The Glutamatergic Effects of Clinical Repetitive Transcranial Magnetic Stimulation in Depressed Populations: A Preliminary Meta-Analysis of Proton Magnetic Resonance Spectroscopy Studies.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) alleviates symptoms of major depressive disorder, but its neurobiological mechanisms remain to be fully understood. Growing evidence from proton magnetic resonance spectroscopy (1HMRS) studies suggests that rTMS alters excitatory and inhibitory neurometabolites. This preliminary meta-analysis aims to quantify current trends in the literature and identify future directions for the field. METHODS: Ten eligible studies that quantified Glutamate (Glu), Glu+Glutamine (Glx), or GABA before and after an rTMS intervention in depressed samples were sourced from PubMed, MEDLINE, PsychInfo, Google Scholar, and primary literature following PRISMA guidelines. Data were pooled using a random-effects model, Cohen's d effect sizes were calculated, and moderators, such as neurometabolite and 1HMRS sequence, were assessed. It was hypothesized that rTMS would increase cortical neurometabolites. RESULTS: Within-subjects data from 224 cases encompassing 31 neurometabolite effects (k) were analyzed. Active rTMS in clinical responders (n = 128; k = 22) nominally increased glutamatergic neurometabolites (d = 0.15 [95% CI: -0.01, 0.30], p = 0.06). No change was found in clinical nonresponders (p = 0.8) or sham rTMS participants (p = 0.4). A significant increase was identified in Glx (p = 0.01), but not Glu (p = 0.6). Importantly, effect size across conditions were associated with the number of rTMS pulses patients received (p = 0.05), suggesting dose dependence. CONCLUSIONS: Clinical rTMS is associated with a nominal, dose-dependent increase in glutamatergic neurometabolites, suggesting rTMS may induce Glu-dependent neuroplasticity and upregulate neurometabolism. More, larger scale studies adhering to established acquisition and reporting standards are needed to further elucidate the neurometabolic mechanisms of rTMS.

Managing Complexity in Socio-Technical Systems by Mimicking Emergent Simplicities in Nature: A Brief Communication.

In the context of socio-technical systems, traditional engineering approaches are inadequate, calling for a fundamental change in perspective. A different approach encourages viewing socio-technical systems as complex living entities rather than through a simplistic lens, which enhances our understanding of their dynamics. However, these systems are designed to facilitate human activities, and the goal is not only to comprehend how they operate but also to guide their function. Currently, we lack the appropriate terminology. Hence, we introduce two principal concepts, simplexity and complixity, drawing inspiration from how nature conceals intricate mechanisms beneath straightforward, user-friendly interfaces.

Test-retest reliability and validity of vagally-mediated heart rate variability to monitor internal training load in older adults: a within-subjects (repeated-measures) randomized study.

BACKGROUND: Vagally-mediated heart rate variability (vm-HRV) shows promise as a biomarker of internal training load (ITL) during exergame-based training or motor-cognitive training in general. This study evaluated the test-retest reliability of vm-HRV during exergaming in healthy older adults (HOA) and its validity to monitor ITL. METHODS: A within-subjects (repeated-measures) randomized study was conducted that included baseline assessments and 4 measurement sessions. Participants played 5 exergames at 3 standardized levels of external task demands (i.e., "easy", "challenging", and "excessive") in random order for 90 s. Test-retest reliability was assessed on the basis of repeated-measures analyses of variance (ANOVA), intraclass correlation coefficients (ICC3,1), standard errors of measurement (SEM), and smallest detectable differences (SDD). Validity was determined by examining the effect of game level on vm-HRV in the ANOVA. RESULTS: Fourty-three HOA (67.0 ± 7.0 years; 58.1% females (25 females, 18 males); body mass index = 23.7 ± 3.0 kg·m-2) were included. Mean R-R time intervals (mRR) and parasympathetic nervous system tone index (PNS-Index) exhibited mostly good to excellent relative test-retest reliability with no systematic error. Mean SEM% and SDD% were 36.4% and 100.7% for mRR, and 44.6% and 123.7% for PNS-Index, respectively. Significant differences in mRR and PNS-Index were observed between standardized levels of external task demands, with mostly large effect sizes (mean r = 0.847). These results persisted irrespective of the type of neurocognitive domain trained and when only motoric and cognitive demands were manipulated while physical intensity was kept constant. The remaining vm-HRV parameters showed inconsistent or poor reliability and validity. CONCLUSION: Only mRR and PNS-Index demonstrated reliable measurement and served as valid biomarkers for ITL during exergaming at a group level. Nonetheless, the presence of large SEMs hampers the detection of individual changes over time and suggests insufficient precision of these measurements at the individual level. Future research should further investigate the reliability and validity of vm-HRV with a specific focus on comparing different measurement methodologies and exercise conditions, particularly focusing on ultra-short-term HRV measurements, and investigate the potential implications (i.e., superiority to other markers of ITL or monitoring strategies?) of using vm-HRV as a biomarker of ITL.

Central nervous system regulation of diffuse glioma growth and invasion: from single unit physiology to circuit remodeling.

PURPOSE: Understanding the complex bidirectional interactions between neurons and glioma cells could help to identify new therapeutic targets. Herein, the techniques and application of novel neuroscience tools implemented to study the complex interactions between brain and malignant gliomas, their results, and the potential therapeutic opportunities were reviewed. METHODS: Literature search was performed on PubMed between 2001 and 2023 using the keywords "glioma", "glioblastoma", "circuit remodeling", "plasticity", "neuron networks" and "cortical networks". Studies including grade 2 to 4 gliomas, diffuse midline gliomas, and diffuse intrinsic pontine gliomas were considered. RESULTS: Glioma cells are connected through tumour microtubes and form a highly connected network within which pacemaker cells drive tumorigenesis. Unconnected cells have increased invasion capabilities. Glioma cells are also synaptically integrated within neural circuitry. Neurons promote tumour growth via paracrine and direct electrochemical mechanisms, including glutamatergic AMPA-receptors. Increased glutamate release in the tumor microenvironment and loss of peritumoral GABAergic inhibitory interneurons result in network hyperexcitability and secondary epilepsy. Functional imaging, local field potentials and subcortical mapping, performed in awake patients, have defined patterns of malignant circuit remodeling. Glioma-induced remodeling is frequent in language and even motor cortical networks, depending on tumour biological parameters, and influences functional outcomes. CONCLUSION: These data offer new insights into glioma tumorigenesis. Future work will be needed to understand how tumor intrinsic molecular drivers influence neuron-glioma interactions but also to integrate these results to design new therapeutic options for patients.

Components of effective exergame-based training to improve cognitive functioning in middle-aged to older adults - A systematic review and meta-analysis.

BACKGROUND: Exergame-based training is currently considered a more promising training approach than conventional physical and/or cognitive training. OBJECTIVES: This study aimed to provide quantitative evidence on dose-response relationships of specific exercise and training variables (training components) of exergame-based training on cognitive functioning in middle-aged to older adults (MOA). METHODS: We conducted a systematic review with meta-analysis including randomized controlled trials comparing the effects of exergame-based training to inactive control interventions on cognitive performance in MOA. RESULTS: The systematic literature search identified 22,928 records of which 31 studies were included. The effectiveness of exergame-based training was significantly moderated by the following training components: body position for global cognitive functioning, the type of motor-cognitive training, training location, and training administration for complex attention, and exercise intensity for executive functions. CONCLUSION: The effectiveness of exergame-based training was moderated by several training components that have in common that they enhance the ecological validity of the training (e.g., stepping movements in a standing position). Therefore, it seems paramount that future research focuses on developing innovative novel exergame-based training concepts that incorporate these (and other) training components to enhance their ecological validity and transferability to clinical practice. We provide specific evidence-based recommendations for the application of our research findings in research and practical settings and identified and discussed several areas of interest for future research. PROSPERO REGISTRATION NUMBER: CRD42023418593; prospectively registered, date of registration: 1 May 2023.

FROM THE GATE TO THE GATEWAY: PSYCHOANALYTIC NAVIGATIONS ONLINE.

The shift towards remote or online therapy was compelled by the Pandemic. Many colleagues, who neither had practice using this modality, nor had ever considered it as a possibility, ultimately adopted it. This experience brought with it a substantial expansion of online therapy beyond that moment of emergency. It opened up new prospects of intervention, but at the same time it required a greater measure of reflection in order to understand how to inhabit this new therapy space. Setting aside provisory, intermittent, or emergency situations, which temporarily transfer therapy into a "field of tents" (Bolognini, 2021), the author proposes to consider how online psychotherapy redefines an important element of the psychoanalytic setting-the issue of the space. This is no longer the therapist's place of work, envisaged and organized by him/her/them, fixed in time, and contrived only to welcome the therapeutic relationship-one of the crucial aspects of the external setting, which together with the temporal dimension, fulfills the therapy ritual. Assuming the framework to be essential to the psychoanalytic process, this paper will focus on the methodology of online therapy. The author will describe the contributions of the neurosciences, to provide a deeper understanding of the distinctive characteristics of sharing in an online vs. an offline space. Online therapy should be assessed for its distinguishing qualities within a complete theoretical, technical, and clinical reflection specific to each case. Proceeding as if it were a mere relocation of an in-person analysis would enhance the seductiveness of a therapy that is easily accessible with any laptop anywhere, anytime, and in which one could mistake an online connection for a deep connection.

Effect of exercise detraining in cognitive functions of older adults: A systematic review.

OBJECTIVE: Provide a synthesis of the current literature about the effects of detraining on cognitive functions in older adults. METHODS: The PICOS acronym strategy was performed in PubMed/MEDLINE, Web of Science, Cochrane Library and PsycINFO database. The Preferred Reporting Items for Systematic Review and Meta-Analyses statement had been followed in the present study, in which the search was conducted on October 2023. The study selection consisted in original articles including older adults, detraining after training exercise period, use of tests or scales to measure cognitive function. The Downs and Black checklist had been used to assess the studies quality. Sample characteristics, type of previous training, detraining period, cognitive functions measurements and main results were extracted by 2 investigators. RESULTS: From 1927 studies, 12 studies were included, being 11 studies identified via systematic research, and 1 study by citation search. Older adults, ranged from 60 to 87 years old, were assessed after detraining. The cognitive functions most evaluated were global cognition and executive functions. One study evaluated both cognitive outcome and cerebral blood flow. Most of the studies demonstrated a decline in the cognitive function after detraining. CONCLUSION: Exercise detraining period, ranging from 10 days to 16 weeks, can effect negatively the cognitive function in older adults.

"Brain-IT": Exergame training with biofeedback breathing in neurocognitive disorders.

INTRODUCTION: The combination of exergame-based motor-cognitive training with resonance breathing guided by heart-rate variability biofeedback (HRV-BF) targets various relevant mechanisms of action to alleviate the pathological state in mild neurocognitive disorders (mNCD). METHODS: This randomized controlled trial (RCT) investigated the effectiveness of adding this novel intervention approach to usual care in mNCD. The individualized intervention was delivered via the "Brain-IT" training concept, which was iteratively co-designed, tested, and refined with patient and public involvement. RESULTS: We observed statistically significant effects with large effect sizes for global cognitive performance, immediate verbal recall, and delayed verbal recall in favor of the intervention group. Fifty-five percent of participants showed a clinically relevant improvement in response to training. DISCUSSION: Confirmatory RCTs are warranted to investigate whether the observed improvements in cognitive performance translate to affecting the rates of progression to or onset of dementia and test the implementation of the training in clinical practice. HIGHLIGHTS: We proposed a novel intervention approach for mild neurocognitive disorders. It combines exergame-based training with biofeedback-guided resonance breathing. Our results confirm the effectiveness of this approach. Fifty-five percent of participants showed a clinically relevant improvement in response to training.

The origins of film, psychology and the neurosciences.

The invention of film technologies in France at the end of the 19th century inspired neurologists and associated professionals to engage with this new medium to demonstrate their theories of the brain, the nervous system, and the mind. Beginning with the origins of cinema in Paris, this article explores how film technologies were used at La Salpêtrière, and beyond, to visualise internal mental processes, and to support the burgeoning sciences of the mind. This film-making became increasingly sophisticated by the late 1910s and early 1920s, creating innovative ways to present psychological experiences on film. This article focuses on films produced by Albert Londe, Vincenzo Neri, Gheorghe Marinescu, and Jean Comandon. It argues that these polymaths created new filming techniques that built complexity into the visual articulation of psychological concepts. Their films were essential to shaping early debates in neurology, psychology, and the observational sciences during this critical period in the establishment of the modern sciences of the self.

The uniqueness of the human brain: a review.

The purpose of this review is to highlight the most important aspects of the anatomical and functional uniqueness of the human brain. For this, a comparison is made between our brains and those of our closest ancestors (chimpanzees and bonobos) and human ancestors. During human evolution, several changes occurred in the brain, such as an absolute increase in brain size and number of cortical neurons, in addition to a greater degree of functional lateralization and anatomical asymmetry. Also, the cortical cytoarchitecture became more diversified and there was an increase in the number of intracortical networks and networks extending from the cerebral cortex to subcortical structures, with more neural networks being invested in multisensory and sensory-motor-affective-cognitive integration. These changes permitted more complex, flexible and versatile cognitive abilities and social behavior, such as shared intentionality and symbolic articulated language, which, in turn, made possible the formation of larger social groups and cumulative cultural evolution that are characteristic of our species.

Esta revisão se propõe a relatar os aspectos mais importantes da singularidade anatômica e funcional do cérebro humano. Para isso, faz-se uma comparação entre o nosso cérebro e os de nossos parentes evolutivos mais próximos (chimpanzés e bonobos) e os ancestrais humanos. Durante a evolução humana ocorreu aumento absoluto do tamanho do cérebro e do número de neurônios corticais cerebrais, maior grau de lateralização funcional e assimetria anatômica cerebral, citoarquitetura cortical mais diversificada e aumento das redes neurais intracorticais e do córtex cerebral para as estruturas subcorticais acompanhada de mudança em direção ao investimento de redes neurais na integração multissensorial e sensório-motora-afetiva-cognitiva. Essas mudanças possibilitaram capacidades cognitivas e comportamentos sociais complexos, flexíveis e versáteis, destacando-se a intencionalidade compartilhada e a linguagem articulada simbólica, que permitiram a formação de grupos sociais maiores e a evolução cultural cumulativa característica de nossa espécie.

Time-restricted feeding can increase food-related impulsivity: a randomized controlled trial.

OBJECTIVES: Although an increasing number of studies show that time-restricted feeding may improve metabolic health, studies examining the behavioral effects of this eating pattern are limited. This study examined the effect of time-restricted feeding on impulsivity in adults. METHODS: Thirty adults aged 25-41 years participated in this randomized controlled trial. The intervention group followed time-restricted feeding for 4 weeks and there was no energy restriction in the intervention group (n = 15) or control group (n = 15). Impulsivity was assessed before and after the intervention with the Barratt Impulsiveness Scale and the Go/NoGo task. RESULTS: The compliance rate (the percentage of days when participants had a feeding time of ≤ 8 hours/day) of the intervention group to the time-restricted feeding pattern was 92.38 ± 4.24%. The Barratt Impulsiveness Scale-11 total score of the intervention group increased from 55.53 ± 6.37 to 59.47 ± 7.67 (p = 0.02). During the Go/NoGo task, an indicator of inhibitory control, the reaction time to food and non-food stimuli was significantly shortened in the intervention group (respectively; p = 0.009, p = 0.01). In the control group, no significant change was detected in impulsivity determined by the BIS-11 or Go/NoGo task. DISCUSSION: This study showed that although time-restricted feeding may reduce body weight, it can lead to increased impulsivity and impaired inhibitory control.Trial registration: ClinicalTrials.gov identifier: NCT04960969.

Fractal Analysis in Clinical Neurosciences: An Overview.

Over the last years, fractals have entered into the realms of clinical neurosciences. The whole brain and its components (i.e., neurons and astrocytes) have been studied as fractal objects, and even more relevant, the fractal-based quantification of the geometrical complexity of histopathological and neuroradiological images as well as neurophysiopathological time series has suggested the existence of a gradient in the pattern representation of neurological diseases. Computational fractal-based parameters have been suggested as potential diagnostic and prognostic biomarkers in different brain diseases, including brain tumors, neurodegeneration, epilepsy, demyelinating diseases, cerebrovascular malformations, and psychiatric disorders as well. This chapter and the entire third section of this book are focused on practical applications of computational fractal-based analysis into the clinical neurosciences, namely, neurology and neuropsychiatry, neuroradiology and neurosurgery, neuropathology, neuro-oncology and neurorehabilitation, neuro-ophthalmology, and cognitive neurosciences, with special emphasis on the translation of the fractal dimension and other fractal parameters as clinical biomarkers useful from bench to bedside.

The Fractal Geometry of the Brain: AnOverview.

The first chapter of this book introduces some history, philosophy, and basic concepts of fractal geometry and discusses how the neurosciences can benefit from applying computational fractal-based analysis. Further, it compares fractal with Euclidean approaches to analyzing and quantifying the brain in its entire physiopathological spectrum and presents an overview of the first section of this book as well.

CONNECTing Concussion Care with Research Across Ontario.

Common data elements (CDEs) for concussion, as established by international bodies, are not being widely used in Ontario, resulting in significant variability in the data being assessed and collected across clinics. CDEs support standardization of care as well as large-scale data sharing for high impact research. A collaborative network - Concussion Ontario Network: Neuroinformatics to Enhance Clinical care and Translation (CONNECT) - comprised of health care professionals, researchers, members from advocacy groups, and patients was formed to establish and implement CDEs for concussion care and research. While the seeds have been planted and initial effectiveness demonstrated, future challenges exist.

Anton, Balint, Charles Bonnet, and the Others: The ABC of Cerebral Visual Syndromes (A Historical Guide and an Update).

Cerebral visual impairments have been of great interest to neurologists, ophthalmologists, and neuroscientists. Complicated or partial varieties related to cortical blindness are discussed in this review. They are a fascinating alphabet of eponymic clinical syndromes, bordering neurology, ophthalmology, and even psychiatry. Recent functional imaging and experimental studies have contributed further knowledge of cognitive visual organization in addition to the classical lesion evidence.

Neurophobia Among Medical Students: Is Virtual Teaching the Answer?

OBJECTIVE: Neurophobia is well recognized as dissuading medical students from neurocentric specialties and limiting the success of neurology and neurosurgery teaching at medical school. Past studies have associated neurophobia with deficiencies in medical education. We performed a cross-sectional analysis of medical students' confidence and perceived level of knowledge in recognizing the following neurosurgical and neurological emergencies: ischemic stroke, hemorrhagic stroke, status epilepticus, subarachnoid hemorrhage, increased intracranial pressure, acute hydrocephalus, spinal cord injury, cauda equina syndrome, and traumatic brain injury. In addition, we assessed the usefulness of virtual seminars in neurosurgery and neurology teaching. METHODS: Medical students from King's College London were invited to a virtual teaching session. We obtained preteaching and postteaching scores for students' subjective ability to recognize specific neurologic and neurosurgical emergencies, along with their confidence in the subject. RESULTS: Ninety-seven medical students attended the teaching session. For our sample group's subjective rating on their confidence in neurology or neurosurgery as a subject, we obtained a mean score of 3.87 and a median score of 4. Across all domains, there was a significant forward shift in the distribution curve of scores after teaching. We obtained statistically significant differences for all 9 neurologic and neurosurgical emergencies evaluated in our questionnaire (asymptotic significance <0.001). Median scores for all 9 conditions improved after the teaching session, with >50% positive ranks seen within each group. Across the teaching modalities compared, placement teaching was the highest scoring, whereas online lectures received a better rating than in-person lectures. CONCLUSIONS: In neurosurgery teaching, virtual seminars may compensate for deficiencies that exist within medical education, hence limiting the effects of neurophobia.

Trauma e literalidade: a razão psicodinâmica no espírito da traumatização neurocientífica / Trauma and literality: psychodynamic reason in the spirit of neuroscientific traumatization

Resumo Desde o seu nascimento na medicina cirúrgica do século XVII, a pesquisa do trauma admitiu interpretações múltiplas e associadas ora às lesões visíveis de órgãos e tecidos, ora à influência de agentes psíquicos patogênicos sobre a memória, a consciência e a personalidade. Com o aprofundamento do papel dos sistemas classificatórios desde DSM-III, o fenômeno do trauma será incorporado ao prisma psiquiátrico através do Transtorno de Estresse Pós-Traumático e destinado, finalmente, à circunscrição da pesquisa neurocientífica. A partir de revisão narrativa, este artigo abordará uma das premissas epistemológicas fundamentais para essa transição, que informa como o trauma psicológico ganhou autonomia sobre as descrições anatômicas para ser, cerca de um século depois, por ela reanexado enquanto fenômeno essencialmente corporal e aderido à gramática das neurociências.

Abstract Since its origin in the surgical medicine of the 17th century, trauma research has had multiple interpretations and has been associated either with visible injuries to organs and tissues, or with the influence of pathogenic psychic agents on memory, consciousness and personality. With the intensification of the role of classification systems since DSM-III, the phenomenon of trauma came to be incorporated into the psychiatric realm through Post-Traumatic Stress Disorder and destined finally to the constraints of neuroscientific research. Based on a narrative review, this article will address one of the fundamental epistemological premises for this transition, which informs how psychological trauma gained autonomy over anatomical descriptions to be reclassified, around a century later, as an essentially bodily phenomenon and incorporated into the jargon of neurosciences.

The uniqueness of the human brain: a review / A singularidade do cérebro humano: uma revisão

ABSTRACT The purpose of this review is to highlight the most important aspects of the anatomical and functional uniqueness of the human brain. For this, a comparison is made between our brains and those of our closest ancestors (chimpanzees and bonobos) and human ancestors. During human evolution, several changes occurred in the brain, such as an absolute increase in brain size and number of cortical neurons, in addition to a greater degree of functional lateralization and anatomical asymmetry. Also, the cortical cytoarchitecture became more diversified and there was an increase in the number of intracortical networks and networks extending from the cerebral cortex to subcortical structures, with more neural networks being invested in multisensory and sensory-motor-affective-cognitive integration. These changes permitted more complex, flexible and versatile cognitive abilities and social behavior, such as shared intentionality and symbolic articulated language, which, in turn, made possible the formation of larger social groups and cumulative cultural evolution that are characteristic of our species.

RESUMO Esta revisão se propõe a relatar os aspectos mais importantes da singularidade anatômica e funcional do cérebro humano. Para isso, faz-se uma comparação entre o nosso cérebro e os de nossos parentes evolutivos mais próximos (chimpanzés e bonobos) e os ancestrais humanos. Durante a evolução humana ocorreu aumento absoluto do tamanho do cérebro e do número de neurônios corticais cerebrais, maior grau de lateralização funcional e assimetria anatômica cerebral, citoarquitetura cortical mais diversificada e aumento das redes neurais intracorticais e do córtex cerebral para as estruturas subcorticais acompanhada de mudança em direção ao investimento de redes neurais na integração multissensorial e sensório-motora-afetiva-cognitiva. Essas mudanças possibilitaram capacidades cognitivas e comportamentos sociais complexos, flexíveis e versáteis, destacando-se a intencionalidade compartilhada e a linguagem articulada simbólica, que permitiram a formação de grupos sociais maiores e a evolução cultural cumulativa característica de nossa espécie.

Somatic comorbidity and the progression of cognitive impairment.

Background: There are usually multiple factors underlying dementia in old age. Somatic comorbidity is one important element that influences the progression of cognitive impairment. Objective: The goal of this study was to assess the relationship between the progression of cognitive impairment and the presence and severity of comorbidities based on a four-year observation. Material: Out of 128 patients from the Clinic for Outpatients in Gdansk, who were recruited into the study based on the criteria of the Working Group on Mild Cognitive Impairment, a total of 93 participants completed the four-year observation. Only the data from participants who completed the full period of observations were analysed. The mean age of the group was M = 75.93 (SD = 9.43). The level of progression of cognitive impairment was measured using the Clinical Dementia Rating Scale - Sum of Boxes, the severity of comorbidities was measured using the modified Cumulative Illness Rating Scale, and, additionally, at the time of inclusion in the study, participants were assessed using the MMSE scale and the Activity Scale, and sociodemographic data were collected. The Generalized Estimating Equations method was employed to fit a marginal model for analyzing the data collected in a repeated measures design. The tested model elucidated the role of the overall severity of comorbidities in explaining the progression of cognitive impairment, while controlling for everyday activity and basic demographic variables. Results: During the four-year observation, a significant decline in cognitive function (B = 1.86, p < 0.01) was observed in the examined sample. The statistical analysis revealed that individuals with higher overall severity of comorbidities exhibited significantly more pronounced progression of cognitive impairment over time. Regarding particular comorbidities, metabolic diseases were found to be associated with a poorer prognosis (rho = 0.41, p < 0.05). Furthermore, a time physical activity interaction was identified as predicting cognitive impairment, indicating that individuals who were more physically active at the beginning of the study exhibited significantly less pronounced progression of cognitive impairment over the course of the 4 years. Conclusion: This study suggests the important roles of comorbidities and physical activity for the prognosis of mild cognitive impairment.