American Journal of Alzheimers Disease and Other Dementias最新文献

Most of neurodegenerative diseases (NDD) have no cure. The common etiology of neurodegenerations is unclear. Air pollutant-gaseous formaldehyde is notoriously known to induce demyelination and cognitive impairments. Unexpectedly, an amount of formaldehyde has been detected in the brains. Multiple factors can induce the generation and accumulation of endogenous formaldehyde. Excessive formaldehyde can induce oxidative stress to generate H₂O₂; in turn, H₂O₂ promote formaldehyde production. Clinical investigations have shown that an abnormal high level of formaldehyde but low level of coenzyme Q10 (coQ10) was observed in patients with NDD. Further studies have proven that excessive formaldehyde directly inactivates coQ10, reduces the ATP generation, enhances oxidative stress, initiates inflammation storm, induces demyelination; subsequently, it results in neurodegeneration. Although the low water solubility of coQ10 limits its clinical application, nanomicellar water-soluble coQ10 exhibits positive therapeutical effects. Hence, nanopackage of coQ10 may be a promising strategy for treating NDD.

Background: Shift work is associated with impaired sleep quality and disrupted circadian rhythms, but the way in which it increases the risk of dementia remains controversial. We conducted a systematic review and meta-analysis to assess the integrated risk of dementia with shift work. Methods: Searching in PubMed, Cochrane Library, and the Web of Science databases, the relative risks of dementia with shift work were extracted from 12 included studies with 3975 dementia cases from 84 492 participants. The subgroup analysis was stratified by age, gender, sample size, dementia cases, shift schedule, occupation, and follow-up time. Heterogeneity analysis and publication bias analysis were conducted for quality control. Results: The pooled risk ratios (RRs) of dementia with shift work were 1.15 (95%CI = 1.02-1.30). The subgroup analysis found that continuous evening shifts reversibly reduced the risk, but continuous night shifts remarkedly increased the risk of dementia. In addition, a larger cohort and longer follow-up significantly increased the risk of dementia with shift work. Conclusion: Shift work shows mild increases in the risk of dementia using meta-analysis.

Cognitive dysfunction is a very common postoperative complication. The study aimed at investigating the effects of ketamine on the cognition of elderly mice after anesthesia and surgery (AS). We reported that AS impaired the cognition of elderly mice, while ketamine helped to maintain the cognitive function. Ketamine decreased the levels of TNF-α, IL-6, IL-1β and the expression of p-TAU, S100B in hippocampal induced by AS. In addition, AS triggered severe oxidative stress in hippocampal, while ketamine inhibited it. Oxidative stress induced autophagy of hippocampal neurons via inhibiting PI3K/AKT/mTOR pathway. Ketamine could activate PI3K pathway and inhibit autophagy in hippocampal, thus maintain the loss of hippocampal neurons. The study suggested that ketamine inhibited the neuroinflammation and oxidative stress, reduced the autophagy of hippocampal neurons via PI3K/AKT/mTOR pathway. It may provide novel methods for the protection of cognitive function in elderly during perioperative period.

We described behavioral studies to highlight emotional processing deficits in Alzheimer's disease (AD). The findings suggest prominent deficit in recognizing negative emotions, pronounced effect of positive emotion on enhancing memory, and a critical role of cognitive deficits in manifesting emotional processing dysfunction in AD. We reviewed imaging studies to highlight morphometric and functional markers of hippocampal circuit dysfunction in emotional processing deficits. Despite amygdala reactivity to emotional stimuli, hippocampal dysfunction conduces to deficits in emotional memory. Finally, the reviewed studies implicating major neurotransmitter systems in anxiety and depression in AD supported altered cholinergic and noradrenergic signaling in AD emotional disorders. Overall, the studies showed altered emotions early in the course of illness and suggest the need of multimodal imaging for further investigations. Particularly, longitudinal studies with multiple behavioral paradigms translatable between preclinical and clinical models would provide data to elucidate the time course and underlying neurobiology of emotion processing dysfunction in AD.

The ketone bodies, especially the β-hydroxybutyrate, had been shown to modulate the function of the central nervous system and prevent the pathological progression of Alzheimer's disease (AD). However, little is known about the role of acetoacetate in the AD brain. Thus, we intraventricularly injected acetoacetate into familial AD mice (APPSWE) for 14 days and monitored their memory and biochemical changes. During the behavior test, acetoacetate at 100 mg/kg led to significant improvement in both Y-maze and novel object recognition tests (NORTs) (both P < .05), indicating ameliorating spatial and recognition memory, respectively. Biomedical tests revealed two mechanisms were involved. Firstly, acetoacetate inhibited the GPR43-pERK pathway, which led to apparent inhibition in tumor necrosis factor-α and Interleukin-6 expression in the hippocampus in a concentration-dependent manner. Secondarily, acetoacetate stimulated the expression of hippocampal brain-derived neurotrophic factor (BDNF). We concluded that acetoacetate could ameliorate AD symptoms and exhibited promising features as a therapeutic for AD.

Dementia is one of neurodegenerative disease without preventive medicine currently. Dextromethorphan (DXM) has been reported to reduce neuronal damage and neurodegeneration in animal and human models. The effect of DXM on the dementia has not been fully examined. We examined the medical records over 40 years old in Taiwan's National Health Insurance Research Database between 2000 and 2015 to establish matched cohorts. We used a Cox regression hazard model to identify risk factors of dementia during 16 years of follow-up, and the results indicate that a significantly lower percentage of subjects with DXM use (P < .001) developed dementia compared with those without DXM use (11.38%, 4541/39 895 vs 18.66%, 29 785/159 580). After adjustment for age and other variables [adjusted hazard ratio: .567 (95% confidence interval: .413-.678, P < .001)], this study also demonstrated that DXM use appeared to reduce the risk of developing dementia. DXM use may potentially provide a protective effect against dementia.

Objective: The present study aims to investigate the underlying neurochemical mechanism of physical exercise on striatum synapsis and memory function in vascular dementia model.

Methods: 32 Sprague-Dawley (SD) rats were randomly divided into 4 groups: control group (C group, n = 6), vascular dementia group (Vascular dementia group, n = 7), physical exercise and vascular dementia group (Exe-VD group, n = 6), physical exercise and black group (Exe group, n = 6). 4 weeks of voluntary wheel running were used as pre-exercise training. Vascular dementia model was established by bilateral common carotid arteries occlusion (BCCAo) for 1 week. Passive avoidance test (PAT) were used to test memory function. The level of striatum catecholamine in the microdialysate were detected by enzyme linked immunosorbent assy (ELISA). Golgi staining was used to analyze striatum neuronal spine density.

Results: Behavioral data indicated that 4 weeks of physical exercise ameliorated memory impairment in vascular dementia model. Striatum catecholamine level significantly decreased in VD group when compared with C group (P < .001). But this phenomenon can be rescue by physical exercise (P < .001). In addition, compared with C group, neuronal spine density significantly decreased in VD group (P < .01), but 4 weeks of physical exercise can rescue this phenomenon (P < .05).

Conclusion: 4 weeks of physical exercise improves memory function by mitigate the decline of striatum catecholamine and spine density in VD model.

Background: Dementia-friendly community has been promoted in Macao since 2016. There is no study investigating the understanding of nor attitudes towards dementia among public contact staff in Macao. This study aimed to (i) understand the level of knowledge of dementia, (ii) examine the attitudes towards people living with dementia, and (iii) explore the associated factors of the willingness to help people with dementia symptoms among police officers, bank officers, bus drivers, and building superintendents.

Methods: A cross-sectional survey was conducted between January and May 2019 using a structured questionnaire.

Results: A total of 351 valid questionnaires were received. Building superintendents had more knowledge while police officers and bank officers had more positive attitudes. All practitioners were more willing to help people with dementia symptoms when they were on official duty. Participants who had more knowledge about dementia were associated with a higher willingness to help people with dementia symptoms.

Objective: To study the evolution of the Tree Drawing Test (TDT) in a group of Alzheimer's disease (AD) patients.

Methods: A total of 33 AD patients were consecutively evaluated by Mini Mental State Evaluation (MMSE) and TDT. The evolution of the TDT parameters, trunk-to-crown (TC) and space occupation (SO) index, were analyzed.

Results: The median age at first visit was 79 years. Globally, trees drawn by patients showed an evolution characterized by a progressive reduction of the crown compared to the trunk. TC index showed a significant linear growth change (2.52 points per year) while SO index did not significantly increase. No significant associations were found examining the relations between MMSE and TC and SO index.

Conclusions: TDT could represent a complementary technique to the main neuropsychological screening tests for orienting cognitive impairment diagnosis and an aid in following the evolution of cognitive impairment over time in AD patients.

Backgrounds: Post-stroke cognitive dysfunction (PSCI), a set of illnesses ranging from moderate cognitive impairment to dementia, which is one of the most prevalent consequences following a stroke. Homocysteine (Hcy) has been related to a number of neurological and systemic diseases. It's also a known risk factor for cardiovascular disease and systemic atherosclerosis (CVD). The link between Hcy and PSCI, on the other hand, is unknown.

Methods: Our hospital evaluated 325 patients with acute cerebral infarction between January 1, 2018 and December 1, 2021. There are biological markers and baseline data available. Patients were divided into two groups based on the results of the Montreal Cognitive Assessment (MoCA). The researchers performed logistic regression analysis to find variables that may be linked to PSCI.

Results: HCY levels were significantly higher in PSCI patients than in non-PSCI patients. Age, education, seizure manifestation, and income level were all shown to be independent risk variables for PSCI in a multivariate logistic analysis. Hcy levels in PSCI patients differed considerably between the high and low groups. The high and low Hcy levels groups had significantly varied hypertension histories and urine levels. Hcy levels in PSCI patients differed considerably between the high and low groups. The high and low Hcy levels groups had significantly varied hypertension histories and urine levels.

Conclusion: Serum Hcy levels have been linked to PSCI in post-stroke patients, and researchers believe that serum Hcy levels will diminish PSCI.