healthcare systems throughout the world. One of the most effective prevention mechanisms against dementia lies in increasing brain- and cognitive-reserve capacity, which has been found to reduce the behavioral severity of dementia symptoms as neurological degeneration progresses. To date though, most of the factors known to enhance this reserve stem from largely immutable history factors, such as level of education and occupational attainment. Here, we review the potential for basic lifestyle activities, including physical exercise, meditation and musical experience, to contribute to reserve capacity and thus reduce the incidence of dementia in older adults. Relative to other therapies, these activities are low cost, are easily scalable and can be brought to market quickly and easily. Overall, although preliminary evidence is promising at the level of randomized control trials, the state of research on this topic remains underdeveloped. As a result, several important questions remain unanswered, including the amount of training required to receive any cognitive benefit from these activities and the extent to which this benefit continues following cessation. Future research directions are discussed for each lifestyle activity, as well as the potential for these and other lifestyle activities to serve as both a prophylactic and a therapeutic treatment for dementia.

Signal enhancement, not active suppression, follows the contingent capture of visual attention.

Irrelevant visual cues capture attention when they possess a task-relevant feature. Electrophysiologically, this contingent capture of attention is evidenced by the N2pc component of the visual event-related potential (ERP) and an enlarged ERP positivity over the occipital hemisphere contralateral to the cued location. The N2pc reflects an early stage of attentional selection, but presently it is unclear what the contralateral ERP positivity reflects. One hypothesis is that it reflects the perceptual enhancement of the cued search-array item; another hypothesis is that it is time-locked to the preceding cue display and reflects active suppression of the cue itself. Here, we varied the time interval between a cue display and a subsequent target display to evaluate these competing hypotheses. The results demonstrated that the contralateral ERP positivity is tightly time-locked to the appearance of the search display rather than the cue display, thereby supporting the perceptual enhancement hypothesis and disconfirming the cue-suppression hypothesis. (PsycINFO Database Record

Inability to suppress salient distractors predicts low visual working memory capacity.

According to contemporary accounts of visual working memory (vWM), the ability to efficiently filter relevant from irrelevant information contributes to an individual's overall vWM capacity. Although there is mounting evidence for this hypothesis, very little is known about the precise filtering mechanism responsible for controlling access to vWM and for differentiating low- and high-capacity individuals. Theoretically, the inefficient filtering observed in low-capacity individuals might be specifically linked to problems enhancing relevant items, suppressing irrelevant items, or both. To find out, we recorded neurophysiological activity associated with attentional selection and active suppression during a competitive visual search task. We show that high-capacity individuals actively suppress salient distractors, whereas low-capacity individuals are unable to suppress salient distractors in time to prevent those items from capturing attention. These results demonstrate that individual differences in vWM capacity are associated with the timing of a specific attentional control operation that suppresses processing of salient but irrelevant visual objects and restricts their access to higher stages of visual processing.

Searching for inefficiency in visual search.

The time required to find an object of interest in the visual field often increases as a function of the number of items present. This increase or inefficiency was originally interpreted as evidence for the serial allocation of attention to potential target items, but controversy has ensued for decades. We investigated this issue by recording ERPs from humans searching for a target in displays containing several differently colored items. Search inefficiency was ascribed not to serial search but to the time required to selectively process the target once found. Additionally, less time was required for the target to "pop out" from the rest of the display when the color of the target repeated across trials. These findings indicate that task relevance can cause otherwise inconspicuous items to pop out and highlight the need for direct neurophysiological measures when investigating the causes of search inefficiency.

Mental rotational ability is correlated with spatial but not verbal working memory performance and P300 amplitude in males.

This study investigated how both sex and individual differences in a mental rotation test (MRT) influence performance on working memory (WM). To identify the neural substrate supporting these differences, brain electrical activity was measured using the event-related potential technique. No significant sex differences were observed in a test of verbal WM, however males were significantly faster than females to respond to probe stimuli in a test of spatial WM. This difference was no longer significant after controlling for differences in MRT score, suggesting that rotational ability mediates performance in the spatial memory task for both sexes. A posterior P300 was observed in both tasks as participants encoded information into memory, however the amplitude of the P300 correlated with RT in the spatial task but not in the verbal task. Individual differences in the MRT also correlated with RT and with the amplitude of the P300, but again only in the spatial task. After splitting the analysis by sex, partial correlations controlling for MRT revealed that for males, individual differences in rotational ability completely mediated the correlation between the P300 and RT in the spatial task. This mediating effect was not observed for the female participants. The results therefore suggest a relatively stronger association in males between innate mental rotational ability, spatial memory performance, and brain electrophysiological processes supporting spatial memory.

Problem gamblers exhibit reward hypersensitivity in medial frontal cortex during gambling.

Problem gambling (PG) is increasingly conceptualized as an addiction akin to substance abuse, rather than an impulse control disorder, however the mechanism of addiction remains unclear. Neuroimaging investigations have supported a "reward deficiency" hypothesis for PG by suggesting a blunted response to gambling, particularly in the striatum. Here we describe electrophysiological evidence of a hypersensitive response to gambling feedback in problem gamblers. Previous research in healthy participants has shown that feedback during gambling tasks triggers stereotypical neural responses including the Feedback-Related Mediofrontal Negativity (FRN), the feedback-related P300, and an increase in induced theta-band (4-8 Hz) power. We tested the theory that abnormal feedback processing characterizes brain activity in problem gamblers while gambling. EEG was recorded from non-gamblers and self-identified gamblers as they engaged in a computerized version of the Iowa Gambling Task. Feedback about valence (win vs. loss) triggered a FRN in both groups, but in gamblers this was preceded by an early-latency hypersensitive fronto-central difference to feedback. This early FRN was correlated with gambling severity and was localized to medial frontal cortex using distributed source imaging (CLARA). Gamblers also differed in responses to risk, showing a blunted P300 component and less EEG power in the theta band. Here we suggest that a more nuanced interpretation of reward deficiency is called for with respect to PG. For certain aspects of brain function, gamblers may exhibit hypersensitivity to reward feedback more akin to drug sensitization than reward deficiency. Our results also suggest that the neurologically normal brain employs dissociable systems in the processing of feedback from tasks involving risky decision making.

Selective attention modulates electrical responses to reversals of optic-flow direction.

Attended stimuli typically evoke larger event-related potentials (ERPs) than unattended stimuli. We previously reported an exception when an optic-flow pattern is interleaved with stationary dots. Reversals of motion direction evoked a larger N200 peak when attention was directed to the stationary dots. We replicated and further characterized this result: the N200 enhancement was eliminated when the dots moved randomly rather than in optic flow. The effect was also attenuated with isoluminant stimuli. Electrical source analysis suggested the attentional modulation of a configuration of dorsal extrastriate generators. The ERP evoked by reversals of optic flow may reflect the operation of independently configurable attentional filters within visual cortex.

Right frontal cortex generates reward-related theta-band oscillatory activity.

When participants in a gambling game are given feedback as to whether they won or lost the previous bet, a series of stereotypical brain electrical responses can be observed in the electroencephalogram (EEG) and the stimulus-locked Event-Related Potential (ERP). These include the Feedback-Related Mediofrontal Negativity (FRN), a posterior P300, and a feedback-induced increase in power at the theta (4 to 8 Hz) band over frontal scalp. Although the generators of the FRN and P300 have been studied previously, little is known about the generator of feedback-induced theta. We employed a gambling game in which participants chose either high-risk/high-reward or low-risk/low-reward bets to investigate these feedback-related responses. The FRN was not modulated by the riskiness of the bet, but both P300 and feedback-induced theta were of greater amplitude following high- relative to low-risk bets. Using a bilateral multi-source Beamformer approach, we localized the induced theta-band responses following wins and losses to partially overlapping regions in the right medial frontal cortex, possibly including the Anterior Cingulate. Using a dipole-fitting approach, we found that the generators of feedback-induced theta are anatomically distinct from those of the FRN and P300.