Effects of home-based and telerehabilitation exercise on mental and physical health, and disease cost in people with Alzheimer's disease: A meta-analysis.

BACKGROUND: Alzheimer's disease (AD) is a very disabling long-term disease that requires continuous regular care. A cost-effective and sustainable means of such care may be physical activity or exercise delivered at home or through telerehabilitation. The aim of this study is to determine the effects of home-based or telerehabilitation exercise in people with AD. METHOD: PubMED, Embase, Web of Science (WoS), PEDro, and CENTRAL were searched for randomized controlled trials until January 2024. The data extracted include the characteristics of the participants, the interventions used for both experimental and the control groups, the baseline, post-intervention and follow-up mean and standard deviation values on the outcomes assessed and the findings of the included studies. Cochrane risks of bias assessment tool and PEDro scale were used to assess the risks of bias and methodological quality of the studies. The results were analyzed using narrative and quantitative syntheses. RESULT: Eleven articles from nine studies (n=550) were included in the study. The results showed that, only global cognitive function (SMD = 0.72, 95% CI = 0.19-1.25, p=0.007), neuropsychiatric symptom (MD = -5.28, 95% CI =-6.22 to -4.34, p<0.0001) and ADL (SMD =3.12, 95% CI =0.11-6.13, p=0.04) improved significantly higher in the experimental group post-intervention. At follow-up, the significant difference was maintained only in neuropsychiatric symptoms (MD =-6.20, 95% CI =-7.17 to -5.23, p<0.0001). CONCLUSION: There is a low evidence on the effects of home-based physical activity or exercise on global cognitive function, neuropsychiatric symptoms and ADL.

Socially Assistive Robots for patients with Alzheimer's Disease: A scoping review.

BACKGROUND: The most common form of dementia, Alzheimer's Disease (AD), is challenging for both those affected as well as for their care providers, and caregivers. Socially assistive robots (SARs) offer promising supportive care to assist in the complex management associated with AD. OBJECTIVES: To conduct a scoping review of published articles that proposed, discussed, developed or tested SAR for interacting with AD patients. METHODS: We performed a scoping review informed by the methodological framework of Arksey and O'Malley and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist for reporting the results. At the identification stage, an information specialist performed a comprehensive search of 8 electronic databases from the date of inception until January 2022 in eight bibliographic databases. The inclusion criteria were all populations who recive or provide care for AD, all interventions using SAR for AD and our outcomes of inteerst were any outcome related to AD patients or care providers or caregivers. All study types published in the English language were included. RESULTS: After deduplication, 1251 articles were screened. Titles and abstracts screening resulted to 252 articles. Full-text review retained 125 included articles, with 72 focusing on daily life support, 46 on cognitive therapy, and 7 on cognitive assessment. CONCLUSION: We conducted a comprehensive scoping review emphasizing on the interaction of SAR with AD patients, with a specific focus on daily life support, cognitive assessment, and cognitive therapy. We discussed our findings' pertinence relative to specific populations, interventions, and outcomes of human-SAR interaction on users and identified current knowledge gaps in SARs for AD patients.

Use of conditional-discrimination training in remembering relatives in a man with Alzheimer’s Disease

In this study, a 72-year-old man with Alzheimer’s disease and a Mini-Mental Status (MMS) score of 25 participated. The participant was presented for class-formation sorting tests and conditionaldiscrimination training sequences and tests with portraits of close family members, their names, and family relationships as stimuli. The purpose of the study was to identify intact relations between stimuli, stimulus control issues and thereafter reestablish relations between stimuli. In the sorting tests, intact and weakened stimulus relations were identified. In addition, the results showed how correct stimulus control was reestablished after tailoring the conditional-discrimination training after the participant had shown systematical incorrect responding to some of the presented stimuli. Key words: conditional discrimination, matching-to-sample, dementia, sorting test, stimulus control (AU)

Regular Physical Exercise Modulates Iron Homeostasis in the 5xFAD Mouse Model of Alzheimer's Disease.

Dysregulation of brain iron metabolism is one of the pathological features of aging and Alzheimer's disease (AD), a neurodegenerative disease characterized by progressive memory loss and cognitive impairment. While physical inactivity is one of the risk factors for AD and regular exercise improves cognitive function and reduces pathology associated with AD, the underlying mechanisms remain unclear. The purpose of the study is to explore the effect of regular physical exercise on modulation of iron homeostasis in the brain and periphery of the 5xFAD mouse model of AD. By using inductively coupled plasma mass spectrometry and a variety of biochemical techniques, we measured total iron content and level of proteins essential in iron homeostasis in the brain and skeletal muscles of sedentary and exercised mice. Long-term voluntary running induced redistribution of iron resulted in altered iron metabolism and trafficking in the brain and increased iron content in skeletal muscle. Exercise reduced levels of cortical hepcidin, a key regulator of iron homeostasis, coupled with interleukin-6 (IL-6) decrease in cortex and plasma. We propose that regular exercise induces a reduction of hepcidin in the brain, possibly via the IL-6/STAT3/JAK1 pathway. These findings indicate that regular exercise modulates iron homeostasis in both wild-type and AD mice.

Physical Exercise and Alzheimer's Disease: Effects on Pathophysiological Molecular Pathways of the Disease.

Alzheimer's disease (AD), the most common form of neurodegenerative dementia in adults worldwide, is a multifactorial and heterogeneous disorder characterized by the interaction of genetic and epigenetic factors and the dysregulation of numerous intracellular signaling and cellular/molecular pathways. The introduction of the systems biology framework is revolutionizing the study of complex diseases by allowing the identification and integration of cellular/molecular pathways and networks of interaction. Here, we reviewed the relationship between physical activity and the next pathophysiological processes involved in the risk of developing AD, based on some crucial molecular pathways and biological process dysregulated in AD: (1) Immune system and inflammation; (2) Endothelial function and cerebrovascular insufficiency; (3) Apoptosis and cell death; (4) Intercellular communication; (5) Metabolism, oxidative stress and neurotoxicity; (6) DNA damage and repair; (7) Cytoskeleton and membrane proteins; (8) Synaptic plasticity. Moreover, we highlighted the increasingly relevant role played by advanced neuroimaging technologies, including structural/functional magnetic resonance imaging, diffusion tensor imaging, and arterial spin labelling, in exploring the link between AD and physical exercise. Regular physical exercise seems to have a protective effect against AD by inhibiting different pathophysiological molecular pathways implicated in AD.

The Cognition and Flow Study: A Feasibility Randomized Controlled Trial of the Effects of Cognitive Training on Cerebral Blood Flow.

BACKGROUND: Cognitive training (CT) has demonstrated benefits for healthy older adults (HG) and mild cognitive impairment (MCI), but the effects on vascular function are unknown. OBJECTIVE: This is a feasibility trial investigating the effects of CT on cerebral blood flow velocity (CBFv). METHODS: Twenty HG, 24 with Alzheimer's disease (AD), and 12 with MCI were randomized to 12 weeks of multi-domain CT or control. Outcomes included: cognition (Addenbrooke's Cognitive Examination III), mood, quality of life (QoL), physical, and neurovascular function (transcranial Doppler ultrasonography measured task activation of CBFv responses). Data are presented as mean difference (MD) and 95% confidence interval (CI). RESULTS: 47 participants completed the trial. There were three dropouts from the training arm in the AD group, and one in the HG group. The intervention was acceptable and feasible to the majority of participants with a high completion rate (89%). The dropout rate was higher among participants with dementia. Few changes were identified on secondary analyses, but QoL was significantly improved in HG post-training (MD: 4.83 [95% CI: 1.13, 8.54]). CBFv response rate was not significantly different in HG (MD: 1.84 [95% CI: -4.81, 1.12]), but a significant increase was seen in the patient group (MD: 1.79 [95% CI: 0.005, 3.58]), requiring sample sizes of 56 and 84 participants respectively for a fully-powered trial. CONCLUSION: A 12-week CT program was acceptable and feasible in HG, AD, and MCI. CT may be associated with alterations in vascular physiology which require further investigation in an appropriately powered randomized controlled trial.

The Fragility of Temporal Memory in Alzheimer's Disease.

BACKGROUND: Although episodic memory impairment is one of the hallmarks of Alzheimer's disease (AD), the relative decline in the components of episodic memory (What, Where, and When) and the effects of cognitive training on each of them are still unknown. OBJECTIVE: We aimed to independently assess the impairment in each component of episodic memory in early to moderate AD and address whether it can be enhanced through active, spatiotemporal episodic training. METHODS: A non-verbal scene-based episodic memory task was developed to assess the ability to remember What, Where, and When information. Experiment 1 tested whether this task can differentiate AD subjects (N = 16) from healthy controls (N = 16). In Experiment 2, 13 AD subjects underwent 16 training sessions, followed by a re-administration of the scene-based memory task. Experiment 3 tested 42 healthy older adults and 51 younger adults on the same task to investigate the effects of normal aging. RESULTS: Of the three components, When memory had the highest predictive power in distinguishing AD from normal aging. Following training of AD subjects, only Where memory improved. Only What memory revealed a significant decline in healthy subjects from 65-85 years of age. CONCLUSION: These findings shed new light on the importance of the temporal component of episodic memory as a behavioral marker of AD. The selective improvement of spatial but not temporal memory through training further demonstrates the fragility of temporal memory even in early AD. Neuroscientific research is needed to distinguish whether the Where component was enhanced by improvements in hippocampal spatial representation or by other compensatory mechanisms.

Stressor-Oriented MUlticomponent Intervention and the WeLl-Being of Patients with Alzheimer's Disease: A Randomized Controlled Trial (SOUL-P).

BACKGROUND: Patients with Alzheimer's disease (AD) experience various stressors that negatively impact well-being. Most studies have, however, small effect size and are limited by the experiences of severe patients. Therefore, we conducted a single-blind, randomized controlled trial, which has included patients at different stages. OBJECTIVE: The stressor-oriented multicomponent program was designed as an intervention for AD patients to enhance well-being. METHODS: Patients were randomly assigned to control or SOUL-P conditions according to disease severity. The SOUL-P group received 15 intensive sessions over 6 months and 6 maintenance sessions over a 6-month follow-up by a multidisciplinary team comprising psychologists, occupational therapists, and community nurses. The control group received a similar number of sessions by community nurses. Stress-related outcomes (primary stressors and well-being outcomes) were obtained from in-person baseline and follow-up interviews conducted at 6- and 12-months post-baseline. A treatment compliance survey was conducted at the intervention endpoint for patients. RESULTS: Of the 863 patients screened, 218 (25.3%) were eligible. At 6 months, compared to controls, SOUL-P patients had improved quality of life (QoL) (p < 0.001; Cohen d = 0.56), depression (p = 0.020; Cohen d = -0.33), neurobehavioral symptoms (p = 0.034; Cohen d = -0.30), perceived stress (p = 0.030; Cohen d = -0.31), and family conflict (p = 0.026; Cohen d = -0.32). QoL, depression, perceived stress, and family conflict were still significantly different at 12 months. Most patients were satisfied with SOUL-P, while caregivers in the SOUL-P group reported overloading tasks. CONCLUSION: SOUL-P may reduce perceived stress and improve psychological outcomes in AD patients. Stressor-based interventions, patient-oriented goals, and a multidisciplinary team are essential features for a successful SOUL-P.

The Effects of a Recollection-Based Occupational Therapy Program of Alzheimer's Disease: A Randomized Controlled Trial.

Considering the high socioeconomic costs related to the increasing number of dementia patients and their poor quality of life and that of their families, it is important to identify the condition early on and provide an appropriate intervention. This study organized a recollection-based occupational therapy program: a nonpharmacological intervention consisting of five categories of activities (physical, horticultural, musical, art, and instrumental activity of daily living; IADL) and applied it to those having a mild stage of Alzheimer's disease. The experimental group participated in a total of 24 sessions--five times per week for one hour per session--while the control group took part in regular activities offered by the existing facilities. The experimental group presented improved cognitive functions, reduced depression, and enhanced quality of life; the two groups showed a statistically significant difference in every category. This study is meaningful in that it made a cognitive stimulation program concerning five different categories, implemented it for people suffering mild dementia, and confirmed positive outcomes. If a systemic version of the program is offered in dementia care facilities, it is expected to make a considerable contribution to the care of dementia patients.

[Sensorimotor synchronization and non-verbal behaviors in Alzheimer's disease: the influence of social and musical context]. / Synchronisation sensorimotrice et comportements non verbaux dans la maladie d'Alzheimer : l'influence du contexte social et musical.

BACKGROUND: Considering the limited efficacy of pharmacological treatments, the use of musical interventions as non-drug treatment for patients with Alzheimer's disease are strongly recommended. Musical interventions seem to improve the socio-emotional and cognitive functioning of these patients, with benefits increasing when patients are engaged at the motor level. OBJECTIVE: Our study evaluates the factors that may influence patients' socio-emotional and motor engagement during musical activities, and measures their sensorimotor synchronization (SMS) abilities. METHODS: Each participant was asked to tap with a metronomic or a musical rhythm, in the presence of a musician who performed the task with them. The presence of the musician was real (live condition) or virtual (video condition). Two tempi were tested: a slow tempo (inter-onset interval of 800 ms) and a fast tempo (inter-onset interval of 667 ms). RESULTS: Patients spontaneously produced more rhythmic movements in response to the music than to the metronome. However, the consistency and accuracy of sensorimotor synchronization were better with the metronome than with the music, and also better in video than in live condition. These effects were modulated by the tempo of the auditory sequences. CONCLUSION: These results confirm the importance of the musical context and social interactions on these different performances. By evaluating in parallel the hand sensorimotor synchronization, spontaneous motor and socio-emotional behaviors with quantitative and controlled measurements, this study validates a multimodal approach to evaluate the patients' engagement in a musical task. These initial results open up promising application prospects while providing clinicians and researchers a rigorous methodology for understanding the factors that are at the origin of the therapeutic benefits of musical activities on the behavior and well-being of patients and their caregivers.

The Role of the Family in the Care of Alzheimer Patients.

According to the World Health Organisation (WHO 2002), people's life expectancy worldwide is continuously growing, and on the one hand, that is one of the greatest triumphs of humanity to date. But at the same time, it is also one of the most important challenges as the aging of the population raises economic and social requirements in all countries.

Spaced Retrieval and Episodic Memory Training in Alzheimer's Disease.

INTRODUCTION: This study replicated and extended the findings from the author's previous pilot study to further explore how a spaced retrieval (SR) memory training program might be effectively applied to help persons with Alzheimer's disease (AD)  improve both short- and long-term recall of recent episodic events. METHODS: A quasi-experimental within-subject group study was conducted with 15 participants with a diagnosis of AD. RESULTS: Compared to a control condition, all participants were able to spontaneously recall significantly more specific details about trained events, and their recall was significantly enhanced when they were provided with cues. Although the findings indicated that people with AD were able to encode information during training, recall gains diminished by the end of the maintenance period. DISCUSSION: This study provides evidence that individuals with mild to moderate AD can learn and recall new episodic information through SR training. These findings support the use of SR as an intervention tool to help individuals maintain their functioning in episodic recent memory. However, more research into maintaining the long-term recall of recent episodic events is warranted.

Supporting caregivers of veterans with Alzheimer's disease and traumatic brain injury: study protocol for a randomized controlled trial.

BACKGROUND: Patients with Alzheimer's disease and related dementias (ADRD) and traumatic brain injury (TBI) and their caregivers require cognitive and behavioral symptom management, interdisciplinary care, support for caregivers, and seamless care coordination between providers. Caring for someone with ADRD or TBI is associated with higher rates of psychological morbidity and burden, social isolation, financial hardship, and deterioration of physical health. Tremendous need exists for primary care-based interventions that concurrently address the care needs of dyads and aim to improve care and outcomes for both individuals with ADRD and TBI and their family caregivers. METHODS: The Aging Brain Care Acquiring New Skills While Enhancing Remaining Strengths (ABC ANSWERS) study is a randomized controlled trial that tests the effectiveness of an intervention based on two evidence-based programs that have been developed for and previously tested in populations with ADRD, TBI, stroke, and late-life depression and/or who have survived an intensive care unit stay. This study includes 200 dyads comprised of a veteran with a diagnosis of ADRD or TBI and the veteran's primary informal caregiver. Dyads are randomized to receive the ABC ANSWERS intervention or routine Veterans Health Administration (VHA) primary care with a standardized educational and resource information packet. Data collection occurs at baseline and three follow-up time points (3 months, 6 months, and 12 months). The primary outcome is caregiver quality of life (QoL). A secondary measure for the caregiver is caregiver burden. Secondary measures for both the veteran and caregiver include symptoms of depression and anxiety. DISCUSSION: The ABC ANSWERS intervention integrates common features of an evidence-based collaborative care model for brain health while concurrently attending to the implementation barriers of delivering care and skills to dyads. We hypothesize that caregivers in dyads randomized to the ABC ANSWERS program will experience higher levels of QoL and lower levels of depression, anxiety, dyadic strain, and caregiver burden at 12 months than those receiving usual VHA primary care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03397667. Registered on 12 January 2018.

Caregiver perspectives on a smart home-based socially assistive robot for individuals with Alzheimer's disease and related dementia.

Purpose: Innovative assistive technology can address aging-in-place and caregiving needs of individuals with Alzheimer's disease and related dementia (ADRD). The purpose of this study was to beta-test a novel socially assistive robot (SAR) with a cohort of ADRD caregivers and gather their perspectives on its potential integration in the home context.Methods: The SAR involved a programmable research robot linked with commercially available Internet of things sensors to receive and respond to care recipient's behaviour. Eight caregivers observed the SAR perform two care protocols concerning the care recipient's daily routine and home safety, and then participated in a focus group and phone interview. The researchers used grounded theory and the Unified Theory of Acceptance and Use of Technology as a framework to gather and analyse the data.Results: The caregivers' asserted the potential of the SAR to relieve care burden and envisioned it as a next-generation technology for caregivers. Adoption of the SAR, as an identified theme, was subject to the SAR's navigability, care recipient engagement, adaptability, humanoid features, and interface design. In contrast, barriers leading to potential rejection were technological complexity, system failure, exasperation of burden, and failure to address digital divide.Conclusion: From a broader outlook, success of SARs as a home-health technology for ADRD is reliant on the timing of their integration, commercial viability, funding provisions, and their bonding with the care recipient. Long-term research in the home settings is required to verify the usability and impact of SARs in mediating aging-in-place of individuals with ADRD.IMPLICATIONS FOR REHABILITATIONSocially assistive robots (SARs), an emerging domain of assistive technology, are projected to have a crucial role in supporting aging-in-place of individuals with Alzheimer's disease and related dementia (ADRD).Caregivers of individuals with ADRD who observed and interacted with a novel SAR asserted their acceptance of the technology as well as its scope and feasibility for the upcoming generation of caregivers.Navigability, care recipient engagement, adaptability, humanoid features, and interface design were stated to be critical factors for SAR's acceptance by caregiver and care recipient dyads.In contrast, technological complexity, system failure, exasperation of burden, and failure to address digital divide are detrimental to SAR's adoption.Several design and implementation requirements must be considered towards the full-scale development and deployment of the SARs in the home context.

Seis semanas de ejercicio físico mejoran la capacidad funcional y la composición corporal en pacientes con Alzheimer / Six weeks of physical exercise improve functional capacity and body composition in Alzheimer's patients

OBJETIVO: El propósito de este estudio fue conocer si seis semanas de ejercicio físico podrían mejorar la condición física y la composición corporal en personas diagnosticadas de Alzheimer. MÉTODO: Se llevó a cabo un programa de entrenamiento donde 13 individuos (78,5±6,4 años) diagnosticados de Alzheimer, realizaron dos sesiones semanales de entrenamiento, en una de ellas se hizo ejercicio aeróbico en cicloergómetro y en la otra, trabajo de equilibrio, fuerza y coordinación. RESULTADOS: Encontramos cambios significativos en la composición corporal (disminución de masa grasa, y aumento de masa muscular), y en la capacidad funcional, reflejados por la mejora en el test de "sentarse y levantarse de una silla", el test de "levantarse, caminar y volverse a sentar", en la escala de Berg y en las mediciones de la velocidad de la marcha. Las mediciones de dinamometría manual se mantuvieron constantes o mejoraron levemente sin significación suficiente. CONCLUSIÓN: La combinación de entrenamiento aeróbico con ejercicios de fuerza, equilibrio y coordinación, dos veces por semana, durante seis semanas en personas con Alzheimer, podría mejorar la capacidad funcional y la composición corporal. Sin embargo, no parece claro que este protocolo de entrenamiento permita mejorar la fuerza de prensión manual

OBJECTIVE: The purpose of this study was to know if six weeks of physical exercise allowed to improve physical condition and body composition in people diagnosed with Alzheimer's. METHOD: A training program was carried out where 13 individuals (78.5 ± 6.4 years) diagnosed with Alzheimer's disease, performed two weekly training sessions, in one of them aerobic exercise was performed in a cycle ergometer and in the other, they performed balance, strength and coordination exercises. RESULTS: We found significant changes in body composition (decrease in fat mass, and increase in muscle mass), and in functional capacity, reflected by the improvement in the "sitting and getting up from a chair" test, the "getting up," walk and sit down again ", on the Berg scale and on gait speed measurements. The manual dynamometry measurements remained constant or improved slightly without sufficient significance. CONCLUSION: The combination of aerobic training with strength, balance and coordination exercises, twice a week, for six weeks in people with Alzheimer's, could improve functional capacity and body composition. However, it is not clear that this training protocol allows to improve manual grip strength

Effects of the cognitive stimulation therapy based on Roy's adaptation model on Alzheimer's patients' cognitive functions, coping-adaptation skills, and quality of life: A randomized controlled trial.

PURPOSE: This study aims to specify the effects of Cognitive Stimulation Therapy based on Roy's adaptation model (RAM) on Alzheimer's patients' coping and adaptation skills, cognitive functions, and quality of life (QOL). DESIGN AND METHODS: This is an experimental and randomized controlled trial. Patients in the experimental group received cognitive stimulation therapy (CST) based on RAM. FINDINGS: The cognitive function level of the experimental group was found to be higher than that of the control group at the end of the measurements (performed in the 7th week); the difference was found to be statistically significant (P < .05). In the experimental group, dimensions of troubleshooting and focusing, making physical decisions, attention processing, systematizing, learning, and establishing relationships were found to be better than those of the control group after the application, and the difference was found to be statistically significant (P < .05). However, after the application, QOL of the experimental group was found to be better than that of the control group following the measurements; the difference was found to be statistically significant (P < .05). PRACTICE IMPLICATIONS: Psychiatric nurses should evaluate the patients using Standardize Mini-Mental Test Examination before applying RAM-based CST, and they should apply CST to early- and mid-stage Alzheimer's disease (AD) patients at the end of the evaluation and work with groups consisting of six persons at most. Since the cognitive functions of individuals with AD decline from the first stage, coping-adaptation, and QOL levels will also be affected, so it is recommended to evaluate the cognitive functions, coping-adjustment and QOL levels of individuals before applying RAM-based CST. TRIAL REGISTRATION NUMBER: NCT02229474.

Blood biomarkers as surrogate endpoints of treatment responses to aerobic exercise and cognitive training (ACT) in amnestic mild cognitive impairment: the blood biomarkers study protocol of a randomized controlled trial (the ACT Trial).

BACKGROUND: Alzheimer's disease (AD) is an epidemic with tremendous public health impacts because there are currently no disease-modifying therapeutics. Randomized controlled trials (RCTs) for prevention of AD dementia often use clinical endpoints that take years to manifest (e.g., cognition) or surrogate endpoints that are costly or invasive (e.g., magnetic resonance imaging [MRI]). Blood biomarkers represent a clinically applicable alternative surrogate endpoint for RCTs that would be both cost-effective and minimally invasive, but little is known about their value as surrogate endpoints for treatment responses in the prevention of AD dementia. METHODS: The objective of this study is to investigate blood neuropathological, neurodegenerative, and neurotrophic biomarkers as surrogate endpoints for treatment responses to three interventions in older adults with amnestic mild cognitive impairment (aMCI, a prodromal stage of AD): aerobic exercise, cognitive training, and combined aerobic exercise and cognitive training (ACT). We chose these three sets of biomarkers for their unique mechanistic associations with AD pathology, neurodegeneration and neurogenesis. This study is built on the ACT Trial (1R01AG055469), a single-blinded, multi-site, 2 × 2 factorial phase II RCT that examines the synergistic effects of a 6-month ACT intervention on cognition and MRI biomarkers (AD-signature cortical thickness and hippocampal volume) (n = 128). In this ACT Trial blood biomarkers study, we will enroll 120 ACT Trial participants with aMCI and measure blood biomarkers at baseline and at 3, 6, 12, and 18 months. The goals are to (1) determine the effect of interventions on blood biomarkers over 6 months, (2) evaluate blood biomarkers as surrogate endpoints for predicting cognitive responses to interventions over 18 months, and (3, exploratory) examine blood biomarkers as surrogate endpoints for predicting brain MRI biomarker responses to interventions over 18 months. DISCUSSION: This study aims to identify new blood biomarkers that can track cognitive decline or AD-related brain atrophy among patients with aMCI subjected to a regimen of aerobic exercise and cognitive training. Findings from this study will drive the further use of blood biomarkers in developing effective prevention and treatment strategies for AD dementia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03313895. Registered on 18 October 2017.

Effects of the online computerized cognitive training program BEYNEX on the cognitive tests of individuals with subjective cognitive impairment and Alzheimer's disease on rivastigmine therapy

Background/aim: Clinical trials conducted on the efficacy of computerized cognitive training (CCT) programs have not led to any important breakthroughs. CCT is a safe and inexpensive approach, but its efficacy in patients on rivastigmine therapy has not been evaluated. This study aims to compare effects of CCT and examines rivastigmine to determine whether CCT has any further contributions to make. Materials and methods: Sixty individuals with subjective memory complaint (SCI) and 60 individuals with early stage Alzheimer's dementia (AD) were subjected to the Montreal Cognitive Assessment (MoCA), Cambridge Cognition (CANTAB tests: MOT, PRM, DMS, SWM, PAL, RTI), and Bayer-ADL. After screening patients who were diagnosed with AD, we started rivastigmine patch treatment (10 cm2 = 9.5 mg). The SCI and AD groups were randomly divided, and one each of the SCI and AD groups were accessed using BEYNEX, a web-based program. After a minimum of at least 1200 min of use, the diagnostic tests were repeated. Results: The AD groups' MoCA scores of the BEYNEX-practicing group demonstrated meaningfully increase, whereas they decreased in the control group, and the Bayer-ADL scores indicated improvement in ADL. The CANTAB tests both in SCI and AD and in groups using BEYNEX showed positive improvement in MOT, DMS, and PAL data. Conclusion: This study is a rare example that focuses on both groups with SCI and AD. The efficacy of CCT varies across cognitive domains and shows significant efficacy for AD but small improvements in cognitively healthy older adults. In future studies, integration with a smart learning algorithm may lead to interesting observations on which parameters are more sensitive to change under long-term use of CCT in a large number of subjects.

Changes in brain activation related to visuo-spatial memory after real-time fMRI neurofeedback training in healthy elderly and Alzheimer's disease.

Cognitive decline is a symptom of healthy ageing and Alzheimer's disease. We examined the effect of real-time fMRI based neurofeedback training on visuo-spatial memory and its associated neuronal response. Twelve healthy subjects and nine patients of prodromal Alzheimer's disease were included. The examination spanned five days (T1-T5): T1 contained a neuropsychological pre-test, the encoding of an itinerary and a fMRI-based task related that itinerary. T2-T4 hosted the real-time fMRI neurofeedback training of the parahippocampal gyrus and on T5 a post-test session including encoding of another itinerary and a subsequent fMRI-based task were done. Scores from neuropsychological tests, brain activation and task performance during the fMRI-paradigm were compared between pre and post-test as well as between healthy controls and patients. Behavioural performance in the fMRI-task remained unchanged, while cognitive testing showed improvements in visuo-spatial memory performance. Both groups displayed task-relevant brain activation, which decreased in the right precentral gyrus and left occipital lobe from pre to post-test in controls, but increased in the right occipital lobe, middle frontal gyrus and left frontal lobe in the patient group. While results suggest that the training has affected brain activation differently between controls and patients, there are no pointers towards a behavioural manifestation of these changes. Future research is required on the effects that can be induced using real-time fMRI based neurofeedback training and the required training duration to elicit broad and lasting effects.