bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between physical activity and markers of brain pathology in autosomal dominant Alzheimer’s disease: A preliminary report
Authors: Guzman‐Velez Edmarie , Vila‐Castelar Clara , Pardilla‐Delgado Enmanuelle , Fox‐Fuller Joshua T , Bocanegra Yamile , Baena Ana , Ramirez‐Gomez Liliana A , Lopera Francisco , Taylor J Andrew , Quiroz Yakeel T 
Published: December 2020

AbstractBackgroundPhysical activity is a promising lifestyle factor that could protect against memory decline in preclinical Alzheimer’s disease (AD). Greater physical activity has been shown to attenuate the relationship between amyloid‐b and cognitive decline and neurodegeneration in individuals at risk for dementia. Yet, little is known about the relation of physical activity with tau pathology, a strong predictor of cognitive decline. Autosomal dominant Alzheimer’s disease (ADAD) provides a unique opportunity to study preclinical AD since carriers of ADAD mutations are destined to develop dementia at early age, have a well‐characterized disease trajectory, and do not present age‐related comorbidities. We examined physical activity levels in young mutation carriers and non‐carriers from a Colombian kindred with ADAD, and explored the associations among physical activity, brain pathology (amyloid and tau), hippocampus volume, and memory performance.MethodsTen Presenilin‐1 E280A cognitively unimpaired mutation carriers and 23 matched non‐carriers (ages: μ=37.46, σ:6.01) traveled from Colombia to Boston for 11C Pittsburgh compound B‐PET (amyloid), Flortaucipir‐PET (tau), MRI and cognitive testing. All completed the 7‐day Physical Activity Recall questionnaire, which provides a measure of metabolic equivalents (METS) based on an estimate of the energy expenditure for common physical activities. Group differences were tested using the Mann Whitney U test. Linear regressions were used to examine associations between METS, imaging markers, and memory.ResultsCompared to non‐carriers, mutation carriers had greater cortical amyloid (non‐carriers: μ=1.05, σ=0.03, carriers: μ=1.26, σ=0.20, p<.001), and performed worse on the CERAD word list recall test (non‐carriers: μ=7.96, σ=1.24, carriers: μ=5.83, σ=2.75, p=.012). Groups did not differ in age, sex, education or METS (non‐carriers: μ=248.89, σ:27.53; carriers: μ=249., σ:20.81). Further, METS were not significantly associated with pathology levels, age, hippocampus volume or memory. However, those carriers (n=4) with the highest entorhinal and inferior temporal tau burden also had the lowest METS.ConclusionPreliminary findings of this ongoing study suggest that physical activity levels may not be associated with markers of neurodegeneration or memory performance in early preclinical ADAD. Future studies with larger samples and longitudinal follow‐up are needed to better understand the role of physical activity in the risk and progression of AD.
Trans‐ethnic meta‐analysis of interactions between genetics and early life socioeconomic status on memory performance and decline in older Americans
Authors: Faul Jessica D. , Kho Minjung A. , Zhao Wei , Rumfelt Kalee E. , Mitchell Colter , Smith Jennifer A. 
Published: December 2020

AbstractBackgroundLater life cognitive function is influenced both by genetics as well as early‐ and later‐life socioeconomic context, and these factors may also interact with each other. Previous research has demonstrated interactions between adult socioeconomic status and several gene regions that influence memory performance and decline in older adulthood, but few studies have examined whether genetics also interacts with childhood socioeconomic factors.MethodsWe used growth curve modeling to estimate episodic memory performance at age 65 (trajectory intercept) and decline thereafter (trajectory slope) in European ancestry (EA, N = 10,468) and African ancestry (AA, N = 2,252) participants from the Health and Retirement Study. Early‐life socioeconomic context included measures of parental education and financial strain. We selected 39 gene regions previously associated with cognitive performance, dementia, and related traits from GWAS. We tested whether all variants (1000 Genomes imputed data) and/or rare exomic variants (exome chip data) in these gene regions interacted with childhood socioeconomic context to influence memory using gene‐based tests (Interaction Sequence Kernel Association Test (iSKAT) or iSKAT Optimal Unified Test (iSKAT‐O)). For iSKAT analyses, we conducted a trans‐ethnic meta‐analysis.ResultsOf the 39 genes, 22 in EA and 19 in AA had nominally significant interactions (p < 0.05) with at least one childhood socioeconomic measure on memory performance and/or decline; however, all but one (father’s education by SLC24A4 gene region in AA) were not significant after multiple testing correction (FDR <0.1). In trans‐ethnic meta‐analysis, two gene regions interacted with childhood socioeconomic context (FDR <0.05). Both interactions were robust to adjustment for respondent’s own educational attainment and APOE ε4. For both interactions (mother’s education by MS4A4A on memory performance (meta‐analysis p = 0.0005), and father’s education by SLC24A4 on memory decline (meta‐analysis p = 0.0009)) in both EA and AA, the genetic effect was stronger in participants with low parental education.ConclusionsExamination of common and rare variants in genes discovered through GWAS shows that childhood socioeconomic context may interact with a few key gene regions to jointly impact memory function and decline in later life. Genetic effects may be more salient for those with lower childhood socioeconomic status.
Regional distribution of tau pathology in cognitively unimpaired, genetically identical twins
Authors: Coomans Emma M. , Tomassen Jori , Wolters Emma E. , Golla Sandeep S.V. , den Hollander Marijke , Verfaillie Sander C.J. , Collij Lyduine , Windhorst Albert D. , Boellaard Ronald , Barkhof Frederik , Ossenkoppele Rik , de Geus Eco J.C. , Scheltens Philip , Visser Pieter Jelle , Van Berckel Bart N.M. , den Braber Anouk ,   the AMYPAD consortium
Published: December 2020

AbstractBackgroundLimited information is available on the genetic and environmental contributions to early AD pathology. Within a sample of cognitively unimpaired genetically identical older twins we aimed to assess 1) effects of amyloid‐ß pathology on [18F]flortaucipir (tau) binding and 2) spatial similarities in tau patterns within twin pairs.MethodTo date, ten twin pairs (i.e. twenty twins) from the on‐going EMIF‐AD PreclinAD study underwent dynamic (0‐30min and 80‐100min) [18F]flortaucipir PET. Two twin pairs were concordant amyloid‐ß positive, four twin pairs concordant amyloid‐ß negative and four twin pairs amyloid‐ß discordant (i.e. one twin positive and co‐twin negative) based on [18F]flutemetamol visual read. [18F]flortaucipir binding potential (BPND) images were generated using receptor parametric mapping (reference region: cerebellar gray matter). First, we compared [18F]flortaucipir BPND in an early (entorhinal), intermediate (limbic) and late (neocortical) stage tau pathology region between amyloid‐ß positive and negative twins using generalized estimated equation correcting for twin dependency. Next, we examined spatial tau pattern similarities within twin pairs by correlating (Spearman) [18F]flortaucipir BPND across 46 ROIs from the Hammers template between each twin and their co‐twin for each true twin pair. Correlations were also performed for all non‐twin “random” pairs. Correlation coefficients within true twin pairs were compared to the correlation coefficients within random pairs, correcting for age and twin amyloid‐ß status.ResultsAmyloid‐ß positive twins showed higher [18F]flortaucipir BPND in entorhinal (p=0.01) and limbic (p=0.04) regions(Table‐1). Fig‐1 shows representative [18F]flortaucipir images of an amyloid‐ß concordant positive, concordant negative and discordant pair, with regional similarities observed in amyloid‐ß concordant pairs as well as dissimilarities in amyloid‐ß discordant pairs (Fig‐1;Fig‐2). Between‐twin correlations across regional [18F]flortaucipir BPND, to assess spatial tau pattern similarities, were higher for true twin pairs (r=0.71±0.17) compared to random pairs (r=0.45±0.23) (p=0.002)(Table‐2).ConclusionIn line with previous studies, amyloid‐ß positive cognitively unimpaired twins showed higher tau deposition in early and intermediate tau stage regions. Furthermore, we observed higher spatial tau pattern similarities within true twin pairs compared to random pairs, suggesting a moderate genetic contribution to mechanisms underlying tau spread. With the upcoming larger sample we aim to further assess genetic and environmental contributions to early AD pathology.
Different abnormalities of electroencephalographic (EEG) markers in quiet wakefulness are related to visual hallucinations in patients with Parkinson’s and Lewy body diseases
Authors: Babiloni Claudio , Lopez Susanna , Pascarelli Maria Teresa , Lizio Roberta , Noce Giuseppe , Ferri Raffaele , Soricelli Andrea , Nobili Flavio Mariano , Arnaldi Dario , Famà Francesco , Orzi Francesco , Buttinelli Carla , Giubilei Franco , Salvetti Marco , Cipollini Virginia , Bonanni Laura , Franciotti Raffaella , Onofrj Marco , Fuhr Peter , Gschwandtner Ute , Ransmayr Gerhard , Aarsland Dag , Parnetti Lucilla , Farotti Lucia , Marizzoni Moira , D'Antonio Fabrizia , de Lena Carlo , Güntekin Bahar , Hanoğlu Lutfu , Yener Görsev , Emek‐Savas Derya Durusu , Triggiani Antonio Ivano , Taylor John‐Paul , McKeith Ian , Stocchi Fabrizio , Vacca Laura , Hampel Harald , Frisoni Giovanni B , De Pandis Maria Francesca , Del Percio Claudio 
Published: December 2020

AbstractBackgroundParkinson’s disease (PD) is the second‐most common neurodegenerative disorder that affects 2–3% of the population ≥ 65 years of age and may belong to cognitive deficits and dementia in 50% of cases. Disease with Lewy Bodies (DLB) is emerging as another important cause of dementia in pathological aging. PD and DLB are both due to intra‐neuronal Lewy bodies and are characterized not only by motor dysfunctions but also cognitive and/or psychiatric symptoms. An open issue is the extent to which these diseases are distinct entities. In this respect, here we compared cortical sources of resting state eyes‐closed electroencephalographic (rsEEG) rhythms in PD and DLB patients as a function of global cognitive status.MethodClinical and rsEEG rhythms in demographic matched PD (N = 93), DLB (N = 46), Alzheimer’s disease dementia (AD, N= 70) and healthy elderly (Nold, N = 60) subjects were available from an international archive. Pathological groups were matched as cognitive status. Individual alpha frequency peak was used to determine the delta, theta, alpha1, alpha2, and alpha3 frequency band ranges. Fixed beta1, beta2, and gamma bands were considered. The eLORETA freeware estimated rsEEG cortical sources.ResultCompared to the Nold subjects, the AD, DLB, and PD patients showed higher widespread delta source activities and lower posterior alpha source activities. Specifically, posterior alpha source activities were more abnormal in the AD than the DLB and PD groups, while widespread delta source activities were more abnormal in the PD and DLB than the AD group. As main novel results, in relation to the DLB and PD patients with low cognitive deficits and the control groups (Nold, AD), those with high cognitive deficits were characterized by higher parietoccipital delta source activities (DLB, Figure 1) and widespread alpha sources activities (PD, Figure 2).ConclusionThese novel results suggest that in DLB and PD patients resting in the quiet wakefulness, abnormalities in cortical neural synchronization at delta and alpha frequencies are differently related to cognitive status despite the essence of alpha‐synucleinopathy.
Influence of cerebral glucose metabolic rate on cognitive function in Alzheimer's subjects
Authors: Edison Paul , Femminella Grazia Daniela , Livingston Nicholas R , Raza Sanara , Nowell Joseph , Carver Stefan , Holmes Clive , Blunt Eleanor G , Lawrence Robert M , McFarlane Brady , Tadros George , Ritchie Craig W , Ridha Basil H , Bannister Carol , Walker Zuzana , Archer Hilary , Coulthard Elizabeth , Underwood Ben , Prasanna Aparna , Koranteng Paul , Karim Salman , Junaid Kehinde , McGuinness Bernadette , Nilforooshan Ramin , Macharouthu Ajayverma , Donaldson Andrew , Thacker Simon , Russell Gregor , Malik Naghma , Mate Vandana , Knight Lucy , Kshemendran Sajeev , Harrison John E , Brooks David J , Passmore Anthony Peter , Ballard Clive 
Published: December 2020

AbstractBackground18F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) measures regional cerebral glucose metabolism –which is a biomarker of neuronal function in Alzheimer’s disease (AD) Neuropsychological measures such as the Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS‐Cog) – a measure of memory, language and praxis has been used as an outcome measure in AD clinical trials. ADAS‐Cog‐12 attempts to overcome such limitations, by including an additional delayed word recall measure. The objective of this study was to compare baseline ADAS‐Cog‐12 scores with cerebral glucose metabolic rate measured with FDG‐PET with arterial input in subjects who have undergone baseline scans for the Evaluation of Liraglutide in treatment of Alzheimer’s disease (ELAD) study.Method107 subjects diagnosed with AD underwent baseline FDG‐PET scans with continuous online blood sampling along with discrete sampling for radioactivity and plasma glucose. They also underwent detailed neurological and neuropsychological testing including ADAS‐Cog. FDG PET was analysed using spectral analysis with arterial input and following regions were sampled : hippocampus, medial temporal lobe, temporal, anterior cingulate, posterior cingulate, frontal, parietal and occipital cortices. ADAS‐Cog scores were calculated for all the subjects.ResultPearson’s product‐moment correlation showed that ADAS‐Cog scores (at 0.01 level) negatively correlated with all FDG‐PET ROIs derived from spectral analysis (‐0.36≤|r|≤‐0.54). Greatest correlations occurred between ADAS‐Cog and the temporal cortex (‐0.54), parietal cortex (‐0.51) and frontal lobe (‐0.51).ConclusionIn this study, ADAS‐Cog‐12 scores correlated well with the cerebral glucose metabolism, suggesting cerebral glucose metabolism could be used as a surrogate marker for cognitive function in Alzheimer’s disease intervention studies, and is a sensitive maker for neuronal function.
Association of white matter hyperintensities with sub‐threshold amyloid accumulation
Authors: Moscoso Alexis , Rey‐Bretal David , Silva‐Rodríguez Jesús , Grothe Michel , Schöll Michael , Aguiar Pablo 
Published: December 2020

AbstractBackgroundPrevious studies investigating the relationship between amyloid‐β (Aβ) pathology and white matter lesions have led to inconsistent results. A potential explanation for these disparities is the cross‐sectional design of most of these studies, which might have increased the confounding effect of vascular pathology. Here, we used a longitudinal design to investigate whether white matter lesion burden is associated with faster rates of longitudinal Aβ accumulation among cognitively normal older adults without PET‐evidenced Aβ pathology.MethodOne hundred fifty‐nine cognitively normal participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) who were Aβ‐negative at baseline were examined. All the participants had a T1 and FLAIR MRI scan at baseline, as well as baseline and at least one follow‐up [18F]florbetapir PET scans acquired in 2‐year intervals for up to 8 years. The Geometric Transfer Matrix method was used to correct for partial volume effects, including those coming from spill‐in counts from the white matter. A previously defined cortical summary region including frontal, parietal, cingulate, and temporal cortices was used to assess global amyloid burden. Standardized Uptake Value Ratios (SUVR) were computed using the cerebellar gray matter as reference region. The association between global and regional white matter hypertense (WMH) burden, and Aβ accumulation was assessed using linear mixed models adjusted by demographics and baseline SUVR.ResultPartial volume correction increased the measured annual rate of change of cortical SUVR (+2.4%) compared to non‐corrected data (+0.5%). There were no significant correlations between baseline WMH and baseline subthreshold cortical SUVR. In the longitudinal analysis, increased baseline cortical SUVR and increased baseline burden of global (p = 0.006), frontal (p = 0.006), and parietal WMH (p = 0.003) were associated with faster amyloid accumulation (Fig.1). WMH‐related Aβ accumulation occurred in parietal, frontal, and, to a lesser extent, cingulate cortices. These results remained unchanged after a sensitivity analysis excluding participants with the highest cortical SUVRs.ConclusionWe demonstrate that a specific spatial distribution of WMH is predictive of future Aβ accumulation among cognitively normal elderly without PET‐detectable Aβ pathology. These findings add to recent studies pointing to a direct relationship between WMH and Aβ pathology in early Alzheimer’s Disease.
Tau deletion enhances neurogenesis in adult MAPT‐/‐ mice
Authors: Criado‐Marrero Marangelie , Sabbagh Jonathan J. , Blair Laura J. 
Published: December 2020

AbstractBackgroundTau is the major microtubule associated protein (MAPT) that, under normal conditions, supports neuronal microtubule’s stability. However, pathological tau self‐aggregates and disrupts microtubules function contributing to common hallmarks in neurodegenerative diseases like Alzheimer's disease (AD) and frontotemporal dementia (FTD). Besides dementia, tau pathology has been associated with the progressive development of behavioral symptoms because it affects brain regions in the limbic system and there are comorbid symptoms of depression with AD. However, it is not known if this is a direct consequence of neuropathological changes or a response to the psychological burden of dementia.MethodsThe current study investigated the effect of tau deletion in depressive‐like behavior and neurogenesis using the Mapt
‐/‐ mouse model, which contains a targeted deletion of tau gene. We used behavioral (forced swim, tail suspension, learned helplessness) tests and molecular (cell culture, immunohistochemistry and proteomic mass spectrometry) tools to evaluate tau‐induced changes.ResultsAt 6‐months of age, we found that both female and male Mapt
‐/‐ mice are resistant to depressive behaviors. Unlike depressed patients, the hypothalamic pituitary adrenal axis was not affected in Mapt‐/‐ mice suggesting that the glucocorticoid signaling is not responsible for conferring protection from depression in these mice. Since depression has also been linked to deficient adult neurogenesis, we measured neurogenesis in the hippocampal dentate gyrus and subventricular zone using 5‐bromo‐2‐deoxyuridine (BrdU) labeling. We found that tau deletion promotes long‐lasting effects in hippocampal neurogenesis as observed at 14‐months‐old mice. Induction of proteins involved in neurogenesis was observed in limbic areas including the hippocampus, frontal cortex and amygdala of the Mapt
‐/‐ mice.ConclusionAll together, these findings suggest that tau may have a role in the depressive symptoms observed in many neurodegenerative diseases and identify tau as a potential molecular target for treating depression.
Metabolic risk factors, but not vascular lesions and β‐amyloid, are associated with functional connectivity across the Alzheimer’s disease spectrum
Authors: Köbe Theresa , Gaubert Malo , Lange Catharina , Garnier‐Crussard Antoine , Bougacha Salma , Gonneaud Julie , de Flores Robin , Landeau Brigitte , De la Sayette Vincent , Chetelat Gael , Wirth Miranka 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) is a multifactorial disease, characterized not only by pathological protein aggregation (Ab and tau), but also by early vascular dysfunctions and functional connectivity alterations (Iturria‐Medina 2016; van der Kant 2019). The study objective was to investigate the association between different markers of vascular health as well as brain β‐amyloid burden and brain network functional connectivity across the AD spectrum.MethodThe sample included 131 participants with normal cognition, subjective cognitive decline, mild cognitive impairment and clinical AD from the IMAP cohort (Caen, France). Vascular risk factors comprised mean arterial pressure, body‐mass‐index (BMI), glycemia and HbA1c levels. White matter hyperintensities (WMH) were segmented from FLAIR‐MRI using the “lesion‐segmentation‐tool” (Schmidt, 2017). Brain β‐amyloid burden was measured by the mean of AV45‐SUVR in an AD‐related neocortex mask (LaJoie 2012). Resting‐state functional connectivity (RSFC) was determined within seven predefined functional networks (Schaefer 2018, Verfaillie 2018). Partial correlation analyses were run to assess associations of vascular risk factors, total WMH load and β‐amyloid burden with RSFC. Additionally, we tested for interaction effects with β‐amyloid status in linear regression analyses. All models were age‐ and sex‐adjusted.ResultParticipant characteristics are presented in Figure 1. Across all participants, higher BMI and higher glycemia were associated with lower RSFC within the default‐mode, salience/ventral‐attention, fronto‐parietal and dorsal‐attention networks (Figure 2 and 3). Results remained significant after correction for diagnostic group status. No associations were found between RSFC and total WMH load or β‐amyloid burden (p≥0.05). There were no significant moderation effects by β‐amyloid positivity (p≥0.05).ConclusionThese findings demonstrate that metabolic‐related vascular risk factors, but not cerebrovascular or β‐amyloid pathologies, are associated with functional connectivity specifically within cognition‐related functional networks. Our study further highlights that connectivity alterations associated with metabolic risk, previously shown in diabetes patients (Musen 2012; Chen 2015), are also present in a non‐diabetic aging and AD cohort. Given that functional connectivity supports reserve capacity, connectivity failure within higher‐order networks may limit resilience against aging and pathological processes.