Impact of Helicobacter pylori eradication on age-specific risk of incident dementia in patients with peptic ulcer disease: a nationwide population-based cohort study.

The impact of peptic ulcer disease (PUD) and Helicobacter pylori (H. pylori) eradication therapy on dementia risk in high H. pylori prevalence populations remains uncertain. This study investigates the relationship between PUD, H. pylori eradication, and dementia risk, including Alzheimer's disease (AD), in an elderly South Korean cohort, considering age and eradication timing. Data from the Korean National Health Insurance Service (2002-2015) for individuals aged 55-79 were analyzed. Participants were divided based on PUD and H. pylori therapy status. Propensity score matching was used to evaluate dementia incidence and hazard ratios over 5 and 10 years, alongside the timing of eradication therapy. PUD is linked to higher dementia risk at 5 and 10 years, more for overall dementia than AD, with eradication status not significantly altering the risk. Age-specific analysis showed increased AD risk in the 60s and 70s age groups. Late eradication therapy is correlated with a higher dementia risk. PUD is a risk factor for dementia in elderly South Koreans, particularly with delayed H. pylori therapy. The findings emphasize timely H. pylori management and its potential role in neurodegenerative disease prevention.

Effects of transcranial direct current stimulation on cognition in MCI with Alzheimer's disease risk factors using Bayesian analysis.

Despite the growing interest in precision medicine-based therapies for Alzheimer's disease (AD), little research has been conducted on how individual AD risk factors influence changes in cognitive function following transcranial direct current stimulation (tDCS). This study evaluates the cognitive effects of sequential tDCS on 63 mild cognitive impairment (MCI) patients, considering AD risk factors such as amyloid-beta deposition, APOE ε4, BDNF polymorphism, and sex. Using both frequentist and Bayesian methods, we assessed the interaction of tDCS with these risk factors on cognitive performance. Notably, we found that amyloid-beta deposition significantly interacted with tDCS in improving executive function, specifically Stroop Word-Color scores, with strong Bayesian support for this finding. Memory enhancements were differentially influenced by BDNF Met carrier status. However, sex and APOE ε4 status did not show significant effects. Our results highlight the importance of individual AD risk factors in modulating cognitive outcomes from tDCS, suggesting that precision medicine may offer more effective tDCS treatments tailored to individual risk profiles in early AD stages.

A Comparative Analysis of Two Automated Quantification Methods for Regional Cerebral Amyloid Retention: PET-Only and PET-and-MRI-Based Methods.

Accurate quantification of amyloid positron emission tomography (PET) is essential for early detection of and intervention in Alzheimer's disease (AD) but there is still a lack of studies comparing the performance of various automated methods. This study compared the PET-only method and PET-and-MRI-based method with a pre-trained deep learning segmentation model. A large sample of 1180 participants in the Catholic Aging Brain Imaging (CABI) database was analyzed to calculate the regional standardized uptake value ratio (SUVR) using both methods. The logistic regression models were employed to assess the discriminability of amyloid-positive and negative groups through 10-fold cross-validation and area under the receiver operating characteristics (AUROC) metrics. The two methods showed a high correlation in calculating SUVRs but the PET-MRI method, incorporating MRI data for anatomical accuracy, demonstrated superior performance in predicting amyloid-positivity. The parietal, frontal, and cingulate importantly contributed to the prediction. The PET-MRI method with a pre-trained deep learning model approach provides an efficient and precise method for earlier diagnosis and intervention in the AD continuum.

Development of a prediction model for cognitive impairment of sarcopenia using multimodal neuroimaging in non-demented older adults.

INTRODUCTION: Despite prior research on the association between sarcopenia and cognitive impairment in the elderly, a comprehensive model that integrates various brain pathologies is still lacking. METHODS: We used data from 528 non-demented older adults with or without sarcopenia in the Catholic Aging Brain Imaging (CABI) database, containing magnetic resonance imaging scans, positron emission tomography scans, and clinical data. We also measured three key components of sarcopenia: skeletal muscle index (SMI), hand grip strength (HGS), and the five times sit-to-stand test (5STS). RESULTS: All components of sarcopenia were significantly correlated with global cognitive function, but cortical thickness and amyloid-beta (Aß) retention had distinctive relationships with each measure. In the path model, brain atrophy resulting in cognitive impairment was mediated by Aß retention for SMI and periventricular white matter hyperintensity for HGS, but directly affected by the 5STS. DISCUSSION: Treatments targeting each sub-domain of sarcopenia should be considered to prevent cognitive decline. HIGHLIGHTS: We identified distinct impacts of three sarcopenia measures on brain structure and Aß. Muscle mass is mainly associated with Aß and has an influence on the brain atrophy. Muscle strength linked with periventricular WMH and brain atrophy. Muscle function associated with cortical thinning in specific brain regions. Interventions on sarcopenia may be important to ease cognitive decline in the elderly.

Effects of Serious Games in Older Adults With Mild Cognitive Impairment.

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.

Current Understanding on Psilocybin for Major Depressive Disorder: A Review Focusing on Clinical Trials.

Previous studies suggested effectiveness of psilocybin in the field of mental health. FDA designated psilocybin as a "breakthrough therapy" for the treatment of treatment-resistant depression (TRD) in 2018. This paper provided a review of psilocybin's potential role in treatment of depression by focusing on published clinical trials. Studies showed that psilocybin, an agonist on 5-HT2A receptors, manifests antidepressant and anxiolytic effects by increasing glutamate transmission, reducing brain inflammation, decreasing default mode network activity. In terms of clinical trials, eleven studies (six open-label and five double blinded randomized clinical trials [DB-RCTs]) trials exploring psilocybin's impact on depression were found. Among open-label studies, a pilot study on TRD patients demonstrated significant reductions in depressive symptoms after two psilocybin sessions. Psilocybin also improved cognitive bias associated with depression. Extension studies confirmed sustained improvements and high remission rates. Among five DB-RCTs, two showed that psilocybin led to significant reductions in anxiety and depression in cancer patients, and the improvements sustained for over six months. In MDD, psilocybin showed rapid reductions in depression, with higher remission rates compared to escitalopram in a DB-RCT. Another DB-RCT showed that psilocybin induced higher decrease in depression around 6 hours after their administrations than placebo. The last DB-RCT showed that in patients with TRD, a single dose of psilocybin 25 mg, but not psilocybin 10 mg, resulted in superior antidepressant effect than psilocybin 1 mg. Overall, psilocybin showed promise in treating depression and anxiety, with notable safety profiles. Further research should explore optimal dosages and long-term effects.

Safety and feasibility of optimized transcranial direct current stimulation in patients with mild cognitive impairment due to Alzheimer's disease: a multicenter study protocol for a randomized controlled trial.

Introduction: Transcranial direct current stimulation (tDCS) may effectively preserve and improve cognitive function in patients with mild cognitive impairment (MCI). Research has shown that Individual brain characteristics can influence the effects of tDCS. Computer three-dimensional brain modeling based on magnetic resonance imaging (MRI) has been suggested as an alternative for determining the most accurate tDCS electrode position based on the patients' individual brain characteristics to enhance tDCS effects. Therefore, this study aims to determine the feasibility and safety of applying tDCS treatment using optimized and personalized tDCS electrode positions in patients with Alzheimer's disease (AD)-induced MCI using computer modeling and compare the results with those of a sham group to improve cognitive function. Method: A prospective active-sham group feasibility study was set to recruit 40 participants, who will be randomized into Optimized-tDCS and Sham-tDCS groups. The parameters for tDCS will be 2 mA (disk electrodes R = 1.5 cm) for 30 min during two sets of 15 sessions (2 weeks of resting period in between), using two electrodes in pairs. Using computer modeling, the tDCS electrode positions of each participant will be personalized. Outcome measurements are going to be obtained at three points: baseline, first post-test, and second post-test. The AD assessment scale-cognitive subscale (ADAS-Cog) and the Korean version of Mini-Mental State Examination (K-MMSE), together with other secondary outcomes and safety tests will be used. Discussion: For the present study, we hypothesize that compared to a sham group, the optimized personalized tDCS application would be effective in improving the cognitive function of patients with AD-induced MCI and the participants would tolerate the tDCS intervention without any significant adverse effects.Clinical trial registration: https://cris.nih.go.kr, identifier [KCT0008918].

Impact of Apolipoprotein E4 on the Locus Coeruleus Functional Connectivity in Preclinical Alzheimer's Disease.

Background: Recent interest has surged in the locus coeruleus (LC) for its early involvement in Alzheimer's disease (AD), notably concerning the apolipoprotein ɛ4 allele (APOE4). Objective: This study aimed to discern LC functional connectivity (FC) variations in preclinical AD subjects, dissecting the roles of APOE4 carrier status and amyloid-ß (Aß) deposition. Methods: A cohort of 112 cognitively intact individuals, all Aß-positive, split into 70 APOE4 noncarriers and 42 carriers, underwent functional MRI scans, neuropsychological assessments, and APOE genotyping. The research utilized seed to voxel analysis for illustrating LC rsFC discrepancies between APOE4 statuses and employed a general linear model to examine the interactive influence of APOE4 carrier status and Aß deposition on LC FC values. Results: The investigation revealed no significant differences in sex, age, or SUVR between APOE4 carriers and noncarriers. It found diminished LC FC with the occipital cortex in APOE4 carriers and identified a significant interaction between APOE4 carrier status and temporal lobe SUVR in LC FC with the occipital cortex. This interaction suggested a proportional increase in LC FC for APOE4 carriers. Additional notable interactions were observed affecting LC FC with various brain regions, indicating a proportional decrease in LC FC for APOE4 carriers. Conclusions: These findings confirm that APOE4 carrier status significantly influences LC FC in preclinical AD, showcasing an intricate relationship with regional Aß deposition. This underscores the critical role of genetic and pathological factors in early AD pathophysiology, offering insights into potential biomarkers for early detection and intervention strategies.

Plasma oligomer beta-amyloid is associated with disease severity and cerebral amyloid deposition in Alzheimer's disease spectrum.

BACKGROUND: Multimer detection system-oligomeric amyloid-ß (MDS-OAß) is a measure of plasma OAß, which is associated with Alzheimer's disease (AD) pathology. However, the relationship between MDS-OAß and disease severity of AD is not clear. We aimed to investigate MDS-OAß levels in different stages of AD and analyze the association between MDS-OAß and cerebral Aß deposition, cognitive function, and cortical thickness in subjects within the AD continuum. METHODS: In this cross-sectional study, we analyzed a total 126 participants who underwent plasma MDS-OAß, structural magnetic resonance image of brain, and neurocognitive measures using Korean version of the Consortium to Establish a Registry for Alzheimer's Disease, and cerebral Aß deposition or amyloid positron emission tomography (A-PET) assessed by [18F] flutemetamol PET. Subjects were divided into 4 groups: N = 39 for normal control (NC), N = 31 for A-PET-negative mild cognitive impairment (MCI) patients, N = 30 for A-PET-positive MCI patients, and N = 22 for AD dementia patients. The severity of cerebral Aß deposition was expressed as standard uptake value ratio (SUVR). RESULTS: Compared to the NC (0.803 ± 0.27), MDS-OAß level was higher in the A-PET-negative MCI group (0.946 ± 0.137) and highest in the A-PET-positive MCI group (1.07 ± 0.17). MDS-OAß level in the AD dementia group was higher than in the NC, but it fell to that of the A-PET-negative MCI group level (0.958 ± 0.103). There were negative associations between MDS-OAß and cognitive function and both global and regional cerebral Aß deposition (SUVR). Cortical thickness of the left fusiform gyrus showed a negative association with MDS-OAß when we excluded the AD dementia group. CONCLUSIONS: These findings suggest that MDS-OAß is not only associated with neurocognitive staging, but also with cerebral Aß burden in patients along the AD continuum.

Effect of Anti-Aging Standard Forest Healing Program With Multiple Visits to a Forest Facility on Cognition in Older Age Patients.

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.

The Usefulness of 18F-FDG PET to Differentiate Subtypes of Dementia: The Systematic Review and Meta-Analysis.

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 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-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 18F-FDG PET in dementia. The search included studies up to November 16, 2022, focusing on peer-reviewed journals and applying the gold-standard 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: 18F-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.

Tunable defect engineering of Mo/TiON electrode in angstrom-laminated HfO2/ZrO2ferroelectric capacitors towards long endurance and high temperature retention.

A novel defect control approach based on laminated HfO2/ZrO2with multifunctional TiN/Mo/TiOxNyelectrode is proposed to significantly improve the endurance and data retention in HZO-based ferroelectric capacitor. The O-rich interface reduces leakage current and prolong the endurance up to 1011cycles while retaining a 2Pr value of 34 (µC cm-2) at 3.4 MV cm-1. Using first-principles calculations and experiments, we demonstrate that the enhancement of endurance is ascribed to the higher migration barrier of oxygen vacancies within the laminated HZO film and higher work function of MoOx/TiOxNybetween top electrode and the insulating oxide. This 2.5 nm thick TiOxNybarrier further increase the grain size of HZO, lowering the activation field and thus improving polarization reversal speed. This interfacial layer further decreases the overall capacitance, increases the depolarization field, thereby enhancing the data retention. By fitting the data using the Arrhenius equation, we demonstrate a 10 years data retention is achieved at 109.6 °C, surpassing traditional SS-HZO of 78.2 °C with a 450 °C rapid thermal annealing (required by backend-of-the-line). This work elucidates that interfacial engineering serves as a crucial technology capable of resolving the endurance, storage capability, and high-temperature data retention issues for ferroelectric memory.

Development of Efficient Brain Age Estimation Method Based on Regional Brain Volume From Structural Magnetic Resonance Imaging.

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.

Associations between Education Years and Resting-state Functional Connectivity Modulated by APOE ε4 Carrier Status in Cognitively Normal Older Adults.

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 whole-brain 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.

Increased Likelihood of Dementia with Coexisting Atrophy of Multiple Regions of Interest.

BACKGROUND: Brain volume is associated with cognitive decline in later life, and cortical brain atrophy exceeding the normal range is related to inferior cognitive and behavioral outcomes in later life. OBJECTIVE: To investigate the likelihood of cognitive decline, mild cognitive impairment (MCI), or dementia, when regional atrophy is present in participants' magnetic resonance imaging (MRI). METHODS: Multi-center MRI data of 2,545 adults were utilized to measure regional volumes using NEUROPHET AQUA. Four lobes (frontal, parietal, temporal, and occipital), four Alzheimer's disease-related regions (entorhinal, fusiform, inferior temporal, and middle temporal area), and the hippocampus in the left and right hemispheres were measured and analyzed. The presence of regional atrophy from brain MRI was defined as ≤1.5 standard deviation (SD) compared to the age- and sex-matched cognitively normal population. The risk ratio for cognitive decline was investigated for participants with regional atrophy in contrast to those without regional atrophy. RESULTS: The risk ratio for cognitive decline was significantly higher when hippocampal atrophy was present (MCI, 1.84, p < 0.001; dementia, 4.17, p < 0.001). Additionally, participants with joint atrophy in multiple regions showed a higher risk ratio for dementia, e.g., 9.6 risk ratio (95% confidence interval, 8.0-11.5), with atrophy identified in the frontal, temporal, and hippocampal gray matter, than those without atrophy. CONCLUSIONS: Our study showed that individuals with multiple regional atrophy (either lobar or AD-specific regions) have a higher likelihood of developing dementia compared to the age- and sex-matched population without atrophy. Thus, further consideration is needed when assessing MRI findings.

Functional Connectivity Change Associated With Apolipoprotein E Allotypes Precedes Structural Connectivity and Neurodegeneration in Cognitive Normal Older Adults Without Cerebral Aß Deposition.

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 (Aß) 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 Aß deposition, structural changes, and neurodegeneration.

Neuroplastic and Pro-cognitive Effects of Granulocyte Colony Stimulating Factor in Healthy Adults: A Pilot Study.

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.

Sex-Related Disparities in the Resting State Functional Connectivity of the Locus Coeruelus and Salience Network in Preclinical Alzheimer's Disease.

Recent studies have demonstrated the pivotal role of locus coeruleus (LC) and salience network (SN) resting state functional connectivity (rsFC) changes in the early stage of Alzheimer's disease (AD). Moreover, sex has been a crucial point of discussion in understanding AD pathology. We aimed to demonstrate the sex-related disparities in the functional connectivity (FC) of the SN and LC in preclinical AD. A total of 89 cognitively normal patients with evidence of amyloid beta (Aß) accumulation ([18F] flutemetamol +) were recruited in the study. A seed-to-voxel analysis was conducted to measure the LC and SN rsFC differences between sexes. In addition, sex by Aß interactive effects on FC values were analyzed with a general linear model. There were statistically significant sex by regional standardized uptake value ratio (SUVR) interactions in the LC FC with the parietal, frontal, and occipital cortices. Moreover, there was a significant sex by global SUVR interaction in the SN FC with the temporal cortex. The findings suggest that there are differential patterns of LC FC and SN FC in males and females with preclinical AD, which interact with regional Aß deposition.

Plasma Oligomer ß-Amyloid and White Matter Microstructural Integrity in Cognitively Normal Older Adults According to Cerebral Amyloid Deposition.

BACKGROUND: Multimer detection system-oligomeric amyloid-ß (MDS-OAß) measure plasma OAß level, which is associated with earlier Alzheimer's disease (AD) pathology. However, no study has investigated MDS-OAß differences in cognitive normal older adults (CN) with or without cerebral Aß burden and its correlation with Aß deposition and white matter (WM) integrity. OBJECTIVE: To investigate associations among cerebral Aß burden, MDS-OAß, and WM integrity in CN. DESIGN: This is a single center, cross-sectional study which used data from Catholic Aging Brain Imaging (CABI) database. SETTING: CABI database contains brain scans of patients who visited the outpatient clinic at Catholic Brain Health Center, Yeouido St. Mary's Hospital, The Catholic University of Korea, between 2017 and 2022. PARTICIPANTS: A total 34 amyloid-PET negative CN and 23 amyloid-PET positive CN were included. MEASUREMENTS: Plasma Aß level using MDS-OAß, cerebral Aß deposition level using global standardized uptake value ratio (SUVR) values, WM integrity using fractional anisotropy (FA) and mean diffusivity (MD), and cortical thickness from structural MRI were utilized. RESTULS: The amyloid-PET positive group showed higher MDS-OAß level than the amyloid-PET negative group (0.997 ± 0.19 vs. 0.79 ± 0.28, P <0.005), but they did not differ in WM integrity or cortical thickness. The MDS-OAß positive group showed higher global cerebral Aß deposition or mean global SUVR values (0.609 ± 0.135 vs. 0.533 ± 0.121 vs. P <0.05), lower regional FA of left forceps minor and the right superior longitudinal fasciculus (family-wise error rate, p <0.05), and lower cortical thickness of left fusiform (p <0.05, Monte Carlo simulation) than the MDS-OAß negative group. MDS-OAß was positively associated with global cerebral Aß deposition (r=0.278, P <0.05) and negatively associated (r = - 0.324, P < 0.05) with regional WM integrity. CONCLUSIONS: In this study, MDS-OAß value demonstrated earlier and different AD pathology than cerebral Aß retention according to amyloid-PET. Longitudinal studies are needed to elucidate the causal relationships of plasma OAß and cerebral Aß with WM integrity disturbance and cortical atrophy during the AD trajectory.

Modulation of associations between education years and cortical volume in Alzheimer's disease vulnerable brain regions by Aß deposition and APOE ε4 carrier status in cognitively normal older adults.

Background: Education years, as a measure of cognitive reserve, have been shown to affect the progression of Alzheimer's disease (AD), both pathologically and clinically. However, inconsistent results have been reported regarding the association between years of education and intermediate structural changes in AD-vulnerable brain regions, particularly when AD risk factors were not considered during the preclinical phase. Objective: This study aimed to examine how Aß deposition and APOE ε4 carrier status moderate the relationship between years of education and cortical volume in AD-vulnerable regions among cognitively normal older adults. Methods: A total of 121 participants underwent structural MRI, [18F] flutemetamol PET-CT imaging, and neuropsychological battery assessment. Multiple regression analysis was conducted to examine the interaction between years of education and the effects of potential modifiers on cortical volume. The associations between cortical volume and neuropsychological performance were further explored in subgroups categorized based on AD risk factors. Results: The cortical volume of the left lateral occipital cortex and bilateral fusiform gyrus demonstrated a significant differential association with years of education, depending on the presence of Aß deposition and APOE ε4 carrier status. Furthermore, a significant relationship between the cortical volume of the bilateral fusiform gyrus and AD-nonspecific cognitive function was predominantly observed in individuals without AD risk factors. Conclusion: AD risk factors exerted varying influences on the association between years of education and cortical volume during the preclinical phase. Further investigations into the long-term implications of these findings would enhance our understanding of cognitive reserves in the preclinical stages of AD.