bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sleep apnea is associated with entorhinal cortex and hippocampal subfield atrophy in asymptomatic amyloid‐positive older adults
Authors: André Claire , de Flores Robin , Kuhn Elizabeth , Rehel Stéphane , Landeau Brigitte , Mézenge Florence , De la Sayette Vincent , Chetelat Gaël , Rauchs Géraldine ,   Medit‐Ageing Research Group
Published: December 2021

AbstractBackgroundSleep‐disordered breathing (SDB) has been associated to greater amyloid deposition and dementia risk. However, the pattern of SDB‐associated structural brain changes is unclear, especially within the medial temporal lobe (MTL). We investigated the associations between SDB severity and the volume of MTL subregions, and hypothesized that SDB would be associated with atrophy in regions early affected by Alzheimer’s disease (AD) pathology and/or sensitive to hypoxia (i.e., the perirhinal and entorhinal cortices, and CA1 hippocampal subfield), particularly in amyloid‐positive participants.MethodWe included 120 cognitively unimpaired older participants from the Age‐Well randomized controlled trial (mean age=69 ± 3,8 years; 25 Aβ+ and 95 Aβ‐ participants). They underwent a structural MRI, including a high‐resolution T2‐weighted sequence of the MTL (0.4x0.4x2.5mm3), a Florbetapir‐PET scan to measure amyloid deposition, as well as a polysomnography. The ASHS (Automatic Segmentation of Hippocampal Subfields) software was used to segment the entorhinal, perirhinal, and parahippocampal cortices, as well as hippocampal subfields (i.e., the subiculum, CA1, CA2‐3, the dentate gyrus, their sum representing total hippocampal volume) on high‐resolution MRI sequences. Bilateral volumes normalized to the total intracranial volume were used in statistical analyses. We performed linear regressions with the volume of each MTL subregion as dependent variables, the apnea‐hypopnea index (AHI, reflecting SDB severity) and amyloid status as independent variables, and age, sex, education and the ApoE4 status as covariates.ResultWe found significant interactions between the AHI and amyloid status on the volumes of the entorhinal cortex (p<0.001), whole hippocampus (p<0.001), subiculum (p<0.001), CA1 (p=0.003) and dentate gyrus (p=0.007), such that the AHI significantly predicted the volume of these MTL subregions only in amyloid‐positive participants (Figure 1).ConclusionUntreated SDB has been previously associated with increased amyloid deposition, even in the absence of cognitive or sleep symptoms. Our data complement these findings by showing that once amyloid deposition reaches positivity, greater SDB severity is related to neurodegeneration in several MTL subregions, including the entorhinal cortex and hippocampus. Thus, the presence of SDB in cognitively unimpaired older adults who are engaged in the Alzheimer’s continuum may increase the risk of developing memory impairment over time.
Stability of blood‐based biomarkers of cognitive impairment
Authors: Thyagarajan Bharat , Crimmins Eileen M. , Barcelo Helene , Langa Kenneth M. , Weir David , Faul Jessica D. 
Published: December 2021

AbstractBackgroundWidespread investigation of these biomarkers in large population studies has been hampered as several blood biomarkers of cognitive impairment need the blood to be processed immediately into plasma/serum. We evaluated the stability of these biomarkers to delayed blood processing using an ultra‐sensitive assay.MethodWe processed blood collected from 20 volunteers immediately (0 hours), and after a delay of 24 hours and 48 hours to obtain serum. In addition, we also processed blood from five volunteers immediately (0 hours) and after a delay of 24 hours, 48 hours and 72 hours to obtain plasma. All serum and plasma samples were analyzed in duplicate for Aβ42, Aβ40, tau and neurofilament light (NfL) on the Quanterix platform using commercially available assays.ResultThe decrease in plasma Aβ42 and Aβ40 values were relatively modest in blood processed after a delay of 24 hours (6% and 11% respectively), 48 hours (20% and 21% respectively) and 72 hours (30% and 32% respectively) as compared to samples processed immediately. Furthermore, the plasma Aβ42/ Aβ40 ratio showed only a 9% decrease in plasma processed after a delay of 72 hours. Plasma tau levels decreased by 20% at 48 hours as compared to a 9% decrease in serum. Plasma levels of Aβ42, Aβ40 and tau were substantially higher than serum levels. However, even at 48 hours, plasma tau levels were higher as compared to serum levels. NfL levels were comparable in serum and plasma and NfL levels decreased 10% and 6% in plasma and serum at 48 hours.ConclusionDespite a decrease in plasma levels of Aβ42 and Aβ40 was substantial after 48 hours the Aβ42/ Aβ40 was stable in plasma processed up to 72 hours after blood collection. Plasma and serum levels of NfL appear to be stable even when blood was processed for up to 48 hours after blood collection while plasma tau levels showed only modest reduction in values over 48 hours. These results suggest that blood‐based biomarkers of cognitive impairment can be reliably measured in plasma samples that were processed even after a delay of up to 48 hours after blood collection.
CSF biomarkers and blood pressure trajectories in normotensive individuals and subjects with controlled and uncontrolled hypertension
Authors: Glodzik Lidia , Butler Tracy , Li Yi , Tanzi Emily , Harvey Patrick , Blennow Kaj , Zetterberg Henrik , de Leon Mony J. 
Published: December 2021

AbstractBackgroundHypertension is a risk factor for Alzheimer’s disease, however relationships between this disease and CSF amyloidβ42, total tau and phosphorylated tau (p‐181) are inconclusive. Even less is known about associations between trajectories of blood pressure and AD biomarkers.MethodLongitudinal CSF examinations were performed in 132 normotensive subjects (BP<140/90, and no antihypertensive treatment), 35 subject with controlled hypertension ((BP<140/90, and antihypertensive treatment), and 32 subjects with uncontrolled hypertension (BP≥140/90, irrespective of treatment), mean age 64.3 ± 9.3 years, 61% women.Biomarker changes over time, and relationship between changes in biomarkers and changes in systolic and diastolic blood pressure were tested using repeated measures mixed model.ResultNormotensive group was younger than 2 other groups, percentage of women did not differ. Baseline biomarkers levels were not different between groups.After a mean follow‐up time of 3.7±2.7 years total tau and p‐tau181 increased in the normotensive and uncontrolled groups, but did not change in the controlled group (group*time: F=3.2, p=.04 and F=3.2, p=.04 for total tau and p‐tau181, respectively). Amyloidβ42 remained unchanged in the normotensive and controlled groups, but decreased in the uncontrolled group (group*time: F=3.1, p=.04).Change in systolic blood pressure was inversely related to change in total tau only in the uncontrolled group (group*time: F=5.0, p=.007). Change in diastolic blood pressure was inversely related to change in ptau‐181 tau only in the uncontrolled group (group*time: F=4.2, p=.02). No other relationship between blood pressure and biomarkers was detected.ConclusionSubjects with baseline uncontrolled hypertension experienced longitudinal changes in amyloid and tau markers most consistent with progression toward Alzheimer’s disease. Interestingly, in this group increases in tau and p‐tau181 coincided with reduction in blood pressure. This may indicate relationship with relative hypoperfusion in subjects with vasculature compromised by years of high blood pressure.
Correlations between cognitive assessment and RNFL changes in OCT in healthy aging subjects
Authors: Shen Ting , Sheriff Samran , Schulz Angela , You Yuyi , Graham Stuart , Gupta Vivek K 
Published: December 2021

AbstractBackgroundThe retinal nerve fibre layer (RNFL) comprises retinal ganglion cell axons and link the outer neuroretina to the higher visual cortex. The retina is the only part of the central nervous system that can be visualised directly and non‐invasively by optical coherence tomography (OCT). The study aimed to examine whether changes in the visual pathway are correlated with various domains of cognitive function assessment. We evaluated correlation between retinal structural (OCT) and neuropsychological (trail making test, TMT; Boston naming test, BNT) measures in healthy aging subjects.MethodIn the present cross‐sectional clinical study, 74 healthy aging subjects were recruited from the Optic Nerve Decline and Cognitive Changes (ONDCC) study. All participants underwent OCT peripapillary ring scan protocol for RNFL analysis, TMT testing for attention and executive function and BNT neuropsychological examination for the detection of word‐retrieval or naming difficulties. Averaged RNFL thickness measures were used to analyse the relationship with TMT and BNT. Correlations between TMT, BNT and OCT parameters were analysed using partial correlation and controlled for age and gender (P < 0.05).ResultThe mean (SD) age of the current cohort is 67.5 (± 9.0 years). At baseline, significant correlation was observed between TMT‐test A and nasal RNFL thickness (r = ‐0.33, P = 0.009). The BNT also demonstrated mild but significant positive correlations with global (r = 0.32, P = 0.01), nasal (r = 0.27, P = 0.03) and nasal inferior (r = 0.33, P = 0.01) sectoral RNFL thicknesses respectively.ConclusionThe results indicated a significant correlation between RNFL thickness and executive function domain of cognitive assessment. Sectoral RNFL was also significantly correlated with naming ability (BNT) across the cohort of healthy elderly. These findings suggest that the RNFL measures may parallel cognitive decline in the aging population. Further studies are planned in confirmed cognitively impaired subjects.
Language learning for people living with dementia and their carers: A feasibility study
Authors: Mendoza Mariana Vega , Blankinship Brittany , Norval Robbie , Bak Thomas H 
Published: December 2021

AbstractBackgroundConverging evidence from across the world suggests positive effects of bilingualism on cognitive ageing and dementia, including a ca. 4‐6 years delay in the onset of dementia and’or Mild Cognitive Impairment. However, it is less clear whether language learning can also have a positive effect after the onset of dementia. A positive influence would include psychological and social variables, such as patients’ well‐being and their relationship with relatives and carers.MethodWe examined the feasibility and tolerability of language learning for people in early stages of dementia and their family carers in two Scottish Dementia Day Care Centres. A total of 12 people with dementia and 7 family carers participated in the study. All participants had only limited experience of language learning and none were bi‐/multilingual. The 2‐week courses of beginners Italian were delivered by specially trained tutors from Lingo Flamingo, a social enterprise specialising in language teaching for older learners and learners with Dementia. Before and after the course, we conducted focus group sessions with learners and their carers as well as interviews with teachers and Day Centre care workers.ResultsQualitative analyses revealed a positive perception of the courses by patients, carers, and centre managers, impacting both the individual (e.g., boosting self‐esteem) and group (e.g., socialising) levels. No adverse effects (e.g., confusion) were reported. The family carers perceived the courses as empowering, as they allowed them to take an active part. The courses led also to a higher attendance in other activities conducted in the Day Care Centre.ConclusionsDespite initial fears from professional carers that being confronted with the task of learning a new language might be stressful and lead to frustration and confusion, all participants reported a highly positive experience of the course, including a higher self‐esteem and self‐confidence as well as establishment of new social contacts and a more positive attitude to other activities of the day care centre. Further studies will be required to determine the optimal frequency, intensity and duration of language courses for people with dementia as well as the best practice of their delivery.
Racial differences in Alzheimer biomarkers among early‐stage symptomatic and cognitively normal Alzheimer Disease Research Center (ADRC) participants
Authors: Morris John C. , Ances Beau M. , Meeker Karin L. , Schindler Suzanne E. , Xiong Chengjie ,   Knight Alzheimer Disease Research Center, Washington University, St. Louis, Missouri USA
Published: December 2021

AbstractBackgroundThere are few assessments of possible racial differences in Alzheimer disease (AD) biomarkers because research cohorts typically are not diverse. Should differences exist, they may inform the understanding of AD pathogenesis as well as the role of social determinants of health (SDOH).MethodWe assessed a non‐clinic‐based cohort of 1255 community living persons, age 45 and older, who were enrolled in studies of aging and dementia at the Knight ADRC (St Louis, Missouri, USA). Participants completed at least one brain magnetic resonance imaging (MRI) study, and/or at least one amyloid positron emission tomography (PET) scan, and/or at least one lumbar puncture to obtain cerebrospinal fluid (CSF) for biomarker assays. The cohort included 1082 white participants and 173 participants who self‐identified as Black or African American (AA); 33% of participants in each group had early‐stage symptomatic AD and 67% in each group were cognitively normal.ResultBoth racial groups demonstrated expected biomarker changes as a function of clinical status (eg, lower hippocampal volumes in persons with symptomatic AD). Higher body mass index and HgA1c levels were noted in AAs, but there was no racial difference in the frequency of MRI‐confirmed cerebral infarcts. There also were no differences in the mean cortical standardized uptake value ratios for Pittsburgh Compound B or in amyloid‐beta42 concentrations in CSF. However, mean CSF concentrations of tau and phosphorylated tau181 were lower in AA participants, a finding that was evident primarily in carriers of the ε4 allele of APOE. The CSF concentrations of soluble TREM2, a mediator of the inflammatory response to AD pathology, also were lower in AAs. Finally, decreased volumes in brain regions comprising the AD cortical signature were lower in AAs but this difference was mediated, at least in part, by SDOH.ConclusionThere are racial differences in AD biomarkers between white and AA research participants, including for the AD cortical signature, a putative marker of neurodegeneration in the AT(N) framework. SDOH contribute to these differences, either independently or through interactions with biological factors.
Long‐term effects of repetitive head impacts on gray matter cortical thickness
Authors: Brekke Bailee , DeVivo Renee , McKee Ann C. , Stein Thor D. , Tripodis Yorghos , Phelps Alyssa , Weller Jason , Martin Brett M , Palmisano Joseph , Steinberg Eric , Turk Katherine W , Budson Andrew , O'Connor Maureen K , Au Rhoda , Qiu Wendy , Goldstein Lee E , Kowall Neil W , Stern Robert A , Killiany Ronald J , Mez Jesse , Alosco Michael L 
Published: December 2021

AbstractBackgroundRepetitive head impact (RHI) exposure has been associated with the neurodegenerative disease chronic traumatic encephalopathy (CTE). Magnetic resonance imaging (MRI) and postmortem research suggest frontotemporal atrophy may be characteristic of CTE. The late effects of RHI on cortical volume remain poorly understood due to focus on male former professional American football players and lack of examination of specific lobar gyri. We leveraged the Boston University Alzheimer’s Disease Research Center (BU ADRC) to compare frontal, temporal, and parietal gyri gray matter thickness between participants with and without RHI exposure.Method39 participants exposed to RHI and 33 similar‐aged (+/‐ 5 years) participants without RHI from the BU ADRC, all spanning the cognitive continuum, underwent MRI on a 3T Philips. Freesurfer was used to derive regional gray matter cortical thickness values. For the frontal, temporal, and parietal lobes, we computed mean composites of superior, middle, and inferior gyri gray matter measures. Analysis of covariance compared participants with and without RHI, controlling for age, sex, race, education and hippocampal volume.ResultMean age was 62.31 (SD=8.87), 34 (47.2%) were female, and 65 (90.3%) were White. Of the RHI group, 23 (59.0%) played American football, 9 (23.1%) ice hockey, 5 (12.8%) were boxers, and 3 (7.7%) were amateur wrestlers. Compared to non‐RHI, RHI‐exposed participants had decreased gray matter thickness of superior (marginal mean diff [MD]=0.10, p<0.01) and middle frontal gyri (MD=0.06, p=0.03), and the middle temporal gyrus (MD=0.07, p=0.03). There were no differences in gray matter thickness for inferior frontal, superior or inferior temporal, or parietal gyri. Because the CTE tau lesion is uniquely at the sulcal depths, we examined the gray matter thickness of the banks of superior temporal sulcus and RHI participants had reduced thickness (MD=0.09, p=0.02).ConclusionFrontotemporal atrophy may be a characteristic late effect of RHI exposure. Further examination of thickness of different lobar gyri in the setting of RHI may facilitate disease differentiation. Larger samples will be important to examine how the effects of RHI on gray matter cortical thickness differ by sex, sport played, etc.
In vivo validation of therapeutic efficacy of a small molecule lead targeting tau self‐association in JNPL3 mice
Authors: Moe James G. , Lopez Patricia , Jimenez Heidy , Adrien Leslie , Eun John D , Wolin Adam , Koppel Jeremy , Davies Peter , Davidowitz Eliot J. 
Published: December 2021

AbstractBackgroundSmall molecules were screened and optimized for inhibiting tau self‐association, the initial step in the formation of soluble toxic tau oligomers and larger insoluble aggregates. This approach is differentiated from other tau aggregation inhibitor programs that have largely focused on inhibiting formation and/or dissociating large and relatively inert fibrils which could generate toxic tau oligomer seeds. Small molecules inhibitors are agnostic to specific post‐translational modifications, conformational changes or strains of tau aggregates, and have superior access to their target in the CNS relative to immunotherapeutic approaches. We have previously shown in vivo efficacy of a lead compound in preventive studies in htau (Davidowitz et al., 2020) and human tau P301L JNPL3 mouse models of tauopathy. The tau P301L mutation is the most common FTDP‐17 mutation and causes tau aggregation and motor deficits with age (Lewis et al., 2000).MethodBlinded studies of homozygous female tau 4R/0N P301L JNPL3 mice were performed at an independent laboratory where mice were treated for five months by administration of our lead compound in feed from 7 to 12 months‐of‐age. The four groups of mice in the study were baseline (7 months; n=20), vehicle, and two treatment groups (40 and 80 mg/kg doses; n=25 each). To quantify levels of Sarkosyl‐insoluble tau, self‐associated tau, and phosphorylated tau in the treated and control groups of mice ELISAs were performed (Acker et al., 2012; Forest et al., 2019). Rotarod and open field studies were performed to evaluate motor behavior.ResultEfficacy was shown in the cortex of treated mice that had reduced levels of self‐associated tau below baseline, baseline levels of insoluble tau aggregates, and reduced levels of aberrantly phosphorylated tau with statistical significance. In the hindbrain there was reduction of insoluble tau aggregates in the 40 mg/kg group compared to vehicle. Treatment groups showed improved Rotarod performance compared to baseline and vehicle groups.ConclusionTreatment with the lead compound reduced tau aggregation and improved motor behavior in aged JNPL3 mice and support preclinical development of the lead for clinical studies.
Characterising spoken interactions of healthy ageing adults with CognoSpeak, a web‐based cognitive assessment tool
Authors: Brewer Elena , Mirheidari Bahman , O'Malley Ronan , Reuber Markus , Christensen Heidi , Blackburn Daniel J. 
Published: December 2021

AbstractBackgroundAutomatic conversation analysis presents a useful aid for diagnosis and management of people with cognitive impairments, having already successfully differentiated between people with Alzheimer’s disease (AD) and healthy controls. Current clinical brief cognitive tests such as Addenbrooke’s Cognitive Examination are influenced by age, education and practice effects but it is unknown how these factors influence automated analysis of speech. This study characterised the effects of age, education and repetition on measures of speech and language of cognitively healthy ageing adults.MethodAudio recordings of memory related questions and verbal fluency tasks from 37 cognitively healthy adults’ conversations with CognoSpeak were analysed (mean age 73.11 ± 7.97). Linguistic analysis comprised of pause to speech ratio (pause length/speech length), age of acquisition of words, phonemes per minute, words per minute and total word count. Spearman’s correlations assessed relationships with age and education. 6 participants repeated testing at an average of 4.05 and 12.25 months later. Friedman’s ANOVA and post‐hoc related‐samples Wilcoxon signed ranks tests assessed longitudinal changes.ResultPause to speech ratio was significantly higher for recent memory questions than remote memory. Age of acquisition was significantly higher for phonemic fluency than semantic fluency. A moderate negative correlation was found for age with ACE‐R score and phonemic fluency. A strong positive correlation was found with education and ACE‐R score, and a moderate positive correlation with education and words per minute. No further relationships for age or education were found. Semantic fluency showed practice effects, whereas linguistic measures did not. Further follow‐up data will be available by July 2021.ConclusionThese results support the theory of semantic memory preservation with age. It is indicated that age, education and time do not have large effects on linguistic measures, giving conversation analysis a practical advantage over the ACE‐R for longitudinal monitoring of people with Mild Cognitive Impairment or Subjective Cognitive Impairment.