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Introduction: Low educational attainment is a potential risk factor for Alzheimer's disease (AD) development. Alpha-secretase ADAM10 plays a central role in AD pathology, attenuating the formation of beta-amyloid peptides and, therefore, their aggregation into senile plaques. This study seeks to investigate ADAM10 as a blood-based biomarker in mild cognitive impairment (MCI) and AD in a diverse group of community-dwelling older adults, focusing on those with limited educational attainment., Methods: Participants were recruited from public health services. Cognition was evaluated using Mini-Mental State Examination (MMSE) and Addenbrooke's Cognitive Examination - Revised (ACE-R) batteries. Blood samples were collected to analyze plasma ADAM10 levels. A logistic regression was conducted to verify the influence of plasma ADAM10 on the AD diagnosis., Results: Significant differences in age, years of education, prescribed medications, and cognitive test scores were found between the MCI and AD groups. Regarding cognitive performance, both ACE-R and MMSE scores displayed significant differences between groups, with post hoc analyses highlighting these distinctions, particularly between AD and cognitively unimpaired individuals. Elevated plasma ADAM10 levels were associated with a 4.5-fold increase in the likelihood of a diagnosis of MCI and a 5.9-fold increase in the likelihood of a diagnosis of AD. These findings suggest ADAM10 levels in plasma as a valuable biomarker for assessing cognitive status in older individuals with low education attainment., Conclusion: This study underscores the potential utility of plasma ADAM10 levels as a blood-based biomarker for cognitive status, especially in individuals with low educational backgrounds, shedding light on their relevance in AD development and diagnosis., (© 2024 S. Karger AG, Basel.)

Background: Age-related hearing loss (ARHL) is prevalent in adults over 70, impairing hearing sensitivity and speech perception. ARHL has been linked to an increased risk of cognitive decline and dementia. However, most affected adults are not receiving adequate treatment, including hearing aids., Objective: This study aimed to evaluate the impact of ARHL on cognitive decline in older adults participating in the Irish Longitudinal Study on Aging (TILDA)., Design: METHODS: Data from four TILDA waves, a 6-year follow-up, was collected and analyzed using zero-inflated Poisson regression. The primary outcome, cognitive function, was assessed using Mini-Mental State Examination (MMSE) total score and error counts., Results: Our analysis revealed that age, education, use of aids to help with hearing, and history of stroke were significantly associated with error counts at baseline. Additionally, poor hearing was associated with a negative change in MMSE score from wave 4, indicating the potential role of ARHL in cognitive decline. When further adjusted for age, sex, history of stroke, hypertension, any emotional, nervous, or psychiatric problem, polypharmacy, and hearing aids, the zero-inflated Poisson model indicated that poor hearing, use of hearing aids, stroke, hypertension, and polypharmacy all predicted MMSE error counts in follow-up assessments. Moreover, the use of hearing aids was associated with a decreased likelihood of cognitive decline., Conclusion: ARHL was independently associated with cognitive decline, underscoring the importance of addressing hearing loss in older adults. Future research should explore the potential of hearing aids to protect cognitive functioning in older adults., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Mild cognitive impairment (MCI) associated with physical frailty gave rise to the new concept of cognitive frailty. Previous studies have suggested that MCI may represent a condition that precedes Alzheimer's disease (AD), in view of its higher conversion rate to dementia, when compared with the conversion rate of cognitively healthy older adults. Therefore, and considering that MCI represents a reversible condition, the identification of biomarkers for this condition is imperative to early diagnosis. Accordingly, this study aimed to assess whether the platelet and plasma levels of ADAM10 could be related with the concomitant conditions of MCI and physical frailty, in order to support a new blood-based biomarker for the construct of cognitive frailty. Sixty-one adults aged 60 years or older participated in this study. The results showed that ADAM10 levels are reduced in platelets (p < 0.05) and increased in plasma (p < 0.05) of older adults with MCI compared to healthy controls, regardless of the physical frailty condition. The analysis of the ROC curve of ADAM10 in platelets showed sensitivity and specificity of 72.7 and 73.9%, respectively, to correct differentiate between participants with preserved cognition from those with MCI. For plasma samples, ADAM10 presented 62.5 and 90.0%, sensitivity and specificity respectively, to differentiate the aforementioned conditions. Together with other clinical criteria blood ADAM10 could be a relevant, low-invasive, low-cost and fast processing biomarker tool to help in the early and accurate diagnosis of MCI, however this marker was not able to identify cognitive frailty., (Copyright © 2021 Elsevier Inc. All rights reserved.)

ADAM10 is the main α-secretase that participates in the non-amyloidogenic cleavage of amyloid precursor protein (APP) in neurons, inhibiting the production of β-amyloid peptide (Aβ) in Alzheimer's disease (AD). Strong recent evidence indicates the importance of the localization of ADAM10 for its activity as a protease. In this study, we investigated ADAM10 activity in plasma and CSF samples of patients with amnestic mild cognitive impairment (aMCI) and mild AD compared with cognitively healthy controls. Our results indicated that plasma levels of soluble ADAM10 were significantly increased in the mild AD group, and that in these samples the protease was inactive, as determined by activity assays. The same results were observed in CSF samples, indicating that the increased plasma ADAM10 levels reflect the levels found in the central nervous system. In SH-SY5Y neuroblastoma cells, ADAM10 achieves its major protease activity in the fraction obtained from plasma membrane lysis, where the mature form of the enzyme is detected, confirming the importance of ADAM10 localization for its activity. Taken together, our results demonstrate the potential of plasma ADAM10 to act as a biomarker for AD, highlighting its advantages as a less invasive, easier, faster, and lower-cost processing procedure, compared to existing biomarkers.

The benefits of physical exercise to reduce low-grade inflammation and improve Brain-Derived Neurotrophic Factor (BDNF) levels and cognitive function became a growing field of interest. Low-grade inflammation is common during aging and seems to be linked to neurodegenerative process. Regular physical exercises can help to reduce pro-inflammatory cytokines levels and to improve BDNF peripheral concentrations. The main goal of this research was to analyze the effects of a 16-week multimodal physical exercise program on peripheral BDNF levels and on Tumor Necrosis-α (TNF-α) and Interleukin- 6 (IL-6) as pro-inflammatory markers in cognitive healthy elderly individuals and in elderly with mild cognitive impairment (MCI). Cognitive functions were assessed by the Montreal Cognitive Assessment (MoCA) prior to and after the intervention. Thirty cognitively healthy participants and thirty-seven MCI participants were assigned to the control (CG) and trained (TG) groups. The TG participated in a multimodal physical training program for a 16-week period. The results showed a significant between-subjects interaction, which indicates the beneficial contribution of training on the reduction of TNF-α (p=0.001) and IL-6 (p<0.001) and on the improvement of BDNF (p<0.001) peripheral concentrations. Cognitive functions also presented significant improvements for MCI trained group (p=0.03). In conclusion, physical exercise was effective to reduce pro-inflammatory cytokines and to improve BDNF peripheral levels, with positive reflexes on cognition. To the best of our knowledge, this is the first study that evaluated longitudinally the effects of a multimodal physical exercises protocol on peripheral concentrations of pro-inflammatory cytokines and cognition performance in elderly MCI individuals.