The direct and mediating effects of cognitive impairment on the occurrence of falls: a cohort study based on community-dwelling old adults.

Background: Cognitive impairment has been reported to be associated with falls in older adults. However, the complex relationship among falls, cognitive impairment and its associated factors, which could be targeted with specific interventions, remains to be elucidated. This study aimed to examine the direct effects of cognitive impairment on falls, to identify the factors associated with cognitive impairment and to explore the mediation role of cognitive impairment in the association of fall with cognition related factors. Methods: This 1-year follow-up cohort study enrolled old adults aged 60 years or over. Information about demographic and anthropometric characteristics, fall outcomes, function and nutritional status were collected through face-to-face interview. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCA). Multivariable regression analyses were used to test the association between cognitive impairment and falls and to identify the factors related to cognitive impairment. Additionally, we conduct causal mediation analyses to estimate the mediation effects of cognitive impairment in the pathways of fall occurrence. Results: Of the 569 participants included in this study, 366 (64.32%) had cognitive impairment, 96 (16.87%) had fall history in the past 1 year, 81 (14.24%) experienced fall and 47 (8.26%) received treatment because of falling during the 1-year follow-up. The association between cognitive impairment and 1-year fall risk was confirmed after adjusting for multiple covariates [odds ratio (OR):2.03, 95% confidence interval (CI): 1.13-3.80]. IADL disability, depression and low grip strength were associated with a higher prevalence of cognitive impairment. While overweight, higher education and higher income level were found to be related to a lower risk of cognitive impairment. Among these associated factors, cognitive impairment mediated the positive association of falling with IADL ability and depression, and a negative relationship with education and income level. Conclusion: Our study not only confirmed the direct influence of cognitive impairment on fall risk in older adults, but also suggested a mediating role that cognitive impairment played in the pathways of fall occurrence. Our finding could help develop more specific interventions for fall prevention.

Relationship Between the ApoE Gene Polymorphism and Type 2 Diabetes Mellitus Complications.

Background: Apolipoprotein E (ApoE) polymorphisms are associated with type 2 diabetes mellitus (T2DM) and its complications, but studies have shown conflicting results. Objective: To examine the relationship of ApoE gene polymorphisms with T2DM and its complications. Materials and Methods: This case-control study of patients with T2DM was conducted between June 2016 and July 2019. Healthy individuals were recruited as controls. The patients were grouped according to coronary heart disease (CHD), cerebral infarction (CI), diabetic nephropathy (DN), and neurological complications. The ApoE genotype was determined using a commercial gene chip. Results: Compared with controls, the frequencies of genotype ɛ3/4 (20.8% vs. 11.7%, p = 0.04) and allele ɛ4 (14.3% vs. 8.3%, p = 0.03) of patients with T2DM were higher. The frequency of genotype ɛ3/4 was higher in the T2DM with CHD group (30.4% vs. 17.4%, p = 0.01 vs. non-CHD) and in T2DM with CI (29.2% vs. 18.1%, p = 0.045 vs. non-CI). The frequency of genotype ɛ2/3 was higher in the T2DM with DN group (19.3% vs. 9.1%, p = 0.01 vs. non-DN). There were no significant differences between T2DM with and without neuropathy (p > 0.05). Conclusion: The ApoE allele ɛ4 may be a risk factor for T2DM, CHD in T2DM, and CI in T2DM, while the ApoE allele ɛ2 may be a risk factor for DN.

18F-fallypride PET-CT of dopamine D2/D3 receptors in patients with sporadic amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease with unclear pathogenesis. To date, there have been no reports regarding the distribution of dopamine receptors outside the striatum in ALS patients. In this study, 17 ALS patients and 11 healthy controls underwent 18F-fallypride positron emission tomography/computed tomography (PET/CT) and completed cognitive-related tests for assessment of the distribution of dopamine receptors inside and outside the striatum in ALS and evaluation of the relationships between the distribution of dopamine receptors and cognitive function. The results showed that ALS patients showed significantly lower scores only in language and delayed recall of Montreal Cognitive Assessment scale. There were no significant differences between the two groups in the cognitive-related test results. Statistical parametric mapping (SPM) data showed that the binding affinity of 18F-fallypride in ALS patients was decreased in the bilateral nucleus accumbens septi, bilateral frontal lobes, and the superior frontal gyrus, left temporal lobe, and angular gyrus regions. In conclusion, the levels of dopamine receptors were significantly decreased in some areas outside the striatum in patients with ALS, which may contribute to mild cognitive impairment in ALS patients.

Long-Term Alcohol-Induced Activation of Mammalian Target of Rapamycin is a Key Risk Factor of Epilepsy.

BACKGROUND The aim of this study was to determine whether activation of mammalian target of rapamycin (mTOR) is a key epileptogenic mechanism in the development of alcohol-related seizure. MATERIAL AND METHODS C57BL/6 mice were administered 10% ethanol in drinking water for 9 weeks. Video-electroencephalography (EEG) monitoring was then used to assess seizure frequency after alcohol and rapamycin treatment. In addition, mouse neuroblastoma NG108-15 cells were treated ethanol for 3 days and subsequently treated with AKT inhibitor LY294002 for 2-12 h. The in vitro kinase assay was performed for determining mTOR activity. Western blot analysis was used to determine the expression of P-AKT, P-S6K, and P-S6. RESULTS Long-term ethanol treatment markedly increased the seizure frequency of C57/BL6 mice over time. Moreover, ethanol treatment increased the expression level of P-S6 over time. Ethanol-induced seizure can be reversed by rapamycin. In addition, the in vitro kinase assay showed mTOR activity was activated by ethanol. Compared with NG108-15 cells treated without both ethanol and LY294002, ethanol increased the expression level of P-AKT, P-S6K, and P-S6, whereas LY294002 had opposite effects on expression levels of these proteins. CONCLUSIONS Our findings indicate that long-term alcohol intake increases the risk of epilepsy via activation of mTOR signaling. Moreover, ethanol-induced mTOR activation may be dependent on the AKT-mTOR signaling pathway. The key molecules involved in AKT-mTOR signaling pathway may serve as potential targets in the treatment of epilepsy.