Cerebrospinal Fluid 7-Ketocholesterol Level is Associated with Amyloid-β42 and White Matter Microstructure in Cognitively Healthy Adults

Background:Abnormal cholesterol metabolism changes the neuronal membrane and may promote amyloidogenesis. Oxysterols in cerebrospinal fluid (CSF) are related to Alzheimer’s disease (AD) biomarkers in mild cognitive impairment and dementia. Cholesterol turnover is important for axonal and white matter (WM) microstructure maintenance. Objective:We aim to demonstrate that the association of oxysterols, AD biomarkers, and WM microstructure occurs early in asymptomatic individuals. Methods:We studied the association of inter-individual variability of CSF 24-hydroxycholesterol (24-OHC), 27-hydroxycholesterol (27-OHC), 7-ketocholesterol (7-KC), 7β-hydroxycholesterol (7β-OHC), amyloid-β42 (Aβ42), total-tau (t-tau), phosphorylated-tau (p-tau), neurofilament (NfL), and WM microstructure using diffusion tensor imaging, generalized linear models and moderation/mediation analyses in 153 healthy adults. Results:Higher 7-KC levels were related to lower Aβ42, indicative of greater AD pathology (p = 0.041) . Higher 7-KC levels were related to lower fractional anisotropy (FA) and higher mean (MD), axial (AxD), and radial (RD) diffusivity. 7-KC modulated the association between AxD and NfL in the corpus callosum splenium (B = 39.39, p = 0.017), genu (B = 68.64, p = 0.000), and fornix (B = 10.97, p = 0.000). Lower Aβ42 levels were associated to lower FA and higher MD, AxD, and RD in the fornix, corpus callosum, inferior longitudinal fasciculus, and hippocampus. The association between AxD and Aβ42 was moderated by 7K-C (p = 0.048). Conclusion:This study adds clinical evidence to support the role of 7K-C on axonal integrity and the involvement of cholesterol metabolism in the Aβ42 generation process

Down Syndrome—Basque Alzheimer Initiative (DS-BAI): Clinic-Biological Cohort

Background: Down syndrome (DS) is the most common genetically determined intellectual disability. In recent decades, it has experienced an exponential increase in life expectancy, leading to a rise in age-related diseases, including Alzheimer’s disease (AD). Specific health plans for the comprehensive care of the DS community are an unmet need, which is crucial for the early and accurate diagnosis of main medical comorbidities. We present the protocol of a newly created clinical and research cohort and its feasibility in real life. Methods: The Down Syndrome—Basque Alzheimer Initiative (DS-BAI) is a population-based, inclusive, multidisciplinary initiative for the clinical-assistance and clinical-biological research approach to aging in DS led by the CITA-Alzheimer Foundation (Donostia, Basque Country). It aims to achieve the following: (1) provide comprehensive care for adults with DS, (2) optimize access to rigorous and quality training for socio-family and healthcare references, and (3) create a valuable multimodal clinical-biological research platform. Results: During the first year, 114 adults with DS joined the initiative, with 36% of them showing symptoms indicative of AD. Furthermore, adherence to training programs for healthcare professionals and families has been high, and the willingness to collaborate in basic and translational research has been encouraging. Conclusion: Specific health plans for DS and conducting clinical and translational research on the challenges of aging, including AD, are necessary and feasible

Additional file 1 of GOIZ ZAINDU study: a FINGER-like multidomain lifestyle intervention feasibility randomized trial to prevent dementia in Southern Europe

Additional file 1: Table 1S. Adherence degrees to each intervention component. Table 2S. Baseline cognitive performance per group. Table 3S. Post-intervention characteristics per groups. Table 4S. Effect of intervention in cognitive change between pre-intervention and post-intervention visits per group. Table 5S. Effect of intervention in cognitive change between pre-intervention and post-intervention visits per groups. Table 6S. Baseline demographic, CAIDE, and Cognition characteristics differences between good and bad adherence groups. Table 7S. Cognitive domain z scores at pre-intervention and post-intervention visits. Table 8S. Cognitive z scores at pre-intervention and post-intervention visits per group. Figure 1S. Number of participants in each adherence category

Late twentieth-century patterns and trends in Amazon tree turnover

Previous work found that tree turnover, biomass, and large liana densities increased in mature tropical forests in the late 20th century, indicating a concerted shift in forest ecological processes. However, the findings have proved controversial. Here, regional-scale patterns of tree turnover are characterized, using improved datasets available for Amazonia that span the last twenty-five years. The main findings include: trees at least 10 cm in diameter recruit and die twice as fast on the richer soils of western Amazonia compared to trees on the poorer soils of eastern Amazonia; turnover rates have increased throughout Amazonia over the last two decades; mortality and recruitment rates have tended to increase in every region and environmental zone; recruitment rates consistently exceed mortality rates; and increases in recruitment and mortality rates are greatest in western Amazonia. These patterns and trends are not caused by obvious artefacts in the data or the analyses, and cannot be directly driven by a mortality driver such as increased drought because the biomass in these forests has simultaneously increased. Apparently, therefore, widespread environmental changes are stimulating the growth and productivity of Amazon forests. © The Royal Society 2005. All rights reserved