Dohertygold9956

The AB-ADs group showed a significant reduction in NAA/CR ratio in the left frontal cortex and Cho/Cr ratio in the left amygdala, and elevation in Glu/Cr ratio in the bilateral amygdala, compared with the NA-ADs group. The NAA/Cr ratio in the left frontal cortex was positively associated with immediate memory (r=0.60, P<0.05), and the Glu/Cr ratio in the right amygdala was negatively associated with delayed memory (r=-0.44,P<0.05) in AB-ADs group.

Metabolite alterations in the frontal cortex and amygdala may be involved in the pathophysiology of AB in AD and its associated cognitive impairment, especially immediate memory and delayed memory.

Metabolite alterations in the frontal cortex and amygdala may be involved in the pathophysiology of AB in AD and its associated cognitive impairment, especially immediate memory and delayed memory.Aging is the time-dependent functional decline that increases the vulnerability to different forms of stress, constituting the major risk factor for the development of neurodegenerative diseases. Dysfunctional mitochondria significantly contribute to aging phenotypes, accumulating particularly in post-mitotic cells, including neurons. To cope with deleterious effects, mitochondria feature different mechanisms for quality control. One such mechanism is the mitochondrial unfolded protein response (UPRMT), which corresponds to the transcriptional activation of mitochondrial chaperones, proteases, and antioxidant enzymes to repair defective mitochondria. Transcription of target UPRMT genes is epigenetically regulated by Histone 3-specific methylation. Age-dependency of this regulation could explain a differential UPRMT activity in early developmental stages or aged organisms. At the same time, precise tuning of mitochondrial stress responses is crucial for maintaining neuronal homeostasis. However, compared to other mitochondrial and stress response programs, the role of UPRMT in neurodegenerative disease is barely understood and studies in this topic are just emerging. In this review, we document the reported evidence characterizing the evolutionarily conserved regulation of the UPRMT and summarize the recent advances in understanding the role of the pathway in neurodegenerative diseases and aging.Vision, which requires extensive neural involvement, is often impaired in Alzheimer's disease (AD). Over the last few decades, accumulating evidence has shown that various visual functions and structures are compromised in Alzheimer's dementia and when measured can detect those with dementia from those with normal aging. These visual changes involve both the afferent and efferent parts of the visual system, which correspond to the sensory and eye movement aspects of vision, respectively. There are fewer, but a growing number of studies, that focus on the detection of predementia stages. Visual biomarkers that detect these stages are paramount in the development of successful disease-modifying therapies by identifying appropriate research participants and in identifying those who would receive future therapies. This review provides a summary and update on common afferent and efferent visual markers of AD with a focus on mild cognitive impairment (MCI) and preclinical disease detection. We further propose future directions in this area. Given the ease of performing visual tests, the accessibility of the eye, and advances in ocular technology, visual measures have the potential to be effective, practical, and non-invasive biomarkers of AD.

Recent studies regarding the relationships between plasma amyloid-β (Aβ) levels and cognitive performance had inconsistent results. In this study, we aimed to characterize the relationship between cognitive decline and plasma Aβ levels in a large-sample cognitively normal population.

This population-based, prospective cohort study included 1,240 participants with normal cognition. The Mini-Mental State Examination (MMSE) was used to assess cognitive function at baseline and 2 years later. Restricted cubic splines, multivariate logistic regression, and multivariate linear regression models were used to evaluate the type of relationship between cognitive decline during the 2-year follow-up period and plasma Aβ levels (Aβ

, Aβ

, and Aβ





).

Participants with moderate Aβ

levels had the highest risk of cognitive decline during a 2-year follow-up relative to individuals with low Aβ

[odds ratio (OR) 0.60, 95% confidence interval (CI) 0.45-0.81,

< 0.001] or high Aβ

(OR 0.65, 95% CI 0.49-0.87,

tively normal population. The underlying mechanism requires further investigation.Acetylcholinesterase inhibitors (AChEIs) including donepezil (DNP) are considered to be the most promising therapeutic possibilities of Alzheimer's disease (AD). The response to DNP in AD patients varies and it is valuable to identify the potential markers that can predict the efficacy. Moreover, DNP has been found to affect bone function, but the exact mechanism is still unclear. Lipids and adipokine may link to AD and DNP directly or indirectly and might be potential biomarkers or therapeutic drug targets. The goal of this study was to investigate the relationships among adiponectin (APN), lipids levels, and the response to DNP, and to identify whether the effect of DNP in AD treatment is related to its effect on the level of APN in systemic circulation. The study recruited 85 AD patients with DNP treatment, of whom 47 were DNP responders and 38 were DNP nonresponders. The Mini-Mental State Examination was performed to evaluate the memory impairment. Plasma APN was measured with ELISA. The genotypes of single nucleotide polymorphisms rs1501299 and rs22417661 in APN for each patient were identified. Plasma lipids were quantified with gas chromatography coupled with mass spectrometry. Correlations among APN, lipid metabolomics, and DNP responded were evaluated. APN was significantly decreased in DNP responders. Methyl stearate and glycerol-3-phosphate, used for characterizing adipogenic differentiation, were significantly decreased in DNP responders compared to DNP nonresponders. FF10101 APN and small-molecule lipids can be used as potential biomarkers to evaluate the efficacy of DNP. The results of metabolomics indicated that there was no change in the metabolic pathway of fatty acid metabolism and glucose metabolism in DNP responders, suggesting that APN-related biological function did not decrease in DNP responders. Our result suggests that more attention should be pay to the sources and biological functions of APN in AD with DNP treatment.