Alzheimer’s disease (AD) is a progressive neurodegenerative disease. Although it has been studied for years, the pathogenesis of AD is still controversial. Genetic factors may play an important role in pathogenesis, with the apolipoprotein E (APOE) gene among the greatest risk factors for AD. In this review, we focus on the influence of genetic factors, including the APOE gene, the interaction between APOE and other genes, and the polygenic risk factors for cognitive function and dementia. The presence of the APOE ε4 allele is associated with increased AD risk and reduced age of AD onset. Accelerated cognitive decline and abnormal internal environment, structure, and function of the brain were also found in ε4 carriers. The effect of the APOE promoter on cognition and the brain was confirmed by some studies, but further investigation is still needed. We also describe the effects of the associations between APOE and other genetic risk factors on cognition and the brain that exhibit a complex gene–gene interaction, and we consider the importance of using a polygenic risk score to investigate the association between genetic variance and phenotype.

Background: The widespread adoption of information and communication technologies (ICTs) further deepens disparities in resource access, particularly among the aging population. However, the relationship between these factors and their resulting impact on cognitive abilities remains uncertain. Objective: This study aims to investigate the potential impact of the digital divide on individuals’ cognitive function and its association with the development and reversion of mild cognitive impairment (MCI). Methods: This cohort study used data from Beijing Aging Brain Rejuvenation (BABRI) study applying a multistage cluster sampling design between 2008 and 2020. The digital divide was quantified by the frequency of using ICTs. Analysis of covariance (ANCOVA), mixed linear models, and Cox proportional hazards models were used to model the association of digital divide and multidomain cognition. Results: Among the 10098 participants, nearly half (n=4941, 48.9%) faced the digital divide, which was associated with a worse performance in processing speed (F10096=10.67; P<.001; effect size r=0.42), rather than memory, executive function, and language. The model indicated that individuals’ physical and mental health, combined with their educational and occupational prestige, influenced the resources they attained, which ultimately caused the digital divide. Moreover, longitudinal data revealed that older adults who successfully crossed the digital divide during the tracking process and those who had already done so prior to tracking showed significantly slower rates of decline in processing speed (B=–1.98, P<.05; B=–2.62, P<.01) and general cognitive function (B=3.50, P<.001; B=3.13, P<.01). Additionally, overcoming the digital divide was also associated with a lower risk of developing MCI (hazard ratio [HR] 0.5, 95% CI 0.34-0.74; HR 0.43, 95% CI 0.29-0.62) and a greater probability of reversion from MCI to normal cognition (HR 6, 95% CI 3.77-9.56; HR 9.22, 95% CI 5.63-15.11). Conclusions: Overcoming the digital divide was significantly associated with improved cognitive function, a slower aging rate in cognitive performance, a reduced risk of developing MCI, and a higher likelihood of reverting from MCI to normal cognition.

Background. Traditional Chinese herbal medicine draws more attention to explore an effective therapeutic strategy for Alzheimers disease (AD). Shenqi Yizhi granule (SQYG), a Chinese herbal recipe, has been applied to ameliorate cognitive impairment in mild-to-moderate AD patients. However, the overall molecular mechanism of SQYG in treating AD has not been clarified. Objective. This study aimed to investigate the molecular mechanism of SQYG on AD using an integration strategy of network pharmacology and molecular docking. Methods. The active compounds of SQYG and common targets between SQYG and AD were screened from databases. The herb-compound network, compound-target network, and protein-protein interaction network were constructed. The enrichment analysis of common targets and molecular docking were performed. Results. 816 compounds and 307 common targets between SQYG and AD were screened. KEGG analysis revealed that common targets were mainly enriched in lipid metabolism, metal ion metabolism, IL-17 signaling pathway, GABA receptor signaling, and neuroactive ligand-receptor interaction. Molecular docking analysis showed high binding affinity between ginsenoside Rg1 and Aβ_1–42, tanshinone IIA and BACE1, baicalin, and AchE. Conclusions. The therapeutic mechanisms of SQYG on AD were associated with regulating lipid metabolism, metal ion metabolism, IL-17 signaling pathway, and GABA receptor signaling. Ginsenoside Rg1, tanshinone IIA, baicalin, astragaloside IV, and folic acid may play an important role in AD treatment.

Allele 4 of the apolipoprotein E gene (APOE ε4) and hypertension are considered risk factors for Alzheimer’s Disease (AD). The detection of differences in cognitive function and brain networks between hypertensive patients who are APOE ε4 carriers and non-carriers may help in understanding how hypertension and risk genes cumulatively impair brain function, which could provide critical insights into the genetic mechanism by which hypertension serves as a potential risk factor for cognitive decline and even AD. Using behavioral data from 233 elderly hypertensive patients and neuroimaging data from 38 of them from Beijing, China; the study aimed to assess the effects of APOE ε4 on cognition and to explore related changes in functional connectivity. Cognitively, the patients with APOE ε4 showed decreased executive function, memory and language. In the MRI sub-cohort, the frontoparietal networks in the APOE ε4 carrier group exhibited an altered pattern, mainly in the left precentral regions, inferior frontal lobe and angular gyrus. More importantly, the decline of cognitive function was correlated with abnormal FC in the left precentral regions in APOE ε4 carriers. APOE ε4 aggravated the dysfunction in frontal and parietal regions in hypertensive patients. This highlights the importance of brain protection in hypertensive patients, especially those with a genetic risk of AD.

Introduction: Vascular cognitive impairment (VCI) is one of the most common types of dementia. Naoxin'an capsule (NXA), a traditional Chinese medicine compound, has been used to treat VCI for a long time in the clinic. Previous studies proved that the NXA capsules could ameliorate the cerebral mitochondrion deficits of VCI animals. This study aimed to investigate the protectiveness of NXA on human brain structure and function in patients with VCI.Methods: In total, 100 VCI patients were enrolled in this 24-week trial and randomly divided into the NXA capsules group (n = 50) and the ginkgo biloba capsules control group (n = 50). Before and after the treatment, cognitive behavior tests and multimodal brain magnetic resonance imaging were analyzed to comprehensively evaluate the effectiveness of NXA treatment on VCI patients after 24 weeks.Results: We found that the NXA group significantly improved overall cognitive ability (Alzheimer's Disease Assessment Scale-Cognitive section, p = 0.001; Mini-Mental Status Examination, p = 0.003), memory (Rey-Osterrieth Complex Figure test, p < 0.001) and executive function (Trail Making Test-A, p = 0.024) performance after treatment compared with the control group. For brain function, the degree of centrality in the left middle frontal gyrus, right postcentral gyrus, and left supplementary motor area increased in the NXA group and decreased in the ginkgo biloba group after treatment. The fractional amplitude of low-frequency fluctuation (fALFF) of the left precentral and right superior parietal gyrus increased, and the fALFF of the right parahippocampal and left inferior temporal gyrus decreased in the NXA group after treatment. For brain structure, the gray matter density of the left postcentral gyrus increased in the NXA group after treatment, and the total volume of white matter hyperintensity showed a decreasing trend but was not statistically significant. Furthermore, the improvement effect of NXA on executive function was associated with changes in brain function.Conclusion: These findings suggest that the NXA capsules improved cognitive performance and multiregional brain function, as well as gray matter structure in the postcentral gyrus.

BACKGROUND The widespread adoption of information and communication technologies (ICTs) further deepens disparities in resource access, particularly among the aging population. However, the relationship between these factors and their resulting impact on cognitive abilities remains uncertain. OBJECTIVE This study aims to investigate the potential impact of the digital divide on individuals’ cognitive function and its association with the development and reversion of mild cognitive impairment (MCI). METHODS This cohort study used data from Beijing Aging Brain Rejuvenation (BABRI) study applying a multistage cluster sampling design between 2008 and 2020. The digital divide was quantified by the frequency of using ICTs. Analysis of covariance (ANCOVA), mixed linear models, and Cox proportional hazards models were used to model the association of digital divide and multidomain cognition. RESULTS Among the 10098 participants, nearly half (n=4941, 48.9%) faced the digital divide, which was associated with a worse performance in processing speed (F10096=10.67; P<.001; effect size r=0.42), rather than memory, executive function, and language. The model indicated that individuals’ physical and mental health, combined with their educational and occupational prestige, influenced the resources they attained, which ultimately caused the digital divide. Moreover, longitudinal data revealed that older adults who successfully crossed the digital divide during the tracking process and those who had already done so prior to tracking showed significantly slower rates of decline in processing speed (B=–1.98, P<.05; B=–2.62, P<.01) and general cognitive function (B=3.50, P<.001; B=3.13, P<.01). Additionally, overcoming the digital divide was also associated with a lower risk of developing MCI (hazard ratio [HR] 0.5, 95% CI 0.34-0.74; HR 0.43, 95% CI 0.29-0.62) and a greater probability of reversion from MCI to normal cognition (HR 6, 95% CI 3.77-9.56; HR 9.22, 95% CI 5.63-15.11). CONCLUSIONS Overcoming the digital divide was significantly associated with improved cognitive function, a slower aging rate in cognitive performance, a reduced risk of developing MCI, and a higher likelihood of reverting from MCI to normal cognition.