bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal FDG‐PET and FTP‐PET demonstrates the relationship between glucose metabolism and tau accumulation in Alzheimer’s disease atrophy‐associated brain regions in cognitively normal older adults
Authors: Crook Harry , Nowell Joseph , Raza Sanara , Edison Paul 
Published: February 2022

AbstractBackgroundIn certain brain regions, glucose hypometabolism, amyloid‐β and tau accumulation all increase in the pre‐clinical stages of mild cognitive impairment and Alzheimer’s disease (AD). Studies demonstrate associations between glucose metabolism, amyloid‐β, and tau protein and neurodegeneration, however, little has been done to elucidate any direct associations between tau accumulation and glucose metabolism in the pre‐clinical stage of AD. Here, we evaluate the relationship between cerebral tau accumulation and glucose metabolism longitudinally, in a cohort of cognitively normal older adults.MethodTo assess cerebral glucose metabolism and tau accumulation, the standardised uptake value (SUV) from fluorine‐18 fluorodeoxyglucose (FDG) and fluorine‐18 flortaucipir (FTP) positron emission tomography (PET) was calculated from a cohort of cognitively normal participants recruited through the Harvard Ageing Brain Study. This included 43 subjects (mean±SD age at baseline, 73.6 ±5.6 years) who had both baseline and follow‐up (mean±SD time from baseline, 3.1 ±0.19 years) FDG‐ and FTP‐PET scans. Regional glucose metabolism and tau accumulation was calculated using SUV ratios, and correlations were calculated for different AD pathology‐specific brain regions to assess any potential relationship between cerebral tau and glucose metabolism.ResultIn this cohort, tau accumulation significantly increased in the inferior temporal lobe (p=0.001) and temporal pole (p=0.024), while glucose metabolism significantly decreased in the entorhinal cortex (p=0.035) and the temporal pole (p=0.033) from baseline to follow‐up assessment. The rate of tau accumulation was significantly correlated with baseline tau levels in the inferior temporal lobe (r=0.344, p=0.024), and baseline FDG levels in the left hippocampus (r=0.527 , p<0.001).ConclusionCerebral tau accumulation and glucose metabolism seem to be linked in cognitively normal older adults, especially in temporal regions of the brain. This highlights the potential requirement for Alzheimer’s disease treatments to be administered in the pre‐clinical stage of the disease, before cognitive symptoms develop.
Head‐to‐head comparison of [18F]Flortaucipir and amyloid PET visual reads for differential diagnosis: An international, multi‐center study
Authors: Soleimani‐Meigooni David N. , Smith Ruben , Provost Karine , Lesman‐Segev Orit H. , Cho Hanna , Edwards Lauren , Iaccarino Leonardo , La Joie Renaud , Ossenkoppele Rik , Strandberg Olof , Strom Amelia , Lyoo Chul Hyoung , Hansson Oskar , Rabinovici Gil D. 
Published: February 2022

AbstractBackgroundQuantitative [18F]Flortaucipir (FTP) tau PET analysis has good discriminative accuracy for Alzheimer’s disease (AD), but visual reads are used clinically. We aimed to compare the diagnostic accuracy of FTP‐PET to amyloid PET visual reads for distinguishing AD dementia and amyloid‐positive mild cognitive impairment (MCI) from other neurodegenerative diseases and cognitively normal (CN) controls.MethodWe included 661 participants studied with FTP and amyloid PET at UCSF, Lund University, and Gangnam Severance Hospital (Table 1). Amyloid PET tracers were site‐specific (UCSF, [11C]PIB; Lund, [18F]Flutemetamol; Gangnam, [18F]Florbetaben). Three visual raters interpreted amyloid PET using tracer‐specific criteria and FTP‐PET using a recently proposed method (Figure 1; Sonni et al. Alzheimer's Dement. 2020, 12:e12133. doi: 10.1002/dad2.12133). Amyloid and FTP‐PET were read in separate, randomized batches, blinded to the reads of the other physicians. The majority interpretation of each scan as amyloid positive/negative and tau positive/negative was used in the primary analysis. Diagnostic performance of FTP and amyloid PET visual reads, including sensitivity and specificity, were calculated. Kappa statistics for intra‐ and inter‐rater reliability were calculated.ResultAmyloid and FTP‐PET visual reads had similar sensitivity (92.6%, 95%‐confidence interval [88.7‐95.5%], 92.2% [88.2‐95.2%], respectively) and specificity (82.9% [78.9‐86.5%], 78.2% [73.9‐82.1%], respectively) for distinguishing AD and amyloid‐positive MCI from all other dementias and CN controls (Table 2). Amyloid PET and FTP‐PET visual reads had similar diagnostic performance for distinguishing AD or amyloid‐positive MCI from non‐AD neurodegenerative disorders or CN controls (Table 3). FTP‐PET intra‐rater reliability ranged from κ=0.80‐1.00 (p<0.0001), and inter‐rater reliability between reader pairs ranged from κ=0.78‐0.85 (p<0.0001). Amyloid PET intra‐rater reliability was κ=0.97 (p<0.0001) for each reader, and inter‐rater reliability between reader pairs ranged from κ=0.82‐0.88 (p<0.0001).ConclusionFTP and amyloid PET visual reads have similar diagnostic performance and high intra‐ and inter‐rater reliability. Further analysis will be performed to determine if patient characteristics can predict when one PET modality will outperform the other for AD diagnosis.
White matter network structure as a substrate of cognitive brain reserve in cerebral small‐vessel disease: The Maastricht Study
Authors: De Jong Nathan , Backes Walter H. , Jansen Jacobus F.A. , van Boxtel Martin P.J. , Schram Miranda T. , Stehouwer Coen D.A. , Dagnelie Pieter C. , van Greevenbroek Marleen M.J. , van der Kallen Carla J.H. , Kroon Abraham A. , Schaper Nicolaas C. , Eussen Simone J.P.M. , Koster Annemarie , Wesselius Anke , Sep Simone J.S. , Koehler Sebastian 
Published: February 2022

AbstractMethodThe Maastricht Study is a population‐based cohort study with extensive phenotyping, enriched for type‐2 diabetes. Cognitive test scores, structural connectivity data, and 3T MRI were available for n=4798 participants (mean age(±SD)=59.2(±8.7), 50.0% male). Images were assessed by Fazekas score (£1 or ≥2), presence of microbleeds and lacunar infarcts in terms of dichotomous measures, and combined into a cSVD score (range 0‐3). Node degree (ND), a measure of the mean interconnectedness of nodes in the structural connectome, was used as connectivity score. A composite cognition score (CS) was taken as the mean score across three cognitive domains (Memory, Information Processing Speed and Executive Function). Multivariable linear regression analyses were used to investigate the interaction effect between ND and cSVD score on CS, adjusted for age, sex, education, and diabetes status.ResultHigher cSVD score was associated with lower CS. ND modified the association between cSVD score and CS in the adjusted model (p for interaction p<0.004). While there were clear cognitive differences across cSVD levels if ND was low, the association between cSVD and cognition was attenuated in a dose‐response fashion with increasing ND (Figure 1).ConclusionStructural ND provides evidence of an individual’s CR based on white matter organization in the presence of damage from cSVD. Even in participants with the highest cSVD burden, sufficiently high ND score was associated with normal CS.
Genetic association of APOE epsilon2 genotype with neurophysiological characteristics in healthy adults
Authors: Ponomareva Natalya V. , Andreeva Tatiana , Protasova Maria , Kolesnikova Ekaterina V. , Malina Daria , Fokin Vitaly , Illarioshkin Sergey , Rogaev Evgeny I 
Published: February 2022

AbstractBackgroundThe association of apolipoprotein E genotype with late‐onset AD (LOAD) is well established. APOE e4 allele is the major common risk factor for LOAD (Saunders et al., 1993), and the rare APOE e2 allele appears to confer protective effect for LOAD (Goldberg et al., 2020). The mechanisms underlying the impact of the APOE e2 allele on LOAD development remain largely unknown. The study was aimed at determining the possible APOE e2 genotype effect on EEG and cognitive event‐related potentials (ERP) in non‐demented adults.MethodThe enrolled cohort included 135 healthy volunteers, age range 20‐69 years, stratified by APOE genotype. APOE e2/e3 subgroup included 21 subjects, APOE e3/e3 subgroup ‐ 76 subjects, APOE e4/e3 subgroup ‐ 38 subjects. Informed written consent was obtained from all participants. All subjects underwent a neurological examination and cognitive screening. The significance of the differences between the EEG and cognitive ERP characteristics in different subgroups was estimated using ANOVA in the general linear modelResultThe presence of the APOE e2/e3 genotype was associated with higher individual alpha peak frequency (IAPF) relative to the presence of APOE e3/e3 and APOE e4/e3 genotypes. IAPF a stable neurophysiological 'trait' marker which has been shown to correlate with better memory scores (Grandy et al., 2013). In the carriers of APOE e2 allele P300 latency remained stable during aging, while in the carriers of APOE e3/e3 as well as APOE e4/e3 genotypes P300 latency showed positive correlation with age.ConclusionAPOE e2 genotype is associated with higher EEG IAPF and stable P300 latency during aging that can underlie better cognitive reserve and protective effect against LOAD. The effect may be related to larger hippocampal volume and better maintenance of neuronal connections in APOE e2 healthy carriers compared to non‐carriers.
Identification of a robust cortical thickness signature of AD in the Framingham Heart Study
Authors: Satizabal Claudia L. , Beiser Alexa S. , Fletcher Evan M. , Seshadri Sudha , DeCarli Charles S. 
Published: February 2022

AbstractBackgroundAlzheimer’s disease (AD) starts decades before the onset of clinical symptoms, posing enormous challenges for the development and administration of timely treatments. Therefore, the development of robust AD biomarkers continues to be a high priority in the field. MRI‐derived measures are suitable, non‐invasive biomarkers in populations at risk. We aimed to identify and validate a signature region of AD in the Framingham Heart Study (FHS).MethodFor the training set, we identified a group of cases with prevalent AD at the time of MRI (n=69), and controls matched on age and sex (n=133). Cortical thickness maps from 3DT1 sequences were compared between cases and controls to derive an AD signature ROI (Figure 1). For validation, we computed signature ROI cortical thickness means in a non‐overlapping stroke‐ and dementia‐free sample. We used Cox proportional hazard models to relate the cortical AD signature in those aged ≥60 years to dementia risk over 10‐years adjusting for age and sex, and linear regression models to assess the cross‐sectional association between the cortical AD signature and cognitive function adjusting for age, sex, and education. In analyses, a second model additionally adjusted for MRI markers.ResultThe validation sample included n=1,146 participants (mean age 70±7 years, 53% women), of whom 95 developed AD. Participants in the bottom quartile of the AD signature ROI had more than four times increased AD risk compared to those in the upper three quartiles (Table 1; Hazard Ratio [HR]= 4.44, 95% CI 2.84‐6.94, p<0.0001). This association remained after the inclusion of classic MRI markers of brain aging (i.e., hippocampal, total brain, and white matter hyperintensity volumes; HR=2.54, 95%CI 1.56‐4.13, p<0.0001). Our cross‐sectional sample included n=2,163 participants (mean age 63±10 years, 54% women). Greater thickness in the AD signature ROI was related to better general cognitive function (Beta=0.04±0.02, p=0.02), and logical memory (Beta=0.22±0.08, p=0.004), although adjustment for other MRI markers attenuated the association with general cognitive function (Table 2).ConclusionWe have identified a strong neuroimaging biomarker for risk stratification of persons at increased risk of AD. Additional analyses are underway to validate this signature region in multiethnic samples.
Pupillary responses as a biomarker of early risk for Alzheimer’s disease: Association with tau not beta‐amyloid
Authors: Granholm Eric L. , Elman Jeremy A. , Galasko Doug R. , Kremen William S. , Salmon David P. , Holden Jason , Delay Christophe , Macomber Alyssa , Link Peter , Bondi Mark W. 
Published: February 2022

AbstractBackgroundWe examined pupillary responses as a novel biomarker of early risk for Alzheimer’s disease (AD). Pupil dilation recorded during cognitive tasks provides a biomarker of the extent of cognitive effort required to achieve a given test score. Greater dilation indicates greater effort. Test scores decline when capacity to compensate is exceeded, so individuals allocating more effort are likely closer to maximum compensatory capacity and at higher risk for decline. We previously found greater pupil dilation in individuals with mild cognitive impairment (MCI) relative to cognitively‐normal (CN) controls. Pupillary responses reflect neuromodulatory activity in the locus coeruleus (LC), and studies implicate the LC as an early site of AD degenerative changes, especially tauopathy. The present study, therefore, examined whether greater pupil dilation (compensatory cognitive effort) on the digit span task was associated with greater tau biomarker levels.MethodPupillary responses were recorded using a Tobii pupillometer during the digit span task and CSF biomarkers of AD (Aβ40; Aβ42 and p‐tau181) were collected in CN (N=37) and MCI (N=17) participants. Three trials at each span length (3‐9 digits) were administered until reaching max span (highest span with at least one correct trial).ResultIn the total sample, greater p‐tau was significantly associated with greater pupil dilation during the digit span task. However, pupil dilation was not significantly associated with beta‐amyloid. Importantly, performance (max span or total accuracy of digit recall) was not significantly correlated with pupil dilation or any of these biomarkers, so pupil dilation, but not performance, was associated with p‐tau biomarker risk.ConclusionGreater tau deposition, but not beta‐amyloid, was associated with greater compensatory cognitive effort during the digit span task. This simple 5‐min pupil dilation task holds promise as a novel marker of early AD risk specifically linked to tauopathy and impaired functionality of the LC years prior to cognitive decline and diagnosis.
Memory and executive function are associated with distinct patterns of regional cerebral perfusion in dementia‐free APOE‐ε4 carriers and non‐carriers
Authors: Dutt Shubir , Yew Belinda , Li Yanrong , Gaubert Aimee , Ho Jean K , Jang Jung Yun , Blanken Anna E , Sible Isabel J , Marshall Anisa J , Kapoor Arunima , Shao Xingfeng , Wang Danny JJ , Nation Daniel A 
Published: February 2022

AbstractBackgroundThe primary genetic risk factor for Alzheimer’s disease is the apolipoprotein ε4 (APOE‐ε4) allele, which confers significant risk for early symptom onset and future dementia. Prior studies have examined links between memory function and medial temporal perfusion in APOE‐ε4 carriers and non‐carriers, but findings have been mixed regarding the direction of relationships. Additionally, prior work has not examined whether other cognitive domains, such as executive function, are similarly associated with functionally relevant regional perfusion (i.e., in frontal regions). The present study aimed to 1) clarify the relationship between medial temporal perfusion and memory performance and 2) examine novel links between executive function and frontal perfusion in APOE‐ε4 carriers and non‐carriers.MethodDementia‐free older adults recruited from the community were classified as APOE‐ε4 carriers (n=18) or non‐carriers (n=30) via genotype analysis. We used pseudocontinuous arterial spin labeling MRI to quantify cerebral perfusion in regions involved in memory (medial temporal) and executive function (medial frontal). Comprehensive neuropsychological testing assessed memory (Logical Memory I & II; Visual Reproduction I & II) and executive function (Stroop color‐word interference; Trail making tests A & B, category fluency). Multiple linear regression, modeled separately within carriers and non‐carriers, examined associations between perfusion and cognition, with age, sex, and education as covariates.ResultWithin APOE‐ε4 carriers, medial temporal hypoperfusion was associated with worse immediate and delayed recall memory in verbal and visual paradigms. Similarly, frontal hypoperfusion was associated with worse verbal category fluency. In non‐carriers, relationships between medial temporal perfusion and memory were absent. Relationships between frontal perfusion and executive function were in the opposite direction as those observed in APOE‐ε4 carriers, with frontal hyperperfusion predicting worse Stroop color‐word, Trails A, and Trails B performance.ConclusionWe observed positive associations between regional perfusion and corresponding cognitive domains in APOE‐ε4 carriers, while relationships were absent or negative within non‐carriers. Our findings highlight the importance of examining preclinical cerebrovascular dysfunction in relation to cognition in individuals at risk for progression to dementia. Future longitudinal studies will be needed to further examine the value of perfusion, cognition, and APOE‐ε4 carrier status in predicting future decline.
Engaging Vietnamese Americans in research on aging and dementia
Authors: Meyer Oanh L , Nguyen Julia Phuong , Nam Bora , Nguyen Khue , Zhu Jeanette , Vuong Quyen , Bang Joon , Hinton Ladson , Tsoh Janice Y , Park Van Ta 
Published: February 2022

AbstractBackgroundVietnamese Americans are a large Asian American group in the U.S. and at high risk for health disparities, partially due to their limited English proficiency, low socioeconomic status, history of war and trauma, and a lack of culturally and linguistically appropriate care. As this relatively recent refugee population continues to age in the U.S., it is important to engage them in research around Alzheimer’s disease and related dementias (ADRD). Yet few studies have examined their perceptions of aging, dementia, and ADRD research participation. This qualitative study examined the perceptions of Vietnamese in Northern and Southern California, the state with the largest population of Vietnamese Americans in the U.S.MethodWe conducted three focus groups with a total of 20 Vietnamese individuals in both Vietnamese and English. The focus group guide assessed participants’ attitudes and experiences with research participation, perceptions of ADRD and aging, and insights into registry outreach and recruitment. There were nine women, and the mean age was 40 years, SD = 17.74 (range 18‐73). Participants consisted of key stakeholders including community leaders, ADRD caregivers, and community members.ResultSeveral themes emerged from the analyses, including (1) Motivations to participate in research to gain knowledge: (a) for oneself, (b) for family’s benefit, and (c) for the Vietnamese American community as a whole; (2) The necessity of trustworthy and credible individuals/spokespersons to promote the research initiative; (3) Recruitment strategies that are age‐specific and culturally appropriate, and (4) Importance of monetary incentives.ConclusionResults highlight key issues that are important to Vietnamese Americans’ participation in aging and dementia research. Practical implications of these results will be discussed.
Simulation as an innovative approach in dementia caregiver education: A literature review
Authors: Chan Hoi Man , Wong Cho Lee 
Published: February 2022

AbstractBackgroundSimulation has well been used for training healthcare professional; however, such innovative approach in dementia caregiver education is still at infancy. This study aims to review the application of simulation in the education of dementia family caregiver regarding the simulation modality, skills trained and outcomes.MethodKeywords including “caregiv*”, “simulation” and “caregiver education” were used for searching in PubMed, CIHNAL, Medline, Psyinfo and Embase databases. Publications were searched up to 2021 and 7 studies were reviewed.ResultStudies were conducted in US, Netherland, Canada and South Korea of sample size ranging from 28 to 264. Study designs included RCT, quasi experimental and non‐experimental. Virtual reality was employed to enhance empathy and competency of caregivers; simulated patient (SP) was employed to enhance communication skill and problem‐solving technique; low‐fidelity simulator (Dementia LiveTM) was employed to enhance empathy and problem solving. Outcomes included improvement in empathy, caregiving competency and decreased use of emotion‐focused and avoidance‐focused coping. None of the studies provided detailed simulation design.ConclusionSimulation as an innovative approach may inform nursing intervention in dementia care. Nurses could incorporate simulation into psychoeducation to enhance dementia family caregivers’ self‐efficacy. Communication skill, problem‐solving technique and behavioral problem can be addressed through therapeutic simulation with the use of SP methodology (Sadvoy et al, 2020). Scenario design should be person‐centered and simulation design should be stringent. Experimental studies are urged to determine the effectiveness.
Free water in T2 FLAIR white matter hyperintensity lesions
Authors: Yu Xiaowei , Scheel Norman , Zhang Lu , Zhu David C. , Zhang Rong , Zhu Dajiang 
Published: February 2022

AbstractBackgroundWhite matter (WM) free water (FW) is likely associated with cerebral small vessel disease (CSVD). FW is the fraction of unconstrained water within an image voxel, which can be estimated from diffusion‐weighted images. T2‐weighted Fluid‐Attenuated Inversion Recovery (FLAIR) white matter hyperintensity (WMH) is a widely used index to assess the damages caused by CSVD. It is critical to characterize how FW content is altered in WMH lesions. In this work, we proposed a data processing framework to assess FW distributions in WMH and normal‐appearing WM as well as in different WM fiber tracts.MethodSingle‐shell diffusion‐weighted image (SS‐DWI) and T2 FLAIR image data of 133 cognitively normal (CN) adults (Table 1) were obtained from the ADNI dataset (http://adni.loni.usc.edu). FW maps were generated from SS‐DWI images using the DIPY software package (https://dipy.org/). WMH lesions were identified with the lesion segmentation toolbox implemented in SPM. We co‐registered FW and WMH maps of individual subjects in the MNI space. Then we derived group WM fiber tracts using the tract‐based spatial statistics (TBSS). Finally, we examined the localization of WMH and FW in the major WM tracts.ResultFigure 1 shows the FW map, FLAIR image, and WMH lesion from a representative subject. Figure 2 shows group average and individual FW distributions in WMH and normal‐appearing WM. Two sample T‐Test found that FW content in WMH is significantly higher than that in normal‐appearing WM (mean FW and standard deviation FW in WMH are 0.430 and 0.112, mean FW and standard deviation FW in normal‐appearing WM are 0.203 and 0.06, P < 1×10‐30). TBSS based analysis showed that: 1) WMH lesions are mainly located in the corona radiata, posterior thalamic radiation, tapetum, superior fronto‐occipital fasciculus, superior longitudinal fasciculus, corpus callosum, and sagittal stratum; 2) Compared with mean FW in normal‐appearing WM, elevated FW content is mainly at the fornix, tapetum, cingulum hippocampus, superior fronto‐occipital fasciculus, corpus callosum, sagittal stratum, and posterior thalamic radiation.ConclusionWe developed an image processing pipeline to estimate FW changes in WMH lesions and normal‐appearing WM. Free water content is elevated in WMH lesions, which is likely driven by CSVD.