The functional connectivity of basal forebrain is associated with superior memory performance in older adults: a case-control study.

BACKGROUND: Aging is related with memory deterioration. However, some older adults demonstrate superior performance compared to age- and education-matched adults, who are referred to as superagers. To explore the neural mechanisms that mediate their unusually successful memory is important not only for the ameliorate the effects of aging in brain, but also for the prevention of neurodegenerative diseases, including Alzheimer's disease. This case-control study is aimed to investigate the effects of volume and function of basal forebrain cholinergic neurons on the cognition of superagers. METHODS: The morphometric and resting-state functional MRI analysis, including 34 superagers and 48 typical older adults, were conducted. We compared the basal forebrain gray matter density and related resting-state functional connectivity (FC) in the two groups. To investigate the relationship of FC with cognition, we measure the correlation of significant altered FC and individual cognitive domain. RESULTS: No significant differences of gray matter density was observed between superagers and typical older adults. The superagers had stronger cortical FC of Ch1-3 with left putamen and insular cortex. The strength of FC positively correlated with global cognition, memory and executive function. CONCLUSIONS: These findings demonstrated that the stronger FC of basal forebrain correlated with specific cognitive difference in global cognition and domains of memory and executive function in superagers.

[Expert consensus on clinical application of Compound Congrong Yizhi Capsules in treatment of vascular dementia].

Compound Congrong Yizhi Capsules is widely used in clinic for the long-term treatment and synergistic treatment of vascular cognitive impairment. After years of clinical observation, it has an obvious curative effect on the treatement of vascular cognitive impairment and has been recommended by multiple guidelines, consensuses, and series. This consensus was formulated for the treatment of vascular dementia. On the basis of summarizing the application experience of clinicians, and combined with the existing evidence-based evidence, 11 recommendations/consensus recommendations were finally reached through the nominal group method. The indications, usage and dosage, course of treatment, medication time, concomitant medication, and precautions of Congrong Yizhi Capsules in the treatment of vascular dementia were proposed, and the safety of the clinical application was described. This consensus is applicable to the use of Compound Congrong Yizhi Capsules in the treatment of patients with vascular dementia, and can be used by clinicians from the departments of encephalopathy(neurology), geriatrics, and traditional Chinese medicine in general hospitals. This consensus has been approved by China Association of Chinese Medicine, with the number of GS/CACM 298-2022.

Clinical and genetic study of ataxia with vitamin E deficiency: A case report.

BACKGROUND: Ataxia with vitamin E deficiency (AVED) is a type of autosomal recessive cerebellar ataxia. Clinical manifestations include progressive cerebellar ataxia and movement disorders. TTPA gene mutations cause the disease. CASE SUMMARY: We report the case of a 32-year-old woman who presented with progressive cerebellar ataxia, dysarthria, dystonic tremors and a remarkably decreased serum vitamin E concentration. Brain magnetic resonance images showed that her brainstem and cerebellum were within normal limits. Acquired causes of ataxia were excluded. Whole exome sequencing subsequently identified a novel homozygous variant (c.473T>C, p.F158S) of the TPPA gene. Bioinformatic analysis predicted that F185S is harmful to protein function. After supplementing the patient with vitamin E 400 mg three times per day for 2 years, her symptoms remained stable. CONCLUSION: We identified an AVED patient caused by novel mutation in TTPA gene. Our findings widen the known TTPA gene mutation spectrum.

N6-methyladenine-modified DNA was decreased in Alzheimer's disease patients.

BACKGROUND: In recent years, the prevalence of Alzheimer's disease (AD) has increased, which places a great burden on society and families and creates considerable challenges for medical services. N6-methyladenine (m6A) deoxyribonucleic acid (DNA) adenine methylation is a novel biomarker and is abundant in the brain, but less common in AD. We support to analyze the relationship between DNA m6A and cognition in patients with AD and normal controls (NCs) in China. AIM: To analyze the relationship between the novel m6A DNA and cognition in patients with AD and NCs in China. METHODS: A total of 179 AD patients (mean age 71.60 ± 9.89 years; males: 91; females: 88) and 147 NCs (mean age 69.59 ± 11.22 years; males: 77; females: 70) who were age- and sex-matched were included in our study. All subjects underwent neuropsychological scale assessment and magnetic resonance imaging examination. Apolipoprotein E (APOE) genotypes were measured through agarose gel electrophoresis. Global m6A levels were evaluated by a MethylFlash m6A DNA Methylation ELISA Kit (colorimetric). Global m6A levels in total DNA from ten AD patients with 18F-AV-45 (florbetapir) positron emission tomography (PET) positivity and ten NCs with PET negativity were analyzed by dot blotting to determine the results. RESULTS: Our ELISA results showed that the global m6A DNA levels in peripheral blood were different between patients with AD and NCs (P = 0.002; < 0.05). And ten AD patients who were PET positive and ten NCs who were PET negative also showed the same results through dot blotting. There were significant differences between the two groups, which indicated that the leukocyte m6A DNA levels were different (P = 0.005; < 0.05). The m6A level was approximately 8.33% lower in AD patients than in NCs (mean 0.011 ± 0.006 vs 0.012 ± 0.005). A significant correlation was found between the Montreal Cognitive Assessment score and the peripheral blood m6A level in the tested population (r = 0.143, P = 0.01; < 0.05). However, no relationship was found with APOE ε4 (P = 0.633, > 0.05). Further studies should be performed to validate these findings. CONCLUSION: Our results show that reduced global m6A DNA methylation levels are significantly lower in AD patients than in NCs by approximately 8.33% in China.

Corrigendum: Changes in Resting-State Functional Connectivity of Cerebellum in Amnestic Mild Cognitive Impairment and Alzheimer's Disease: A Case-Control Study.

[This corrects the article DOI: 10.3389/fnsys.2021.596221.].

Changes in Resting-State Functional Connectivity of Cerebellum in Amnestic Mild Cognitive Impairment and Alzheimer's Disease: A Case-Control Study.

This case-control study is aimed to investigate the correlation of altered functional connectivity (FC) in cerebellum with cognitive impairment in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). The morphometric and resting-state FC MRI analysis including 46 participants with AD, 32 with aMCI and 42 age-matched normal controls (NCs) were conducted. We compared the cerebellar gray matter volume and cerebellar FC with cerebral cortical regions among three groups. To investigate the relationship of cerebellar FC with cognition, we measure the correlation of significant altered FC and individual cognitive domain. No significant morphometric differences of cerebellum was observed across three groups. The patients with AD had weaker cerebral cortical FCs in bilateral Crus I and left VIIb compared to NCs, and in bilateral Crus I compared to patients with aMCI. For patients with aMCI, the weaker FC were found between right Crus I, left VIIb and cerebral cortical regions compared to NCs. The strength of left cerebellar FC positively correlated with specific cognitive subdomains, including memory, executive function, visuospatial function, and global cognition in AD and aMCI. These findings demonstrated the alteration of cerebellar FC with cerebral cortical regions, and the correlation of cerebellar FC and cognitive impairment in AD and aMCI.

Amide proton transfer magnetic resonance imaging of Alzheimer's disease at 3.0 Tesla: a preliminary study.

BACKGROUND: Amide proton transfer (APT) imaging has recently emerged as an important contrast mechanism for magnetic resonance imaging (MRI) in the field of molecular and cellular imaging. The aim of this study was to evaluate the feasibility of APT imaging to detect cerebral abnormality in patients with Alzheimer's disease (AD) at 3.0 Tesla. METHODS: Twenty AD patients (9 men and 11 women; age range, 67-83 years) and 20 age-matched normal controls (11 men and 9 women; age range, 63-82 years) underwent APT and traditional MRI examination on a 3.0 Tesla MRI system. The magnetic resonance ratio asymmetry (MTR asym ) values at 3.5 ppm of bilateral hippocampi (Hc), temporal white matter regions, occipital white matter regions, and cerebral peduncles were measured on oblique axial APT images. MTR asym (3.5 ppm) values of the cerebral structures between AD patients and control subjects were compared with independent samples t-test. Controlling for age, partial correlation analysis was used to investigate the associations between mini-mental state examination (MMSE) and the various MRI measures among AD patients. RESULTS: Compared with normal controls, MTR asym (3.5 ppm) values of bilateral Hc were significantly increased in AD patients (right 1.24% ± 0.21% vs. 0.83% ± 0.19%, left 1.18% ± 0.18% vs. 0.80%± 0.17%, t = 3.039, 3.328, P = 0.004, 0.002, respectively). MTR asym (3.5 ppm) values of bilateral Hc were significantly negatively correlated with MMSE (right r = -0.559, P = 0.013; left r = -0.461, P = 0.047). CONCLUSIONS: Increased MTR asym (3.5 ppm) values of bilateral Hc in AD patients and its strong correlations with MMSE suggest that APT imaging could potentially provide imaging biomarkers for the noninvasive molecular diagnosis of AD.

[Study on the mechanism of Alzheimer disease-related gene presenilin-1].

OBJECTIVE: To study the pathogenic mechanism of Alzheimer disease-related gene presenilin-1 (PS-1) mutation causing AD. METHODS: Four neural cells, including SY5Y cell, transgenic cells harboring PS-1 mutation, wild-type PS-1 and lipofectin were measured for neuronal Ca(2+) homeostasis and cell apoptosis. Intracellular calcium antagonist and antioxidant, such as Ginaton and nimodipine, were used in cultured neural cell and neuronal Ca(2+) level and cell apoptosis were examined. RESULTS: Elevation of intracellular calcium level and cell apoptosis induced by amyloid beta-peptide (Abeta) were enhanced in PS-1 mutation cell, as compared with others cells (P < 0.01). Intracellular calcium antagonist and antioxidant could inhibit apoptosis and decrease intracellular calcium level for PS-1 mutation (P > 0.05). There was significant correlation between the percentage of apoptosis and intracellular calcium level for PS-1 mutation. CONCLUSIONS: The pathogenic mechanism of PS-1 gene mutation causing AD was PS-1 mutation enhancing apoptosis by intracellular calcium overload. Intracellular calcium blocker and antioxidant could decrease intracellular calcium overload and inhibit apoptosis.

[Neuropsychiatric symptoms in dementia and elderly people in the community: results from the Beijing Dementia Cooperative Study].

OBJECTIVE: To determine the prevalence of neuropsychiatric symptoms in dementia and normal elderly people living in the Chinese community of Beijing. METHODS: A cross-sectional study derived from the Beijing Dementia Cooperative Study was carried out a population survey was carried out on a total of 1540 participants aged 65 years and older living in Beijing city and rural areas. All the individuals and 373 demented elderly people completed a series of neuropsychological examination and the Neuropsychiatric Inventory (NPI). RESULTS: Among the dementia participants, 49.33% had exhibited neuropsychiatric symptoms (35.66% rated as clinically significant), in which 80.4% reported 2 or more disturbances, with depression (23.86%), apathy (21.72%) and anxiety (20.38%) being most common. Of the 1540 normal individuals, 18.25% of them exhibited neuropsychiatric symptoms (6.49% rated as clinically significant), in which 53% reported 2 or more disturbances, with sleepless (10%), depression (8.9%) and anxiety (6.97%) being the most common. CONCLUSION: To our knowledge, this was the first multi-center study on neuropsychiatric disturbances in dementia and cognitive normal elderly people. Neuropsychiatric symptoms occurred mainly in persons with dementia and of clinical severity. Though the neuropsychiatric disturbances reported in cognitive normal individuals were lower and less serious compared to dementia, they should not be neglected. These finding suggested that a screening programme focusing on identifying these symptoms should be included in the physician's diagnostic tools for dementia.