Physical exercise frequency and cognition: a multicenter cross-sectional cohort study.

Background and aims: Dementia imposes a heavy burden on society and families, therefore, effective drug treatments, exploring and preventing factors associated with dementia, are paramount. To provide reference points for the best frequency of physical exercise (physical exercise), we investigated the association between frequency of PE and cognition in Chinese old adults. Methods: 16,181 Chinese participants aged 65 years or older were included in this study. Associations between PE and cognition were estimated multivariate logistic and linear regression analyses. Associations were further investigated across dementia subtypes (Alzheimer dementia, vascular dementia, and other types of dementia). Subgroup analyses were performed in different age groups, in populations with and without stroke, and those with and without hypertension. Results: PE associated with dementia after adjusting for full covariates (OR: 0.5414, 95% CI: 0.4536-0.6491, p < 0.001). Exercise performed at ≥3 times/week associated with lower risk of dementia (OR: 0.4794-0.6619, all p value <0.001). PE was associated with improved cognition (ß: 12851, p < 0.001), and any PE frequency contributed to cognitive improvement (p values for exercise performed ≥1 time/week were <0.001). Similar conclusions were identified when we repeated analyses in different dementia subtypes and age groups. Subgroup analyses suggested that the cognition of individuals without hypertension also benefitted from exercising 1-2 times/week (OR: 0.6168, 95% CI: 0.4379-0.8668, p = 0.005). Conclusion: The best exercise frequency is exercising ≥3 times/week for individuals from different dementia subtypes and age groups. While for those without hypertension, PE at 1-2 times /week is also beneficial.

Dyrk1a Phosphorylation of α-Synuclein Mediating Apoptosis of Dopaminergic Neurons in Parkinson's Disease.

Objective: To investigate the role of aberrant Dyrk1a expression in phosphorylation modification at the α-synuclein serine 129 (Ser129) site to analyze its molecular mechanism in mediating apoptosis of PD. Methods: The protein level of P-α-synuclein (Ser129), α-synuclein, Bcl-2, Bax, active caspase 3, GSK3ß, PI3K, AKT, and cyclinD1 were detected. The mRNA transcript levels of Dyrk1a and DAT and protein levels of IL-1ß, IL-6, COX-2, and TNF-α were detected. Results: P-α-synuclein (Ser129), α-synuclein, Bax, active caspase 3, GSK3ß, and cyclinD1 expressions were decreased in Dyrk1a-AAV-ShRNA (P < 0.05), and Bcl-2, AKT, and PI3K expressions were increased (P < 0.05). Increased TH protein expression was shown in Dyrk1a-AAV-ShRNA (P < 0.05). Dyrk1a mRNA was decreased in the Dyrk1a-AAV-ShRNA group (P < 0.05), and DAT mRNA was increased (P < 0.05). IL-1ß, IL-6, COX-2, and TNF-α protein levels were decreased in Dyrk1al-AAV-Sh-RNA (P < 0.05). Transcriptome sequencing showed that Fam220a, which was expected to activate STAT family protein binding activity and participate in the negative regulation of transcription through RNA polymerase II and protein dephosphorylation showed differentially upregulated expression. The untargeted metabolome showed that the major compounds in the Dyrk1a-AAV-ShRNA group were hormones and transmission mediators and the most metabolism-related pathways. Fam220a showed differentially upregulated expression, and differentially expressed genes were enriched for the neuroactive ligand-receptor interaction, vascular smooth muscle contraction, and melanogenesis-related pathways. Conclusion: Abnormal Dyrk1a expression can affect α-synuclein phosphorylation modifications, and dyrk1a knockdown activates the PI3K/AKT pathway and reduces dopaminergic neuron apoptosis. It provides a theoretical basis for the group to further investigate the molecular mechanism.

Corrigendum: Blood pressure control and risk of post-stroke dementia among the elderly: A population-based screening study.

[This corrects the article DOI: 10.3389/fneur.2022.956734.].

Association between prevalence rate of dementia with Lewy bodies and sleep characteristics in Chinese old adults.

Introduction: Few studies are available on the prevalence and sleep-related factors of dementia with Lewy bodies (DLB) in Chinese older adults, aiming to explore the associations between sleep characteristics and DLB. Methods: A cross-sectional study with 7,528 individuals aged ≥65 years in 106 communities in Northern China was conducted from April 2019 to January 2020. Questionaries (including demographic characteristics, comorbidities, lifestyles, and sleep characteristics) were administered, and neuropsychological assessments and physical examination were conducted in phase I; screening for probable DLB was done in phase II. Logistic regressions were used to assess associations. Results: A total of 919 (12.2%, 919/7,528) participants had dementia, and 101 (1.3%, 101/7,528) participants were diagnosed with DLB. The prevalence of dementia and DLB were slightly higher or equal in women, increased with age, and roughly decreased with nighttime sleep duration. Of the 101 participants, all of them (100.0%) had cognitive impairment, 46 (44.54%) displayed fluctuating cognition, 72 (71.29%) of them showed visual hallucination, 22 (21.78%) individuals reported RBD, and 27.71% showed Parkinsonism. Sleeping for <5 h (adjusted OR = 1.795, 95%CI: 1.055-3.054, p < 0.05) or having hypersomnolence (adjusted OR = 31.213, 95% CI: 17.618-55.301, p < 0.001) were significantly associated with the occurrence of DLB. Sleep duration of <5 h or >8 h had combined diagnostic value for DLB (AUC = 0.783, 95%CI: 0.734-0.831, p < 0.001). Conclusions: The current prevalence of DLB is 1.3% in Northern China. Short or long nighttime sleep duration is independently associated with the occurrence of dementia and DLB.

Blood pressure control and risk of post-stroke dementia among the elderly: A population-based screening study.

Background: Post-stroke dementia (PSD) has adverse effects on the quality of work and life in elderly stroke survivors. There are inconsistent results on the impacts of blood pressure control on the risk of PSD in people aged 65 years and above. Objective: This study was performed to explore whether poorly-controlled blood pressure was associated with an increasing risk of PSD. Methods: The study population was enrolled from cross-sectional research conducted in 106 communities of rural northern China. In Phase I, a total of 7,448 people aged ≥65 years, including 830 with stroke history, completed a questionnaire, a physical examination, and a cognitive assessment. Phase II further confirmed the diagnosis of PSD. Well-controlled blood pressure was defined as an average systolic blood pressure of <140 mmHg and average diastolic blood pressure of <90 mmHg over two readings in person. Failure to meet these criteria was considered as poorly-controlled blood pressure. Results: The crude prevalence rate of PSD among stroke survivors aged 65 years and over was 17.8% [95% confidence interval (CI) 15.2-20.4%]. Among the 830 stroke survivors, the proportions of PSD gradually increased with age and the crude prevalence rates for PSD were 10.2% (95% CI 5.6-14.9%), 14.8% (95% CI 10.1-19.5%), 18.8% (95% CI 14.1-23.5%), and 27.4% (95% CI 20.8-34.1%) in subjects aged 65-69, 70-74, 75-79 and ≥80 years, respectively. Participants in the poorly-controlled blood pressure group were more likely to suffer from PSD (28.4 vs.15.3%, P < 0.001), be older (75.81 ± 4.97 vs. 74.74 ± 5.83, P < 0.05), and have a worse cognitive level (22.26 ± 7.05 vs. 24.10 ± 6.02, P < 0.05). Compared with well-controlled blood pressure patients, poorly-controlled blood pressure in stroke survivors significantly increased risk of PSD (odds ratio = 2.20, 95% CI 1.45-3.32) after adjusting for age, gender, and education. Conclusions: The crude prevalence of PSD among stroke survivors aged ≥65 years was 17.8% at community level. In addition to lower education level and older age, poorly-controlled blood pressure was also an independent risk factor for PSD among the elderly, which is amenable to intervention. Therefore, it is essential to control blood pressure to reduce PSD incidence.

Association between marital status and cognitive impairment based on a cross-sectional study in China.

BACKGROUND: Marital status may have an impact on the elderly population's health, but few studies in China discussed about the association between marital status and cognitive impairment. OBJECTIVE: To investigate the relationship between marital status and cognitive impairment. To compare the influences of marital status on dementia between men and women. METHODS: This study was based on a representative national cross-sectional epidemiological survey in China. We randomly selected 13 provinces and municipalities and included 19,276 participants aged 65 years or older in our study. Data was collected by interviewing the participants about their sociodemographic characteristics, and neuropsychological testing was administered to the participants by neurologists. To analyze the association between marital status and cognitive impairment, multiple logistic regression was based on a series of models. RESULTS: Among the 19,276 subjects, about 77.2% were married, 1.6% were single, 21.2% were divorced/separated or widowed. The odds ratios (OR) of dementia were higher in single (OR: 2.13, CI: 1.53-2.97; p < 0.001), divorced/separated/widowed when they were ≤55 years old (OR: 1.75, CI: 1.30-2.35; p < 0.001), and divorced/separated/widowed when they were >55 years old (OR: 1.16, CI: 1.03-1.31; p < 0.001) participants than in married ones. Divorced/separated/widowed ≤55 men had about 2.75 times increase in dementia risk than married men. CONCLUSION: People with long-term divorced/separated/widowed status would be associated to cognitive impairment more than those with short-term divorced/separated/widowed status. Men may be affected by marriage disruption more than women in terms of increasing the risk of dementia.

The Association Between Hyperhidrosis and Dementia: A Community-Based Research.

BACKGROUND: Dementia and hyperhidrosis (HH) are common in the elderly while there is little research to investigate the association between them. OBJECTIVE: To clarify a possible association between HH and dementia in population of adults ≥65 years old in China. METHODS: A cross-sectional survey for elderly adults ≥65 years old was conducted from April to December 2019. A total of 5,958 participants were analyzed after two phases investigation. Goodness-of-fit tests (Pearson and deviance) were used to estimate the dispersion parameter and examine the adequacy of the models. Logistic and linear regression analyses were used to evaluate the association between HH and dementia. RESULTS: The overall prevalence of all-cause dementia was 10.17%, that of dementia with Lewy bodies (DLB) was 1.41%, and HH was 14.97%. Prevalence rates of HH were higher in participants with dementia and DLB. There was a significant positive relationship between HH duration and MMSE score (r = 0.207, p < 0.001, Durbin-Watson test = 1.806). Participants with HH were 1.275 (95% CI: 1.015-1.601, p = 0.037) times to have dementia, and 3.616 (95% CI: 2.267-5.767, p < 0.001) times to suffer from DLB than those without HH. Pearson and deviance chi square tests did not indicate overdispersion (p > 0.05 in the logistic regression models). CONCLUSION: HH was common in the Chinese population ≥65 years old. It can increase the risk of dementia, particularly in DLB, in the elderly. It is important to improve the awareness of HH among dermatologists and neurologists.

Identification of Dysregulated Mechanisms and Potential Biomarkers in Ischemic Stroke Onset.

OBJECTIVE: Ischemic stroke (IS) is a major cause of severe disability. This study aimed to identify potential biomarkers closely related to IS diagnosis and treatment. METHODS: Profiles of gene expression were obtained from datasets GSE16561, GSE22255, GSE112801 and GSE110993. Differentially expressed mRNAs between IS and controls were then subjected to weighted gene co-expression network analysis as well as multiscale embedded gene co-expression network analysis. The intersection of the two sets of module genes was subjected to analyses of functional enrichment and of microRNAs (miRNAs) regulation. Then, the area under receiver operating characteristic curves (AUC) was calculated to assess the ability of genes to discriminate IS patients from controls. IS diagnostic signatures were constructed using least absolute shrinkage and selection operator regression. RESULTS: A total of 234 common co-expression network genes were found to be potentially associated with IS. Enrichment analysis found that these genes were mainly associated with inflammation and immune response. The aberrantly expressed miRNAs (hsa-miR-651-5p, hsa-miR-138-5p, hsa-miR-9-3p and hsa-miR-374a-3p) in IS had regulatory effects on IS-related genes and were involved in brain-related diseases. We used the criterion AUC > 0.7 to screen out 23 hub genes from IS-related genes in the GSE16561 and GSE22255 datasets. We obtained an 8-gene signature (ADCY4, DUSP1, ATP5F1, DCTN5, EIF3G, ELAVL1, EXOSC7 and PPIE) from the training set of GSE16561 dataset, which we confirmed in the validation set of GSE16561 dataset and in the GSE22255 dataset. The genes in this signature were highly accurate for diagnosing IS. In addition, the 8-gene signature significantly correlated with infiltration by immune cells. CONCLUSION: These findings provide new clues to molecular mechanisms and treatment targets in IS. The genes in the signature may be candidate markers and potential gene targets for treatments.

Prevalence of Constipation in Elderly and Its Association With Dementia and Mild Cognitive Impairment: A Cross-Sectional Study.

BACKGROUND: Constipation and dementia have similar epidemiological characteristics. Changes in intestinal flora and characteristics of the brain-gut axis play roles in the pathogeneses of the two diseases, suggesting that there may be a close connection between the two. Most of the studies on constipation in dementia patients have focused on the population with α-synucleinopathies [Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB)]. Few studies have reported the prevalence of constipation in all-cause dementia and mild cognitive impairment (MCI) populations. OBJECTIVE: To assess the prevalence of constipation in patients with all-cause dementia and MCI subtypes and to explore the association between constipation with dementia and MCI subtypes. METHODS: From May 2019 to December 2019, we conducted a population-based cross-sectional survey. A total of 11,743 participants aged 65 or older from nine cities in China were surveyed. Participants underwent a series of clinical examinations and neuropsychological measurements. Constipation, dementia, MCI and MCI subtype were diagnosed according to established criteria through standard diagnostic procedures. RESULTS: The overall age- and sex-adjusted prevalence of constipation in individuals aged 65 years and older was 14.8% (95% CI, 14.6-15.0). The prevalence rates of constipation were19.2% (95% CI, 17.3-21.0), 19.1% (95% CI, 16.8-21.5), 14.4% (95% CI, 12.8-15.9), and 13.8% (95% CI, 13.0-14.6) in the dementia, non-amnestic (na)-MCI, amnestic (a)-MCI and normal cognition populations, respectively. Multivariate logistic regression analysis showed that higher prevalence of constipation was associated with dementia (p = 0.0.032, OR = 1.18, 95% CI: 1.02-1.38) and na-MCI (p = 0.003, OR = 1.30, 95% CI: 1.09-1.54). CONCLUSION: The present study found a high prevalence of constipation in elderly individuals in China, and higher in patients with dementia and na-MCI.

Effects of environmental enrichment on cognitive behavior and the expression of adenosine triphosphate binding cassette transporter A7 in hippocampus of adolescent mice with high fat diet. / ä¸°å¯ŒçŽ¯å¢ƒå¯¹é’æ˜¥æœŸé«˜è„‚é¥®é£Ÿå°é¼ è®¤çŸ¥è¡Œä¸ºå’Œæµ·é©¬ä¸‰ç£·é ¸è ºè‹·ç»“åˆç›’è½¬è¿å­A7表达的影响.

OBJECTIVES: To investigate the effects of environmental enrichment on cognitive behavior and the expression of adenosine triphosphate binding cassette transporter A7 (ABCA7) in hippocampus of the adolescent mice with high fat diet. METHODS: A total of healthy 3-week-old male C57BL/6J mice were randomly divided into 3 groups: a control (Con) group, a high fat diet (HFD) group, and a high fat diet+environmental enrichment (HFD+EE) group, with 10 mice in each group. The Con group was given normal diet. The HFD group was given high fat diet. The HFD+EE group was given high fat diet; at the same time, they treated by environmental enrichment. After 10 weeks, open field test was used to detect activity. Novel object recognition test and Y maze test were used to detect cognitive behavior. After the test, the brain was collected and used to detect the protein expression of ABCA7 in the hippocampus by immunohistochemistry and Western blotting. And quantitative RT-PCR (RT-qPCR) was used to detect the ABCA7 mRNA expression level in the hippocampus. RESULTS: There was no significant difference in the total movement distance in the mice among the 3 groups (P>0.05). In the novel object recognition test, the discrimination index of the HFD group was much lower than that of the Con group, and the difference was significant (P<0.01). The discrimination index of the HFD+EE group was higher than that of the HFD group, and the difference was significant (P<0.01). In the Y maze test, there was no significant difference in the percentage of time spent on the new arm among the mice in the 3 groups (P=0.1279). The percentage of entries in new arm in the HFD group was much lower than that in the Con group, and the difference was significant (P<0.01). The percentage of the entries in new arm in the HFD+EE group was significantly higher than that in the HFD group (P<0.05). The results of immunohistochemistry showed that ABCA7 was positively expressed in the cytoplasm of hippocampal neurons in the mice from these 3 groups, and the expression of ABCA7 in the hippocampus of the HFD group was lower than that of the Con group (CA1: P<0.01, CA3: P=0.06), while the expression of ABCA7 in hippocampus of HFD+EE group was higher than that of HFD group (CA1: P=0.23, CA3: P<0.05). Western blotting results showed that compared with the Con group, the protein level of ABCA7 in the hippocampus of the HFD group was significantly reduced (P<0.05), while compared with the Con group, the protein level of ABCA7 in the hippocampus of the HFD+EE group showed an upward trend (P=0.06). The results of RT-qPCR showed that the mRNA level of ABCA7 in the hippocampus of HFD group was significantly lower than that of the Con group (P<0.01), while the mRNA level of ABCA7 in the hippocampus of HFD+EE group was significantly higher than that of the HFD group (P<0.01). CONCLUSIONS: High fat diet in adolescent can impair cognitive function with a decrease in the expression of ABCA7 in hippocampus, which can be ameliorate by environmental enrichment.