bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does oxaloacetate preserve mitochondrial function in the aged brain?
Authors: Gupte Raeesa , Keselman Paul L. , Christian Sarah K. , Hu Jinxiang , Swerdlow Russell H. , Harris Janna L. 
Published: December 2020

AbstractBackgroundAge is the main risk factor for many neurodegenerative disorders including Alzheimer’s disease (AD). One hallmark of brain aging is mitochondrial impairment resulting in bioenergetic dysfunction. Therefore, limiting age‐related decline in mitochondrial function may be an attractive therapeutic strategy to mitigate the risk of AD. Oxaloacetate (OAA) is a metabolic intermediate in the TCA cycle, gluconeogenesis, and amino acid biosynthesis. Treatment with OAA has been shown to enhance neuronal bioenergetics, neurogenesis, and mitochondrial biogenesis in young adult mice, but its effects in aged subjects are unknown. We sought to determine whether OAA treatment in aged rats can alter brain metabolism and mitochondrial function.MethodIn aged male F344 rats (20‐22 months) we used in vivo proton magnetic resonance spectroscopy (1H‐MRS) to obtain baseline neurometabolic readings from two regions of interest: Ctx+ (cortex and subcortical tissue) and Hipp (hippocampus and dorsal striatum). We then treated rats with 1 g/kg/day i.p. OAA (n=14) or vehicle (n=14) for 7 days, followed by post‐treatment 1H‐MRS scans. On day 8 we used an Oxygraph‐2k to compare brain mitochondrial respiration in the OAA vs. vehicle‐treated groups.ResultOAA treatment significantly increased levels of N‐acetylaspartate, glutamate, aspartate, phosphocreatine, lactate, alanine, and ascorbate in a region‐dependent manner. No significant differences were observed in mitochondrial respiratory flux between the OAA and vehicle‐treated groups.ConclusionAfter 1 week of treatment with OAA, aged rats showed changes in brain metabolites linked with bioenergetic function but did not show significant differences in the kinetics or capacity of brain mitochondrial respiration. These findings diverge from previously reported effects of OAA in younger adult mice, highlighting the critical importance of testing novel AD therapies across a range of ages.
MRI decline pattern in early onset MCI due to Alzheimer’s disease
Authors: Contador José , Sala‐Llonch Roser , Pérez‐Millan Agnés , Balasa Mircea , Borrego‐Écija Sergi , Sanchez‐Valle Raquel , Lladó Albert ,   Alzheimer’s Disease Neuroimaging Initiative
Published: December 2020

AbstractBackgroundStructural neuroimaging longitudinal studies in Alzheimer’s disease (AD) have consistently defined a “cortical signature” of gray matter loss. Apparently, early‐onset AD (EOAD) has a greater density of amyloid, a more generalized atrophy and a more aggressive evolution than late‐onset AD (LOAD). We hypothesize EOAD would show pronounced longitudinal cortical atrophy, especially in associative areas like precuneus and in addition to temporal lobe loss.MethodsWe investigate longitudinal 3T‐MRI structural data from the Alzheimer’s disease Neuroimaging Initiative (ADNI) 2 cohort. We included patients aged ≤65 years with a baseline mild cognitive impairment (MCI) diagnosis. According to AD biomarkers at baseline, patients were divided into MCI due to AD with high likelihood (MCI‐AD) and MCI unlikely due to AD (MCI‐nonAD). We downloaded the summary of longitudinal measures for volume and cortical thickness. We used linear mixed effects in SPSS25 with data at baseline and month 24 to compare atrophy progression between groups. We focused on “AD's cortical signature”, including entorhinal, inferior temporal, middle temporal, inferior parietal, fusiform areas, and also precuneus and posterior cingulate. In addition, we studied volume of hippocampus (HpV) and total subcortical supratentorial (SSupratV). We tested for group by time interactions and significance level was set at p<0.05, FDR corrected.ResultsWe included 22 MCI‐AD and 26 MCI‐nonAD patients. MMSE mean score was lower in MCI‐AD [Table1]. MCI‐AD had significant lower baseline Cth in precuneus, middle temporal and entorhinal and lower HpV. At group by time interactions, MCI‐AD showed significant greater CTh atrophy in middle temporal, enthorhinal and posterior cingulate, and higher volume decrease in HpV and SSupratV than MCI‐nonAD [Figure1]. Notably, the rest of areas studied were not significantly different at baseline or at group by time effects.ConclusionCompared to MCI‐nonAD, MCI‐AD showed greater decline in only some of the areas previously defined as the cortical AD signature and in hippocampal volume and global subcortical volume. The study could be biased by the small sample size, by the age being close to LOAD and by no stratification by clinical symptoms. Further analyses are needed to understand AD atrophy progression pattern in relation to age at onset.
Oral administration of Byrophyllum pinnatum flavonoid ameliorates cognitive impairment via modulating cortical neurochemicals and oxidative stress in aluminum chloride‐induced Alzheimer’s disease‐like condition in wistar rats
Authors: Ogidigo Joyce Oloaigbe 
Published: December 2020

AbstractBackgroundAluminum, a potent neurotoxicant is a major risk factor involved in the perturbation of neurochemicals leading to the development and progression of Alzheimer’s disease. Byrophyllum pinnatum is widely distributed in Southern Nigeria and used locally for the treatment of various ailments including neurological disorders. This study was aimed to access the neuro restorative potential of B. pinnatum flavonoids (BPF) in aluminum chloride (AlCl3)‐induced AD‐like condition in Wistar ratsMethods
B. pinnatum flavonoids were characterized using FTIR and ultra‐high‐performance Liquid chromatography coupled with a mass spectrometry UPLC‐MS/MS. Thirty (30) male adult Wistar rats were used in this study and divided into five groups (n=6). Symptoms mimicking AD were induced in rats by administering 150mg/kg b.w of AlCl3 orally for 21 days. After the induction, animals were divided into five groups (n=6) and treated with BPF (50 and 100 mg/kg body weight) and 3 mg/kg of Rivastigmine for another 21 days. Neuro behavioral activities were assessed using Morris water maze tasks. Acetyl‐cholinesterase (AChE), BACE‐1 and oxidative stress markers were assessed following standard protocols. Semi‐quantitative reverse transcriptase‐PCR (RT‐PCR) was used to access the expression patterns of AChE and BACE‐1 mRNA in the cortex of rats.ResultsCharacterization of BPF revealed the presence of flavonols and flavone as the major constituents. Furthermore, AlCl3 overload caused behavioral alterations and showed impaired cognitive function similar to AD alongside increased brain cortical AChE activity, MDA level and decrease in antioxidant enzymes. In addition, AlCl3 induction caused the up‐regulation of AChE and BACE‐1 mRNA expressions in the cortex of rats. Conversely, oral administration of BPF (50 and 100 mg/kg body weight) significantly ameliorated cognitive deficits, restored oxidant‐antioxidant balance and modulated neurochemical markers, as evidenced by the improvement in brain function. Besides, BPF contributed towards the down‐regulation of AlCl3‐increased AChE and BACE‐1 mRNA expressions in the cortex.ConclusionThe current work demonstrates the therapeutic potential of B. pinnatum and suggests that it can ameliorate cognitive impairment caused by AlCl3 through reverting oxidative stress, restoring neurochemical function.
Mild to moderate levels of anxiety in a healthy population cohort are related to face recognition with negative emotions and white matter integrity
Authors: Chen Pin‐Yu , Chen Chang‐Le , Hsu Yung‐Chin , Tseng Hui‐Ming , Can Cam , Tseng Wen‐Yih Isaac 
Published: December 2020

AbstractBackgroundThe face recognition tasks were applied to test the healthy population cohort with mild to moderate levels of anxiety and they underwent MRI scans to evaluate their brains' white matter integrity.MethodMAP‐MRI analysis applied to estimate diffusion indexes Generalised Fractional Anisotropy (GFA) of segmented white matter tracts in a healthy (N=174) population‐based sample (mean MMSE 28.39) from the Cambridge Centre for Ageing and Neuroscience (Cam‐CAN) data including normal adults ages 18‐88 to examine microstructural properties of specific association fiber tracts involved in face recognition processing. Half sample (n=88) had anxiety symptoms ( Hospital Anxiety Scale 9.7) and half sample (n=88) were matched with age and sex and without anxiety symptoms. Two kinds of behavioral face tests to white matter measures including three pairs of association tracts, namely inferior fronto‐occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF) and uncinated fasciculus (UF). The two kinds of behavioral face tests applied were Benton Test of Facial Recognition which assesses the ability to match pictures of unfamiliar faces with variation of head orientation and lighting, and face recognition test of emotion assessing recognition of positive emotion (happiness), negative emotions (angry, disgust, fear, and sad) and surprise emotion. Paired sample t test were applied to compare the two groups' HAS, behavioral tests, and GFA of white matter tracts.ResultPaired t test results showed hospital Anxiety Scale, mean reaction time (RT) of face recognition test in negative emotion, GFA of left IFOF and left UF were significantly different in two groups. Pearson correlation analysis showed mean RT of face recognition test in negative emotion was significantly negative correlated with GFA of left UF.ConclusionHealthy life‐span population cohort with mild to moderate anxiety symptoms spent longer time recognizing faces with negative emotions and white matter integrity of the specific tract UF reflected this characteristic. There was brain‐behavior relationship.
The changing of cognitive function and the influence of learning effect on the results before and after the CSF tap test in patients with normal pressure hydrocephalus
Authors: Liu Caiyan , Li Jie , Huang Xinying , Dong Liling , Mao Chenhui , Hou Bo , Feng Feng , Wei Junji , Cui Liying , Gao Jing ,   PUMCH NPH Research Group
Published: December 2020

AbstractBackgroundThe CSF tap test evaluation needs repetitive test of walking ability and cognition. Our study aimed to explore the changes of cognitive function and the influence of learning effect on the results in CSF tap test when evaluating the patients with normal pressure hydrocephalus (NPH).MethodCSF tap test was carried out in 134 patients with NPH 2013‐2018 in neurology clinic of Peking Union Medical College Hospital. All patients underwent detailed neuropsychological evaluation (MMSE, MOCA, Trail Making test, Digital symbol, Stroop‐c test) and walking ability (10 meter walking test, up and go test), and head MRI examination. Patients who did not complete the four time point evaluations of CSF tap test due to severe dementia or any other reasons were excluded. Nonparametric test was used to test the difference of z‐scores of executive function (including connection test, number sign and shop‐c test) between the baseline and the four time points after CSF tap test. According to the baseline MMSE scores, the subjects were divided into MMSE > = 26 and MMSE < 26 groups. The changes of z‐scores of three executive function tests were observed in the group.ResultCompared with the baseline, the Z‐score of executive function began to improve at 24 hours and 72 hours, and there was a statistically significant difference (P 0.001 and 0.000, respectively). Within the MMSE > = 26 group, there was a significant improvement in executive function at 24 hours and 72 hours compared with baseline (P <0.05). In the group with MMSE < 26, the executive function Z‐score at 72 hours was significantly improved compared with that at baseline (P = 0.000), while the improvement at 8 hours and 24 hours was not significant.ConclusionIt was found that the executive function of CSF was improved with different evaluation points. According to the classification of MMSE scores, it was found that patients with different cognitive states had different characteristics of executive function curve, which could not be explained by learning effect.
Functional neuroanatomy of episodic memory in the human brain
Authors: Maass Anne 
Published: December 2020

AbstractBackgroundAβ and tau pathology progress along distinct anatomical networks before they overlap in the course of Alzheimer’s disease. Tau neurofibrillary tangles early and almost universally deposit in lateral parts of the entorhinal cortex (EC) in old age, the major gateway for hippocampal‐neocortical communication. Aβ plaques preferentially accumulate in posterior‐midline and medial frontal regions, where pathologies converge in the transition towards AD.MethodIn the first part of our FRS we will summarize the current knowledge about the functional neuroanatomy of memory, with focus on the entorhinal cortex and its neocortical connectivity. Our knowledge builds on intrinsic functional connectivity data and task‐based fMRI. We will further review our current understanding about the stereotypical accumulation patterns of tau and Aβ pathologies based on recent in vivo PET data in cognitively normal older adults and cogntiviely impaired patients.ResultThe human EC can be functionally subdivided into anterior‐lateral (alEC) and posterior‐medial (pmEC) subregions based on its differential functional connectivity with neocortical streams and hippocampus. The alEC shows preferential connectivity with perirhinal cortex and anterior‐temporal regions, which are highly vulnerable to tau pathology as shown by in vivo PET data. The pmEC shows preferential connectivity with parahippocampal cortex and a posterior‐medial network, regions that show early Aβ PET signal. These two neocortical networks are also differentially involved in the processing of and memory for object/items vs scenes/spatial information. Tau pathology in the entorhinal cortex even in the absence of Aβ plaques relates to memory deficits in cognitively yet unimpaired older adults.ConclusionAβ and tau pathology likely affect different functional brain networks, which might lead to differential memory deficits in the course of Alzheimer’s disease.
Tau, neural function, and episodic memory in the medial temporal lobe
Authors: Berron David 
Published: December 2020

AbstractBackgroundThe human medial temporal lobe (MTL) is heavily connected with neocortical regions in the posterior‐medial and the anterior‐temporal system. In order to achieve successful memory functioning, those systems have to interact with each other as well as with the hippocampus. At the same time, subregions in the MTL are affected by neurofibrillary tangle (NFT) pathology in aging and Alzheimer's disease (AD) which is strongly associated with memory impairment.MethodIn three different samples of cognitively unimpaired (CU) individuals, we analyzed how tau pathology (measured using Tau PET and CSF pTau levels) was associated with altered resting‐state functional connectivity, task‐related functional activity, MTL subregional atrophy, white matter tract integrity and memory function.ResultIn the first sample (n=322 CU), we identified the sequence of MTL subregions being affected by tau accumulation. Tau accumulates early in the perirhinal cortex (Area 35) and was associated with memory function ‐ an effect that was partially mediated by anterior hippocampal atrophy. In the second sample (n=359 CU), we show that while entorhinal/perirhinal cortex functional connectivity with the anterior‐temporal system was predominantly reduced in beta amyloid (Ab) + vs. Ab‐ CU, functional connectivity with the posterior‐medial system was increasingly reduced with increasing levels of pTau in Ab+ CU. Reduced functional connectivity was both related to baseline memory and future cognitive decline, however, not significantly associated with entorhinal thickness or white matter tract integrity. Finally, we show in a third sample (n=22 CU) that increasing levels of pTau are related to increased hippocampal functional activity which are both individually associated with reduced performance in an object memory task.ConclusionTaken together, our results from three independent samples suggest that tau pathology affects memory function in early disease stages predominantly via aberrant MTL functional connectivity and activity rather than atrophy or degeneration of white matter tracts.
Memory impairment is a clinical marker of tau pathology in cerebral amyloid angiopathy
Authors: Schoemaker Dorothee , Charidimou Andreas , Zotin Maria Clara Zanon , Raposo Nicolas , Johnson Keith A , Sanchez Justin S , Greenberg Steven M , Viswanathan Anand 
Published: December 2020

AbstractBackgroundCerebral Amyloid Angiopathy (CAA) shows a high comorbidity with Alzheimer’s Disease (AD). Nonetheless, CAA is an independent neuropathological disorder, and over half of CAA cases present without AD‐related tau pathology. Differentiating CAA patients with or without concomitant tau pathology could have important implications for therapeutic approaches. We aimed to determine whether memory impairments in CAA are indicative of underlying tau pathology.MethodThis study included 29 patients fulfilling criteria for mild cognitive impairment (MCI) and probable CAA. Subjects underwent a neuropsychological evaluation, a MRI, and PET scans for in‐vivo estimation of amyloid ([11C]– PiB) and tau ([18F]‐AV‐1451) burden. Structural markers of small vessel disease, total brain volume and hippocampal volume were quantified on MRI images. [11C]‐PiB specific binding was expressed as distribution volume ratios (DVR) and [18F]‐AV‐1451 specific binding as standardized uptake value ratio (SUVR), using the cerebellar cortex as the reference region. CAA subjects were classified as “amnestic” or “non‐amnestic” based on neuropsychological performance. Groups were contrasted on demographic features and quantified MRI markers. Between‐group voxel‐wise comparisons of SUVR [18F]‐AV‐1451 and DVR [11C]‐PiB maps were performed. Mean [18F]‐AV‐1451 SUVR in areas of group differences was extracted for each subject and correlated to memory performance.ResultIn our sample, 14 CAA subjects were classified as “amnestic”, and 15 as “non‐amnestic”. Amnestic and non‐amnestic subjects did not differ in age, education, or sex representation. Groups did not differ on any MRI markers of small vessel disease, nor in total brain volume (p>0.05, for all). However, amnestic subjects showed smaller hippocampal volume (F(1,28)=5.65, p<0.05). Voxel‐wise comparison of DVR [11C]‐PiB maps did not reveal any differences between amnestic and non‐amnestic CAA. Comparison of SUVR [18F]‐AV‐1451 maps revealed significant increase in tau PET binding in several regions for amnestic subjects (Figure 1). Mean tau PET binding in these regions was correlated with memory performance (r=‐0.68, p<0.001), and hippocampal volume (r=‐0.44, p<0.05), after accounting for age.ConclusionAmnestic CAA subjects present higher tau PET binding, and smaller hippocampal volume than non‐amnestic CAA. Our results suggest that memory impairments in CAA are related to tau pathology and medial temporal lobe neurodegeneration, consistent with the presence of concomitant AD.
Multilingual text normalization for computer‐based detection of Alzheimer’s disease
Authors: Abiven Frederic , Ratté Sylvie 
Published: December 2020

AbstractBackgroundUnderstanding how Alzheimer’s Disease affects linguistic functions could improve early detection of the disease, since many studies have demonstrated that language alterations can appear at an early stage. In order to measure those functions, we process and analyze transcripts from multiple corpora based on the Cookie‐Theft picture description task. Text normalization plays a big role when it comes to creating a solid dataset from a heterogeneous corpus of patients’ interviews. Current tools for this type of task are limited and tend to be language and context dependant.MethodThis paper presents a simple and efficient method to process textual data in a pipeline architecture, sequencing sub‐problems of cleaning and normalization tasks. Since some of them are language and context dependant, they were made easily configurable, increasing scalability when dealing with new corpora. Then, multiple measures are extracted while cleaning transcripts, as it also contains valuable information, like the number of repetitions or incomplete words removed.ResultResults show that we are able to improve performance on this time consuming task when working with a multilingual dataset compared to previous studies. In fact, we were able to normalize a French and English Cookie‐Theft corpus easily. Given the great diversity of languages and related structures, this method therefore has certain limitations. Moreover, our findings have shown great potential in cleaning and normalizing measures extracted for detecting Alzheimer’s disease. For instance, the number of retracings removed from transcripts revealed a significant correlation (> 0.5) with the severity of cognitive impairment.ConclusionThus, this paper contributes to Alzheimer’s disease literature by presenting an efficient tool which allows to speed up the cleaning and normalization process of transcripts. Furthermore, extracted measures from this task could improve results when training for a predictive model in AD detection, since it captures some metrics highly correlated with the patient’s mental health status. Finally, this tool could eventually be used for different types of description tasks since it is not dependant of the context.
Tau‐induced brain atrophy and neuroinflammation accelerated by low‐protein diet and decelerated by selected essential amino acids in a murine model of tauopathies
Authors: Takado Yuhei , Sato Hideaki , Tsukamoto‐Yasui Masako , Minatohara Keiichiro , Takahashi Manami , Urushihata Takuya , Takuwa Hiroyuki , Ono Maiko , Maeda Jun , Sahara Naruhiko , Aoki Ichio , Toyoda Sakiko , Karakawa Sachise , Isokawa Muneki , Kawasaki Noriko , Ueno Satoko , Kanda Mayuka , Nishimura Mai , Suzuki Katsuya , Mitsui Akira , Nagao Kenji , Higuchi Makoto , Kitamura Akihiko 
Published: December 2020

AbstractBackgroundNutritional epidemiology has implicated dietary protein intake in senile dementias. However, mechanistic links of protein and amino acids to age‐related neurodegenerative conditions remain unclear. Here, we tested the hypothesis that dietary intake of protein and amino acids could affect neuronal functions and survival in a mouse model of tauopathies, which develops tau pathologies leading to progressive brain atrophy with aging.MethodsNon‐transgenic (nTg) and tauopathy model (rTg4510) mice were fed a normal protein diet (NPD) or low protein diet (LPD) from 3 months of age, and brain volume and tau pathologies were measured at 6.5 months of age by MRI and PET, respectively. These imaging assays were also applied to NPD‐ and LPD‐fed mice treated with essential amino acids (EAAs), seven essential amino acids (EAAs), which are primarily composed of leucine, phenylalanine, and lysine with high fluxes into the brain and contain minimum levels of tryptophan, an origin of inflammation‐related kynurenine pathways. Moreover, we performed gene expression profiling of the cortical tissues collected from these mice.ResultsLPD profoundly accelerated the brain atrophy in rTg4510 mice relative to NPD. EAA supplementation to rTg4510 mice markedly suppressed cortical volume reductions in both LPD‐ and NPD‐fed rTg4510. LPD and EAA did not overtly alter PET‐detectable tau depositions uncorrected for atrophy‐induced partial volume effects, raising a possibility of decreased tau burdens in each of surviving neurons to some extent. Gene expression profiling demonstrated neuroinflammatory changes and neuronal dysfunctions in rTg4510 mice, which were worsened by LPD and attenuated by EAAs. Notably, kynurenine levels were elevated by LPD, and this alteration was reversed by EEAs, presumably by competition between EEAs and kynurenine on the entry into the brain.ConclusionOur findings highlight the critical roles of specific EEAs in the protection of neurons against tau‐induced toxicity and neuroinflammation.