"Guttmann Cognitest®," a digital solution for assessing cognitive performance in adult population: A feasibility and usability pilot study.

Background: As the world population continues to age, the prevalence of neurological diseases, such as dementia, poses a significant challenge to society. Detecting cognitive impairment at an early stage is vital in preserving and enhancing cognitive function. Digital tools, particularly mHealth, offer a practical solution for large-scale population screening and prompt follow-up assessments of cognitive function, thus overcoming economic and time limitations. Objective: In this work, two versions of a digital solution called Guttmann Cognitest® were tested. Methods: Two hundred and one middle-aged adults used the first version (Group A), while 132 used the second one, which included improved tutorials and practice screens (Group B). This second version was also validated in an older age group (Group C). Results: This digital solution was found to be highly satisfactory in terms of usability and feasibility, with good acceptability among all three groups. Specifically for Group B, the system usability scale score obtained classifies the solution as the best imaginable in terms of usability. Conclusions: Guttmann Cognitest® has been shown to be effective and well-perceived, with a high potential for sustained engagement in tracking changes in cognitive function.

Brain Connectivity Correlates of Cognitive Dispersion in a Healthy Middle-Aged Population: Influence of Subjective Cognitive Complaints.

OBJECTIVES: Cognitive dispersion, representing intraindividual fluctuations in cognitive performance, is associated with cognitive decline in advanced age. We sought to elucidate sociodemographic, neuropsychological, and brain connectivity correlates of cognitive dispersion in middle age, and further consider potential influences of the severity of subjective cognitive complaints (SCC). METHODS: Five hundred and twenty healthy volunteers from the Barcelona Brain Health Initiative (aged 40-66 years; 49.6% females, 453 with magnetic resonance imaging acquisitions) were included and stratified into high and low SCC groups. Two analysis steps were undertaken: (1) for the whole sample and (2) by groups. Generalized linear models and analysis of covariance were implemented to study associations between cognitive dispersion and performance (episodic memory, speed of processing, and executive function), white matter integrity, and resting-state functional connectivity (rs-FC) of the default mode network (DMN) and dorsal attentional networks (DAN). RESULTS: Across-domain dispersion was negatively related to cognitive performance, rs-FC within the DMN, and between the DMN and the DAN, but not to white matter integrity. The rs-FC values were not explained by cognitive performance. When considering groups, the above findings were significant only for those with high SCC. DISCUSSION: In healthy middle-aged individuals, high cognitive dispersion was related to poorer cognition and DMN dysregulation, being these associations stronger among subjects with high SCC. The present results reinforce the interest in considering dispersion measures within neuropsychological evaluations, as they may be more sensitive to incipient age-related cognitive and functional brain changes than traditional measures of performance.

Brain system segregation and pain catastrophizing in chronic pain progression.

Pain processing involves emotional and cognitive factors that can modify pain perception. Increasing evidence suggests that pain catastrophizing (PC) is implicated, through pain-related self-thoughts, in the maladaptive plastic changes related to the maintenance of chronic pain (CP). Functional magnetic resonance imaging (fMRI) studies have shown an association between CP and two main networks: default mode (DMN) and dorsoattentional (DAN). Brain system segregation degree (SyS), an fMRI framework used to quantify the extent to which functional networks are segregated from each other, is associated with cognitive abilities in both healthy individuals and neurological patients. We hypothesized that individuals suffering from CP would show worst health-related status compared to healthy individuals and that, within CP individuals, longitudinal changes in pain experience (pain intensity and affective interference), could be predicted by SyS and PC subdomains (rumination, magnification, and helplessness). To assess the longitudinal progression of CP, two pain surveys were taken before and after an in-person assessment (physical evaluation and fMRI). We first compared the sociodemographic, health-related, and SyS data in the whole sample (no pain and pain groups). Secondly, we ran linear regression and a moderation model only in the pain group, to see the predictive and moderator values of PC and SyS in pain progression. From our sample of 347 individuals (mean age = 53.84, 55.2% women), 133 responded to having CP, and 214 denied having CP. When comparing groups, results showed significant differences in health-related questionnaires, but no differences in SyS. Within the pain group, helplessness (ß = 0.325; p = 0.003), higher DMN (ß = 0.193; p = 0.037), and lower DAN segregation (ß = 0.215; p = 0.014) were strongly associated with a worsening in pain experience over time. Moreover, helplessness moderated the association between DMN segregation and pain experience progression (p = 0.003). Our findings indicate that the efficient functioning of these networks and catastrophizing could be used as predictors of pain progression, bringing new light to the influence of the interplay between psychological aspects and brain networks. Consequently, approaches focusing on these factors could minimize the impact on daily life activities.

Purpose in life promotes resilience to age-related brain burden in middle-aged adults.

BACKGROUND: Disease-modifying agents to counteract cognitive impairment in older age remain elusive. Hence, identifying modifiable factors promoting resilience, as the capacity of the brain to maintain cognition and function with aging and disease, is paramount. In Alzheimer's disease (AD), education and occupation are typical cognitive reserve proxies. However, the importance of psychological factors is being increasingly recognized, as their operating biological mechanisms are elucidated. Purpose in life (PiL), one of the pillars of psychological well-being, has previously been found to reduce the deleterious effects of AD-related pathological changes on cognition. However, whether PiL operates as a resilience factor in middle-aged individuals and what are the underlying neural mechanisms remain unknown. METHODS: Data was obtained from 624 middle-aged adults (mean age 53.71 ± 6.9; 303 women) from the Barcelona Brain Health Initiative cohort. Individuals with lower (LP; N = 146) and higher (HP; N = 100) PiL rates, according to the division of this variable into quintiles, were compared in terms of cognitive status, a measure reflecting brain burden (white matter lesions; WMLs), and resting-state functional connectivity, examining system segregation (SyS) parameters using 14 common brain circuits. RESULTS: Neuropsychological status and WMLs burden did not differ between the PiL groups. However, in the LP group, greater WMLs entailed a negative impact on executive functions. Subjects in the HP group showed lower SyS of the dorsal default-mode network (dDMN), indicating lesser segregation of this network from other brain circuits. Specifically, HP individuals had greater inter-network connectivity between specific dDMN nodes, including the frontal cortex, the hippocampal formation, the midcingulate region, and the rest of the brain. Greater functional connectivity in some of these nodes positively correlated with cognitive performance. CONCLUSION: Expanding previous findings on AD pathology and advanced age, the present results suggest that higher rates of PiL may promote resilience against brain changes already observable in middle age. Furthermore, having a purposeful life implies larger functional integration of the dDMN, which may potentially reflect greater brain reserve associated to better cognitive function.

The age-related contribution of cognitive function to dual-task gait in middle-aged adults in Spain: observations from a population-based study.

BACKGROUND: Poor dual-task gait performance is associated with a risk of falls and cognitive decline in adults aged 65 years or older. When and why dual-task gait performance begins to deteriorate is unknown. This study aimed to characterise the relationships between age, dual-task gait, and cognitive function in middle age (ie, aged 40-64 years). METHODS: We conducted a secondary analysis of data from community-dwelling adults aged 40-64 years that took part in the Barcelona Brain Health Initiative (BBHI) study, an ongoing longitudinal cohort study in Barcelona, Spain. Participants were eligible for inclusion if they were able to walk independently without assistance and had completed assessments of both gait and cognition at the time of analysis and ineligble if they could not understand the study protocol, had any clinically diagnosed neurological or psychiatric diseases, were cognitively impaired, or had lower-extremity pain, osteoarthritis, or rheumatoid arthritis that could cause abnormal gait. Stride time and stride time variability were measured under single-task (ie, walking only) and dual-task (ie, walking while performing serial subtractions) conditions. Dual-task cost (DTC; the percentage increase in the gait outcomes from single-task to dual-task conditions) to each gait outcome was calculated and used as the primary measure in analyses. Global cognitive function and composite scores of five cognitive domains were derived from neuropsychological testing. We used locally estimated scatterplot smoothing to characterise the relationship between age and dual-task gait, and structural equation modelling to establish whether cognitive function mediated the association between observed biological age and dual tasks. FINDINGS: 996 people were recruited to the BBHI study between May 5, 2018, and July 7, 2020, of which 640 participants completed gait and cognitive assessments during this time (mean 24 days [SD 34] between first and second visit) and were included in our analysis (342 men and 298 women). Non-linear associations were observed between age and dual-task performance. Starting at 54 years, the DTC to stride time (ß=0·27 [95% CI 0·11 to 0·36]; p<0·0001) and stride time variability (0·24 [0·08 to 0·32]; p=0·0006) increased with advancing age. In individuals aged 54 years or older, decreased global cognitive function correlated with increased DTC to stride time (ß=-0·27 [-0·38 to -0·11]; p=0·0006) and increased DTC to stride time variability (ß=-0·19 [-0·28 to -0·08]; p=0·0002). INTERPRETATION: Dual-task gait performance begins to deteriorate in the sixth decade of life and, after this point, interindividual variance in cognition explains a substantial portion of dual-task performance. FUNDING: La Caixa Foundation, Institut Guttmann, and Fundació Abertis.

Functional Brain Connectivity Prior to the COVID-19 Outbreak Moderates the Effects of Coping and Perceived Stress on Mental Health Changes: A First Year of COVID-19 Pandemic Follow-up Study.

BACKGROUND: The COVID-19 pandemic provides a unique opportunity to investigate the psychological impact of a global major adverse situation. Our aim was to examine, in a longitudinal prospective study, the demographic, psychological, and neurobiological factors associated with interindividual differences in resilience to the mental health impact of the pandemic. METHODS: We included 2023 healthy participants (age: 54.32 ± 7.18 years, 65.69% female) from the Barcelona Brain Health Initiative cohort. A linear mixed model was used to characterize the change in anxiety and depression symptoms based on data collected both pre-pandemic and during the pandemic. During the pandemic, psychological variables assessing individual differences in perceived stress and coping strategies were obtained. In addition, in a subsample (n = 433, age 53.02 ± 7.04 years, 46.88% female) with pre-pandemic resting-state functional magnetic resonance imaging available, the system segregation of networks was calculated. Multivariate linear models were fitted to test associations between COVID-19-related changes in mental health and demographics, psychological features, and brain network status. RESULTS: The whole sample showed a general increase in anxiety and depressive symptoms after the pandemic onset, and both age and sex were independent predictors. Coping strategies attenuated the impact of perceived stress on mental health. The system segregation of the frontoparietal control and default mode networks were found to modulate the impact of perceived stress on mental health. CONCLUSIONS: Preventive strategies targeting the promotion of mental health at the individual level during similar adverse events in the future should consider intervening on sociodemographic and psychological factors as well as their interplay with neurobiological substrates.

Investigating the application of "Guttmann Cognitest"® in older adults and people with acquired brain injury.

Introduction: Digital solutions for cognitive assessment are currently not only widely used in experimental contexts but can also be useful in clinical practice for efficient screening and longitudinal follow-up. The "Guttmann Cognitest"®, which includes seven computerized tasks designed to assess main cognitive functions, revealed in a previous validation study to be a potential useful tool to assess cognitive functioning in healthy middle-aged adults. Method: Here, we present results from a validation in two different populations: one consisting of older adults, and the other comprising young and middle-aged individuals, some of them affected by acquired brain injury. To perform a convergent validity test, older adults were also administered with the MOCA, while young and middle-aged individuals were administered with a short neuropsychological assessment including gold-standard neuropsychological tests. We also conducted sensitivity and specificity analysis to establish the utility of this instrument in identifying potential cognitive dysfunctions in the two groups. Results: Results demonstrated strong convergent validity as well as good specificity and sensitivity characteristics. Discussion: This tool is a valid and useful instrument to assess cognitive functioning and detecting potential cases of cognitive dysfunctions in older adults and clinical populations.

Independent living, emotional well-being, and quality of life in people with disabilities: the mediator role of self-determination and satisfaction with participation.

Background: In the field of disability and rehabilitation, participation in society has become an important therapeutic objective due to its potential impact on rehabilitation, prognosis, and patient's mid and long-term well-being. However, only a few studies have explored this issue in relation with the subjective perspective of individuals with disabilities about their decision-making capacity and satisfaction with the activities in which they participate. Objective: Our aim is to analyze the relationship between participation in society of people with disabilities and both emotional well-being and quality of life, including variables about subjective perspective of participation (satisfaction) and the ability to decide and pursue their own preferences. Method: The cross-sectional study presented here includes 424 participants with disabilities over 18-years-old from Spain. This research is part of a larger ongoing longitudinal cohort study called Participa (https://participa.guttmann.com/en/). Participants were asked to complete several on-line surveys to explore quality of life, emotional well-being, participation in society, self-determination, and independent living. Results: The results revealed an association between the dimensions of participation satisfaction, self-determination, and levels of independent living with both quality of life and emotional well-being. Mediation models indicated that satisfaction and self-determination partially mediated the relationship between independent living and both quality of life and emotional well-being. Conclusion: The level of independent living, self-determination, and satisfaction with participation are fundamental aspects for promoting a high quality of life and emotional well-being in people with disabilities. These findings carry significant implications for health and social services, as well as policies guidelines, highlighting the need to prioritize empowerment and self-determination in all interventions designed for people with disabilities.

"Guttmann Cognitest"®, preliminary validation of a digital solution to test cognitive performance.

Thanks to technological advances, the administration of cognitive assessments via digital solutions continues to increase, both in research and clinical practice. "Guttmann Cognitest"°ledR is a digital solution for cognitive assessment which includes seven computerized tasks designed to assess main cognitive functions requiring approximately 20 min to be completed. The purpose of the present study was to validate it against standard and more extensive in-person neuropsychological assessments in the context of the Barcelona Brain Health Initiative (BBHI) cohort study. We studied 274 participants of the BBHI (126 women, mean age = 56.14, age range 44-69), who underwent an extensive in-person assessment, including a classical paper-and-pencil neuropsychological assessment and a cognitive assessment via the "Guttmann Cognitest"°ledR. Principal component analysis indicated that "Guttmann Cognitest"°ledR measures four main cognitive domains and convergent validity analysis demonstrated that cognitive performance was associated with gold standard paper and pencil tests. Results also showed an expected negative correlation with age, a relation with educational level as well as a gender effect. Regression-based norming equations for the sample tested are also reported. Performing a cognitive assessment with this digital solution is feasible and potentially useful to gather information about cognitive functioning in large samples and experimental settings.

Corrigendum to "Prefrontal reactivity to TMS perturbation as a toy model of mental health outcomes during the COVID-19 pandemic"[Heliyon 8 (8), (August 2022) Article e10208].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e10208.].

Long-interval intracortical inhibition in primary motor cortex related to working memory in middle-aged adults.

Introduction: Excitability of the primary motor cortex measured with TMS has been associated with cognitive dysfunctions in patient populations. However, only a few studies have explored this relationship in healthy adults, and even fewer have considered the role of biological sex. Methods: Ninety-seven healthy middle-aged adults (53 male) completed a TMS protocol and a neuropsychological assessment. Resting Motor Threshold (RMT) and Long-Interval Intracortical Inhibition (LICI) were assessed in the left motor cortex and related to attention, episodic memory, working memory, reasoning, and global cognition composite scores to evaluate the relationship between cortical excitability and cognitive functioning. Results: In the whole sample, there was a significant association between LICI and cognition; specifically, higher motor inhibition was related to better working memory performance. When the sample was broken down by biological sex, LICI was only associated with working memory, reasoning, and global cognition in men. No associations were found between RMT and cognitive functions. Conclusion: Greater intracortical inhibition, measured by LICI, could be a possible marker of working memory in healthy middle-aged adults, and biological sex plays a critical role in this association.

Prefrontal reactivity to TMS perturbation as a toy model of mental health outcomes during the COVID-19 pandemic.

Psychosocial hardships associated with the COVID-19 pandemic led many individuals to suffer adverse mental health consequences, however, others show no negative effects. We hypothesized that the electroencephalographic (EEG) response to transcranial magnetic stimulation (TMS) could serve as a toy-model of an individual's capacity to resist psychological stress, in this case linked to the COVID-19 pandemic. We analyzed data from 74 participants who underwent mental health monitoring and concurrent electroencephalography with transcranial magnetic stimulation of the left dorsolateral prefrontal cortex (L-DLPFC) and left inferior parietal lobule (L-IPL). Within the following 19 months, mental health was reassessed at three timepoints during lock-down confinement and different phases of de-escalation in Spain. Compared with participants who remained stable, those who experienced increased mental distress showed, months earlier, significantly larger late EEG responses locally after L-DLPFC stimulation (but not globally nor after L-IPL stimulation). This response, together with years of formal education, was significantly predictive of mental health status during the pandemic. These findings reveal that the effect of TMS perturbation offers a predictive toy model of psychosocial stress response, as exemplified by the COVID-19 pandemic.

The Importance of Motivation to Older Adult Physical and Cognitive Exercise Program Development, Initiation, and Adherence.

Brain health is essential to successful aging, and exercise is essential to brain health. Evidence supports the benefits of regular physical and cognitive exercise in preventing or delaying progressin of mild cognitive impairment and dementia. Despite known benefits, motivation to initiate and adhere to an exercise program can be challenging to older adults. We propose that assessment of motivation in the older adult population be part of individualized physical and cognitive exercise program initial development and ongoing precision health coaching to facilitate initiation of-and adherence to-individualized multi-modal exercise programs and sustained exercise engagement. We suggest one published, physical exercise motivation questionnaire and present a new, psychometrically supported, parallel cognitive exercise questionnaire to do so. Needs for-and implications of-continued exercise motivation research using neurophysiologic and neuropsychologic metrics are discussed.

Sense of Coherence Mediates the Relationship Between Cognitive Reserve and Cognition in Middle-Aged Adults.

In recent years, supported by new scientific evidence, the conceptualization of cognitive reserve (CR) has been progressively enriched and now encompasses not only cognitive stimulating activities or educational level, but also lifestyle activities, such as leisure physical activity and socialization. In this context, there is increasing interest in understanding the role of psychological factors in brain health and cognitive functioning. In a previous study, we have found that these factors mediated the relationship between CR and self-reported cognitive functioning. In this study, we have confirmed an association between two important constructs included in the psychological wellbeing and salutogenic models, "purpose in life" and "sense of coherence," CR, as assessed using a questionnaire, and cognitive functioning, as evaluated using a comprehensive neuropsychological battery. Results from 888 middle-aged healthy participants from the Barcelona Brain Health Initiative indicate that both sense of coherence (SoC) and CR were positively associated with verbal memory, reasoning and attention, working memory, and global cognition. Moreover, the relation between CR and cognitive functioning in the different domains is partially mediated by SoC. When we controlled for brain integrity, introducing into the model neurofilament light chain measures, the mediator role of SoC was confirmed for reasoning and attention and global cognition. However, purpose in life was not associated with cognitive functioning. These results reveal the central role of the SoC construct, which mediates the association between classic CR estimates and cognitive functions, potentially representing a modifiable target for interventions that aim to promote brain health.

Validation and Normative Data of the Spanish Version of the Rey Auditory Verbal Learning Test and Associated Long-Term Forgetting Measures in Middle-Aged Adults.

Rey Auditory Verbal Learning Test (RAVLT) is an episodic memory helpful measure to detect changes associated with abnormal aging. There is a lack of RAVLT validation and normalization studies in Spain. The aim was to determine its psychometric properties and explore long-term forgetting (LTF) performance through 1-week delayed recall under three different modes of administration. The RAVLT was administered to 602 cognitively healthy volunteers, aged between 41 and 65 years, of whom 251 completed the LTF assessment. Findings reveal a factorial structure of four components, with satisfactory goodness of fit, and adequate convergent and divergent validity. We also demonstrated the differential effect of three methodologies used in LTF assessment, supporting that test expectancy positively influences long-term storage. Finally, normative data were generated according to age, sex, and education. The test, including the LTF measure, is a promising tool to estimate memory in middle-aged adults and develop predictive brain aging models.

Local Prefrontal Cortex TMS-Induced Reactivity Is Related to Working Memory and Reasoning in Middle-Aged Adults.

INTRODUCTION: The prefrontal cortex (PFC) plays a crucial role in cognition, particularly in executive functions. Cortical reactivity measured with Transcranial Magnetic Stimulation combined with Electroencephalography (TMS-EEG) is altered in pathological conditions, and it may also be a marker of cognitive status in middle-aged adults. In this study, we investigated the associations between cognitive measures and TMS evoked EEG reactivity and explored whether the effects of this relationship were related to neurofilament light chain levels (NfL), a marker of neuroaxonal damage. METHODS: Fifty two healthy middle-aged adults (41-65 years) from the Barcelona Brain Health Initiative cohort underwent TMS-EEG, a comprehensive neuropsychological assessment, and a blood test for NfL levels. Global and Local Mean-Field Power (GMFP/LMFP), two measures of cortical reactivity, were quantified after left prefrontal cortex (L-PFC) stimulation, and cognition was set as the outcome of the regression analysis. The left inferior parietal lobe (L-IPL) was used as a control stimulation condition. RESULTS: Local reactivity was significantly associated with working memory and reasoning only after L-PFC stimulation. No associations were found between NfL and cognition. These specific associations were independent of the status of neuroaxonal damage indexed by the NfL biomarker and remained after adjusting for age, biological sex, and education. CONCLUSION: Our results demonstrate that TMS evoked EEG reactivity at the L-PFC, but not the L-IPL, is related to the cognitive status of middle-aged individuals and independent of NfL levels, and may become a valuable biomarker of frontal lobe-associated cognitive function.

Validation and Normative Data of the Spanish Version of the Face Name Associative Memory Exam (S-FNAME).

OBJECTIVE: The relevance of the episodic memory in the prediction of brain aging is well known. The Face Name Associative Memory Exam (FNAME) is a valued associative memory measure related to Alzheimer's disease (AD) biomarkers, such as amyloid-ß deposition preclinical AD individuals. Previous validation of the Spanish version of the FNAME test (S-FNAME) provided normative data and psychometric characteristics. The study was limited to subjects attending a memory clinic and included a reduced sample with gender inequality distribution. The purpose of this study was to assess S-FNAME psychometric properties and provide normative data in a larger independent sample of cognitively healthy individuals. METHOD: S-FNAME was administered to 511 cognitively healthy volunteers (242 women, aged 41-65 years) participating in the Barcelona Brain Health Initiative cohort study. RESULTS: Factor analysis supported construct validity revealing two underlying components: face-name and face-occupation and explaining 95.34% of the total variance, with satisfactory goodness of fit. Correlations between S-FNAME and Rey Auditory-Verbal Learning Test were statistically significant and confirmed its convergent validity. We also found weak correlations with non-memory tests supporting divergent validity. Women showed better scores, and S-FNAME was positively correlated with education and negatively with age. Finally, we generated normative data. CONCLUSIONS: The S-FNAME test exhibits good psychometric properties, consistent with previous findings, resulting in a valid and reliable tool to assess episodic memory in cognitively healthy middle-aged adults. It is a promising test for the early detection of subtle memory dysfunction associated with abnormal brain aging.

Aging in the Digital Age: Using Technology to Increase the Reach of the Clinician Expert and Close the Gap Between Health Span and Life Span.

Age-related cognitive impairment (ARCI) has a profound impact on individuals, families, health care systems, and societies at large. Evidence suggests that ARCI is the consequence of underlying brain pathology. Therefore, efforts to minimize the impact of ARCI and thus closing the gap between health span and life span, which has widened in recent years, requires early detection and timely deployment of targeted, personalized interventions. Access to clinical experts is limited and technology screening and assessment methods are thus appealing. However, as traditionally implemented patients were deprived of the benefit of personalized connection with a clinician, which is particularly critical for the prescription and to ensure the adherence to and ultimate success of therapeutic interventions. We present the concept of Intelligent Technology Therapy Assistant (ITA) as a scalable solution that increases the reach of clinical experts while sustaining the personal connection between each patient and their clinician. We illustrate ITA with the "Guttman Neuro Personal Trainer"®, a tele-rehabilitation platform that provides neuropsychological evaluation and care, and the Barcelona Brain Health Initiative (BBHI) multimodal intervention coaching app, a mobile-based platform that provides lifestyle coaching support in domains related to brain health. In addition, we discuss the translation of these models to a large-scale enterprise with Linus Health. To this end, we conclude with a discussion of challenges and opportunities to move the field forward.