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3%discrepancy (k = 0.68) for the baseline etiological diagnosis. The accuracy of the baseline etiological diagnosis was significantly higher at the consensus conference and was driven mainly by increased accuracy in the MCI group. Confidence in the etiological diagnosis at baseline was significantly higher at the consensus conference (p < 0.005), especially for the frontotemporal dementia diagnosis.
The multidisciplinary consensus conference performed better on diagnostic accuracy of disease etiology and increased clinicians' confidence. This highlights the importance of a multidisciplinary diagnostic evaluation approach for dementia diagnostics, especially when evaluating patients in the MCI stage.
The multidisciplinary consensus conference performed better on diagnostic accuracy of disease etiology and increased clinicians' confidence. This highlights the importance of a multidisciplinary diagnostic evaluation approach for dementia diagnostics, especially when evaluating patients in the MCI stage.Alzheimer's disease (AD) is the most prevalent neurodegenerative disease commonly diagnosed among the elderly population. AD is characterized by the loss of synaptic connections, neuronal death, and progressive cognitive impairment, attributed to the extracellular accumulation of senile plaques, composed by insoluble aggregates of amyloid-β (Aβ) peptides, and to the intraneuronal formation of neurofibrillary tangles shaped by hyperphosphorylated filaments of the microtubule-associated protein tau. However, evidence showed that chronic inflammatory responses, with long-lasting exacerbated release of proinflammatory cytokines by reactive glial cells, contribute to the pathophysiology of the disease. NLRP3 inflammasome (NLRP3), a cytosolic multiprotein complex sensor of a wide range of stimuli, was implicated in multiple neurological diseases, including AD. Herein, we review the most recent findings regarding the involvement of NLRP3 in the pathogenesis of AD. We address the mechanisms of NLRP3 priming and activation in glial cells by Aβ species and the potential role of neurofibrillary tangles and extracellular vesicles in disease progression. Neuronal death by NLRP3-mediated pyroptosis, driven by the interneuronal tau propagation, is also discussed. We present considerable evidence to claim that NLRP3 inhibition, is undoubtfully a potential therapeutic strategy for AD.Old age is critically associated with multi-morbidity, chronic pain, and high risk for dementia. Recognizing and treating pain is very much dependent on language comprehension and production. Both may be impaired in dementia. Moreover, neuropsychiatric symptoms may interact with pain perception. The main aims of the present article were 1) to identify key areas for future research to elucidate the relation between pain and associated neuropsychiatric symptoms in dementia, and 2) to provide a conceptual framework for ameliorating the clinical process of recognizing, assessing, and managing pain in non-communicating patients with advanced dementia.
Alzheimer's disease (AD) is a degenerative disorder, accompanied by progressive cognitive decline, for which there is no cure. Recently, the close correlation between AD and type 2 diabetes mellitus (T2DM) has been noted, and a promising anti-AD strategy is the use of anti-T2DM drugs.
To investigate if the novel glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist DA4-JC shows protective effects in the triple APP/PS1/tau mouse model of AD.
A battery of behavioral tests were followed by in vivo recording of long-term potentiation (LTP) in the hippocampus, quantified synapses using the Golgi method, and biochemical analysis of biomarkers.
DA4-JC improved cognitive impairment in a range of tests and relieved pathological features of APP/PS1/tau mice, enhanced LTP in the hippocampus, increased numbers of synapses and dendritic spines, upregulating levels of post-synaptic density protein 95 (PSD95) and synaptophysin (SYP), normalized volume and numbers of mitochondria and improving the phosphatase and tensin homologue induced putative kinase 1 (PINK1) - Parkin mitophagy signaling pathway, while downregulating amyloid, p-tau, and autophagy marker P62 levels.
DA4-JC is a promising drug for the treatment of AD.
DA4-JC is a promising drug for the treatment of AD.
Longitudinal, but not cross-sectional, cognitive testing is one option proposed to define transitional cognitive decline for individuals on the Alzheimer's disease continuum.
Compare diagnostic accuracy of cross-sectional subtle objective cognitive impairment (sOBJ) and longitudinal objective decline (ΔOBJ) over 30 months for identifying 1) cognitively unimpaired participants with preclinical Alzheimer's disease defined by elevated brain amyloid and tau (A+T+) and 2) incident mild cognitive impairment (MCI) based on Cogstate One Card Learning (OCL) accuracy performance.
Mayo Clinic Study of Aging cognitively unimpaired participants aged 50 + with amyloid and tau PET scans (n = 311) comprised the biomarker-defined sample. A case-control sample of participants aged 65 + remaining cognitively unimpaired for at least 30 months included 64 who subsequently developed MCI (incident MCI cases) and 184 controls, risk-set matched by age, sex, education, and visit number. sOBJ was assessed by OCL z-scores. ΔOBJ was assessed using within subjects' standard deviation and annualized change from linear regression or linear mixed effects (LME) models. Concordance measures Area Under the ROC Curve (AUC) or C-statistic and odds ratios (OR) from conditional logistic regression models were derived. sOBJ and ΔOBJ were modeled jointly to compare methods.
sOBJ and ΔOBJ-LME methods differentiated A+T+ from A-T- (AUC = 0.64, 0.69) and controls from incident MCI (C-statistic = 0.59, 0.69) better than chance; other ΔOBJ methods did not. ΔOBJ-LME improved prediction of future MCI over baseline sOBJ (p = 0.003) but not over 30-month sOBJ (p = 0.09).
Longitudinal decline did not offer substantial benefit over cross-sectional assessment in detecting preclinical Alzheimer's disease or incident MCI.
Longitudinal decline did not offer substantial benefit over cross-sectional assessment in detecting preclinical Alzheimer's disease or incident MCI.
There is a need for feasible, scalable assessments to detect cognitive impairment and decline. The Cogstate Brief Battery (CBB) is validated for Alzheimer's disease (AD) and in unsupervised and bring your own device contexts. The CBB has shown usability for self-completion in the home but has not been employed in this way in a multisite clinical trial in AD.
The objective of the pilot was to evaluate feasibility of at-home, self-completion of the CBB in the Alzheimer's Disease Neuroimaging Initiative (ADNI) over 24 months.
The CBB was included as a pilot for cognitively normal (CN) and mild cognitive impairment (MCI) participants in ADNI-2, invited to take the assessment in-clinic, then at at-home over a period of 24 months follow-up. Data were analyzed to explore acceptability/usability, concordance of in-clinic and at-home assessment, and validity.
Data were collected for 104 participants (46 CN, 51 MCI, and 7 AD) who consented to provide CBB data. Subsequent analyses were performed for the CN and MCI groups only. Test completion rates were 100%for both the first in-clinic supervised and first at-home unsupervised assessments, with few repeat performances required. However, availability follow-up data declined sharply over time. Good concordance was seen between in-clinic and at-home assessments, with non-significant and small effect size differences (Cohen's d between -0.04 and 0.28) and generally moderate correlations (r = 0.42 to 0.73). Known groups validity was also supported (11/16 comparisons with Cohen's d≥0.3).
These data demonstrate the feasibility of use for the CBB for unsupervised at-home, testing, including MCI groups. Optimal approaches to the application of assessments to support compliance over time remain to be determined.
These data demonstrate the feasibility of use for the CBB for unsupervised at-home, testing, including MCI groups. Optimal approaches to the application of assessments to support compliance over time remain to be determined.
Alzheimer's disease (AD) is characterized by cognitive impairment and large loss of grey matter volume and is the most prevalent form of dementia worldwide. Mild cognitive impairment (MCI) is the stage that precedes the AD dementia stage, but individuals with MCI do not always convert to the AD dementia stage, and it remains unclear why.
We aimed to assess grey matter loss across the brain at different stages of the clinical continuum of AD to gain a better understanding of disease progression.
In this large-cohort study (N = 1,386) using neuroimaging data from the Alzheimer's Disease Neuroimaging Initiative, voxel-based morphometry analyses were performed between healthy controls, individuals with early and late and AD dementia stage.
Clear patterns of grey matter loss in mostly hippocampal and temporal regions were found across clinical stages, though not yet in early MCI. MEK inhibitor cancer In contrast, thalamic volume loss seems one of the first signs of cognitive decline already during early MCI, whereas this volume loss does not further progress from late MCI to AD dementia stage. AD dementia stage converters already show grey matter loss in hippocampal and mid-temporal areas as well as the posterior thalamus (pulvinar) and angular gyrus at baseline.
This study confirms the role of temporal brain regions in AD development and suggests additional involvement of the thalamus/pulvinar and angular gyrus that may be linked to visuospatial, attentional, and memory related problems in both early MCI and AD dementia stage conversion.
This study confirms the role of temporal brain regions in AD development and suggests additional involvement of the thalamus/pulvinar and angular gyrus that may be linked to visuospatial, attentional, and memory related problems in both early MCI and AD dementia stage conversion.
Nutritional status has been recognized as an important factor influencing cognitive function-related diseases, but few comprehensive nutrition indicators are available to assess the risk of cognitive decline.
This study aimed to investigate the relationship between the prognostic nutritional index (PNI) and cognitive function in an elderly population, and the differences in nutrient intake between different levels of nutritional risk.
Based on cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014, we included 2,564 older participants. The lower quartile of each of the four cognitive tests was considered to have cognitive function impairment (CFI). Binary and multivariate logistic regression models were used to estimate the relationship between the PNI and the odds ratio of CFI.
After adjustment for confounding variables, we found that the odds of CFI were significantly lower for participants with normal PNI levels than for those with low PNI levels. In a comparison of global cognitive impairment scores, participants with a normal PNI had lower ratios of poor cognitive performance than those with a low PNI.
My Website: https://www.selleckchem.com/MEK.html
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