Nazanin Makkinejad, Arnold M Evia, Ashish A Tamhane, Carles Javierre-Petit, Sue E Leurgans, Melissa Lamar, Lisa L Barnes, David A Bennett, Julie A Schneider, Konstantinos Arfanakis
Brain arteriolosclerosis, one of the main pathologies of cerebral small vessel disease, is common in older adults and has been linked to lower cognitive and motor function and higher odds of dementia. In spite of its frequency and associated morbidity, arteriolosclerosis can only be diagnosed at autopsy. Therefore, the purpose of this work was to develop an in-vivo classifier of arteriolosclerosis based on brain MRI. First, an ex-vivo classifier of arteriolosclerosis was developed based on features related to white matter hyperintensities, diffusion anisotropy and demographics by applying machine learning to ex-vivo MRI and pathology data from 119 participants of the Rush Memory and Aging Project (MAP) and Religious Orders Study (ROS), two longitudinal cohort studies of aging that recruit non-demented older adults...
July 24, 2021: NeuroImage: Clinical
Shingo Koinuma, Nobuhiro Shimozawa, Yasuhiro Yasutomi, Nobuyuki Kimura
Aβ metabolism in the brain is mediated by endocytosis, one part of the intracellular membrane trafficking system. We previously showed that aging attenuates the interaction of dynein with dynactin, which disrupts the endosomal/lysosomal trafficking pathway involved in Aβ metabolism, resulting in intracellular accumulation of Aβ. Several studies have shown that in Alzheimer's disease (AD), intraneuronal accumulation of Aβ precedes extracellular Aβ depositions. However, it is unclear what accounts for this transition from intracellular to extracellular depositions...
July 5, 2021: Neurobiology of Aging
Lara J Mentink, João P O F T Guimarães, Myrthe Faber, Emma Sprooten, Marcel G M Olde Rikkert, Koen V Haak, Christian F Beckmann
Structural and functional alterations of the brain in persons genetically at-risk for Alzheimer's disease (AD) are crucial in unravelling AD development. Filippini et al. found that the default mode network (DMN) is already affected in young APOE ε4-carriers, with increased co-activation of the DMN during rest and increased hippocampal task activation. We aimed to replicate the early findings of Filippini et al, using the APOE gene, still the principal AD risk gene, and extended this with a polygenic risk score (PRS) analysis for AD, using the Human Connectome Project dataset (HCP)...
June 27, 2021: NeuroImage
Wenjie Kang, Lan Lin, Baiwen Zhang, Xiaoqi Shen, Shuicai Wu
Alzheimer's Disease (AD) is a chronic neurodegenerative disease without effective medications or supplemental treatments. Thus, predicting AD progression is crucial for clinical practice and medical research. Due to limited neuroimaging data, two-dimensional convolutional neural networks (2D CNNs) have been commonly adopted to differentiate among cognitively normal subjects (CN), people with mild cognitive impairment (MCI), and AD patients. Therefore, this paper proposes an ensemble learning (EL) architecture based on 2D CNNs, using a multi-model and multi-slice ensemble...
July 22, 2021: Computers in Biology and Medicine
I Šonský, P Vodička, K Vodičková Kepková, H Hansíková
Huntington's disease (HD), as well as Parkinson's disease and Alzheimer's disease, belong to a group of neurodegenerative diseases characterized by common features, such as the progressive loss of neurons and the presence of pathogenic forms of misfolded protein aggregates. A quality control system such as autophagy is crucial for the clearance of protein aggregates and dysfunctional organelles and thus essential for the maintenance of neuronal homeostasis. The constant high energy demand of neuronal tissue links neurodegeneration to mitochondria...
July 27, 2021: Neurochemistry International
Rui Chen, Ziyu Wang, Zhongwen Zhi, Jisha Tian, Ying Zhao, Junshan Sun
β-amyloid (Aβ) accumulation is a major neuropathological characteristic of Alzheimer's disease (AD) and serves as an inflammatory stimulus for microglial cells. Oxysophoridine has multiple pharmacological effects, including anti-inflammatory and anti-oxidative activities. In view of this, the current study aimed to investigate the effects of oxysophoridine on Aβ-induced activation of microglial BV-2 cells. Cell Counting Kit-8 assay showed that oxysophoridine concentration-dependently attenuated Aβ-induced viability reduction of BV-2 cells...
July 27, 2021: Brain Research Bulletin
Kaori Sato, Naoto Watamura, Ryo Fujioka, Naomi Mihira, Misaki Sekiguchi, Kenichi Nagata, Toshio Ohshima, Takashi Saito, Takaomi C Saido, Hiroki Sasaguri
We previously developed single App knock-in mouse models of Alzheimer's disease (AD) harboring the Swedish and Beyreuther/Iberian mutations with or without the Arctic mutation (AppNL-G-F and AppNL-F mice, respectively). These models showed Aβ pathology, neuroinflammation, and cognitive impairment in an age-dependent manner. The former model exhibits extensive pathology as early as 6 months, but is unsuitable for investigating Aβ metabolism and clearance because the Arctic mutation renders Aβ resistant to proteolytic degradation and prone to aggregation...
July 27, 2021: Journal of Biological Chemistry
Tessa V Procter, Anna Williams, Axel Montagne
Dementia is becoming an increasingly important disease due to an aging population and limited treatment options. Cerebral small vessel disease (cSVD) and Alzheimer's disease (AD) are the two most common causes of dementia with vascular dysfunction being a large component of both their pathophysiologies. The neurogliovascular unit (NVU), and in particular the blood-brain barrier (BBB) are required for maintaining brain homeostasis. A complex interaction exists between the endothelial cells, which line the blood vessels and pericytes, which surround them in the NVU...
July 27, 2021: American Journal of Pathology
Guo-Chao Zhong, Tian-Yang Hu, Peng-Fei Yang, Yang Peng, Jing-Jing Wu, Wei-Ping Sun, Long Cheng, Chun-Rui Wang
Few studies with mixed results have examined the association between chocolate consumption and mortality. We aimed to examine this association in a US population. A population-based cohort of 91891 participants aged 55 to 74 years was identified. Chocolate consumption was assessed via a food frequency questionnaire. Cox regression was used to estimate risk estimates. After an average follow-up of 13.5 years, 19586 all-cause deaths were documented. Compared with no regular chocolate consumption, the maximally adjusted hazard ratios of all-cause mortality were 0...
July 29, 2021: Aging
Pascal Lu, Olivier Colliot
This paper introduces a framework for disease prediction from multimodal genetic and imaging data. We propose a multilevel survival model which allows predicting the time of occurrence of a future disease state in patients initially exhibiting mild symptoms. This new multilevel setting allows modeling the interactions between genetic and imaging variables. This is in contrast with classical additive models which treat all modalities in the same manner and can result in undesirable elimination of specific modalities when their contributions are unbalanced...
July 30, 2021: IEEE Journal of Biomedical and Health Informatics
Kai Li, Jiang Wang, Shanshan Li, Haitao Yu, Lin Zhu, Jing Liu, Lingyun Wu
Alzheimer's disease is a neurodegenerative disease in old age, early diagnosis will help to delay the progression of the disease. Presently, the features of brain functional diseases can be obtained with EEG analysis, but the relationship between characteristics of EEG and Alzheimer's disease has not been clearly clarified. In this work, we hypothesize that there exist default brain variables (latent factors) across subjects in disease processes, decoding latent factor from brain activity contributes to the study of cognitive impairment...
July 30, 2021: IEEE Transactions on Neural Systems and Rehabilitation Engineering
Kobra Etminani, Amira Soliman, Anette Davidsson, Jose R Chang, Begoña Martínez-Sanchis, Stefan Byttner, Valle Camacho, Matteo Bauckneht, Roxana Stegeran, Marcus Ressner, Marc Agudelo-Cifuentes, Andrea Chincarini, Matthias Brendel, Axel Rominger, Rose Bruffaerts, Rik Vandenberghe, Milica G Kramberger, Maja Trost, Nicolas Nicastro, Giovanni B Frisoni, Afina W Lemstra, Bart N M van Berckel, Andrea Pilotto, Alessandro Padovani, Silvia Morbelli, Dag Aarsland, Flavio Nobili, Valentina Garibotto, Miguel Ochoa-Figueroa
PURPOSE: The purpose of this study is to develop and validate a 3D deep learning model that predicts the final clinical diagnosis of Alzheimer's disease (AD), dementia with Lewy bodies (DLB), mild cognitive impairment due to Alzheimer's disease (MCI-AD), and cognitively normal (CN) using fluorine 18 fluorodeoxyglucose PET (18F-FDG PET) and compare model's performance to that of multiple expert nuclear medicine physicians' readers. MATERIALS AND METHODS: Retrospective 18F-FDG PET scans for AD, MCI-AD, and CN were collected from Alzheimer's disease neuroimaging initiative (556 patients from 2005 to 2020), and CN and DLB cases were from European DLB Consortium (201 patients from 2005 to 2018)...
July 30, 2021: European Journal of Nuclear Medicine and Molecular Imaging
Patricia O'Loughlin, Pavithra Pavithra, John Regan, Marc Bennett, Rachel Knight, Bert Lenaert, Melissa Marquez, Michelle Taddeo, James Griffith, Rita Shapiro, Francesca Farina
BACKGROUND: Dementia is the most feared disease associated with aging. Prolonged fears about memory loss and dementia can have harmful consequences even in the absence of cognitive decline. Fear of dementia is associated with poorer health outcomes and psychological well-being and increased memory failures in older adults. OBJECTIVE: We will conduct a randomized controlled trial to determine the feasibility of a tailored, web-based mindfulness program to reduce fear of memory loss and increase quality of life in older adults experiencing heightened fear...
July 30, 2021: JMIR Research Protocols
Longjian Liu, Stella L Volpe, Jennifer A Ross, Jessica A Grimm, Elisabeth J Van Bockstaele, Howard J Eisen
BACKGROUND: Despite some reports of cardiometabolic disorders associated with the risk of Alzheimer's disease (AD), limited studies have been conducted to examine the association between excessive sugar intake (a risk factor for cardiometabolic disorders) and AD risk. AIM: The purpose of our study was to evaluate if excessive sugar intake has a significant long-term effect on the risk of AD. METHODS: A population sample of 37,689 participants, who enrolled in the United States (US) Women's Health Initiative - Dietary Modification Trial (WHI-DM) in 1993-2005 and its extended observational follow-up study through 1 March 2019, were analyzed...
July 30, 2021: Nutritional Neuroscience
Melissa A Wilson
The Y chromosome is the most gene-deficient chromosome in the human genome (though not the smallest chromosome), and has largely been sequestered away from large-scale studies of the effects of genetics on human health. Here I review the literature, focusing on the last two years, for recent evidence of the role of the Y chromosome in protecting from or contributing to disease. While many studies have focused on Y chromosome gene copy number and variants in fertility, the role of the Y chromosome in human health is now known to extend to many other conditions including the development of multiple cancers and Alzheimer's disease...
July 29, 2021: Human Molecular Genetics
Mukta Agrawal, Shailendra Saraf, Madhulika Pradhan, Ravish J Patel, Gautam Singhvi, Ajazuddin, Amit Alexander
Herbal antioxidant like curcumin holds great potential to treat neurodegenerative disease like Alzheimer's disease. However, its therapeutic potency is obstructed due to rapid metabolism, poor solubility, GI susceptibility, enzymatic degradation and lower bioavailability. Thus, the present work aimed to design and optimize curcumin-loaded NLC (CNL) with higher drug entrapment, prolonged release and better stability. CNL was prepared by modified melt emulsification method followed by ultrasonication. The formulation was optimized by 3 factor 3 level Box-Behnken design using solid: liquid lipid, surfactant concentration and ultrasonication time as independent variable while particle size, entrapment efficiency and % drug release as dependant variable...
July 17, 2021: Biomedicine & Pharmacotherapy
Baoyue Zhang, Jun Zhao, Pengfei Guo, Zhe Wang, Lvjie Xu, Ailin Liu, Guanhua Du
Naodesheng (NDS) tablets have been widely used to treat ischemic stroke clinically. NDS relieves neurological function impairment and improve learning and memory in rats with focal cerebral ischemia, suggesting that NDS has potential for Alzheimer's disease (AD) treatment. However, there are no studies about its effective material basis and possible mechanisms. In this study, a systems pharmacology method was applied to reveal the potential molecular mechanism of NDS in the treatment of AD. First, we obtained 360 NDS candidate constituents through ADMET filter analysis...
July 22, 2021: Biomedicine & Pharmacotherapy
Marjan Talebi, Mohsen Talebi, Tahereh Farkhondeh, Dalia M Kopustinskiene, Jesus Simal-Gandara, Jurga Bernatoniene, Saeed Samarghandian
Neurological diseases are responsible for a large number of morbidities and mortalities in the world. Flavonoids are phytochemicals that possess various health-promoting impacts. Chrysin, a natural flavonoid isolated from diverse fruits, vegetables, and even mushrooms, has several pharmacological activities comprising antioxidant, anti-inflammatory, antiapoptotic, anticancer, and neuroprotective effects. The current study was designed to review the relationship between chrysin administration and neurological complications by discussing the feasible mechanism and signaling pathways...
July 16, 2021: Biomedicine & Pharmacotherapy
Ísis Venturi Biembengut, Isabelle Leticia Zaboroski Silva, Tatiana de Arruda Campos Brasil de Souza, Patrícia Shigunov
In humans, the cytoplasmic FMR1 interacting protein (CYFIP) family is composed of CYFIP1 and CYFIP2. Despite their high similarity and shared interaction with many partners, CYFIP1 and CYFIP2 act at different points in cellular processes. CYFIP1 and CYFIP2 have different expression levels in human tissues, and knockout animals die at different time points of development. CYFIP1, similar to CYFIP2, acts in the WAVE regulatory complex (WRC) and plays a role in actin dynamics through the activation of the Arp2/3 complex and in a posttranscriptional regulatory complex with the fragile X mental retardation protein (FMRP)...
July 29, 2021: Molecular Biology Reports
G Dhamodharan, C Gopi Mohan
Multi-target directed ligand-based 2D-QSAR models were developed using different N-benzyl piperidine derivatives showing inhibitory activity toward acetylcholinesterase (AChE) and β-Site amyloid precursor protein cleaving enzyme (BACE1). Five different classes of molecular descriptors belonging to spatial, structural, thermodynamics, electro-topological and E-state indices were used for machine learning by linear method, genetic function approximation (GFA) and nonlinear method, support vector machine (SVM) and artificial neural network (ANN)...
July 29, 2021: Molecular Diversity
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