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Background@#and purpose: The anti-aging standard forest healing program (ASFHP), which uses forest therapy, was reported to be effective in improving psychological, physical, and cognitive functions. However, there are several challenges to directly visiting the forest. This study aimed to investigate the impact of multi-session ASFHP with forest visit on the mental and physical health of the older people with visits to forest facilities and compared them with those of the same program conducted indoors. @*Methods@#Individuals aged over 70 years with concerns about cognitive decline were recruited at dementia relief centers and divided into control and experimental groups. A total of 33 people were administered ASFHP under the supervision of a forest therapy instructor. The control group stayed indoors, while the experimental group visited a forest healing center and repeated the program 20 weeks. @*Results@#The multiple-session ASFHP positively affected cognitive impairment screening test (CIST) total scores (p=0.002), memory (p=0.014), Korean version of the Repeatable Battery for the Assessment of Neuropsychological Status total scores (p<0.001), immediate recall (p=0.001), visuospatial/construction (p<0.001), language (p<0.001), forest healing standard questionnaire total scores (p=0.002), and cognitive function (p=0.019), regardless of location. The forest visits during the ASFHP showed positive effects on orientation (p=0.035), delayed recall (p=0.042), emotional stability (p=0.032), physical activity (p=0.005), and health (p=0.022). The CIST scores of the memory domain were the strongest indicator of the multiple-session ASFHP effects. @*Conclusions@#The 20-week multi-session ASFHP with forest visit showed effects on cognitive improvement and physical and emotional stability compared to indoor education.
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Objective@#The rising prevalence of mild cognitive impairment (MCI) has spurred interest in innovative cognitive rehabilitation approaches, including serious games. This review summarizes randomized clinical trials (RCTs) exploring the impact of serious games on MCI patients. @*Methods@#We conducted a comprehensive data search using key terms such as “gamification,” “digital therapy,” “cognition,” “mild cognitive impairment,” and “Alzheimer’s disease.” We exclusively considered published RCTs, excluding animal studies and basic research. @*Results@#We identified eight RCTs. Four RCTs examined the effects of serious games using cognitive training for MCI patients. Notably, one study found that non-specific training (Nintendo Wii) significantly enhanced cognitive function and quality of life compared to cognition-specific computer training (CoTras). Among the remaining three RCTs, one specifically demonstrated that personalized serious game-based cognitive training yielded superior cognitive outcomes and reduced depressive symptoms. One RCT focused on serious games incorporating physical exercise, highlighting the effectiveness of kinetic-based exergaming in enhancing overall cognition. Three RCT focused on combined cognitive training and physical exercise. A double-blind RCT revealed that progressive resistance training or standalone physical exercise outperformed the combined approach in improving executive function and global cognition. Two additional RCTs reported positive outcomes, including improvements in cognitive function and electroencephalogram patterns associated with game-based interventions. @*Conclusion@#Serious games, whether focusing on cognitive training, physical exercise, or a combination of both, have potential to improve cognitive and functional outcomes in individuals with MCI. Further research and standardization of protocols are needed to better understand the full potential of serious games in MCI.
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Exercise has long been recognized as an important component of treatment for various diseases. However, the benefits and risks of exercise interventions must be carefully evaluated to ensure the former outweighs the latter. As cancer patients undergo diverse treatment modalities with distinct objectives, a systematic approach partitioning the cancer journey into distinct phases is necessary to inform tailored exercise prescriptions. This narrative review summarizes exercise benefits and mechanisms for cancer patients and survivors across four distinct survivorship periods—before surgery, after surgery and before adjuvant treatment, during nonsurgical treatment (adjuvant and neoadjuvant), and during extended survival. In summary, exercise reduces the risks of complications and declines in physical functioning while improving fatigue, quality of life, and the ability to manage treatment effects. Although additional research is warranted, existing evidence is sufficient to integrate exercise into clinical oncology practice and cancer survivorship programs.
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Objective@#We aimed to create an efficient and valid predicting model which can estimate individuals’ brain age by quantifying their regional brain volumes. @*Methods@#A total of 2,560 structural brain magnetic resonance imaging (MRI) scans, along with demographic and clinical data, were obtained. Pretrained deep-learning models were employed to automatically segment the MRI data, which enabled fast calculation of regional brain volumes. Brain age gaps for each subject were estimated using volumetric values from predefined 12 regions of interest (ROIs): bilateral frontal, parietal, occipital, and temporal lobes, as well as bilateral hippocampus and lateral ventricles. A larger weight was given to the ROIs having a larger mean volumetric difference between the cognitively unimpaired (CU) and cognitively impaired group including mild cognitive impairment (MCI), and dementia groups. The brain age was predicted by adding or subtracting the brain age gap to the chronological age according to the presence or absence of the atrophy region. @*Results@#The study showed significant differences in brain age gaps among CU, MCI, and dementia groups. Furthermore, the brain age gaps exhibited significant correlations with education level and measures of cognitive function, including the clinical dementia rating sum-of-boxes and the Korean version of the Mini-Mental State Examination. @*Conclusion@#The brain age that we developed enabled fast and efficient brain age calculations, and it also reflected individual’s cognitive function and cognitive reserve. Thus, our study suggested that the brain age might be an important marker of brain health that can be used effectively in real clinical settings.
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Objective@#Cognitive reserve has emerged as a concept to explain the variable expression of clinical symptoms in the pathology of Alzheimer’s disease (AD). The association between years of education, a proxy of cognitive reserve, and resting-state functional connectivity (rFC), a representative intermediate phenotype, has not been explored in the preclinical phase, considering risk factors for AD. We aimed to evaluate whether the relationship between years of education and rFC in cognitively preserved older adults differs depending on amyloid-beta deposition and APOE ε4 carrier status as effect modifiers. @*Methods@#A total of 121 participants underwent functional magnetic resonance imaging, [ 18F] flutemetamol positron emission tomography-computed tomography, APOE genotyping, and a neuropsychological battery. Potential interactions between years of education and AD risk factors for rFC of AD-vulnerable neural networks were assessed with wholebrain voxel-wise analysis. @*Results@#We found a significant education years-by-APOE ε4 carrier status interaction for the rFC from the seed region of the central executive (CEN) and dorsal attention networks. Moreover, there was a significant interaction of rFC between right superior occipital gyrus and the CEN seed region by APOE ε4 carrier status for memory performances and overall cognitive function. @*Conclusion@#In preclinical APOE ε4 carriers, higher years of education were associated with higher rFC of the AD vulnerable network, but this contributed to lower cognitive function. These results contribute to a deeper understanding of the impact of cognitive reserve on sensitive functional intermediate phenotypic markers in the preclinical phase of AD.
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Background@#and Purpose: Dementia subtypes, including Alzheimer’s dementia (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD), pose diagnostic challenges. This review examines the effectiveness of 18 F-Fluorodeoxyglucose Positron Emission Tomography ( 18 F-FDG PET) in differentiating these subtypes for precise treatment and management. @*Methods@#A systematic review following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was conducted using databases like PubMed and Embase to identify studies on the diagnostic utility of 18 F-FDG PET in dementia. The search included studies up to November 16, 2022, focusing on peer-reviewed journals and applying the goldstandard clinical diagnosis for dementia subtypes. @*Results@#From 12,815 articles, 14 were selected for final analysis. For AD versus FTD, the sensitivity was 0.96 (95% confidence interval [CI], 0.88–0.98) and specificity was 0.84 (95% CI, 0.70–0.92). In the case of AD versus DLB, 18F-FDG PET showed a sensitivity of 0.93 (95% CI 0.88-0.98) and specificity of 0.92 (95% CI, 0.70–0.92). Lastly, when differentiating AD from non-AD dementias, the sensitivity was 0.86 (95% CI, 0.80–0.91) and the specificity was 0.88 (95% CI, 0.80–0.91). The studies mostly used case-control designs with visual and quantitative assessments. @*Conclusions@#18 F-FDG PET exhibits high sensitivity and specificity in differentiating dementia subtypes, particularly AD, FTD, and DLB. This method, while not a standalone diagnostic tool, significantly enhances diagnostic accuracy in uncertain cases, complementing clinical assessments and structural imaging.
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Objective@#Apolipoprotein E (APOE) gene is known to influence cerebral functional connectivity (FC) in Alzheimer’s disease continuum. We investigated association between APOE allotypes and FC, structural connectivity, and cortical thickness in amyloid-PET negative cognitive normal older adults (CN). @*Methods@#A total of 188 CN (37 had ε2/ε2 or ε2/ε3 [ε2 group], 113 had ε3/ε3 [ε3 group], and 38 had ε3/ε4 or ε4/ε4 [ε4 group]) were recruited. Voxel-based morphometry and cortical thickness analysis were used to investigate differences in cortical thickness between three APOE allotypes. To investigate integrity of structural connectivity, we analyzed diffusion weighted imaging using fractional anisotropy and mean diffusivity. In terms of FC, differences of FC in default mode network (DMN) among APOE allotypes were measured using functional magnetic resonance imaging. @*Results@#There were no significant differences in age, sex, education, cerebral beta-amyloid (Aβ) deposition severity, or neuropsychological profiles. No significant differences were found in cortical thickness and structural connectivity among the APOE allotypes. However, FC within the DMN was significantly lower in ε4 and ε2 carriers compared to ε3 homozygotes. @*Conclusion@#This study suggests that both ε4 and ε2 exhibit APOE-associated DMN FC changes before Aβ deposition, structural changes, and neurodegeneration.
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Objective@#Granulocyte colony-stimulating factor (G-CSF) is a growth factor used to regulate the mobilization of bone marrow progenitor cells and has been shown to promote brain repair and reduce inflammation. This study aimed to investigate the pro-cognitive and neuroplastic effects of G-CSF in healthy adults. @*Methods@#Sixteen healthy adults or donors of hematopoietic stem cell transplantation received G-CSF injections for 5 consecutive days, and their blood samples were collected before, immediately after, and 3 weeks after the G-CSF injections. Twelve subjects underwent neuropsychological testing before and 12 weeks after the G-CSF injections. @*Results@#The study found that G-CSF administration resulted in significant improvements in cognitive function, as measured by the Rey– Osterrieth Complex Figure test for immediate recall, delayed recall, and recognition score at 12 weeks after the injections. The blood levels of brain-derived neurotrophic factor, interleukin-4, and interleukin-8 were significantly increased immediately after the injections and returned to baseline levels after 3 weeks. There was no significant change in the plasma level of Multimer Detection System-oligomerized amyloid beta. @*Conclusion@#Our results might suggest that G-CSF has neuroplastic and pro-cognitive effects in healthy adults. However, further study containing a larger sample size is needed to confirm our findings.
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Objective@#We aimed to evaluate the impact of interaction between APOE ε4 carrier status and body composition measurements on intra- and inter-regional functional connectivity (FC) in mild cognitive impairment (MCI) patients with Aβ deposition. @*Methods@#MCI patients with and without APOE ε4 allele (carrier, n=86; non-carrier, n=95) underwent neuropsychological battery, resting-state functional magnetic resonance imaging scans, positron emission tomography scans with [18 F]flutemetamol, and bioelectrical impedance analysis for measuring body composition. We employed a priori defined regions of interest to investigate the intra- and inter-network FC profiles of default mode network (DMN), central executive network (CEN), and salience network. @*Results@#There was a significant interaction of APOE ε4 carrier status with body fat mass index, visceral fat area, and waist-hip circumference ratio for inter-network FC between DMN and CEN, contributing higher fat-related body composition measurements in the APOE ε4 carrier with lower DMN-CEN FC. @*Conclusion@#The present results highlight the detrimental effect of APOE ε4 carrier status on the associations between the fat-related body composition measurements and FC in the MCI patients with Aβ accumulation.
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Objective@#Despite a high prevalence of dementia in older adults hospitalized with severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2), or so called COVID-19, research investigating association between preexisting diagnoses of dementia and prognosis of COVID-19 is scarce. We aimed to investigate treatment outcome of patients with dementia after COVID-19. @*Methods@#We explored a nationwide cohort with a total of 2,800 subjects older than 50 years who were diagnosed with COVID-19 between January and April 2020. Among them, 223 patients had underlying dementia (dementia group). We matched 1:1 for each dementia- non-dementia group pair yielding 223 patients without dementia (no dementia group) using propensity score matching. @*Results@#Mortality rate after COVID-19 was higher in dementia group than in no dementia group (33.6% vs. 20.2%, p=0.002). Dementia group had higher proportion of patients requiring invasive ventilatory support than no dementia group (34.1% vs. 22.0%, p=0.006). Multivariable analysis showed that dementia group had a higher risk of mortality than no dementia group (odds ratio=3.05, p<0.001). We also found that patients in dementia group had a higher risk of needing invasive ventilatory support than those in no dementia group. @*Conclusion@#Our results suggest that system including strengthen quarantines are required for patients with dementia during the COVID- 19 pandemic.
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Objective@#Despite a high prevalence of dementia in older adults hospitalized with severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2), or so called COVID-19, research investigating association between preexisting diagnoses of dementia and prognosis of COVID-19 is scarce. We aimed to investigate treatment outcome of patients with dementia after COVID-19. @*Methods@#We explored a nationwide cohort with a total of 2,800 subjects older than 50 years who were diagnosed with COVID-19 between January and April 2020. Among them, 223 patients had underlying dementia (dementia group). We matched 1:1 for each dementia- non-dementia group pair yielding 223 patients without dementia (no dementia group) using propensity score matching. @*Results@#Mortality rate after COVID-19 was higher in dementia group than in no dementia group (33.6% vs. 20.2%, p=0.002). Dementia group had higher proportion of patients requiring invasive ventilatory support than no dementia group (34.1% vs. 22.0%, p=0.006). Multivariable analysis showed that dementia group had a higher risk of mortality than no dementia group (odds ratio=3.05, p<0.001). We also found that patients in dementia group had a higher risk of needing invasive ventilatory support than those in no dementia group. @*Conclusion@#Our results suggest that system including strengthen quarantines are required for patients with dementia during the COVID- 19 pandemic.
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Objective@#Recent evidence shows that the quantitative value of amyloid-beta (Aβ) deposition below the threshold of Aβ positivi-ty carries biological and clinical significance regarding future cognitive decline. We evaluated whether the quantitative value of sub-threshold Aβ deposition had a significant correlation with neuropsychological test scores in cognitively normal older adults without the APOE ε4 allele. @*Methods@#Sixty cognitively normal APOE ε4 allele non-carriers with negative Aβ retention aged 60 to 85 years were included in this study. We assessed neuropsychological performance with the Korean version of the Consortium to Establish a Registry for Al-zheimer’s Disease (CERAD-K) and obtained standardized [ 18 F] flutemetamol uptake values in the pons as a reference (SUVR PONS), evaluated with PET. Multiple regression analyses were conducted to assess the effect of global and regional Aβ load on cognitive performance, adjusting for age, sex, years of education, and volumes of white matter hyperintensities. @*Results@#We found that Aβ deposition in the precuneus, posterior cingulate cortex, and parietal lobe had a significant association with the total CERAD-K scores. There was also a significant correlation between the SUVR PONS in the precuneus and the CERAD-K total score after Bonferroni correction. @*Conclusion@#Subthreshold Aβ retention in the core brain regions of the default mode network could affect cognitive functions in the cognitively normal APOE ε4 non-carriers, considered to be the lowest risk group for Alzheimer’s disease (AD).
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Objective@#Alzheimer’s disease (AD) is the most common type of dementia and the prevalence rapidly increased as the elderly population increased worldwide. In the contemporary model of AD, it is regarded as a disease continuum involving preclinical stage to severe dementia. For accurate diagnosis and disease monitoring, objective index reflecting structural change of brain is needed to correctly assess a patient’s severity of neurodegeneration independent from the patient’s clinical symptoms. The main aim of this paper is to develop a random forest (RF) algorithm-based prediction model of AD using structural magnetic resonance imaging (MRI). @*Methods@#We evaluated diagnostic accuracy and performance of our RF based prediction model using newly developed brain segmentation method compared with the Freesurfer’s which is a commonly used segmentation software. @*Results@#Our RF model showed high diagnostic accuracy for differentiating healthy controls from AD and mild cognitive impairment (MCI) using structural MRI, patient characteristics, and cognitive function (HC vs. AD 93.5%, AUC 0.99; HC vs. MCI 80.8%, AUC 0.88). Moreover, segmentation processing time of our algorithm (<5 minutes) was much shorter than of Freesurfer’s (6–8 hours). @*Conclusion@#Our RF model might be an effective automatic brain segmentation tool which can be easily applied in real clinical practice.
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Objective@#No previous study examined impact of dementia in the outcome of allogeneic hematopoietic stem cell transplantation (HSCT). We aimed to investigate overall survival (OS) of patients with dementia after receiving HSCT. @*Methods@#Among 8,230 patients who underwent HSCT between 2002 and 2018, 5,533 patients younger than 50 years were first excluded. Remaining patients were divided into those who were and were not diagnosed with dementia before HSCT (dementia group: n = 31; no dementia: n = 2,666). Thereafter, among 2,666 participants without dementia, 93 patients were selected via propensity-matched score as non-dementia group. Patients were followed from the day they received HSCT to the occurrence of death or the last follow-up day (December 31, 2018), whichever came first. @*Results@#With median follow-up of 621 days for dementia group and 654 days for non-dementia group, 2 year-OS of dementia group was lower than that of non-dementia group (53.3% [95% confidence interval, 95% CI, 59.0−80.2%] vs. 68.8% [95% CI, 38.0−68.2%], p = 0.076). In multivariate analysis, dementia had significant impacts on OS (hazard risk = 2.539, 95% CI, 1.166−4.771, p = 0.017). @*Conclusion@#Our results indicated that patients diagnosed with dementia before HSCT have 2.539 times higher risk of mortality after transplantation than those not having dementia. With number of elderly needing HSCT is increasing, further work to establish treatment guidelines for the management of HSCT in people with dementia is needed.
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Objective@#No previous study examined impact of dementia in the outcome of allogeneic hematopoietic stem cell transplantation (HSCT). We aimed to investigate overall survival (OS) of patients with dementia after receiving HSCT. @*Methods@#Among 8,230 patients who underwent HSCT between 2002 and 2018, 5,533 patients younger than 50 years were first excluded. Remaining patients were divided into those who were and were not diagnosed with dementia before HSCT (dementia group: n = 31; no dementia: n = 2,666). Thereafter, among 2,666 participants without dementia, 93 patients were selected via propensity-matched score as non-dementia group. Patients were followed from the day they received HSCT to the occurrence of death or the last follow-up day (December 31, 2018), whichever came first. @*Results@#With median follow-up of 621 days for dementia group and 654 days for non-dementia group, 2 year-OS of dementia group was lower than that of non-dementia group (53.3% [95% confidence interval, 95% CI, 59.0−80.2%] vs. 68.8% [95% CI, 38.0−68.2%], p = 0.076). In multivariate analysis, dementia had significant impacts on OS (hazard risk = 2.539, 95% CI, 1.166−4.771, p = 0.017). @*Conclusion@#Our results indicated that patients diagnosed with dementia before HSCT have 2.539 times higher risk of mortality after transplantation than those not having dementia. With number of elderly needing HSCT is increasing, further work to establish treatment guidelines for the management of HSCT in people with dementia is needed.
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Objective@#We aimed to explore the differential impact of cigarette smoking on fracture risks in SCD and dementia. @*Methods@#A nationwide population-based cohort study design was used. Out of all the people aged 66 (n=1,555,103) who went through the National Screening Program from 2009–2014, 968,240 participants with eligible data were included in the study. Time-to-event was calculated as the duration between the NSPTA and fracture incidence. Cox proportional-hazard regression analyses were conducted to evaluate the risk of fractures. @*Results@#Increased risk of all [adjusted hazard ratio (aHR)=1.184; 95% confidence interval (CI)=1.184, 1.093–1.283], hip (aHR=1.518; 95% CI=1.168–4.972), vertebral (aHR=1.235; 95% CI=1.101–1.386) fractures were increased in current smokers with more than 20 or more pack years (≥20 py) of SCD group, after adjusting for all relevant confounding factors. In dementia group, however, current smokers ≥20 py were at reduced risk of hip fractures (aHR=0.249; 95% CI=0.089–0.97). @*Conclusion@#There was a disparate influence of cigarette smoking on the fracture risks in SCD and dementia group. Further studies are warranted to explicate this phenomenon, and personalized preventive measures according to one’s cognitive status are imperative, since risk factors of fractures can exert disparate influence on patients at different stage of cognitive trajectory.
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Objective@#We aimed to explore the impact of moderate intensity exercise on the cortical thickness and subcortical volumes of preclinical Alzheimer’s disease (AD) patients. @*Methods@#Sixty-three preclinical AD patients with magnetic resonance imaging (MRI) and 18-florbetaben positron emission tomography (PET) data were enrolled in the study. Information on demographic characteristics, cognitive battery scores, self-reported exercise habits were attained. Structural magnetic resonance images were analyzed and processed using Freesurfer v6.0. @*Results@#Compared to Exercise group, Non-Exercise group demonstrated reduced cortical thickness in left parstriangularis, rostral middle frontal, entorhinal, superior frontal, lingual, superior parietal, lateral occipital, inferior parietal gyrus, temporal pole, precuneus, insula, fusiform gyrus, right precuneus, superiorparietal, lateral orbitofrontal, rostral middle frontal, medial orbitofrontal, superior frontal, lingual, middle temporal gyrus, insula, supramarginal, parahippocampal, paracentral gyrus. Volumes of right thalamus, caudate, putamen, pallidum, hippocampus, amygdala were also reduced in Non-Exercise group. @*Conclusion@#Moderate intensity exercise affects cortical and subcortical structures in preclinical AD patients. Thus, physical exercise has a potential to be an effective intervention to prevent future cognitive decline in those at high risk of AD.
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Objective@#Previous studies investigating association of alcohol intake and fracture risk in elderly yielded conflicting results. We first examined the association between alcohol intake and total fracture risk in elderly subjects and further analyzed whether the association varied by fracture locations. @*Methods@#This is a nationwide population-based cohort study which included all people aged 66 (n=1,431,539) receiving the National Screening Program during 2009–2014. Time-to-event were defined as duration from study recruitment, the day they received health screening, to the occurrence of fracture. @*Results@#Total fracture was significantly lower in mild drinkers [adjusted hazard ratio (aHR)=0.952; 95% confidence interval (95% CI) =0.931–0.973] and higher in heavy drinkers (aHR=1.246; 95% CI=1.201–1.294) than non-drinkers. Risk pattern of alcohol consumption and fracture differed according to affected bones. Similar J-shaped trends were observed for vertebra fractures, but risk of limb fracture showed a linear relationship with alcohol intake. For hip fracture, risk decrement was more pronounced in mild and moderate drinkers, and significant increment was noted only in very severe drinkers [≥60 g/day; (aHR)=1.446; 1.162–1.801]. @*Conclusion@#Light to moderate drinking generally lowered risk of fractures, but association between alcohol and fracture risk varied depending on the affected bone lesions.
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Asunto(s)
Humanos , Sesgo , Cognición , Disfunción Cognitiva , Pruebas Neuropsicológicas , Proyectos Piloto , Placebos , Corteza Prefrontal , Tamaño de la Muestra , Estimulación Magnética Transcraneal , Resultado del TratamientoRESUMEN
Alzheimer's disease (AD) is a debilitating syndrome with cognitive decline and impairment in daily activities. Although clinical assessment forms the basis for diagnosing AD, structural and functional brain imaging tools have been known to enhance accuracy of differential diagnosis and prognosis prediction by presenting structural and functional signatures for AD. Associated with the important role of brain imaging in diagnosing and treating AD, brain imaging has been recommended in the current diagnostic guidelines of AD. Visual rating scales, a cost-effective diagnostic tool, have been known to assess atrophy and functional changes in patients with cognitive impairment as accurate as quantitative assessment. In this regard, visual rating scales for brain imaging interpretation could be useful in clinical settings. In this review, we interpret structural and functional brain imaging results with standardized visual rating scales, and review recent findings concerning brain imaging tools for differential diagnosing and predicting prognosis of AD.