bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improvements in memory and brain functional connectivity in older adults with subjective cognitive complaints following multiple‐modality exercise and mind‐motor training: An exploratory sub‐study
Authors: Silva Narlon Cassio Boa Sorte , Gill Dawn P , Nagamatsu Lindsay , Owen Adrian M , Petrella Robert J 
Published: December 2020

AbstractBackgroundWhether task‐based brain functional connectivity (FC) following exercise suggests adaptations in preferential brain regions is unclear. The objective of this study was to explore cognitive function and FC changes following multiple‐modality exercise and mind‐motor training in older adults with subjective cognitive complaints.MethodsWe included older adults (n=127, mean age 67.5 [7.3] years, 71% women) randomized to 45 minutes of multiple‐modality exercise with 15 minutes of mind‐motor training (M4 group, n = 63) or an active control group (M2 group, n = 64). Both groups exercised 60 minutes/day, 3 days/week, for 24 weeks. Participants completed twelve cognitive tasks from the Cambridge Brain Sciences (CBS) battery at baseline and follow‐up (memory, reasoning, concentration and planning tasks). A subsample of participants from the M4 group (n = 9, mean age 67.8 [8.8] years, 8 women) also underwent 5 minutes of continuous fMRI data collection while completing four CBS memory tasks. Behavioural data were analyzed using linear mixed models for repeated measures, and paired samples t‐test. All fMRI data were analyzed using group‐level independent component denoising and dual regression procedures, correcting for voxel‐wise comparisons.ResultsThe M4 group showed greater improvements in the Paired Associates tasks compared to the M2 group at 24 weeks (mean difference: 0.47, 95% confidence interval: .08 to .86, p = 0.019). No other results were found to be significant. For our fMRI analysis, dual regression revealed significant decreased FC co‐activation in the right precentral/postcentral gyri after the exercise program during the Spatial Span task (corrected p = 0.008) with no change in the behavioural task performance. Only trends for changes in FC were found for the other tasks (all corrected p < 0.09). For the Paired Associates task, there was a trend for increased co‐activation in the right temporal lobe (Brodmann Area = 38, corrected p = 0.07), and left middle frontal temporal gyrus (corrected p = 0.06).ConclusionsOur findings provide insight into the potential of our multiple‐modality exercise and mind‐motor training intervention to promote improvements in behavioural measures of visuospatial memory, as well as, impart FC adaptations in brain regions relevant to Alzheimer’s disease risk.
Metabolite differences in TDP‐43 proteinopathy and control human brain tissue
Authors: Hammond Tyler C. , Xing Xin , Nelson Peter T. , Ham Stephanie , Lin Ai‐Ling 
Published: December 2020

AbstractBackgroundLimbic‐predominant age‐related TDP‐43 encephalopathy (LATE) is a newly recognized neurodegenerative disease that presents as an amnestic dementia syndrome that mimics Alzheimer’s‐type dementia. The hallmark neurodegenerative feature of LATE is a TDP‐43 proteinopathy distributed throughout the frontotemporal lobe. The main neuropathological and clinical features for LATE have been described elsewhere, but little is understood about the underlying metabolic processes that may contribute to TDP‐43 pathology in LATE. Here we measure the metabolites of control brains and brains with TDP‐43 to understand how they differ.MethodThe global biochemical profiles of post‐mortem human brain tissue from the gray matter of Brodmann area 9 was determined using mass spectroscopy. Brain tissue from 44 subjects with TDP‐43 proteinopathy and 29 controls were analyzed and metabolites were compared. Metabolites were quantified using global untargeted metabolomics (HD4) and compared between cohorts using Welch’s two‐sample t‐test and random forest to rank metabolites in order of importance for predicting TDP‐43 presence in tissue.ResultThere were many metabolites that differed between TDP‐43 and control brains. Many of the metabolites in the top 20 most important predictors overlapped with metabolites deemed important in predicting Alzheimer’s disease, including memantine, sphingadienine, 3‐ureidopropionate, pyridoxal phosphate, 2’‐AMP, 3’‐AMP, pipecolate, 1‐carboxyethylvaline, sphingosine, and malate. However, there were quite a few predictors which were unique to predicting TDP‐43 proteinopathy, including tryptophan – a precursor of serotonin and melatonin, tetradecadienoate – a fatty acid, dihydroxyacetone phosphate (DHAP) – a glycolysis intermediate, homocarnosine – an intermediate in histidine metabolism that can co‐exist with progressive mental deficiency, and phosphatidylcholine and sphingomyelin – important components of the cell membrane.ConclusionMany metabolites differed between the TDP‐43 and control brains. Some metabolite differences were the same as those seen in Alzheimer’s disease, and could be because many of the people in our cohort with TDP‐43 pathology also had Alzheimer’s pathology. Many of the metabolite differences were specific to TDP‐43 proteinopathy, which are critical to maintaining brain function, including changes in neurotransmitters, essential amino acids, fatty acids, glycolysis intermediates, and cell membrane products. Further studies are needed to examine whether these metabolites are consistently altered in TDP‐43 proteinopathy.
Design and support of an online ‘control’ condition for the Tele‐Savvy randomized control trial
Authors: Nocera Joe R , Hepburn Kenneth , Griffiths Patricia , Higgins Melinda , Epps Fayron , Brewster Glenna S , Bonds Kalisha , Nash Rachel 
Published: December 2020

AbstractBackgroundTele‐Savvy is a NIA‐supported randomized trial aimed to evaluate an online version of the Savvy Caregiver, an evidence‐based in‐person psychoeducation program aimed at enhancing caregivers’ capacity to manage the day‐to‐day challenges of caregiving by promoting caregiving mastery and reducing caregiving distress. A critical component of the effective evaluation of this online psychoeducation program was the development of an engaging control condition (“Tele‐Savvy Healthy Living Condition”).MethodsCaregivers were randomly assigned (in a 2:2:1 ratio) to participation in Tele‐Savvy, Healthy Living condition, or waitlist control. For Tele‐Savvy and Healthy Living, groups of 5‐8 caregivers engaged in 7 weekly synchronous online groups led by a trained facilitator. Each condition incorporated daily video lessons which caregivers viewed whenever and as often as they wished. The Healthy Living control condition incorporated evidence‐based, vetted information on healthy lifestyle behaviors (e.g., NIA Go4Life; USDA ChooseMyPlate).ResultsResults demonstrate that engagement of those randomized to the Healthy Living control condition was statistically equal to those in the Tele‐Savvy program (p>0.05). Engagement was assessed by comparison of percent attendance of video conference in the Healthy Living condition (74.08%) versus Tele‐Savvy (68.02%). An intermediate report on the primary outcomes of the trial indicate that, while engaging, the Healthy Living condition did not significantly impact the primary outcomes of the randomized trial. For example, CES‐D‐assessed caregiver depression significantly decreased over time for Tele‐Savvy (p=.002) with no significant changes seen in the Healthy Living condition (p=.689) nor waitlist control (p=.141). Similarly, dyadic strain significantly decreased over time for the Tele‐Savvy group (p=.012) with no significant changes for the Healthy Living condition (p=.968) nor waitlist control (p=.135). Lastly, caregiver competence significantly increased over time for the Tele‐Savvy group (p<.001) with no significant changes for the Healthy Living control group (p=.558) nor waitlist control (p=.327).ConclusionThis initial work supports the improvements seen in the Tele‐Savvy condition are attributed to the online psychoeducation intervention and not simply the attention received via video conferencing. As such, this work supports an engaging “Control” condition which may serve future trials aimed to evaluate the effectiveness of online psychoeducation programs.
Determinants of subjective cognitive decline among older sexual minority Canadians
Authors: Stinchcombe Arne , Hammond Nicole G 
Published: December 2020

AbstractBackgroundSome lines of evidence suggest that older lesbian, gay, and bisexual (LGB) people may be at increased risk of cognitive impairment, stemming from minority stress experiences accumulated throughout the lifespan. Subjective cognitive decline (SCD) is a perceived worsening in cognition and has been associated with dementia in the preclinical stage.MethodWe sought to examine variables associated with SCD among LGB participants in the Canadian Longitudinal Study on Aging (CLSA), a study of over 50,000 individuals. First follow‐up data were used and the mean age was 62.75 (SD=9.34). SCD was measured through the question “Do you feel like your memory is becoming worse?”. The analytic sample included only LGB participants in the study (n=925). Multiple logistic regression was used to estimate the odds of SCD.ResultResults indicated that lesbian/bisexual women had 1.49 higher odds of reporting SCD (p=.006). Participants who were widowed (p=.041) and older (p=.011) were also at higher odds of reporting SCD.ConclusionThe findings highlight factors that may increase risk of cognitive decline among individuals within aging sexual minority communities.
Social cognitive abilities in older adults with mild cognitive impairment and dementia
Authors: Chander Russell J. , Numbers Katya T. , Grainger Sarah A. , Cleary Rhiagh , Das Debjani , Mather Karen A. , Kochan Nicole A. , Brodaty Henry , Henry Julie D. , Sachdev Perminder S. 
Published: December 2020

AbstractBackgroundAging is associated with changes in general cognition and social cognition. Many studies have detailed these functions in isolation, comparing young and older adults. More information is needed on how social cognition, including theory of mind (ToM), affective empathy (AE), social perception (SP), and social behavior (SB), is affected at different cognitive stages in older adults.MethodCross‐sectional study of 305 older adults from the Sydney Memory and Ageing Study. Dementia was classified based on clinical consensus using DSM‐IV criteria, while mild cognitive impairment (MCI) was classified using the International Working Group criteria. Cognitively normal (CN), MCI, and dementia participants were compared on social cognitive domains including: ToM, via the Reading the Mind in the Eyes Test (RMET) and the Interpersonal Reactivity Index – Perspective Taking subscale (IRI‐PT); AE, via the IRI – Empathic Concern subscale (IRI‐EC); and SP, via the Emotion Recognition Task (ERT). Apathy, which is related to SB, was measured via the Apathy Evaluation Scale (AES).ResultMean age 87.00 ± 4.05 years, mean education 11.89 ± 3.36 years, 60.3% female. 141 were CN, 103 had MCI, and 61 had dementia. Across cognitive groups, significant differences were observed for the RMET, ERT (specifically for the recognition of anger, disgust, and happiness), AES, IRI‐PT, and IRI‐EC. In posthoc comparisons, RMET and ERT were significantly poorer in MCI and dementia compared to CN, but not between MCI and dementia. IRI ratings and AES were poorer for dementia compared to MCI and CN, but not between MCI and CN (Table 1). In multivariable logistic regression adjusting for significant risk factors for cognitive impairment, RMET and ERT disgust performance were associated with lower risk of MCI over CN. Only AES significantly differentiated dementia from MCI (Table 2).ConclusionNeurocognitive disorders are associated with social cognition changes. ToM and SP appear to be affected in MCI relative to CN. Apathy, known to be linked to SB, appears to be affected in dementia. MCI seems to be associated with impaired ability to recognize specific social cognitive cues, while dementia may be more associated with overall worse social cognitive functioning and observed behavioral changes.
A Mendelian randomization approach to characterize overlap in the pathophysiology of neurological disorders
Authors: Bahena Jorge Alberto , Eiffert Brett , Farias Fabiana H.G. , Ibanez Laura , Mihindukulasuriya Kathie A. , Budde John P. , Cruchaga Carlos , Harari Oscar 
Published: December 2020

AbstractBackgroundNeurodegenerative diseases are characterized by progressive neuronal death, leading to loss of cognitive function. This process is thought to commence decades before symptom onset. Consequently, there is a dire need to characterize the pre‐clinical phase of neurodegenerative diseases to provide early intervention. We employed a Mendelian randomization approach to identify genetic overlap across neurological disorders and describe common disease mechanisms.MethodWe utilized our web‐based multi‐omics analytic tool ONTIME (Online Neurodegenerative Trait Integrative Multi‐Omics Explorer, http://ngi.pub/ONTIME/) to apply two‐sample Mendelian randomization to neurological disorders. We estimated the causal effect of 59 cerebrospinal fluid (CSF) analytes and 134 plasma analytes on the risk of Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic Lateral Sclerosis (ALS), and stroke. Instrumental variables for CSF (N = 672) and plasma (N = 818) analytes were obtained from quantitative genome‐wide association studies we performed using the RBM Human DiscoveryMAP panel.ResultIn CSF, we identified seven analytes that have a causal effect on AD, two analytes that have a causal effect on ALS, and three analytes that have a causal effect on stroke after false discovery rate (FDR) adjustment (Table 1). In plasma, we identified eleven analytes that have a causal effect on AD, eight analytes that have a causal effect on ALS, and five analytes that have a causal effect on stroke after FDR adjustment (Table 2). Furthermore, we detected overlap in the pathogenesis of AD and ALS as well as AD and stroke.ConclusionOur results support a growing body of evidence that there is significant genetic and pathophysiological overlap across neurodegenerative diseases. Furthermore, our findings provide evidence that vascular factors contribute to neurodegenerative disease onset. Finally, these results highlight the utility of ONTIME and its Mendelian randomization tool. Users can upload disease summary statistics and test if any CSF or plasma analyte in our catalogue has a causal effect on their uploaded health outcomes.
Functional neural correlates of the WAIS‐IV Block Design Test in older adult with mild cognitive impairment and Alzheimer’s disease dementia
Authors: Joung Haejung , Yi Dahyun , Byun Min Soo , Lee Jun Ho , Lee Younghwa , Ahn Hyejin , Kim Hakyeong , Lee Dong Young 
Published: December 2020

AbstractBackgroundWhile the Wechsler Adult Intelligence Scale IV (WAIS‐IV) Block Design Test (BDT) has is widely used in both research and clinical setting as a measure of cognitive decline in the aging population, its functional neural substrates has not been clearly identified. Hence, the aim of the current study is to identify the functional neural correlates of the BDT in older adults with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia patients.MethodThe current study includes 213 cognitively impaired (135 MCI and 78 AD dementia) middle and old‐aged adults. All participants underwent comprehensive clinical and neuropsychological assessments and 18F‐fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) scans. The BDT performance was assessed using the Wechsler Adult intelligence scale‐IV Korean version. Voxel‐wise analyses were used to investigate the correlation between regional cerebral glucose metabolism and BDT performance. The same analyses were conducted on the subgroups categorized by clinical severity based on the Clinical Dementia Rating.ResultThe participants had a mean age of 73.1 (SD = 7.4) years, mean years of education of 9.8 (SD = 4.9), mean BDT score of 20.9 (SD = 9.1), and 67.1% were female. Significant positive correlations between the BDT performance and regional cerebral glucose metabolism were found bilaterally in the inferior parietal lobule and thalamus, the right superior temporal gyrus and left occipital precuneus.ConclusionThe findings indicated that BDT performance in MCI and AD dementia patients functionally relies on the brain regions known to be associated with motor and executive functions as well as visuospatial functions.
Perivascular space alteration in idiopathic and familial Parkinson’s disease
Authors: Murdos Amjad , Sheikh‐Bahaei Nasim , Toga Arthur W. , Sepehrband Farshid ,   Parkinson's Progression Markers Initiative
Published: December 2020

AbstractBackgroundParkinson’s Disease is the second most prevalent neurodegenerative diseases today. There is a growing body of evidence suggesting overlap between Alzheimer’s disease and many Parkinson related neurodegenerative processes. Understanding the vascular impact in patients with Parkinson’s disease can provide new insight on pathological progression and treatment options. Dilation of perivascular spaces has been an important measure of vascular insult in the context of glia‐lymphatic clearance and neurodegenerative diseases. The role of microvascular changes and particularly dilated perivascular spaces in Parkinson’s disease, has not been investigated. Differences in perivascular spaces among patient with idiopathic and familial Parkinson’s disease can provide novel insight on the implications of the genetic components pertaining to Parkinson’s disease.MethodTotal of 470 individuals were analyzed from the PPMI database. Subjects were grouped based on their genetic status of their disease: idiopathic Parkinson’s Disease (n=201), familial Parkinson’s Disease (n=71), healthy controls without genetic risk factor (n=94) and healthy controls with genetic risk factor (n=104). To study the impact of brain glia‐lymphatic pathway pathology on the clinical status of idiopathic and familial Parkinson's disease, total perivascular space volume was compared between these patient populations using a newly developed technique (Figure 1).ResultThe perivascular spaces were significantly larger in the idiopathic and familial Parkinson’s disease subjects compared with the idiopathic and familial control subjects. Interestingly, across different groups the lowest perivascular space volume fraction was observed in the healthy control with genetic risk factor, suggesting a potential protective or compensatory mechanism relating to vascular or glia‐lymphatic system (Figure 2).ConclusionOur findings showed that individuals with symptomatic Parkinson’s disease have more enlarged perivascular spaces compared to clinically intact controls independent of their genetic predisposition. It suggests that microvascular changes and particularly perivascular spaces might contribute to the neurodegenerative symptoms through parallel pathways additional to the primary pathological process. These results are very similar to the effect of perivascular spaces in Alzheimer’s disease. More interestingly, our data showed that presence of Parkinson’s genetic factors, does not increase the risk of glia‐lymphatic impairment while in the later stages this impairment can contribute into the clinical picture.
H. pylori infection is associated with cortical thinning in cognitively normal individuals
Authors: Park Jaehong , Song Joohye , Shin Hee Young , Jang Hyemin , Na Duk L , Seo Sang Won , Kim Tae Joon , Kim Hee Jin 
Published: December 2020

AbstractBackgroundHelicobacter pylori (H.pylori) is a well known bacteria for development of stomach cancer and chronic inflammation. However, H.pylori’s contribution to the neurodegeneration remains largely unknown. We aimed to evaluate the association between H.pylori infection and brain cortical thickness in cognitively normal individuals.MethodWe recruited 1,926 cognitively normal individuals (age≥ 45 years) who underwent brain 3‐dimensional volume MR images and esophagogastroduodenoscopy biopsy to determine H. pylori infection. The participants were recruited from Health Promotion Center in Samsung Medical Center from September 2008 to December 2014. After excluding participants with missing variables, 1,594 were selected in final analysis. We measured cortical thickness using the standard Montreal Neurological Institute image processing tool CIVET. Multiple linear regression analysis was done to evaluate the relationship between H.pylori infection and brain cortical thickness after controlling for age, intracranial volume, education, CRP, and the presence of metabolic syndrome.ResultIn male, H. pylori infection was associated with cortical thinning in the bilateral lateral temporal, lateral frontal, and right occipital areas. However, in female, H. pylori infection was not associated with cortical thickness.ConclusionOur findings suggest that H.pylori infection is associated with neurodegenerative changes in cognitive normal male, regardless of chronic inflammation or metabolic syndrome.
Difference of quantitative EEG between Alzheimer’s disease (AD) dementia and non‐dementia AD
Authors: Kang Seung Wan , Choi Seong Hye , Jeong Jee Hyang , Jang Jae‐Won , Park Kyung‐Won , Kim Eun‐Joo , Kim Hee Jin , Hong Jin Yong , Yoon Soo Jin , Yoon Bora , Kang Dong Won 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) is the most common cause of dementia. However, accumulation of beta amyloid plague in the brain which is main pathology of AD could show the various spectrum of cognitive functional stage from preclinical level to overt dementia. It is important to understand functional differences between dementia and non‐dementia of AD to predict progression forward to dementia at prodromal or preclinical stage of AD.MethodNineteen channels of resting state EEGs were measured from 45 Alzheimer’s disease subjects who were all confirmed by brain amyloid‐beta PET. Neurocognitive test, activity of daily living (ADL) and MRI were conducted for clinical diagnosis. EEG power spectrum analysis and band‐power ratio, cortical source current density estimated by standardized low resolution brain electromagnetic tomography(sLORETA), functional connectivity between 68 region of interest (ROI) based on imaginary coherence(iCoh) and complex brain networks were analyzed.Result20 AD subjects (age: 76.8±7.54) were assessed as dementia, and the other 25 (age: 72.1±6.89) as mild cognitive impairment (MCI) or subjective cognitive decline (SCD) depending on delayed recall memory score. Average CDR was 0.23 in non‐dementia and 1.15 in dementia group. There was no significant difference at delta, but theta power of AD dementia group was significantly increased at all 19 scalp channels. Mid frontal channel (Fz) showed the most distinctive enhancement of theta power. In other hands, beta1 (12∼15Hz) was significantly increased at both temporoparietal area in non‐dementia AD group. These patterns about theta increase and beta 1 decrease in AD dementia group were observed very similarly in cortical source current density. iCoh among ROIs of default mode network (DMN) was significantly decreased at alpha2 band (10∼12Hz). At bilateral frontal pole, rostral middle frontal, anterior cingulate, parahippocampus and precuneus, the degree centrality and characteristic path length significant increased at theta band. In contrast, theta of cluster coefficient and closeness centrality significantly decreased.ConclusionAD dementia showed increase of theta and decrease of bet1 both at scalp and cortical level comparing to non‐dementia AD subjects. Both global and local network efficiencies via theta wave were significantly deteriorated in AD dementia. QEEG could well discriminate the differences between dementia and non‐dementia in ADs.