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showing 10 items of 5435 documents
Cholesterol Hydroxylating Cytochrome P450 46A1: From Mechanisms of Action to Clinical Applications
2021
Cholesterol, an essential component of the brain, and its local metabolism are involved in many neurodegenerative diseases. The blood-brain barrier is impermeable to cholesterol; hence, cholesterol homeostasis in the central nervous system represents a balance betweenin situbiosynthesis and elimination. Cytochrome P450 46A1 (CYP46A1), a central nervous system-specific enzyme, converts cholesterol to 24-hydroxycholesterol, which can freely cross the blood-brain barrier and be degraded in the liver. By the dual action of initiating cholesterol efflux and activating the cholesterol synthesis pathway, CYP46A1 is the key enzyme that ensures brain cholesterol turnover. In humans and mouse models,…
Neuropsychiatric Symptoms as Predictors of Clinical Course in Neurodegeneration. A Longitudinal Study
2019
Background: To study the extent to which neuropsychiatric symptoms (NPS) influence the cognitive and functional decline in frontotemporal degeneration (FTD) and Alzheimer’s disease (AD). Methods: We assessed the progression of NPS and their influence on cognitive and functional progression in a group of FTD (n = 36) and AD patients (n = 47) at two different stages of the disease (2.5 years). A standardized scale was used to assess NPS—the Columbia University Scale for Psychopathology in Alzheimer’s Disease (CUSPAD)—which tracks different symptoms including depression, psychotic symptoms, as well as sleep and conduct problems. In addition, in a subsample of patients (AD n = 14 and FTD n = 14…
Microglia in Alzheimer’s Disease: Activated, Dysfunctional or Degenerative
2018
Microglial activation has been considered a crucial player in the pathological process of multiple human neurodegenerative diseases. In some of these pathologies, such as Amyotrophic Lateral Sclerosis or Multiple Sclerosis, the immune system and microglial cells (as part of the cerebral immunity) play a central role. In other degenerative processes, such as Alzheimer’s disease (AD), the role of microglia is far to be elucidated. In this “mini-review” article, we briefly highlight our recent data comparing the microglial response between amyloidogenic transgenic models, such as APP/PS1 and AD patients. Since the AD pathology could display regional heterogeneity, we focus our work at the hipp…
Heterogeneous Indicators of Cognitive Performance and Performance Variability Across the Lifespan
2020
Reaction time (RT) and RT variability are core components of cognitive performance that can be captured through brief and easy-to-administer tasks of simple RT and choice RT. The current study aims to describe age-related differences in cognitive performance, toward better characterizing normative performance across the lifespan. We examined mean and variability of response times on a simple RT and choice RT tasks in a large and diverse web-based sample (10,060 visitors to TestMyBrain.org). We also examined lifespan-related differences in response time variability using multiple different approaches (raw variability, mean scaled variability, and mean residualized variability). These analyse…
Differential Associations of IL-4 With Hippocampal Subfields in Mild Cognitive Impairment and Alzheimer’s Disease
2019
Background/Aims: A bi-directional communication between the immune system and the central nervous system has been recently suggested. Among many cytokines, the role of IL-4 - with anti-inflammatory properties- in counteracting age-related inflammatory changes in the brain is strongly supported among studies. With this study, we aimed at investigating the association between volumetric measures of hippocampal subregions -in healthy older controls (HC), subjects affected by mild cognitive impairment (MCI) and Alzheimer’s Disease (AD)- with circulating levels of IL-4. Methods: From AddNeuroMed Project 113 HC, 101 stable MCI (sMCI), 22 converter MCI (cMCI) and 119 AD were included. Hippocampal …
Determinants of Quality of Life According to Cognitive Status in Parkinson’s Disease
2020
Background: Quality of life (QoL) was worse in Parkinson's disease patients with mild cognitive impairment (PD-MCI) or dementia (PDD) than PD patients with normal cognition (PD-NC). The aim of this study was to investigate and compare the potential heterogeneous determinants of QoL in PD patients with different cognitive statuses. Methods: We recruited 600 PD patients, including 185 PD-NC patients, 336 PD-MCI patients and 79 PDD patients, in this cross-sectional study. All patients completed the QoL assessment by the 39-item Parkinson's Disease Questionnaire (PDQ-39), as well as clinical evaluations and neuropsychological tests. The determinants of the QoL were analysed by multiple stepwise…
Incidence of Mild Cognitive Impairment and Dementia in Parkinson's Disease: The Parkinson's Disease Cognitive Impairment Study.
2018
Background: Cognitive impairment in Parkinson's disease (PD) includes a spectrum varying from Mild Cognitive Impairment (PD-MCI) to PD Dementia (PDD). The main aim of the present study is to evaluate the incidence of PD-MCI, its rate of progression to dementia, and to identify demographic and clinical characteristics which predict cognitive impairment in PD patients. Methods: PD patients from a large hospital-based cohort who underwent at least two comprehensive neuropsychological evaluations were retrospectively enrolled in the study. PD-MCI and PDD were diagnosed according to the Movement Disorder Society criteria. Incidence rates of PD-MCI and PDD were estimated. Clinical and demographic…
Precuneus Dysfunction in Parkinson's Disease With Mild Cognitive Impairment.
2018
Background: Mild cognitive impairment (MCI) frequently occurs in Parkinson's disease (PD). Neurovascular changes interact with neurodegenerative processes in PD. However, the deficits of cerebral blood flow (CBF) perfusion and the associated functional connectivity (FC) in PD patients with MCI (PD-MCI) remain unclear. Purpose: This study aimed to explore the specific neurovascular perfusion alterations in PD-MCI compared to PD with normal cognition (PD-NC) and healthy controls (HCs), and to further examine the resultant whole brain FC changes in the abnormal perfusion regions. Methods: Relative CBF (rCBF) was calculated using arterial spin labeling (ASL) in 54 patients with PD (27 patients …
Effects of Chronic Dopamine D2R Agonist Treatment and Polysialic Acid Depletion on Dendritic Spine Density and Excitatory Neurotransmission in the mP…
2016
Dopamine D2 receptors (D2R) in the medial prefrontal cortex (mPFC) are key players in the etiology and therapeutics of schizophrenia. The overactivation of these receptors contributes to mPFC dysfunction. Chronic treatment with D2R agonists modifies the expression of molecules implicated in neuronal structural plasticity, synaptic function, and inhibitory neurotransmission, which are also altered in schizophrenia. These changes are dependent on the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-related molecule, but nothing is known about the effects of D2R and PSA-NCAM on excitatory neurotransmission and the structure of mPFC pyramidal n…
Tillage intensity and pasture in rotation effectively shape soil microbial communities at a landscape scale
2018
International audience; Soil microorganisms are essential to agroecosystem functioning and services. Yet, we still lack information on which farming practices can effectively shape the soil microbial communities. The aim of this study was to identify the farming practices, which are most effective at positively or negatively modifying bacterial and fungal diversity while considering the soil environmental variation at a landscape scale. A long-term research study catchment (12 km2 ) representative of intensive mixed farming (livestock and crop) in Western Europe was investigated using a regular grid for soil sampling (n = 186). Farming systems on this landscape scale were described in terms…