Effects of Chronic Heart Failure on Longitudinal Changes of Cognitive Function in Elderly Patients.

Elderly patients with cognitive impairment present problems such as memory loss, impaired judgment, and loss of language function. Severe cases affect daily life and social functions. For the past few years, the possible disease and possible illness of chronic heart failure (CHF) in elderly patients have continued to increase. However, there is not enough research on the effect of CHF on the longitudinal change speed of cognitive function in elderly patients. Most studies focus on the effects of diseases like hypertension, coronary heart disease, and diabetes on cognitive function in elderly patients, which results in incomplete research. In this context, this article used a Bayesian network to build a cognitive function classification model for the elderly. The effects of CHF on the rate of longitudinal changes in cognitive function in elderly patients were studied by mental state examination and statistical methods. The experiment finally concluded by evaluating the attention, language ability, and memory ability of elderly patients. In the elderly with CHF, the incidence of cognitive impairment was about 71.66%. The experimental results further indicated that the higher the degree of CHF in elderly patients, the lower the level of cognitive function. This article could help advance research on preventing or delaying cognitive decline in patients with CHF.

Interspecific differences in sociability, social novelty preference, anxiety- and depression-like behaviors between Brandt's voles and C57BL/6J mice.

The three-chamber test has been widely used to investigate social approach/novelty preference in rodents. Most studies have used the briefly familiar and unfamiliar individuals as stimuli to examine social recognition; however, little is known about the effects of long-term familiar peers in this paradigm. In the present study, we made a slight modification to it: the first phase measured preference for a cage-mate (not a novel individual) over an identical wire cage without an individual stimulus; the later phase measured preference for a novel individual placed in the previous empty wire cage compared to the cage-mate (not the briefly familiar individual). The present study aimed to compare differences in sociability and social recognition between Brandt's voles (Lasiopodomys brandtii) and C57BL/6J mice using this modified three-chamber test. The levels of anxiety-, depression-, and anhedonia-like behaviors were also examined in both species. We found that Brandt's voles preferred the cage-mate over the empty cage in phase 1 and showed a preference for the novel individual in phase 2. In C57BL/6J mice, males showed no preference for familiar peers in phase 1, whereas females failed to show a preference for the novel individual in phase 2, showing a sex-specific difference. Furthermore, Brandt's voles displayed higher levels of locomotor activity and sociability as well as lower levels of anxiety-, depression-, and anhedonia-like behaviors than C57BL/6J mice. Interestingly, sociability and social approach correlated with depression-like behavior, whereas social novelty preference correlated with anhedonia-like behavior. Together, these data indicate that Brandt's voles and C57BL/6J mice show significant differences in sociability, social recognition, and levels of anxiety- and depression-like behaviors. Furthermore, Brandt's voles are more suitable for the study of selective social relationships.

Decreased mitochondrial D-loop region methylation mediates an increase in mitochondrial DNA copy number in CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a typical neurodegenerative disease associated with mitochondrial dysfunction. Methylation of the D-loop region and mitochondrial DNA copy number (mtDNAcn) play a critical role in the maintenance of mitochondrial function. However, the association between D-loop region methylation, mtDNAcn and CADASIL remains unclear. METHODS: Overall, 162 individuals were recruited, including 66 CADASIL patients and 96 age- and sex-matched controls. After extracting genomic DNA from the peripheral white blood cells, levels of D-loop methylation and mtDNAcn were assessed using MethylTarget sequencing and real-time PCR, respectively. RESULTS: We observed increased mtDNAcn and decreased D-loop methylation levels in CADASIL patients compared to the control group, regardless of gender stratification. Besides, we found a negative correlation between D-loop methylation levels and mtDNAcn. Mediation effect analysis shows that the proportion of the association between mtDNAcn and CADASIL that is mediated by D-loop methylation is 11.6% (95% CI 5.6, 22.6). After gender stratification, the proportions of such associations that are mediated by D-loop methylation in males and females were 7.2% (95% CI 2.4, 19.8) and 22.0% (95% CI 7.4, 50.1), respectively. CONCLUSION: Decreased methylation of the D-loop region mediates increased mtDNAcn in CADASIL, which may be caused by a compensatory mechanism of mitochondrial dysfunction in patients with CADASIL.

A Novel Mutation Outside of the EGFr Encoding Exons of NOTCH3 Gene in a Chinese with CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vascular disease caused by the mutations of the NOTCH3 gene. The NOTCH3 gene consists of 33 exons. The pathogenic mutations of the NOTCH3 gene in CADASIL are located in 2-24 exons coding for the 34 EGFr (epidermal growth factor-like repeat) domains. The classical clinical manifestations are recurrent TIA or ischaemic stroke, migraine, cognitive disorder and affective disorder. The deposition of granular osmiophilic material (GOM) in the vascular wall is considered as a hallmark of the disease. METHODS: Here, we report a rare pathogenic mutation on exon 29 of the NOTCH3 gene in a Chinese family. Clinical data for the proband and available relatives is collected. Mutation analysis of the NOTCH3 gene was performed by screening the entire 33 exons in this family and 200 normal controls. A complete imaging evaluation and skin biopsy were performed on the proband. RESULTS: We identified a novel R1761H (c.5282G>A) mutation. The same mutation was not founded in 200 normal controls. The proband had recurrent stroke, depression, cognitive decline and cerebral lobe hemorrhage. Cranial MRI showed white matter lesions and multiple infarction. Susceptibility weighted imaging revealed numerous microbleeds.Most importantly, the deposition of GOM was found in the proband. CONCLUSION: 33 exons of NOTCH3 gene should be performed for individuals with a convincing CADASIL phenotype and positive family history.

Coexistence of Autoimmune Encephalitis and Other Systemic Autoimmune Diseases.

Background: In recent years, the phenomenon of coexisting systemic autoimmune diseases (ADs) in patients with autoimmune encephalitis (AE) has been increasingly found, while its clinical significance remains unexplored. This study aimed to investigate the types and potential clinical associations of autoimmune comorbidities in patients with antibody-positive AE. Methods: A retrospective cohort study of patients with antibody-positive AE was conducted from 2011 to 2018. The demographics, clinical characteristics, and follow-up data were reviewed. Results: We enrolled 517 patients, among whom 45 were affected by one or more types of ADs, including Hashimoto's thyroiditis (HT) (n = 28), systemic lupus erythematosus (SLE) (n = 3), anaphylactoid purpura (n = 3), vitiligo (n = 3), Sjögren's syndrome (SS) (n = 2), chronic urticaria (n = 2), bullous pemphigoid (n = 1), uveitis (n = 1), myasthenia gravis (MG) (n = 1), and the coexistence of SLE and anaphylactoid purpura (n = 1). The proportion of patients with coexisting ADs was higher in those with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis than in those with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis (13/111 vs. 16/307) (P = 0.021). In anti-NMDAR and anti-LGI1 encephalitis patients, there were no significant differences in the age at onset, sex ratio, proportion of patients with tumors, disease severity, or recurrence between the groups with and without ADs. Conclusions: One or more types of ADs developed in AE patients, and patients with anti-LGI1 encephalitis had a higher frequency of autoimmune comorbidities than those with anti-NMDAR encephalitis. And we found that autoimmune comorbidities did not affect the clinical course of AE.

Clinical Features of 4 Novel NOTCH3 Mutations of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy in China.

BACKGROUND This study aimed to identify NOTCH3 mutations and describe the genetic and clinical features and magnetic resonance imaging results in 11 unrelated patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) from Henan province in China. MATERIAL AND METHODS NOTCH3 was directly sequenced in 11 unrelated patients of Chinese descent. The clinical presentations and magnetic resonance imaging features were retrospectively analyzed in the 11 index patients with a definite diagnosis. RESULTS Seven different mutations were identified in 11 unrelated patients, including 4 novel mutations (p.P167S, p.P652S, p.C709R, and p.R1100H) in China and 3 reported mutations (p.C117R, p.R578C, and p.R607C). Four novel mutations (p.P167S, p.P652S, p.C709R, and p.R1100H) were predicted to be probably pathogenic using an online pathogenicity prediction program through comprehensive analysis. Clinical presentations in symptomatic patients included stroke, cognitive decline, psychiatric disturbances, and migraine. Multiple lacunars infarcts and leukoaraiosis were detected on MRI in most symptomatic patients, while white-matter lesions were identified in the temporal pole or the external capsule in all affected patients. CONCLUSIONS The mutation spectrum of CADASIL patients from Henan province in China displayed some differences from that of those reported previously. DNA sequencing was used to diagnose all 11 patients as having CADASIL, and we found 4 novel mutations. The present results further contribute to the enrichment of NOTCH3 mutation databases.

Gene mutations in a Han Chinese Alzheimer's disease cohort.

OBJECTIVE: Alzheimer's disease (AD) is the most common form of dementia characterized by memory loss at disease onset. The gene mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the frequent causes of AD. However, the clinical and genetic features of AD overlap with other neurodegenerative diseases. The present study aimed to identify the clinical and genetic characteristics in a Han Chinese AD cohort. METHODS: Detailed clinical assessment was applied to all the patients. We screened amyloid precursor protein (APP), PSEN1, PSEN2, and microtubule-associated protein tau (MAPT) genes were assessed in 83 sporadic AD patients by Sanger sequencing. A total of 25 probands from families with AD were subjected to next-generation sequencing on 53 dementia-associated genes to capture the target region, and Sanger sequencing was used to detect the variants in the DNA sequence. RESULTS: PSEN1 p.L226R was found in an early-onset AD (EOAD) family characterized by language impairment at disease onset, a novel probably pathogenetic variant (p.D534H) was identified in a frontal-temporal dementia gene, TANK-binding kinase 1 (TBK1) with a typical AD phenotype in a late-onset AD (LOAD) family, and a PSEN2p.H169N mutation and two benign MAPT (p.Q230R and p.V48L) mutations were detected in three EOAD patients. CONCLUSIONS: Thus, five variants were identified in a Han Chinese cohort. In the present study, a novel, probably damaging FTLD gene TBK1variant with a typical AD phenotype was detected. Also, the phenotypic characteristics of PSEN1 p.L226R, a PSEN2pathogenic mutation, and two likely benign MAPT variants were described. Hence, screening for mutations in other dementia genes could be further explored in clinically diagnosed AD patients.

[CADASIL with clinical manifestations of baldness, lumbago and Parkinson's symptoms].

OBJECTIVE: To investigate a cerebral autosomal dominant arteriopathy with the subcortical infarcts and leukoencephalopathy (CADASIL) case with clinical manifestations of baldness, lumbago and Parkinson's symptoms. METHODS: Clinical and imaging data of the patient were analyzed. The patient and his family members were also subjected to genetic testing. RESULTS: The symptoms of the patient included recurrent stroke, dementia, and mood disturbance, in addition with lumbago, baldness and Parkinson's symptoms but no migraine. Cranial MRI of the patient showed bilateral symmetric leukoencephalopathy and multiple small subcortical lacunar infarcts. A point mutation in exon 11 of the NOTCH3 gene (R558C) was discovered in the proband and four asymptomatic relatives. CONCLUSION: CADASIL is characterized by recurrent subcortical ischemic stroke, dementia, pseudobulbar palsy, and mood disturbance. Baldness, lumbago and Parkinson's symptoms may also be seen in such patients.

A novel SYNE1 gene mutation in a Chinese family of Emery-Dreifuss muscular dystrophy-like.

BACKGROUND: In the present study, a novel mutation in exon 46 at codon 2304 (G2304R) of the SYNE1 gene is described in a Chinese family (proband, mother, and sister) with Emery-Dreifuss muscular dystrophy-like, which clinically manifests as muscle weakness, muscle atrophy, joint contracture, and without significant cardiac abnormalities. METHODS: Clinical examination and neuroimaging of the captured target region and high-throughput sequencing were performed in a family of four generations. Muscle changes were evaluated using magnetic resonance imaging and muscle biopsies. RESULTS: Target region capture sequencing yielded a novel missense mutation in codon 2304 (G2304R), which is a heterozygous A to G point mutation at position 6910 (c.6910A > G) in exon 46 of SYNE1 leading to a glycine-to-arginine substitution (p.Gly2304Arg). The results were also identified by Sanger sequencing in three family members but not in the other three unaffected family members and 100 control subjects. CONCLUSIONS: This mutation is probably pathogenic and is the first of its kind reported in a familial Emery-Dreifuss muscular dystrophy-like.