Functional Connectome Analysis in Mild Cognitive Impairment: Comparing Alzheimer's Disease Continuum and Suspected Non-Alzheimer Pathology.

Introduction: Research in brain resting-state functional connectivity (FC) analysis in mild cognitive impairment (MCI) has conflicting results. This work intends to find differences in resting-state FC of 2 groups of MCI subjects due to Alzheimer's disease (MCI-AD) continuum or to suspected non-Alzheimer pathology (MCI-SNAP). Materials and Methods: Ninety-two subjects older than 55 years were enrolled. MCI and controls were grouped using clinical dementia rating and neuropsychological data. Cerebrospinal fluid biomarkers were collected from MCI subjects, resulting in 32 MCI-AD, 25 MCI-SNAP, and 35 controls. A region of interest (ROI)-to-ROI analysis was carried out looking at inter- and intranetwork interactions selecting the following networks: default mode network (DMN), salience network (SN), visuospatial network (VN), and executive network. Pearson correlation coefficients, converted to Z-scores, were compared by T-tests with alpha set to 0.05, and false discovery rate corrected. Results: Groups were similar in age, education, and demographic measures, there were no differences in neuropsychological data between the MCI groups. The ROI-to-ROI analysis of MCI-AD versus MCI-SNAP showed no differences. MCI-AD versus controls showed decreased FC between ROIs of the SN and between ROIs from SN and VN. MCI-SNAP versus controls showed increased FC between an ROI of DMN and VN. Discussion: SN, DMN, and VN are multimodal networks with high value/high cost and may be more vulnerable to AD pathogenic processes. SN and VN were affected in the MCI-AD group, with maintained anticorrelation between DMN and VN. This may indicate subthreshold DMN dysfunction. The result in MCI-SNAP, although discrete, reflects a rearrangement of brain FC, as DMN and VN are expected to be anticorrelated. More research is necessary to confirm these findings.

ADAM10 Plasma and CSF Levels Are Increased in Mild Alzheimer's Disease.

ADAM10 is the main α-secretase that participates in the non-amyloidogenic cleavage of amyloid precursor protein (APP) in neurons, inhibiting the production of ß-amyloid peptide (Aß) 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.

Dementia in Latin America: Paving the way toward a regional action plan.

Across Latin American and Caribbean countries (LACs), the fight against dementia faces pressing challenges, such as heterogeneity, diversity, political instability, and socioeconomic disparities. These can be addressed more effectively in a collaborative setting that fosters open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking, and translational research) and align them to current global strategies to translate regional knowledge into transformative actions. Then we characterize key sources of complexity (genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions), map them to the above challenges, and provide the basic mosaics of knowledge toward a KtAF. Finally, we describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF.