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Background: A minimum spanning tree (MST) is a unique efficient network comprising the necessary connections needed to connect all regions in a network while retaining the lowest possible cost of connection weight.Objective: This study aimed to utilize functional near-infrared spectroscopy (fNIRS) to analyze brain activity in different regions and then construct MST-based regions to characterize the brain topologies of participants with Alzheimer's disease (AD), mild cognitive impairment (MCI), and normal controls (NC).Methods: A 46 channel fNIRS setup was used on all participants, with correlation being calculated for each channel pair. An MST was constructed from the resulting correlation matrix, from which graph theory measures were calculated. The average number of connections within a lobe in the left versus right hemisphere was calculated to identify which lobes displayed and abnormal amount of connectivity.Results: Compared to those in the MCI group, the AD group showed a less integrated network structure, with a higher characteristic path length, but lower leaf fraction, maximum degree, and degree divergence. The AD group also showed a higher number of connections in the frontal lobe within the left hemisphere and a lower number between hemispheric frontal lobes as compared to MCI.Conclusion: These results indicate a deviation in network structure and connectivity within patient groups that is consistent with the theory of dysconnectivity for AD. Additionally, the AD group showed strong correlations between the Hamilton depression rating scale and different graph metrics, suggesting a link between network organization and the recurrence of depression in AD. [ABSTRACT FROM AUTHOR]

Background: Several studies have examined NCAPH2 methylation in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD), but little is known of NCAPH2 methylation in subjective cognitive decline (SCD). Objective: To examine whether methylation of peripheral NCAPH2 are differentially changed at various phases of AD, and whether it could serve as a diagnostic biomarker for SCD. Methods: A total of 40 AD patients, 52 aMCI patients, 148 SCD patients, and 193 cognitively normal controls (NCs) were recruited in the current case-control study. Besides, 54 cognitively normal individuals have received amyloid positron emission tomography (amyloid PET) scans. Using bisulfite pyrosequencing method, we measured blood DNA methylation in the NCAPH2 gene promoter. Results: The main outcomes were: 1) For SCD, there was no significant difference between SCD and NC regarding NCAPH2 methylation; 2) For aMCI, NCAPH2 methylation at CpG2 were significantly lower in aMCI compared with NC and SCD in the entire population and male subgroup; 3) For AD, NCAPH2 methylation at CpG1 were significantly lower in AD compared with NC among females; 4) A relationship with apolipoprotein E (APOE) ɛ4 status was shown. Receiver operating characteristic (ROC) analysis by combining NCAPH2 methylation, age, education, and APOEɛ4 status could distinguish between patients with aMCI (area under the curve (AUC): 0.742) and AD (AUC: 0.873) from NCs. Conclusion: NCAPH2 methylation levels were altered at the aMCI and AD stage and may be convenient and cost-effective biomarkers of AD and aMCI. [ABSTRACT FROM AUTHOR]

Background: Sleep appears to be a sensitive biomarker that facilitates early detection and effective intervention for Alzheimer's disease, while subjective cognitive decline (SCD) is a risk factor for Alzheimer's disease. Prefrontal cortex atrophy is associated with both sleep disruption and cognitive decline. Transcranial brain photobiomodulation (PBM) therapy can enhance frontal cortex oxygen consumption, increasing frontal cortex mediated memory function.Objective: This study aimed to test whether PBM therapy targeting the frontal cortex could improve sleep and cognitive function in SCD.Methods: Fifty-eight SCDs were divided into the PBM group (N = 32) in which real light therapy was administered and a sham light therapy group (N = 26). All the participants received either real light or sham light therapy for 6 days consecutively, while the sleep data were recorded. The n-back task was employed to measure each participant's working memory.Results: We found no differences in sleep efficiency change (F = 211, p = 0.279), REM stage percent change (F = 420, p = 0.91), and wake-up time (F = 212, p = 0.277) between the two groups. The sleep efficiency and REM were improved within the true light group on the fifth day. The true light group perform better than the control group in the n-back test, the accuracy was higher in the 2-back test (88.6% versus 79.6%, p = 0.001), and the reaction time in 1-back was shorter (544.80±202.00 versus 592.87±222.05, p = 0.003).Conclusion: After five days of PBM therapy targeting the prefrontal cortex, sleep efficiency and N-back cognitive performance were improved on the fifth day. [ABSTRACT FROM AUTHOR]

Background: Subjective cognitive decline (SCD) is considered as the first symptomatic manifestation of Alzheimer's disease (AD), which is also affected by different cultural backgrounds. Establishing cross-cultural prediction models of SCD is challenging.Objective: To establish prediction models of SCD available for both the Chinese and European populations.Methods: In this project, 330 SCD from China and 380 SCD from Germany are intended to be recruited. For all participants, standardized assessments, including clinical, neuropsychological, apolipoprotein E (APOE) genotype, blood, and multi-parameter magnetic resonance imaging (MRI) at baseline will be conducted. Participants will voluntarily undergo amyloid positron emission tomography (PET) and are classified into amyloid-β (Aβ) positive SCD (SCD+) and Aβ negative SCD (SCD-). First, baseline data of all SCD individuals between the two cohorts will be compared. Then, key features associated with brain amyloidosis will be extracted in SCD+ individuals, and the diagnosis model will be established using the radiomics method. Finally, the follow-up visits will be conducted every 12 months and the primary outcome is the conversion to mild cognitive impairment or dementia. After a 4-year follow-up, we will extract factors associated with the conversion risk of SCD using Cox regression analysis.Results: At present, 141 SCD from China and 338 SCD from Germany have been recruited. Initial analysis showed significant differences in demographic information, neuropsychological tests, and regional brain atrophy in SCD compared with controls in both cohorts.Conclusion: This project may be of great value for future implications of SCD studies in different cultural backgrounds.Trial Registration: ClinicalTrials.gov, NCT04696315. Registered 3 January 2021. [ABSTRACT FROM AUTHOR]

Background: Subjective cognitive decline (SCD), an at-risk condition of Alzheimer's disease (AD), can involve various cognitive domains, such as memory, language, planning, and attention.Objective: We aim to explore the difference in amyloid load between the single memory domain SCD (sd-SCD) and the multidomain SCD (md-SCD) and assess the relationship of amyloid pathology with quantitative SCD scores and objective cognition.Methods: A total of 63 SCD participants from the SILCODE study underwent the clinical evaluation, neuropsychological assessment, and 18F-florbetapir PET scan. Global amyloid standard uptake value ratio (SUVr) was calculated. Additionally, regional amyloid SUVr was quantified in 12 brain regions of interests. A nonparametric rank ANCOVA was used to compare the global and regional amyloid SUVr between the md-SCD (n = 34) and sd-SCD (n = 29) groups. A multiple linear regression analysis was conducted to test the relationship of amyloid SUVr with quantitative SCD scores and objective cognition.Results: Compared with individuals with sd-SCD, individuals with md-SCD had increased global amyloid SUVr (F = 5.033, p = 0.029) and regional amyloid SUVr in the left middle temporal gyrus (F = 12.309, p = 0.001; Bonferroni corrected), after controlling for the effects of age, sex, and education. When pooling all SCD participants together, the increased global amyloid SUVr was related with higher SCD-plus sum scores and lower Auditory Verbal Learning Test-delayed recall scores.Conclusion: According to our findings, individuals with md-SCD showed higher amyloid accumulation than individuals with sd-SCD, suggesting that md-SCD may experience a more advanced stage of SCD. Additionally, increased global amyloid load was predictive of a poorer episodic memory function in SCD individuals. [ABSTRACT FROM AUTHOR]

Background: Evidence suggests that subjective cognitive decline (SCD) individuals with worry have a higher risk of cognitive decline. However, how SCD-related worry influences the functional brain network is still unknown.Objective: In this study, we aimed to explore the differences in functional brain networks between SCD subjects with and without worry.Methods: A total of 228 participants were enrolled from the Sino Longitudinal Study on Cognitive Decline (SILCODE), including 39 normal control (NC) subjects, 117 SCD subjects with worry, and 72 SCD subjects without worry. All subjects completed neuropsychological assessments, APOE genotyping, and resting-state functional magnetic resonance imaging (rs-fMRI). Graph theory was applied for functional brain network analysis based on both the whole brain and default mode network (DMN). Parameters including the clustering coefficient, shortest path length, local efficiency, and global efficiency were calculated. Two-sample T-tests and chi-square tests were used to analyze differences between two groups. In addition, a false discovery rate-corrected post hoc test was applied.Results: Our analysis showed that compared to the SCD without worry group, SCD with worry group had significantly increased functional connectivity and shortest path length (p = 0.002) and a decreased clustering coefficient (p = 0.013), global efficiency (p = 0.001), and local efficiency (p < 0.001). The above results appeared in both the whole brain and DMN.Conclusion: There were significant differences in functional brain networks between SCD individuals with and without worry. We speculated that worry might result in alterations of the functional brain network for SCD individuals and then result in a higher risk of cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Mounting evidence suggests that sex differences exist in cognitive reserve (CR) for cognitively unimpaired (CU) elderly individuals. Global left frontal connectivity (gLFC connectivity) is a reliable neural substrate of CR.Objective: The purpose of this study was to explore sex differences in gLFC connectivity among CU elderly individuals.Methods: One hundred thirteen normal controls (NCs) (women = 66) and 132 individuals with subjective cognitive decline (SCD) (women = 92) were recruited from the Sino Longitudinal Study on Cognitive Decline (SILCODE) (data 1). Among them, 88 subjects underwent amyloid-β (Aβ) imaging, including 32 Aβ+ and 56 Aβ-subjects. Forty-six subjects underwent another rs-fMRI examination (data 2) to validate the repeatability of the calculation of gLFC connectivity, which was determined through seed-based functional connectivity between the LFC and voxels throughout the whole brain. Independent-sample t-tests were used to evaluate the sex differences in gLFC connectivity across different subgroups (NC versus SCD, Aβ+ versus Aβ-). Partial correlation analysis was used to calculate the correlations between gLFC connectivity and cognitive assessments.Results: Women exhibited lower gLFC connectivity in both the NC (p = 0.001) and SCD (p = 0.020) subgroups than men. Women also exhibited lower gLFC connectivity in both the Aβ-(p = 0.006) and Aβ+ (p = 0.025) groups. However, the significant difference disappeared in the Aβ+ group when considering the covariates of age, education, total intracranial volume, and APOE4-carrying status. In addition, gLFC connectivity values were negatively correlated with Geriatric Depression Scale scores in the SCD group (r = -0.176, p = 0.047).Conclusion: Women showed lower gLFC connectivity among CU elderly individuals. [ABSTRACT FROM AUTHOR]

Background: Subjective cognitive decline (SCD) is the earliest symptomatic manifestation of preclinical Alzheimer's disease (AD). Gut microbiota may serve as a susceptibility factor for AD. Altered gut microbiota has been reported in patients with mild cognitive impairment (MCI) and AD dementia. However, whether gut microbial compositions changed in SCD remains largely unknown.Objective: To characterize the gut microbiota in SCD.Methods: In this study, a total of 105 participants including 38 normal controls (NC), 53 individuals with SCD, and 14 patients with cognitive impairment (CI) were recruited. Gut microbiota of all participants isolated from fecal samples were investigated using 16S ribosomal RNA (rRNA) Illumina Miseq sequencing technique. The gut microbial compositions were compared among the three groups, and the association between altered gut microbiota and cognitive performance was analyzed. To validate the alteration of gut microbiota in SCD, we conducted amyloid positron emission tomography (PET) in selected participants and further compared the gut microbiota among subgroups.Results: The abundance of phylum Firmicutes, class Clostridia, order Clostridiales, family Ruminococcaceae, and genus Faecalibacterium showed a trend toward a progressive decline from NC to SCD and CI. Specifically, the abundance of the anti-inflammatory genus Faecalibacterium was significantly decreased in SCD compared with NC. In addition, altered bacterial taxa among the three groups were associated with cognitive performance. The findings were validated in SCD participants with positive amyloid evidence.Conclusion: The composition of gut microbiota is altered in individuals with SCD. This preliminary study will provide novel insights into the pathophysiological mechanism of AD. [ABSTRACT FROM AUTHOR]

Background: Individuals with subjective cognitive decline (SCD), defined by self-reported memory complaints but normal performance in objective neuropsychological tests, may be at higher risk of worsening or more frequent memory loss until conversion to Alzheimer's disease (AD) or related dementia. Asymmetry in two hemispheres is a cardinal character of human brain's structure and function, and altered brain asymmetry has also been connected with AD.Objective: This study aimed to determine whether the asymmetry of subcortical structures in individuals with SCD and amnestic mild cognitive impairment (aMCI) and AD patients are altered compared with normal controls (NC).Methods: We investigated neuroanatomical alterations in 35 SCD, 43 aMCI, and 41 AD subjects compared with 42 NC, focusing on asymmetrical changes in subcortical structures based on structural magnetic resonance images (sMRI). General linear model was conducted to test group differences, and partial correlation was used to model the interaction between asymmetry measurements and cognitive tests.Results: Individuals with SCD (lateral ventricle and cerebellum-WM), aMCI patients (lateral ventricle, pallidum, hippocampus, amygdala, accumbens, and ventral DC), and AD patients (lateral-ventricle, cerebellum-cortical pallidum, thalamus, hippocampus, amygdala, accumbens, and ventral DC) exhibited significant altered neuroanatomical asymmetries of volume, surface area, and shape compared with NC. Significant associations between shape asymmetry and neuropsychological examinations were found in the hippocampus and accumbens.Conclusion: Altered neuroanatomical asymmetries of subcortical structures were significantly detected in SCD individuals and aMCI patients as well AD patients, and these specific asymmetry alterations are potential to be used as neuroimaging markers and for monitoring disease progression. [ABSTRACT FROM AUTHOR]

Background: Education plays a potential important effect on the prevalence and incidence of dementia. However, most of the evidence based on convenience sampling.Objective: To explore effects of education on cognition in individuals with subjective cognitive decline (SCD) and cognitive impairment (CI) from a population-based study.Methods: We examined the effect of education on cognition among individuals with SCD (n = 451) and CI (n = 280) from a population-based study. A series of neuropsychological tests of memory, executive, language, and general cognitive function were used to assess the participants.Results: Multiple regression analyses revealed that education has a positive effect on cognition in both SCD and CI group in the population-based research. Further stratification study showed that the beneficial effect of education remains in the SCD group regardless of the education level, especially in the SCD participants with a low education level. However, that effect of education exists in the CI group with a low education level and disappears in the high education level.Conclusion: These results from a population-based sample suggest that high educational attainment may delay cognitive decline in the individuals with SCD regardless of high or low educational level, and high education only predicts cognition in those in the low educational level in CI group. [ABSTRACT FROM AUTHOR]

Background: Subjective cognitive decline (SCD) is considered the earliest symptomatic manifestation of preclinical Alzheimer's disease (AD). Currently, given the lack of effective and curable pharmacological treatments for AD, non-pharmacological interventions (NPIs) for individuals with SCD may provide a valuable opportunity for the secondary prevention of AD.Objective: This systematic review and meta-analysis, conducted in accordance with the PRISMA guidelines, aimed to investigate the benefits of current NPIs in the population with SCD.Methods: The online electronic databases, including MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, PsycInfo, and CINAHL, were searched to identify randomized controlled trials of NPIs for SCD. Intervention strategies were psychological and health-related education interventions, mind-body therapy, lifestyle modification, cognitive training, and multidomain interventions. Outcomes included subjective memory, objective memory, global cognitive function, psychological well-being, and mood. Study quality was determined using the criteria of the Cochrane collaboration's tool. The Hedges' g of change was analyzed.Results: Eighteen studies were included in this review and meta-analysis. Overall, psychological and health-related education interventions exhibited a medium effect on objective memory function (Hedges' g = 0.53, p = 0.01). Cognitive training led to a small effect on objective memory, which was marginal statistically (Hedges' g = 0.19, p = 0.05). In addition, cognitive training also significantly improved subjective memory performance (Hedges' g = 0.49, p = 0.0003) and psychological well-being (Hedges' g = 0.27, p = 0.03).Conclusion: Overall, the psychological intervention and cognitive training may be beneficial to cognitive function and psychological well-being. NPIs may be effectively implemented in older adults with SCD. [ABSTRACT FROM AUTHOR]

Background: Visual rating scales for medial temporal lobe atrophy (MTA) and posterior atrophy (PA) have been reported to be useful for Alzheimer's disease diagnosis in routine clinical practice.Objective: To investigate the efficacy of combined MTA and PA visual rating scales to discriminate amnestic mild cognitive impairment (aMCI) patients from healthy controls.Methods: This study included T1-weighted MRI images from two different cohorts. In the first cohort, we recruited 73 patients with aMCI and 48 group-matched cognitively normal controls for training and validation. Visual assessments of MTA and PA were carried out for each participant. Global gray matter volume and density were estimated using voxel-based morphometry analysis as the objective reference. We investigated the discriminative power of a single visual rating scale and the combination of the MTA and PA rating scales for identifying aMCI. The second cohort, consisting of 33 aMCI patients and 45 controls, was used to verify the reliability of the visual assessments.Results: Compared with the single visual rating scale, the combination of the MTA and PA exhibited the best discriminative power, with an AUC of 0.818±0.041, which was similar to the diagnostic accuracy of the gray matter volumetric measures. The discriminative power of the combined MTA and PA was verified in the second cohort (AUC 0.824±0.058).Conclusion: The combined MTA and PA rating scales demonstrated practical diagnostic value for distinguishing aMCI patients from controls, suggesting its potential to serve as a convenient and reproducible method to assess the degree of atrophy in clinical settings. [ABSTRACT FROM AUTHOR]

Background: Cognitive reserve (CR) and brain reserve (BR) could offer protective effects on cognition in the early stage of Alzheimer's disease (AD). However, the effects of CR or BR on cognition in individuals with subjective cognitive decline (SCD) are not clear.Objective: To explore the effects of CR and BR on cognition in subjects with SCD.Methods: We included 149 subjects from the Sino Longitudinal Study on Cognitive Decline (SILCODE) study. Education was used as a proxy for CR, and head circumference was used as a proxy for BR. Multiple linear regression models were conducted to examine the effects of CR and BR on cognitive scores. Furthermore, we assessed differences in effects between APOEɛ4 carriers with SCD (n = 35) and APOEɛ4 non-carriers with SCD (n = 114) and linear trends among 4 reserve levels (low BR/CR, high BR/low CR, low BR/high CR, and high BR/high CR).Results: Both CR and BR had independent positive effects on multiple cognitive measures in SCD participants, and the effects of CR were greater than those of BR. CR has positive effects on cognitive measures in both APOEɛ4 carriers and non-carriers with SCD. However, the positive effects of BR on cognitive measures were observed in APOEɛ4 non-carriers with SCD but not in APOEɛ4 carriers with SCD. Furthermore, there was a linear trend toward better cognitive performance on all cognitive measures in the BR+/CR+ group, followed by the BR-/CR+, BR+/CR-, and BR-/CR-groups.Conclusion: This study suggests that both CR and BR have the potential to delay or slow cognitive decline in individuals with SCD. [ABSTRACT FROM AUTHOR]

Background: Clinical research has demonstrated that brain reserve (BR) could exert positive effects on cognition for patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, the effects of BR on cognition in individuals with subjective cognitive decline (SCD) are not clear.Objective: To examine cross-sectional effects of BR on cognition in SCD populations.Methods: One hundred forty-nine subjects were studied from the Sino Longitudinal Study on Cognitive Decline (SILCODE) study. Head circumference was used as a proxy of BR. Cognition was assessed across four domains (memory, executive, language, and general cognitive functions). Multiple linear regression models were conducted to examine effects of BR on cognitive scores. Furthermore, we addressed the question that whether the degree of self-perception of cognitive decline modified the effect of BR on cognitive performance in SCD subjects.Results: We found a positive effect of BR on language cognition in subjects with SCD. Furthermore, the positive effect of BR on language cognition survived in SCD participants with a low degree of self-perception of cognitive decline while disappeared in SCD participants with a high degree of self-perception of cognitive decline.Conclusion: This study suggests that BR has the potential to delay or slow down cognitive decline in SCD individuals, especially for mild SCD. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), the main cause of dementia, is characterized by the aggregation of amyloid-β (Aβ). This pathophysiological process starts many years to decades before the onset of clinical symptoms. Cerebrospinal fluid analysis and amyloid positron emission tomography scans are two standard methods to measure brain Aβ, but their invasive nature and expense limit their usage as screening tools. Therefore, peripheral Aβ studies have grown exponentially during the past few years. In this review, we discuss recent studies on plasma Aβ and its potential as a reliable biomarker of AD. [ABSTRACT FROM AUTHOR]

Background: Detecting subtle changes in visual attention from electroencephalography (EEG) and the perspective of eye movement in mild cognitive impairment (MCI) patients can be of great significance in screening early Alzheimer's disease (AD) in a large population at primary care.Objective: We proposed an automatic, non-invasive, and quick MCI detection approach based on multimodal physiological signals for clinical decision-marking.Methods: The proposed model recruited 152 patients with MCI and 184 healthy elderly controls (HC) who underwent EEG and eye movement signal recording under a visual stimuli task, as well as other neuropsychological assessments. Forty features were extracted from EEG and eye movement signals by linear and nonlinear analysis. The features related to MCI were selected by logistic regression analysis. To evaluate the efficacy of this MCI detection approach, we applied the same procedures to achieve the Clinical model, EEG model, Eye movement model, EEG+ Clinical model, Eye movement+ Clinical model, and Combined model, and compared the classification accuracy between the MCI and HC groups with the above six models.Results: After the penalization of logistic regression analysis, five features from EEG and eye movement features exhibited significant differences (p < 0.05). In the classification experiment, the combined model resulted in the best accuracy. The average accuracy for the Clinical/EEG/Eye movement/EEG+ Clinical/Eye movement+ Clinical/Combined model was 68.69%, 61.79%, 73.13%, 69.46%, 75.61%, and 81.51%, respectively.Conclusion: These results suggest that the proposed MCI detection tool has the potential to screen MCI patients from HCs and may be a powerful tool for personalized precision MCI screening in the large-scale population under primary care condition. [ABSTRACT FROM AUTHOR]

Background: Subjective cognitive decline (SCD) refers to the self-perception of cognitive decline among cognitively normal elderly individuals. SCD related worry confers a higher risk of developing cognitive decline. However, the clinical characteristics of SCD patients with worry are not clear.Objective: To explore the clinical characteristics of SCD patients with worry.Methods: A cross-sectional study was carried out, with 270 consecutive participants of the Sino Longitudinal Study on Cognitive Decline (SILCODE) study. Participants were classified as normal controls (n = 36), SCD patients without worry (n = 91), or SCD patients with worry (n = 143) and were comprehensively compared on 1) their self-perception of cognitive decline, 2) multiple cognitive domains, 3) neuropsychiatric symptoms, and 4) sleep status.Results: SCD patients with worry had significantly more self-perception of cognitive decline (p < 0.001); increased depression (p < 0.001) and anxiety (p < 0.001); decreased sleep quality (p < 0.001), sleep latency (p < 0.05), sleep time (p < 0.01), and sleep efficiency (p < 0.05); more sleep disorders (p < 0.05) and daytime dysfunction (p < 0.05); and a higher global score on the Pittsburgh Sleep Quality Index (p < 0.001) than normal controls. Although there was a significant increase only in self-perception of cognitive decline (p < 0.001), anxiety (p < 0.001), and Pittsburgh Sleep Quality Index scores (p < 0.05), the severity of the increase in those without worry was between that in SCD patients with worry and normal controls.Conclusion: Our findings show that participants who had SCD with worry showed distinct clinical characteristics compared with normal controls and SCD patients without worry, which could be useful for understanding the higher risk in SCD patients with worry of subsequently developing Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Subjective cognitive decline (SCD) is a risk factor for Alzheimer's disease (AD). Urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) has been identified as a biomarker for AD. It was hypothesized that if urinary AD7c-NTP were also elevated in SCD, as it is in prodromal AD (mild cognitive impairment stage), it could be a convenient and efficient clinical biomarker for the early diagnosis of SCD. SCD is often accompanied by a depressive state (DS), and the impact of DS on urinary AD7c-NTP levels remains unknown. A total of 297 right-handed Chinese Han subjects were recruited, including 98 subjects with SCD, 92 patients with DS, and 107 well-matched cognitively normal controls (NC). The levels of AD7c-NTP in urine samples were measured using an enzyme-linked immunosorbent assay AD7c-NTP kit. Our results demonstrated that urinary AD7c-NTP levels in the SCD group (0.7561±0.5657 ng/mL) were not significantly higher than in either the DS (0.7527±0.5607 ng/mL) or NC (0.7214±0.5077 ng/mL) groups. Furthermore, urinary AD7c-NTP levels were not correlated with Hamilton Depression Rating Scale and Hamilton Anxiety Scale scores, but they were negatively associated with Mini-Mental State Examination scores (r = -0.222, p = 0.033) and Montreal Cognitive Assessment-Basic scores (r = -0.207, p = 0.048). Urinary AD7c-NTP level is not elevated in SCD and is unaffected by DS. Urinary AD7c-NTP may therefore not be a good potential biomarker for SCD and DS, although it may become elevated with more severe cognitive decline. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is one of the most common progressive and irreversible neurodegenerative diseases. The study of the pathological mechanism of AD and early-stage diagnosis is essential and important. Subjective cognitive decline (SCD), the first at-risk stage of AD occurring prior to amnestic mild cognitive impairment (aMCI), is of great research value and has gained our interest. To investigate the entire pathological development of AD pathology efficiently, we proposed a machine learning classification method based on a multimodal support vector machine (SVM) to investigate the structural and functional connectivity patterns of the three stages of AD (SCD, aMCI, and AD). Our experiments achieved an accuracy of 98.58% in the AD group, 97.76% in the aMCI group, and 80.24% in the SCD group. Moreover, in our experiments, we identified the most discriminating brain regions, which were mainly located in the default mode network and subcortical structures (SCS). Notably, with the development of AD pathology, SCS regions have become increasingly important, and structural connectivity has shown more discriminative power than functional connectivity. The current study may shed new light on the pathological mechanism of AD and suggests that whole-brain connectivity may provide potential effective biomarkers for the early-stage diagnosis of AD. [ABSTRACT FROM AUTHOR]

Identifying amnestic mild cognitive impairment (aMCI) is of great clinical importance because aMCI is a putative prodromal stage of Alzheimer's disease. The present study aimed to explore the feasibility of accurately identifying aMCI with a magnetic resonance imaging (MRI) biomarker. We integrated measures of both gray matter (GM) abnormalities derived from structural MRI and white matter (WM) alterations acquired from diffusion tensor imaging at the voxel level across the entire brain. In particular, multi-modal brain features, including GM volume, WM fractional anisotropy, and mean diffusivity, were extracted from a relatively large sample of 64 Han Chinese aMCI patients and 64 matched controls. Then, support vector machine classifiers for GM volume, FA, and MD were fused to distinguish the aMCI patients from the controls. The fused classifier was evaluated with the leave-one-out and the 10-fold cross-validations, and the classifier had an accuracy of 83.59% and an area under the curve of 0.862. The most discriminative regions of GM were mainly located in the medial temporal lobe, temporal lobe, precuneus, cingulate gyrus, parietal lobe, and frontal lobe, whereas the most discriminative regions of WM were mainly located in the corpus callosum, cingulum, corona radiata, frontal lobe, and parietal lobe. Our findings suggest that aMCI is characterized by a distributed pattern of GM abnormalities and WM alterations that represent discriminative power and reflect relevant pathological changes in the brain, and these changes further highlight the advantage of multi-modal feature integration for identifying aMCI. [ABSTRACT FROM AUTHOR]