Fossgotfredsen9406

Cerebrospinal fluid (CSF) synaptosomal-associated protein 25 (SNAP-25) and neurogranin (Ng) are recently described biomarkers for pre- and postsynaptic integrity known to be elevated in symptomatic Alzheimer disease (AD). Their relationship with Apolipoprotein E (APOE) ε4 carrier status, the major genetic risk factor for AD, remains unclear. In this study, CSF SNAP-25 and Ng were compared in cognitively normal APOE ε4 carriers and noncarriers (n = 274, mean age 65 ± 9.0 years, 39% APOE ε4 carriers, 58% female). CSF SNAP-25, not CSF Ng, was specifically elevated in APOE ε4 carriers versus noncarriers (5.95 ± 1.72 pg/mL, 4.44 ± 1.40 pg/mL, p less then 0.0001), even after adjusting for age, sex, years of education, and amyloid status (p less then 0.0001). CSF total tau (t-tau), phosphorylated-tau-181 (ptau181), and neurofilament light chain (NfL) also did not vary by APOE ε4 status. Our findings suggest APOE ε4 carriers have amyloid-related and amyloid-independent presynaptic disruption as reflected by elevated CSF SNAP-25 levels. In contrast, postsynaptic disruption as reflected by elevations in CSF neurogranin is related to amyloid status.Given the controversy about the impact of modifiable risk factors on mood and cognition in ageing, we sought to investigate the associations between cardio-vascular risk, mental health, cognitive performance and brain anatomy in mid- to old age. We analyzed a set of risk factors together with multi-parameter magnetic resonance imaging (MRI) in the CoLaus|PsyCoLaus cohort (n > 1200). Cardio-vascular risk was associated with differences in brain tissue properties - myelin, free tissue water, iron content - and regional brain volumes that we interpret in the context of micro-vascular hypoxic lesions and neurodegeneration. The interaction between clinical subtypes of major depressive disorder and cardio-vascular risk factors showed differential associations with brain structure depending on individuals' lifetime trajectory. There was a negative correlation between melancholic depression, anxiety and MRI markers of myelin and iron content in the hippocampus and anterior cingulate. Verbal memory and verbal fluency performance were positively correlated with left amygdala volumes. The concomitant analysis of brain morphometry and tissue properties allowed for a neuro-biological interpretation of the link between modifiable risk factors and brain health.Diffusion MRI (dMRI) has been able to detect early structural changes related to neurological symptoms present in Huntington's disease (HD). However, there is still a knowledge gap to interpret the biological significance at early neuropathological stages. The purpose of this study is two-fold (i) establish if the combination of Ultra-High Field Diffusion MRI (UHFD-MRI) techniques can add a more comprehensive analysis of the early microstructural changes observed in HD, and (ii) evaluate if early changes in dMRI microstructural parameters can be linked to cellular biomarkers of neuroinflammation. Ultra-high field magnet (16.7T), diffusion tensor imaging (DTI), and neurite orientation dispersion and density imaging (NODDI) techniques were applied to fixed ex-vivo brains of a preclinical model of HD (R6/1 mice). Fractional anisotropy (FA) was decreased in deep and superficial grey matter (GM) as well as white matter (WM) brain regions with well-known early HD microstructure and connectivity pathology. NODDI parameters associated with the intracellular and extracellular compartment, such as intracellular ventricular fraction (ICVF), orientation dispersion index (ODI), and isotropic volume fractions (IsoVF) were altered in R6/1 mice GM. Further, histological studies in these areas showed that glia cell markers associated with neuroinflammation (GFAP & Iba1) were consistent with the dMRI findings. dMRI can be used to extract non-invasive information of neuropathological events present in the early stages of HD. The combination of multiple imaging techniques represents a better approach to understand the neuropathological process allowing the early diagnosis and neuromonitoring of patients affected by HD.External warning cues temporarily increase the brain's sensitivity for upcoming events, helping individuals to flexibly adapt their reactions to the requirements of complex visual environments. Previous studies reported that younger and cognitively normal older adults profit from phasic alerting cues. Such an intact phasic alerting mechanism could be even more relevant in individuals with Alzheimer's disease who are characterized by reduced processing capacities. The present study employed a theory of visual attention based verbal whole report paradigm with auditory cues in order to investigate phasic alerting effects in amnestic mild cognitive impairment (aMCI). Patients with aMCI were also compared to a previously reported sample of cognitively normal older adults. In patients with aMCI, visual processing speed was higher in the cue compared to the no-cue condition. Further, visual processing speed was reduced in patients with aMCI compared to cognitively normal older adults. Taken together, the results suggest that the processing system of patients with aMCI exhibits general declines but can still integrate auditory warning signals on a perceptual level.This study examined the effect of neurodegeneration, and its interaction with Alzheimer's disease (AD) cerebrospinal fluid biomarkers, on longitudinal verbal learning and memory performance in cognitively unimpaired (CU) late middle-aged adults. Three hundred and forty-two CU adults (cognitive baseline mean age = 58.4), with cerebrospinal fluid and structural MRI, completed 2-10 (median = 5) cognitive assessments. MEK inhibitor Learning and memory were assessed using the Rey Auditory Verbal Learning Test (RAVLT). We used sequential comparison of nested linear mixed effects models to analyze the data. Model selection preserved a significant ptau181/Aβ42 × global atrophy × age interaction; individuals with less global atrophy and lower ptau181/Aβ42 levels had less learning and delayed recall decline than individuals with more global atrophy and/or higher levels of ptau181/Aβ42. The hippocampal volume × age × ptau181/Aβ42 interaction was not significant. Findings suggest that in a sample of CU late middle-aged adults, individuals with AD biomarkers, global atrophy, or both evidence greater verbal learning and memory decline than individuals without either risk factor.