Present demographic changes demonstrate that the number of elderly people is growing at a frenetic pace. This shift in population consequently results in many social and economic problems, which burden the social and economic systems of countries. The aging process is associated with age-related diseases, the most common of which are dementia and Alzheimer's disease, whose main symptom is a decline in cognitive function, especially memory loss. Unfortunately, it cannot be cured. Therefore, alternative approaches, which are cost-effective, safe, and easy to implement, are being sought in order to delay and prevent cognitive impairment. The purpose of this review was to explore the effect of multidomain lifestyle intervention strategies on the delay and/or prevention of cognitive impairment in healthy older individuals. The methods are based on a literature review of available sources found on the research topic in three acknowledged databases: Web of Science, Scopus, and PubMed. The results of the identified original studies reveal that multidomain lifestyle interventions generate significant effects. In addition, these interventions seem feasible, cost-effective, and engaging. Thus, there is a call for the implementation of effective lifestyle prevention programs, which would involve goal-setting and would focus on the prevention of crucial risk factors threatening the target group of elderly people, who are at risk of cognitive decline and dementia.

• Klíčová slova
• cognitive impairment, elderly people, lifestyle strategies, multidomain intervention, randomized clinical trials,
• MeSH
• cvičení * MeSH
• lidé MeSH
• rizikové faktory MeSH
• zdravé stárnutí * MeSH
• životní styl * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

OBJECTIVES: Nonpharmacologic interventions (NPIs) constitute an important part of treatment for older adults, cover a broad and diverse range of interventions, and have advantages over pharmacologic interventions (eg, limited adverse side effects). However, an unambiguous definition of NPIs is still lacking. Defining NPIs may facilitate research on this topic and enhance comparability of results between studies, and might help to face the challenges of recognition, acceptation, funding, and implementation. Therefore, the aim of this review was to provide an overview and comparison of the definitions of NPIs used in the current literature on older adults. DESIGN: A systematic review was performed to provide an overview of the definitions of NPIs that are used in the current literature on older populations and to organize the characteristics involved in the definitions. SETTING AND PARTICIPANTS: People ≥60 years of age were included, not limited to a specific setting. METHODS: A systematic search was performed in the following 5 databases: PubMed, Embase, Clarivate Analytics/Web of Science Core Collection, Cumulative Index to Nursing and Allied Health Literature, and Wiley/Cochrane Library. The time frame within the databases was from inception to December 4, 2023. Review articles, editorials and consensus papers were included. RESULTS: We included 28 articles. We organized the definitions of NPI according to 4 different aspects: types of interventions involved, target population, goals the interventions addressed, and requirements of the interventions. Definitions in the current literature can generally be divided into 2 groups: NPIs described as not involving medication, and more elaborated multidomain definitions. Based on the results, we formulated criteria for types of interventions that can be considered an NPI. CONCLUSIONS AND IMPLICATIONS: Using current descriptions and characteristics, elements for a new definition for NPIs were proposed. To improve research in this field, consensus needs to be reached regarding elements covered by a definition of NPIs.

• Klíčová slova
• Older people, care for older persons, nondrug interventions, nonpharmacologic interventions,
• MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• terapie * metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled MeSH

The number of people living with dementia and Alzheimer's disease is growing rapidly, making dementia one of the biggest challenges for this century. Many studies have indicated that depression plays an important role in development of dementia, including Alzheimer's disease; depression, especially, during the late life may either increase the risk of dementia or even being its prodromal stage. Despite a notably large number of carried observational studies and/or clinical trials, the association between the late life depression and dementia remains, due to the complexity of their relationship, still unclear. Moreover, during past two decades multiple other (non-)modifiable risk and possibly protective factors such as the hypertension, social engagement, obesity, level of education or physical (in)activity have been identified and their relationship with the risk for development of dementia and Alzheimer's disease has been extensively studied. It has been proposed that to understand mechanisms of dementia and Alzheimer's disease pathogeneses require their multifactorial nature represented by these multiple factors to be considered. In this review, we first summarize the recent literature findings on roles of the late life depression and the other known (non-)modifiable risk and possibly protective factors in development of dementia and Alzheimer's disease. Then, we provide evidences supporting hypotheses that (i) depressive syndromes in late life may indicate the prodromal stage of dementia (Alzheimer's disease) and, (ii) the interplay among the multiple (non-)modifiable risk and protective factors should be considered to gain a better understanding of dementia and Alzheimer's disease pathogeneses. We also discuss the evidences of recently established interventions considered to prevent or delay the prodromes of dementia and provide the prospective future directions in prevention and treatment of dementia and Alzheimer's disease using both the single-domain and multidomain interventions.

• Klíčová slova
• Alzheimer’s disease, apolipoprotein E, dementia, late life depression, obesity, social engagement, substance abuse, testosterone,
• MeSH
• Alzheimerova nemoc * komplikace   epidemiologie   terapie   MeSH
• demence * komplikace   epidemiologie   terapie   MeSH
• deprese * epidemiologie   prevence a kontrola   MeSH
• lidé MeSH
• ochranné faktory MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Transcranial direct current stimulation combined with cognitive training (tDCS-cog) represents a promising approach to combat cognitive decline among healthy older adults and patients with mild cognitive impairment (MCI). In this 5-day-long double-blinded randomized trial, we investigated the impact of intensified tDCS-cog protocol involving two trains of stimulation per day on working memory (WM) enhancement in 35 amnestic and multidomain amnestic MCI patients. Specifically, we focused to improve WM tasks relying on top-down attentional control and hypothesized that intensified tDCS would enhance performance of visual object matching task (VOMT) immediately after the stimulation regimen and at a 1-month follow-up. Secondarily, we explored whether the stimulation would augment online visual working memory training. Using fMRI, we aimed to elucidate the neural mechanisms underlying the intervention effects by analyzing BOLD activations during VOMT. Our main finding revealed no superior after-effects of tDCS-cog over the sham on VOMT among individuals with MCI as indicated by insignificant immediate and long-lasting after-effects. Additionally, the tDCS-cog did not enhance online training as predicted. The fMRI analysis revealed brain activity alterations in right insula that may be linked to tDCS-cog intervention. In the study we discuss the insignificant behavioral results in the context of the current evidence in tDCS parameter space and opening the discussion of possible interference between trained cognitive tasks.

• MeSH
• dorsolaterální prefrontální kortex MeSH
• dvojitá slepá metoda MeSH
• kognitivní dysfunkce * terapie   MeSH
• krátkodobá paměť fyziologie   MeSH
• lidé MeSH
• mozek diagnostické zobrazování   MeSH
• prefrontální mozková kůra fyziologie   MeSH
• přímá transkraniální stimulace mozku * metody   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

Alzheimer disease (AD) is a life-limiting neurodegenerative disorder that disproportionately affects women. Indeed, sex and gender are emerging as crucial modifiers of diagnostic and therapeutic pathways in AD. This Review provides an overview of the interactions of sex and gender with important developments in AD and offers insights into priorities for future research to facilitate the development and implementation of personalized approaches in the shifting paradigm of AD care. In particular, this Review focuses on the influence of sex and gender on important advances in the treatment and diagnosis of AD, including disease-modifying therapies, fluid-based biomarkers, cognitive assessment tools and multidomain lifestyle interventional studies.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Apoptosis signal-regulating kinase 1 (ASK1) is a crucial stress sensor, directing cells toward apoptosis, differentiation, and senescence via the p38 and JNK signaling pathways. ASK1 dysregulation has been associated with cancer and inflammatory, cardiovascular, and neurodegenerative diseases, among others. However, our limited knowledge of the underlying structural mechanism of ASK1 regulation hampers our ability to target this member of the MAP3K protein family towards developing therapeutic interventions for these disorders. Nevertheless, as a multidomain Ser/Thr protein kinase, ASK1 is regulated by a complex mechanism involving dimerization and interactions with several other proteins, including thioredoxin 1 (TRX1). Thus, the present study aims at structurally characterizing ASK1 and its complex with TRX1 using several biophysical techniques. As shown by cryo-EM analysis, in a state close to its active form, ASK1 is a compact and asymmetric dimer, which enables extensive interdomain and interchain interactions. These interactions stabilize the active conformation of the ASK1 kinase domain. In turn, TRX1 functions as a negative allosteric effector of ASK1, modifying the structure of the TRX1-binding domain and changing its interaction with the tetratricopeptide repeats domain. Consequently, TRX1 reduces access to the activation segment of the kinase domain. Overall, our findings not only clarify the role of ASK1 dimerization and inter-domain contacts but also provide key mechanistic insights into its regulation, thereby highlighting the potential of ASK1 protein-protein interactions as targets for anti-inflammatory therapy.

• Klíčová slova
• ASK1, MAP3K, MAPK signaling, biochemistry, chemical biology, human, molecular biophysics, protein kinase, structural biology, thioredoxin,
• MeSH
• apoptóza MeSH
• biofyzika MeSH
• elektronová kryomikroskopie MeSH
• MAP kinasa-kinasa-kinasa 5 * MeSH
• thioredoxiny * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• MAP kinasa-kinasa-kinasa 5 * MeSH
• thioredoxiny * MeSH