ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Objective@#The aim of this study was to explore the psychometric properties of the Insomnia Severity Index (ISI) based on modern test theory, such as item response theory (IRT) and Rasch analysis, with shortened versions of the ISI among the general population. @*Methods@#We conducted two studies to evaluate the reliability and validity of the shortened versions of the ISI in a Korean population. In Study I, conducted via online survey, we performed an exploratory factor analysis (n=400). In Study II, confirmatory factor analysis (CFA) was conducted (n=400). IRT and Rasch analysis were performed on all samples. Participants symptoms were rated using the ISI, Dysfunctional Beliefs and Attitudes about Sleep–16 items, Dysfunctional Beliefs about Sleep–2 items, Patient Health Questionnaire–9 items, and discrepancy between desired time in bed and desired total sleep time. @*Results@#CFA showed a good fit for the 2-factor model of the ISI (comparative fit index=0.994, Tucker–Lewis index=0.990, root-meansquare-error of approximation=0.039, and standardized root-mean-square residual=0.046). The 3-item versions also showed a good fit for the model. All scales showed good internal consistency reliability. The scale information curve of the 2-item scale was similar to that of the full-scale ISI. The Rasch analysis outputs suggested a good model fit. @*Conclusion@#The shortened 2-factor ISI is a reliable and valid model for assessing the severity of insomnia in the Korean population. The results are needed to be explored further among the clinical sample of insomnia.
ABSTRACT
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.
ABSTRACT
Objective@#This narrative review aims to provide a comprehensive assessment of the existing literature on the relationship between hypnotics and dementia, considering both potential link and inconclusive or lack of association. @*Methods@#Data from studies that investigate the association between hypnotic medications and dementia were reviewed. Studies included both cohort studies and systematic reviews, participants with various type of dementia and hypnotics including benzodiazepines (BZDs) and Z-drugs (ZDs). @*Results@#The existing literatures presents conflicting evidence regarding the association between hypnotics, including BZDs and ZDs, and the risk of dementia. Some studies suggest a potential link between prolonged use of hypnotics and an increased risk of dementia. However, other studies indicate inconclusive or lacking evidence regarding this association. Factors such as study design, sample characteristics, and control of confounding variables contribute to the variability in findings. @*Conclusion@#The relationship between hypnotics and dementia remains complex and controversial. While some studies suggest a potential association, others find inconclusive or conflicting evidence. Future research should focus on addressing methodological limitations, considering classifying dementia subtypes, and try to adjust medication lag time.
ABSTRACT
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.
ABSTRACT
Objective@#Antipsychotic drugs are known as the major cause of non-neoplastic hyperprolactinemia. This study aimed to investigate the levels of serum prolactin depending on the use of antipsychotic drugs in patients through the Clinical Data Warehouse (CDW). @*Methods@#We conducted a cohort search in the CDW application and got 260 patients’ medical records diagnosed with schizophrenia, schizotypal and delusional disorders, manic episodes, and bipolar affective disorders who were taking one of risperidone, blonanserin, amisulpride, and olanzapine. After that, we reviewed the medical data and used the ANCOVA analysis and the post hoc test to compare serum prolactin levels among four antipsychotic drug groups. @*Results@#Among the 117 subjects included in the analysis, the mean serum prolactin level was 64.6 ± 54.6 ng/ml. Serum prolactin levels were significantly higher in subjects taking risperidone or amisulpride compared to blonanserin and olanzapine. The female subjects who took blonanserin, olanzapine, and risperidone had significantly higher prolactin levels, but there was no difference in serum prolactin levels between sex in the subjects who took amisulpride. @*Conclusion@#This study suggests the need for regular monitoring of serum prolactin levels in patients who are taking antipsychotics, especially in female patients. And we showed that there is a possibility to conduct more effective and simpler big data research using the CDW. Further studies on the subjects with controlled confounding variables and larger sample groups are needed.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Objective@#Recently data has been accumulated regarding the role of coping strategies in the relationship between stress and sleep quality. Therefore, we set out to identify the mediating effects of coping strategies between stress and sleep quality. @*Methods@#A online-based cross-sectional study was performed using the Perceived Stress Scale-10, the Pittsburgh Sleep Quality Index, and a simplification of the 60-item Coping Orientation to Problems Experienced (Brief COPE) inventory in the nonclinical adult sample. The 24 items of Brief COPE were categorized into four factors (social support, problem solving, avoidance, positive thinking). Then, we used the PROCESS macro to conduct the multiple mediation analysis for the four coping styles as potential mediators in the relationship between stress and sleep quality, and an additional subgroup analysis was examined to identify a gender difference for the mediation effect. @*Results@#As a group, four coping styles mediated significantly the association between perceived stress and poor sleep quality. And avoidance has maintained its significance thought all regression analyses. Finally, this results remained as same in the females. @*Conclusion@#The effect of perceived stress on poor sleep quality was mediated by coping strategies, especially by avoidance. Thus, further research should consider the coping styles of individuals to reduce the influence of stress on sleep quality.
ABSTRACT
Objective@#The objectives of this study were to investigate the suicide risk in diabetes patients and evaluate the variations in suicide risk by the duration of diabetes using a large population sample in South Korea. @*Methods@#Data from 6,296 adults in the 2019 Korea National Health and Nutrition Examination Survey were included. The suicidal ideation, suicide plans, and suicidal behavior of diabetes patients were compared to the general population. After classifying the patients into ≤1 year, 2 to 9 years, and ≥10 years of diabetes duration, we evaluated the relationship between the duration of diabetes and the suicide risk. @*Results@#Diabetes patients had higher prevalences of suicidal ideation (9.1%, p<0.001) and suicide plans (3.6%, p<0.001) than the general population. After adjusting for potential confounding factors, suicide plans (adjusted odds ratio [aOR]=2.926, 95% confidence interval [CI]=1.325–6.463) were significantly associated with diabetes. In the 2 to 9 years group of diabetes patients, we found an increase in the risk of suicidal ideation (aOR=2.035, 95% CI=1.129–3.670), suicide plans (aOR=3.507, 95% CI=1.538–7.996), and suicidal behavior (aOR=7.130, 95% CI=2.035–24.978) after adjusting for the covariates. However, no increases in suicide risk were observed ≤1 year and ≥10 years after diabetes diagnosis. @*Conclusion@#In adults, diabetes is associated with an increase in suicide risk. Suicide risk in diabetes patients showed an inverted U-shaped depending upon the duration of diabetes.
ABSTRACT
Melatonin is a hormone with neuroregulatory, antioxidant and anti-inflammatory properties. Its benevolent effects on Alzheimer’s disease (AD) has been replicated in both animal models and clinical studies. Melatonin was effective in deterring the toxic effects of amyloid beta (Aβ) and reducing tau phosphorylation. Conflicting results exist for the clinical effectiveness of melatonin administration in AD patients. The positive effects of melatonin in AD have mainly been viewed from its role in sleep and circadian rhythm. Several limitations exist in the previous research on the relationship between melatonin and AD. Future research should focus on sharpening methodology, and adopting more expanded, multi-faceted approach, with consideration for melatonin’s antioxidant and anti-inflam-matory properties.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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).
ABSTRACT
Background@#This study aimed to assess the clinical characteristics of patients with major depressive disorder who were rehospitalized within 1 year and to determine whether the 1-year rehospitalization rate varied depending on the type of medication and treatment method. @*Methods@#Clinical characteristics of 531 patients hospitalized for major depressive disorder were assessed. The use and type of antidepressants, antipsychotics, mood stabilizers, and hypnotics were also evaluated. @*Results@#Of the 531 subjects, 68 (12.8%) were rehospitalized within a year. The number of past depressive episodes (1.56±2.67 vs. 0.90±1.18) (p=0.048) and the number of previous psychiatric hospitalizations (0.82±1.93 vs. 0.29±0.83 times) (p=0.029) were high in the 1-year rehospitalization group. The rate of family history of mood disorder (25.0% vs. 13.6%) (p=0.014) and the rate of comorbid personality disorder (16.2% vs. 8.6%) (p=0.049) were also high in the 1-year rehospitalization group. Multiple logistic regression analysis showed that the number of previous psychiatric hospitalizations affected the rate of 1-year rehospitalization (p=0.003). @*Conclusion@#The number of previous psychiatric hospitalizations could be used to predict rehospitalizations of patients with major depressive disorder within 1 year. In addition, family history of mood disorders and comorbidity of personality disorders may affect rehospitalization of such patients.
ABSTRACT
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.
ABSTRACT
Orexin’s role in human cognition has recently been emphasized and emerging evidences indicate its close relationship with Alzheimer’s disease (AD). This review aimed to demonstrate recent research on the relationship between orexin and AD. Orexin’s role in stress regulation and memory is discussed, with significant findings related to sexual disparities in stress response, with potential clinical implications pertaining to AD pathology. There are controversies regarding the orexin levels in AD patients, but the role of orexin in the trajectory of AD is still emphasized in recent literatures. Orexin is also accentuated in the context of tau pathology, and orexin as a potential therapeutic target for AD is frequently discussed. Future directions with regard to the relationship between orexin and AD are suggested: 1) consideration for AD trajectory in the measurement of orexin levels, 2) the need for objective measure such as polysomnography and actigraphy, 3) the need for close observation of cognitive profiles of orexin-deficient narcolepsy patients, 4) the need for validation studies by neuroimaging 5) the need for taking account sexual disparities in orexinergic activiation, and 6) consideration for orexin’s role as a stress regulator. The aforementioned new perspectives could help unravel the relationship between orexin and AD.
ABSTRACT
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.