bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperbaric oxygen therapy improves cognitive function in D‐galactose‐induced aging via restoring autophagy, apoptosis, microglia activation and synaptic plasticity in hippocampus
Authors: Shwe Thazin , Bo‐Htay Cherry , Leech Tom , Pratchayasakul Wasana , Chattipakorn Nipon , Chattipakorn Siriporn C 
Published: December 2020

AbstractBackgroundAging is the major risk factor for the age‐related diseases such as dementia and Alzheimer's disease. Previous studies found that aging could impair autophagy, microglia morphology and synaptic plasticity in hippocampus, resulting in cognitive decline. Although there are several models that usually used to induce aging, D‐galactose exposure induced aging as similar patterns as shown in naturally aging. Among the various treatments of Alzeimer’s disease, hyperbaric oxygen therapy (HBOT), which inhales 100 % pure oxygen in a pressurized hyperbaric chamber, becomes the focus of interest because it is a non‐invasive and painless treatment. Previous studies also found that HBOT increased antioxidants, decreased oxidative stress and the number of microglia in Alzheimer’s model. However, the effect of HBOT on autophagy, apoptosis, microglia activation, Alzheimer's protein production, synaptic plasticity and cognitive function in the model of D‐galactose‐induced aging has never been studied. We hypothesize that HBOT decreases oxidative stress, microglia hyperactivation, autophagic impairement, apoptosis, synaptic dysplasticity and cognitive impairment in D‐galactose‐induced aging.MethodFifteen Wistar rats (6‐week‐old) were received either vehicle as control rats (0.9% NSS, s,c; n=5) or D‐galactose as D‐gal rats (150mg/kg/d, s.c; n=10) for 10 weeks. After that, control rats were given sham‐treatment (1ATA, 80L/min, 80mins/day; CS; n=5), D‐gal rats were given together with either sham‐treatment (1ATA, 80L/min, 80mins/day; DS; n=5) or HBOT (2ATA, pure O2, 250L/min, 80mins/day; DH; n=5) for 14‐day. Novel object location test and hippocampal pathologies were determined after HBOT.ResultWe found that D‐gal rats had increased hippocampal oxidative stress, autophagy impairment, BACE1, microglial hyperactivation, apoptosis and synaptic dysplasticity, which resulted in cognitive impairment. Interestingly, HBOT decreased hippocampal oxidative stress, autophagy impairment, BACE1, microglial hyperactivation, apoptosis, synaptic dysplasticity and cognitive impairment in D‐galactose‐induced aging rats (p<0.05, Figure 1).ConclusionHBOT decreased cognitive impairment in D‐galactose‐induced aging via reducing hippocampal oxidative stress, autophagic impairment, BACE1, microglial hyperactivation, apoptosis and synaptic dysplasticity. Therefore, HBOT may be used as a safe and effective treatment to prevent the neurodegeneration of aging.
Cognitive fluctuations of object recognition in Lewy body dementia: An EEG/MEG study
Authors: Huang Yujing 
Published: December 2020

AbstractBackgroundLewy body dementia (LBD) shared a common pathological core feature of cognitive fluctuations. However, the clinical identification of attention fluctuation is still controversial. In this study, we combined EEG and MEG to explore the electrophysiological and magnetic biomarkers of attention fluctuations in LBD. We hypothesized that LBD showed stronger fluctuations in sensor‐level and source‐level EEG and MEG.MethodNine LBD and twelve healthy controls (HC) were recruited in this study. We designed an object recognition task, in which an object stimulus appeared on the screen and then the participants were required to respond as quickly and accurately as possible to judge whether this object was an animal or not an animal. There were six blocks, each of which included 12 different animal stimuli and 12 non‐animal stimuli. The animal/non‐animal stimuli were repeated across blocks. EEG and MEG were simultaneously recorded online. Cognitive fluctuations were examined via the variations across all trials (trial‐wise fluctuations) or across blocks (block‐wise fluctuations).Result(1) healthy controls had shorter reaction time and higher accuracy rate than LBD but the variations of reaction time was significantly higher in LBD than healthy controls. (2) HC had stronger overall EEG amplitudes for post stimulus in line with previous studies about the deficit of object recognition in dementia. The overall single‐trial‐wise variations and block‐wise variations of MAG/GRM were higher in LBD than HC. (3)Although time frequency power didn’t showed significant differences between LBD and HC in most electrodes, lower theta phase lock value (PLV) in HC compared to LBD for central‐parietal EEG/MEG electrodes. The central‐parietal EEG/MEG PLV was significantly higher in HC than LBD for alpha, beta and gamma bands. (4) Interestingly, higher single‐trial‐wise phase‐lock values (PLV) variations in LBD compared to HC were mainly from theta band and alpha band for front‐parietal EEG/MEG electrodes. (5) The source localization results showed that trial‐wise and block‐wise source fluctuations in LBD had a tendency to involve a network of parietal areas, including postcentral gyrus, superial parietal areas et al.ConclusionOur study revealed the possible biomarkers of attention fluctuations in LBD by using EEG and MEG.
The association between retinal vascular fractal dimension and cognitive function in the community‐dwelling elderly cohort TIGER
Authors: Wu Ting‐Yu , Chen Jen‐Hau , Chiou Jeng‐Min , Chen Ta‐Fu , Lai Liang‐Chuan , Chen Yen‐Ching 
Published: December 2020

AbstractBackgroundCerebral vascular factor plays an important role in the pathogenesis of cognitive dysfunction, including mild cognitive impairment (MCI) and dementia. The small retinal vessels reflect cerebral microcirculation and its fractal dimension (Df) representing the complexity of the retinal microcirculation. However, the connection between the retinal circulation and cognitive function lacked consistent and longitudinal evidence. This study aimed to explore the association between the retinal vascular Df and cognitive dysfunction in the community‐dwelling older adults.MethodThis study is part of a prospective cohort Taiwan Initiative for Geriatric Epidemiological Research (TIGER, 2011 to present). Participants from the 4‐year (2015–2017) and 6‐year (2017‐2019) follow‐ups were included. Global and domain‐specific cognitive function were assessed at the 4‐year and 6‐year follow‐ups. Fundus photography was taken for each participant at the 4‐year follow‐up, and retinal vessels were segmented for fractal analyses. Multivariable logistic regression analyses were performed to explore the association between Df of the retinal vessels and cognitive decline over 2 years adjusting for age, gender, years of education, diabetes, hypertension, hyperlipidemia, cardiovascular event, smoking, drinking and age‐related macular degeneration.ResultHigher right retinal vascular complexity (right Df) was associated with the decline of logical memory‐recall I [linear right Df: adjusted odds ratio (aOR)= 0.30, 95% confidence interval (CI)= 0.11 to 0.85). No significant linear association was found between Df and global cognition or other cognitive domains. For non‐linear relationship, we found an inverted U shape association between the right Df and global cognitive decline over 2 years [quadratic right Df: aOR=0.10, 95% CI = 0.01‐0.80]. The risk of global cognitive decline (assessed by MoCA‐T) was 0.1 when right Df change 0.1 unit (increase or decrease) from the sample mean (1.36). Similar nonlinear relationship was found for the decline of logical memory‐recall II over 2 years (quadratic right Df: aOR= 0.08, 95% CI= 0.01‐0.59). No significant association was found between left Df and cognitive decline over 2 years.ConclusionThis study demonstrated a nonlinear relationship between the retinal vascular complexity of the right eye and the decline of global cognition and logical memory. This retinal biomarker may be used for screening dementia in the preclinical stage.
Relationship between clinical symptomatology and disease burden in dementia with Lewy bodies: An overview of the DEvELOP baseline results
Authors: van de Beek Marleen , van Steenoven Inger , van der Zande Jessica J. , Teunissen Charlotte E. , Stam Cornelis J. , Raijmakers Pieter G.H.M. , Scheltens Philip , van Der Flier Wiesje , Lemstra Evelien 
Published: December 2020

AbstractBackgroundDementia with Lewy Bodies (DLB) is a heterogeneous disease with a highly variable presentation of core and suggestive symptoms. The relationships between these symptoms and their impact on disease burden remain unclear. The DEmentia with LEwy BOdies Project (DEvELOP) is a longitudinal cohort study that aims to phenotype DLB patients in depth and study the course of symptoms and biomarkers over time. Here, we provide an overview of our baseline results. Additionally, we investigated associations between core and suggestive features and different aspects of disease burden, i.e. instrumental activities of daily living (I‐ADL) functioning, quality of life (QoL) and caregiver burden.MethodDEvELOP is a prospective cohort study conducted at Alzheimer Center Amsterdam. To date, we included 94 DLB patients (69±6yrs, 11%F, MMSE 25±3), who underwent extensive clinical assessment, including assessment of core features, neurological examination, neuropsychological examination, MRI(n=87), EEG(n=65), DAT‐SPECT(n =75) and CSF(n=71). Core features (hallucinations, parkinsonism, fluctuations, RBD) and suggestive features (autonomous dysfunction, neuropsychiatric symptoms) were assessed using standardized questionnaires. We evaluated how each of these features related to the functional activities questionnaire(FAQ), QoL(QoL‐AD), and caregiver burden(ZARIT), using linear regression analyses with backwards selection, adjusted for age, sex and MMSE.ResultIn the DEvELOP cohort, 19% of patients had all four core features, while 11% had merely had one (Figure 1). RBD was most frequently reported feature (75%). 87% had an abnormal DAT‐spect, 95% showed diffuse abnormalities on EEG. Abnormal CSF Aβ42 was found in 49%, abnormal CSF p‐tau in 42%. More severe fluctuations on the Clinical Assessment of Fluctuations (stβ=0.46, p<0.001) and lower MMSE (stβ=‐0.31, p=0.002) were independent determinants of higher FAQ‐scores. More depressive symptoms on GDS (stβ=‐0.51, p<0.001) and more severe obstipation(stβ=‐0.22, p=0.01) were independently associated with lower QoL‐AD‐scores. Last, NPI‐apathy associated with higher caregiver burden on ZARIT (stβ=0.49, p<0.001) (Table 1, Figure 2).ConclusionWe deeply phenotyped our prospective cohort of DLB patients and found clinically relevant associations between symptoms and disease burden. Cognitive symptoms were related to lower I‐ADL functioning, while negative psychiatric symptoms were associated with lower QoL and higher caregiver burden. Follow‐up is currently collected to further study the course of symptoms over time.
Semantic and episodic memory performances of patients with Alzheimer’s disease and minor neurocognitive disorder
Authors: Ozel‐Kizil Erguvan T. , Bastug Gulbahar , Kirici Sevinc 
Published: December 2020

AbstractBackgroundModified Dead‐Alive Test (M‐DAT), which was developed and validated by Ozel‐Kizil et. al. (2018) evaluates semantic and episodic memory together. The original form was developed by Kapur et al. (1989), however it was not adequately studied.MethodM‐DAT consists of 45 names of celebrities who had died in remote past (15), died in the last five years (15) and who are still alive (15) and participants are asked whether they are alive or dead. Correct number of items concerning celebrities who died in remote past gives the semantic memory performance, while half of the the sum of correct number of items concerning celebrities who are still alive and had died in the last five years is accepted as episodic memory performance. Semantic and episodic memory performances of patients with DSM‐5 major neurocognitive disorder due to Alzheimer’s Disease‐MND‐AD (n=69), patients with DSM‐5 minor neurocognitive disorder‐MiND (n=27) who were admitted to geriatric psychiatry clinic and volunteered healthy controls‐HC (n=29) were compared. The groups were compared either by one‐way ANOVA or Kruskal‐Wallis tests and Bonferroni or Mann Whitney U tests was used for post‐hoc analysis.ResultMND‐AD group was older and less educated. Also MND‐AD group had lower MMSE scores while MiND and HCs had similar scores. MND‐AD had lower semantic and episodic scores than MiND and HC, also the scores of MiND group were lower than HCs. Both M‐DAT semantic and episodic scores were positively correlated with education in the whole sample (R=.53, p<0.001; R=.43, p<0.001). Although semantic memory performances were higher than episodic memory performances in all groups, two scores were positively correlated (R=.71, p<0.001).ConclusionThe results of the study suggested a semantic memory impairment as well as episodic memory deficit in patients with major and minor neurocognitive disorder. Although previous studies have conflicting results, semantic memory deficit early in Alzheimer’s disease and in mild cognitive impairment was also reported (3). M‐DAT is an alternative for the assessment of semantic memory that is usually evaluated by verbal fluency tests. Evaluating episodic and semantic memory together is an important advantage however M‐DAT is affected by education and the items require updating.
Emotion recognition of morphed facial expressions in presymptomatic and symptomatic frontotemporal dementia, and Alzheimer’s disease
Authors: Jiskoot Lize C. , Poos Jackie M. , Vollebergh Manon , Papma Janne M. , van Swieten John C. , Kessels Roy P.C. , van den Berg Esther 
Published: December 2020

AbstractBackgroundAn increasing amount of studies are emphasizing the importance of social cognitive assessments to improve early diagnosis between frontotemporal dementia (FTD) and Alzheimer’s Disease (AD). Traditional measures of social cognition, including emotion recognition paradigms, however seem insensitive to the subtle deficits in the earliest dementia stages. The Emotion Recognition Task (ERT) was developed to identify early deficits in the recognition of facial expressions across different levels of intensity.MethodUsing the ERT, we assessed the recognition of morphed facial expressions of six emotions (anger, disgust, fear, happiness, sadness and surprise) across four intensities (40, 60, 80 and 100%) in patients with behavioural variant FTD (bvFTD; n=32), patients with AD (n=32), FTD mutation carriers (presymptomatic n=47, mildly/questionably symptomatic n=5) and controls (n=49). We examined group differences using multilevel linear regression modelling, and performed post hoc analyses on presymptomatic (MAPT, GRN and C9orf72) and mildly/questionably symptomatic mutation carriers. Classification abilities were investigated with logistic regression analyses; we determined sensitivity/specificity with ROC analyses.ResultThe lowest ERT total scores were found in bvFTD and AD patients, whereas equally highest scores were found in mutation carriers and controls. bvFTD patients scored significantly lower than AD patients on anger (p=0.023) and happiness (p<0.001), where subjects with mild/questionable FTD had an intermediate position between patients with dementia and those without (p=0.051) (Figure). Discriminative ability was better at the lowest (40%) than at the highest intensity (100%). Presymptomatic C9orf72 mutation carriers were worse at recognizing anger at the lowest (40%) emotional intensity than controls (p=0.038) and presymptomatic GRN mutation carriers (p=0.047). The ERT classified between patients with bvFTD and controls, patients with AD and controls (both p<0.001), but not between patients with bvFTD and AD, nor the total group of mutation carriers and controls (p>0.05).ConclusionOur results demonstrate clear emotion recognition deficits in bvFTD and AD, and suggest the presence of subtle changes in facial emotion recognition in early‐stage FTD. This provides us more insight into the discrete neural substrates involved in behavioural and emotional changes in developing FTD, but also highlights the importance of incorporating emotion recognition paradigms into standard neuropsychological assessment for early differential diagnosis.
Hospitalization expenses attributable to cognitive‐frailty in the elderly in China
Authors: Yang Ying 
Published: December 2020

AbstractBackgroundTo estimate the hospitalization expenses attributable to Cognitive‐frailty elderly in China and analyze the influencing factors in order to do a reasonable preventive measures, thereby reducing the economic burden of patients.MethodA retrospective study. Patients hospitalized in the department of Neurology or Geriatric for comorbidity from November 2015 to June 2016 were enrolled. Geriatric Comprehensive assessment was scored using FRAIL, MMSE, and ADL respectively. Patients were divided into 4 groups (no‐frailty and no‐Cognitive (N group), no‐frailty and Cognitive(C group), frailty and no‐Cognitive (F group)and Cognitive‐frailty group (CF group )) according to the evaluation results, of which hospitalization expenses and influencing factors were analyzed using single factor and logistic regression analyses.ResultMedicine was the predominant expense during hospitalization of all comorbidity patients, however, the cost of rehabilitation in CF group was lower than that in N group (P=0.006).The total cost of hospitalization in CF group was higher than that in N group (P < 0.001), albumin level was lower than that in N group (P = 0.016), and hospitalization time was longer than that in N group (P = 0.038).In multivariable analysis adjusting for age, gender, marital status, smoking, alcohol use, WBC,HB,PLT,ALB and LDL, the difference of hospitalization expenses between CF group and N group is still statistically significant (OR:1.00057 95%CI:1.00023‐1.00091).ConclusionThe hospitalization expenses of the elderly with Cognitive‐frailty are relatively high at present and medicine was the predominant reasons. However, the rehabilitation exercise of inpatients with cognitive‐frailty is relatively deficient and their nutritional support is insufficient and thus reducing the use of drugs and strengthening the prevention and treatment of geriatric syndrome may reduce the hospitalization costs of the patients with Cognitive‐frailty.
Anosognosia in Alzheimer’s disease associated with tau accumulation and hypometabolism in frontal areas
Authors: Yakac Guelnihan , Maier Franziska , Bohn Karl Peter , Schild Ann‐Katrin , Meiberth Dix U. , Onur Oezguer A. , Fließbach Klaus , Drzezga Alexander , van Eimeren Thilo , Bischof Gerard N , Jessen Frank 
Published: December 2020

AbstractBackgroundImpaired insight in cognitive deficits (anosognosia) in Alzheimer’s disease (AD) is frequent and problematic, but pathophysiological mechanisms are not fully understood. So far, several regions such as the cingulate cortex or frontotemporal regions have been identified as crucial. The aim of the present study was to explore the neural substrates of anosognosia in AD by applying 18‐F fluorodeoxyglucose (FDG) and 18‐F‐AV‐1451 (Tau) positron emission tomography (PET).MethodSeventy‐four AD‐patients with mild cognitive impairment (MCI) or dementia were included in this study. Anosognosia was assessed by a clinician, based on a structured interview compared to patient’s subjective cognitive impairment. Cognition was examined applying the Consortium to Establish a Registry for AD (CERAD‐Plus) neuropsychological assessment battery. All patients underwent FDG‐PET. Additionally, 29 patients received a Tau‐PET. Glucose metabolism and 18‐F‐AV‐1451 binding were analyzed in a whole brain approach by comparing patients with and without anosognosia. Imaging analyses were controlled for age and sex.ResultOf the 74 patients, 28 had anosognosia and 46 were aware of their deficits. Patients with anosognosia were significantly older and less depressed. The number of MCI/dementia patients was similar between groups (MCI+/‐anosognosia 11/25, dementia +/‐anosognosia 17/21, p=.209). Neuropsychological results showed a significantly more impaired verbal fluency in patients with anosognosia (p=.025). When FDG‐PET images were analyzed, patients with anosognosia had a significantly lower glucose metabolism in the inferior frontal gyrus, rectal gyrus and medial frontal gyrus including the anterior cingulate cortex (cluster level, p‐uncorrected<0.001, FWE‐corrected p=.006). Tau‐PET analyses showed a significant higher tracer binding in patients with anosognosia in the inferior and medial frontal gyrus (cluster level, p‐uncorrected=.003, FWE‐corrected p=.048).ConclusionThis is the first study examining FDG‐ and Tau‐PET in AD patients with and without anosognosia. Anosognosia was not only associated with reduced glucose metabolism but also with increased tau accumulation in inferior and medial frontal regions. We speculate that tau‐induced hypometabolism in regions related to self‐referential processes leads to anosognosia.
Sleep disturbances in cognitively asymptomatic patients with histopathologically confirmed AD predict rapid cognitive deterioration
Authors: Atayde Adrienne Lloyd , Fischer Corinne E. , Schweizer Tom A. , Munoz David G. 
Published: December 2020

AbstractBackgroundThe temporal relationship between sleep disturbances, Alzheimer’s Disease (AD) pathology, and related cognitive impairment remains controversial. The objective of this study is to determine whether sleep disturbances at baseline predict the rate of cognitive deterioration in cognitively intact subjects with autopsy confirmed AD neuropathology. We also examine the interaction of sleep disturbances with APOE genotype and cerebral amyloid angiopathy (CAA).MethodThe National Alzheimer’s Disease Coordinating Center (NACC) datasets was used to compare the rate of cognitive decline between subjects with nighttime behaviors [(+)NTB] or without [(‐)NTB] at baseline as assessed by the Neuropsychiatric Inventory Questionnaire Quick Version (NPI‐Q). Cognitive impairment was determined by the Mini‐Mental Status Examination (MMSE) total score. Cognitively normal subjects at baseline were defined as having an initial MMSE score ≥ 24 at the first NACC clinical visit. The rate of cognitive decline was determined based on the individual’s annual MMSE score change over the total clinical visits made. All subjects had a primary neuropathologic diagnosis of Alzheimer’s pathology as determined by both high CERAD score and Braak stage.Result404 subjects fulfilled the inclusion criteria. The rate of cognitive decline was greater in (+)NTB (74 cases; 3.30 points per year) compared to (‐)NTB (330 cases; 2.45 points per year) (p = 0.016). This significant difference was restricted to APOE &epsilon;4 carriers (p = 0.049) and subjects with CAA (p = 0.020), and was absent in non e4 carriers and subjects without CAA. There was no difference between (+)NTB and (‐)NTB in the prevalence of these two factors associated with the rate of cognitive decline (e4 and CAA), suggesting that NTB itself is responsible for the effect observed.ConclusionNPI‐Q assessed nighttime behaviors, a surrogate for sleep disturbances, are associated with more rapidly declining cognition in subjects with Alzheimer’s neuropathology. In addition, this relationship is enhanced in carriers of APOE e4 and cerebral amyloid angiopathy.