bluuebunny/crossref_metadata_2025_split huggingface dataset:
A residual marker of cognitive reserve modifies the cross‐sectional and longitudinal association between memory and glucose hypometabolism in Alzheimer’s disease
Authors: Ersoezlue Ersin , Rauchmann Boris‐Stephan , Perneczky Robert ,   For the Alzhemer's Disease Neuroimaging Initiative
Published: February 2022

AbstractBackgroundThe cognitive reserve (CR) hypothesis was proposed to explain inter‐individual differences in the association between observed cognitive function and estimated neurodegenerative burden, e.g. in Alzheimer’s disease (AD). Latent CR marker approaches were suggested as a promising method to predict reserve.MethodAmyloid‐β (Aβ)‐negative, cognitively normal and Aβ‐positive, cognitive impaired (Clinical Dementia Rating global score >= 0.5) individuals participating in the AD Neuroimaging Initiative (ADNI) were classified as healthy controls (HC, N=138) and AD spectrum (ADS, Baseline N=462, Follow‐Up N=211), respectively. A latent CR marker (CRM) was obtained by multilinear regression analysis in the entire study cohort, defined as the residual global cognitive performance remaining after accounting for neuropathological burden (CSF Aß42 and total Tau levels and APOE ε4 carrier status) and demographic variables. Mean standardized uptake value ratio (SUVR) values for regions of interests (ROIs) of left and right angular gyrus (L/R‐ANG), bilateral posterior cingulate (PCC), left and right inferior temporal gyrus (L/R‐TEMP) were derived from FDG‐PET data. In separate analyses for HC and ADS, the interactive effects of the memory cognitive composite (MEM) and latent CR marker on FDG‐PET SUVR values were tested for the five cortical ROIs at baseline and 24‐months follow‐up data.ResultIn ADS, higher CRM attenuated the relationship between MEM and FDG‐PET SUVR in L‐TEMP, R‐TEMP and L‐ANG at baseline, and in L‐TEMP, R‐TEMP, L‐ANG and R‐ANG in the longitudinal analyses. In HC, however, no interaction was observed.ConclusionPatients with higher CR maintained their memory performance better in the face of AD‐related glucose hypometabolism . Therefore, the present study supports the use of a residual CRM to improve our understand of inter‐individual differences in the resilience against neurodegeneration, both cross‐sectionally and longitudinally.
Cognitive remediation therapy for participants with late‐life schizophrenia
Authors: Golas Angela C , Elgallab Bishoy , Abdool Petal S , Bowie Christopher R , Rajji Tarek K 
Published: February 2022

AbstractBackgroundOlder patients with schizophrenia have an elevated risk of dementia; enhancing their cognitive function holds promise for delaying dementia in this population. Cognitive deficits strongly predict function in schizophrenia. Anticholinergic medication burden (ACB) compounds age‐related cognitive declines in late‐life schizophrenia (LLS). Cognitive remediation (CR) improves cognition in schizophrenia, however literature in LLS is sparse. This study examined the effect of CR on cognitive performance in participants with LLS. We also assessed CR tolerability, the interaction between ACB and the effect of CR on cognition.MethodWe adapted CR from our pilot study to a larger group. CR was provided over 12, twice‐weekly, therapist‐guided group sessions. Computerized drill‐and‐practice exercise difficulty levels were adjusted automatically based on performance. Participants were assessed at baseline and at study completion using clinical and cognitive measures.ResultThirty‐four participants were enrolled, 20 (mean (SD) age: 66.0 [5.8]) completed 92.3% (22.14 [1.98]) CR sessions; the ITT group (N=34) attended 72.9% (17.50 [7.23]) sessions. Global cognition did not improve (completers: p=0.80, ITT: p=0.86) with negligible effect size (completers: d=0.08; ITT d=0.04). There was no significant improvement in executive function (completers: p=0.16; ITT: p=0.33). Medication ACB was inversely associated with total MoCA score, accounting for 8.9% of the variance in final MoCA score (p=0.02).ConclusionOverall, CR was well tolerated but did not improve global cognition or executive functioning in this outpatient sample with LLS. A higher ACB was associated with greater cognitive impairment and a poorer response to CR. Future studies need to better characterize potential variables serving to limit the response to CR, including the number and frequency of CR sessions and the role of ACB.
Sex differences in genetic susceptibility of hippocampal subfields: A polygenic association study
Authors: Genius Patricia , Arenaza‐Urquijo Eider M. , Operto Greg , Evans Tavia E. , Brugulat‐Serrat Anna , Falcon Carles , Minguillón Carolina , Fauria Karine , Adams Hieab H.H. , de Moura Manuel Castro , Piñeyro David , Esteller Manel , Guigó Roderic , Navarro Arcadi , Molinuevo Jose , Gispert Juan Domingo , Vilor‐Tejedor Natalia ,   for the ALFA study
Published: February 2022

AbstractBackgroundThe hippocampus is involved in several complex diseases which display sex differences in their prevalence. Therefore, it can be hypothesized that sex‐specific genetic vulnerability in hippocampal formation might partially explain these differences. The aim of this study was to investigate whether the genetic predisposition to several complex diseases showed sex‐specific associations with the volumes of hippocampal subfields.MethodA total of 1,071 cognitively unimpaired participants (45‐74 years) at increased risk for Alzheimer's disease (AD) (ALFA study), with available genotyping and neuroimaging data were included (62.6% women). Genetic predisposition was calculated through polygenic risk scores (PRSs) computed using the PRSice tool (v.1.25). A total of 33 PRSs were estimated from the most recent genome‐wide association meta‐analyses for several neurodegenerative, vascular and metabolic diseases, as well as for biomarkers of AD. Association analyses included the volumes of the hippocampal subfields quantified through high‐resolution 3D‐T1‐weighted magnetic resonance imaging scans and determined using Freesurfer (v.6.0). Sex‐stratified association analyses were estimated using linear regression models adjusted for age, education, and total intracranial volume. The threshold of significance was established by approximating the total number of effective tests. The resulting adjusted significance threshold was set at p <0.005.ResultPRSs were equally distributed among women and men, sharing a common pattern of variability [Figure 1]. Both groups showed increased genetic susceptibility for abnormal levels of AD biomarkers and for vascular, brain, as well as sleep disorders. Association analyses showed significant sex differences associated to several hippocampal subfields [Figure 2]. Specifically, in women, increased genetic risk of multiple sclerosis and neurodegenerative diseases was associated with larger cornu ammonis 1 (CA1), hippocampal tail and molecular layer, as well as with increased volume of the whole hippocampus. In men, a raised genetic risk of cerebral infarction, epilepsy and both short and long duration of habitual sleep was associated with reduced volumes of CA1, molecular layer, subiculum, and dentate gyrus.ConclusionWe provide evidence that genetic susceptibility differentially influences on hippocampal subfield volumes according to sex. This may explain sex‐specific patterns of neurodegeneration and biological vulnerabilities.
The speed limits of tau spreading: The contribution of regional amyloid and education
Authors: Hönig Merle C. , Bischof Gerard N. , Dzialas Verena , van Eimeren Thilo , Drzezga Alexander ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: February 2022

AbstractBackgroundHere, we investigated the contribution of education and regional amyloid as potential de‐ and accelerators in the spread of tau pathology.Method85 amyloid‐positive subjects (age=76.80±1.08, education=16.70 ±.50 years, M/F=42/43) were included, for whom [18F]AV‐1451 PET at two timepoints, baseline [18F]AV‐45 PET, ApoE‐status and clinical information were available at ADNI. [18F]AV‐1451 PETs were intensity‐standardized (reference: inferior cerebellum) and z‐transformed (control sample: 35 amyloid‐negative subjects). Baseline and follow‐up tau‐PET z‐maps were converted to volume‐maps (z‐score threshold > 1.96). Based on these volume‐maps, tau‐changes over time were assessed: 1) tau speed (i.e. newly affected volume at follow‐up), 2) tau level rise (i.e. tau increase in previously affected volume). These two dependent variables were used in regression analyses including education, global amyloid, baseline tau, ApoE, cognitive function, sex, and age as predictors. Additionally, baseline amyloid‐burden was regionally correlated in 32 Freesurfer‐ROIs with newly tau‐affected volume and with mean z‐score change in five Meta‐ROIs (entorhinal cortex, inferior‐temporal, precuneus, middle‐occipital, oribito‐frontal), correcting for multiple comparisons.ResultEducation contributed as decelerator (β=‐.322, p=.037), whereas global amyloid (β=.262, p=.029) and baseline tau (β=.283, p=.028) facilitated tau speed. Tau level rise was positively associated with age (β=‐.211, p=.017) and baseline tau (β=.710, p<.001). Tau spread to the precuneus was related with greater cingulate amyloid‐burden, whereas tau level rise in temporal, parietal and occipital regions was associated with orbito‐frontal and cingulate amyloid‐burden.ConclusionA combination of de‐ and accelerating factors and regional dissociations likely contribute to the temporo‐spatial evolution of tau pathology.
Prediction of amyloid pathology in cognitively unimpaired individuals using structural MRI
Authors: Cumplido‐Mayoral Irene , Ingala Silvia , Lorenzini Luigi , Wink Alle Meije , Haller Sven , Molinuevo Jose , Wolz Robin , Palombit Alessandro , Schwarz Adam J. , Chetelat Gaël , Payoux Pierre , Martinez‐Lage Pablo , Frisoni Giovanni , Fox Nick C , Ritchie Craig W. , Wardlaw Joanna M , Waldman Adam , Barkhof Frederik , Vilaplana Verónica , Gispert Juan Domingo ,   EPAD Consortium,   ADNI study
Published: February 2022

AbstractBackgroundStructural MRI measurements can contribute to the prediction of amyloid pathology in cognitively unimpaired (CU) individuals. In this work, we aimed at studying the predictive capacity, robustness, and generalizability of ML techniques to predict amyloid‐β pathology in CU individuals, as well as identifying key brain regions contributing to this prediction.MethodWe included 653 and 250 CU individuals from the EPAD and ADNI studies, respectively, with available T1w MRI and CSF Aβ42 measurements. Subjects were categorized as amyloid‐β positive (Aβ+) or negative (Aβ‐) according to established cut‐offs (CSF Aβ42<1000pg/mL for EPAD and <880pg/mL for ADNI). Volumes and cortical thickness in regions of the Desikan‐Kiliany atlas were obtained with Freesurfer 6.0, as well as the Total Intracranial Volume (TIV). We trained XGBoost classifiers to predict amyloid‐β positivity using age, sex, education, MMSE, APOE‐ɛ4 status, volumes/TIV, and cortical thickness measurements. To study the generalizability of the classifier, we performed within‐cohorts classification (train and test within the same cohort); and between‐cohorts classification (train with one cohort and test with another). We performed the latter classification, both with the original samples, and following a bootstrapping approach to force balanced data in the training. With the classification results, we conducted a ROC analysis and, additionally, calculated SHAP values to determine the most important brain regions used to predict Aβ+.ResultSimilar classification performance was achieved when training/testing within ADNI (ROC‐AUC=0.72 (0.59‐0.84)) and within EPAD (ROC AUC=0. 68 (0.60‐0.76)) (Figure 1A). In the between cohort’s analysis, ROC‐AUC decreased slightly in both cases (Figure 1B) but was consistent over subsampling of individuals. Train with ADNI and test with EPAD gave ROC‐AUC=0.61 (0.58‐0.64) and train with EPAD and test with ADNI gave ROC‐AUC=0.59 (0.54‐0.66). The most important features used for prediction were similar for both ADNI and EPAD (Figure 2). The increased volume and/or thickness of some brain regions, such as superior frontal areas, predicted Aβ+. The decrease in cingulate cortex was also seen. APOE‐ɛ4 status also had a high impact on classification performance.ConclusionThe use of structural MRI measurements in combination with Machine Learning can provide additional capacity to predict amyloid‐β status in CU individuals.
Study protocol: SOcial LImitations Turn Up DEmentia (SOLITUDE)—Impact of COVID‐19 social isolation on patients’ cognition and mental health and on carers’ wellbeing
Authors: Manca Riccardo , De Marco Matteo , Blackburn Daniel J , Russell Gregor , Evans Kimberly , Kirkland Sarah , Amin Jay , Davies Lynn , Firth Claire , Raymont Vanessa , Colston Amanda , Collett Zoe , Kumar Pramod , Balckman Sarra , McCoy Shani , Davies Rhys , Robertson Selina , van Diepen Erik , Venneri Annalena 
Published: February 2022

AbstractBackgroundSocial isolation and loneliness are both known to exert detrimental effects on mental health and cognitive functioning, as well as on medial temporal lobe volume in older adults. Reduced social interactions have also been found to increase the risk of cognitive decline and dementia in older people. Since restrictions to social contacts have been imposed to tackle the current Coronavirus Disease 2019 (COVID‐19) pandemic, this study aims to investigate the long‐term impact of the resulting social isolation on people with mild dementia and their carers.MethodThis study has been implemented using a multi‐centre longitudinal observational design to monitor mental health (9‐item Patient Health Questionnaire and Neuropsychiatric Inventory Questionnaire), cognitive performance (telephone Mini‐Mental State Examination and Telephone Assessment of Cognitive Function) and quality of life (Quality of Life in Alzheimer's Disease) of patients with mild dementia due to neurodegenerative aetiologies, as well as carers’ burden (12‐item Zarit Burden Interview). Additionally, a structured interview is included to assess the potential impact of social isolation on everyday functioning of patients and carers. Participants are assessed telephonically at three time‐points: baseline and two follow‐ups after 3 and 6 months.ResultSix centres across the UK have confirmed capacity and capability to recruit up to eighty participants. Between September and December 2020, twenty‐nine participants have been recruited across different sites and completed the baseline assessment. Moreover, nine participants have already completed the 3‐month follow‐up.ConclusionThis study (predicted completion date: July 2021) is expected to provide valuable insights into the potential long‐term consequences of lockdown measures on people with dementia and their carers. Moreover, it will enable the identification of potential risk/protective factors for decline in mental health and cognition due to extensive changes in patients’ social environment. Findings from the SOLITUDE study may inform preventative and management strategies for decline in mental function targeting people with dementia, who may be the most affected by social isolation and loneliness.
COVID‐19‐related loneliness and social isolation in caregivers of people with brain health challenges: The CLIC‐Caregiver Global Survey
Authors: Chen Yaohua Sophie , Beber Bárbara Costa , Higgins Dawn , Galvin Miriam , Ilinca Stefania , Lawlor Brian , Leon Tomas , Leroi Iracema , McGlinchey Eimear , Rogan Carol , Saha Sanjib , Tjin Anna , O'Sullivan Roger ,   CLIC‐Caregivers Study Group
Published: February 2022

AbstractBackgroundPrior to COVID‐19, >90% of caregivers of people with brain health challenges (dementia, mental ill health, intellectual disability) experienced high levels of distress, burden, loneliness and social isolation. The COVID‐19 pandemic has significantly increased these impacts, particularly since these caregivers are often older and physically vulnerable themselves. The aim of this cross‐sectional study is to explore coping and caregiver burden, loneliness and social isolation in caregivers of people with brain health challenges during the COVID‐19 pandemic.MethodCLIC‐Caregiver was a cross‐sectional, online, and global survey (June 2nd ‐ November 15th, 2020) using self‐administered questionnaires directed at informal caregivers of people with long‐term brain health challenges. The study was embedded within a larger survey of loneliness and social isolation for general public (‘Comparing Loneliness and Isolation in COVID‐19’ (CLIC)), including validated loneliness and isolation tools. Translated into ten different languages such as Arabic, French, Romanian, etc, the survey was disseminated over 100 countries. Respondents were included in the CLIC‐caregiver sub‐study if they answered yes to the question ‘Do you provide care and support to a family member or friend with a long‐term or life‐limiting health problem or disability (including mental health)’. The CLIC project received the initial global ethical approval from Ulster University. The data were fully anonymized.ResultFrom the CLIC main study, 5243 (25%) identified themselves as caregivers. This proportion varied in different countries, from 12 % in Romania to 65% in France. 2323 (44%) had care recipients with dementia, 1761 with physical conditions (disability or long‐term illness), 832 with enduring mental health problems, and 404 with intellectual disability. Measures of caregiver burden, loneliness and social isolation will be compared across geographic regions, sociodemographic factors, and risk factors for poor outcomes sought. Findings will be distributed to relevant stakeholders in the form of a project report, with region and country‐specific outcomes. This will support recommendations and actions supporting caregivers of people with brain health challenges.ConclusionThis represents the largest, most widespread survey on the impact of the COVID‐19 pandemic on caregivers of people with long‐term conditions to date. It will be an important resource for support agencies and to inform policy.
Determinants of arterial spin labeling parameters and its association with cerebral small vessel disease and diagnostic groups
Authors: Gyanwali Bibek , Tan Chuen Seng , Escobosa Linda Lizeth Tirado , Vrooman Henri A. , Chen Christopher , Mutsaerts Henri J.M.M. , Hilal Saima 
Published: February 2022

AbstractBackgroundCerebral small vessel disease (SVD) may alter cerebral blood flow (CBF) leading to brain changes and hence cognitive impairment and dementia in elderly. CBF and spatial coefficient of variation (sCoV) can be measured quantitatively by Arterial Spin Labelling (ASL). CBF and sCoV have been related to age and systemic vascular risk factors. The relation of CBF and sCoV with location and severity of SVD and etiologic subtypes of cognitive impairment and dementia have not been explored in detail. We aim to investigate the association of demographic, vascular risk factors, location and severity of SVD with ASL parameters. We further investigate the association of ASL parameters with etiologic subtypes of cognitive impairment and dementia in a memory clinic population.MethodWe included 390 subjects (median: 73 11years, women = 52.3%) from an ongoing memory‐clinic based case‐control study. Patients were classified as no cognitive impairment, cognitive impairment no dementia (CIND), vascular CIND (VCIND) and dementia [Alzheimer’s disease (AD) and Vascular Dementia (VaD)]. Cerebral microbleeds (CMBs) and lacunes were categorized into strictly lobar, strictly deep and mixed‐location; ePVS into centrum semiovale and basal ganglia. Total and region‐specific white matter hyperintensities (WMH) volumes were automatically segmented using a validated pipeline. sCoV and CBF were analyzed with ExploreASL from 2D‐EPI pseudo‐continuous ASL images.ResultIncreasing age, male sex, hypertension, hyperlipidemia, history of heart disease and smoking were associated with CBF and sCoV. Increasing numbers of lacunes and CMBs were associated with reduced CBF and increased sCoV. Location‐specific analysis showed mixed‐location lacunes and CMBs were associated with hypoperfusion. Total WMH volume was associated with associated with increased sCoV. Region specific analysis with anterior and posterior WMH volumes showed similar results. No association was observed between ePVS and ASL parameters. Increased sCoV was associated with the diagnosis of VCIND, AD and VaD.ConclusionIncreased sCoV in ASL is associated with SVD, cognitive impairment and dementia, suggesting that SVD may induce brain changes via vascular insufficiency. Thus future research aimed to elucidate the pathophysiology of SVD and vascular insufficiency in elderly may help in developing prevention and treatment strategies.
Cross‐sectional amyloid and tau PET in cognitively normal older adults enrolled in the U.S. POINTER lifestyle intervention trial
Authors: Harrison Theresa M. , Vemuri Prashanthi , Koeppe Robert A. , Lockhart Samuel N. , Jung Youngkyoo , Borowski Bret J. , Murphy Alice , Ward Tyler , Gordineer Leslie , Woolard Nancy , Espeland Mark A. , Harvey Danielle J. , Jagust William J. , Lovato Laura , Toga Arthur W. , Masdeu Joseph C. , Oh Hwamee , Gitelman Darren R. , Aggarwal Neelum T. , Carrillo Maria C. , Snyder Heather M. , Whitmer Rachel A. , Baker Laura D. , DeCarli Charles S. , Landau Susan M. ,   the U.S. POINTER Study Group
Published: February 2022

AbstractBackgroundThe U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is a 2‐year randomized controlled trial to evaluate the effect of lifestyle interventions in older adults (60‐79 years) who are cognitively unimpaired but at increased risk for cognitive decline/dementia due to factors such as cardiovascular disease and family history. The POINTER Imaging ancillary study is collecting PET and MRI data to evaluate neuroimaging biomarkers of AD and cerebrovascular pathophysiology in this at‐risk sample.MethodPOINTER Imaging is actively enrolling 1250 participants, 23% from under‐represented racial/ethnic groups (URG), recruited from five U.S. POINTER clinical sites. Participants have undergone PET imaging with [18F]Florbetaben (FBB) to measure Aβ and [18F]MK‐6240 to measure tau burden, as well as MRI to measure brain morphometry, white matter hyperintensities and cerebral blood flow. FBB and MK‐6240 data were quality checked, pre‐processed, and quantified using previously validated methods. PET images were coregistered to a structural MRI, which was also used to create FreeSurfer‐defined reference regions and regions of interest. We examined PET imaging measures (global Aβ, regional tau) and basic demographic (age, sex, race/ethnicity) characteristics of the sample.Result96 participants (mean age 69.3±5.0) have been enrolled in POINTER Imaging. Of these, 59 (61%) are women and 22 (23%) are URG, which is similar to rates of women (75%) and URG (22%) in the main trial. This dataset is <10% of targeted enrollment, was predominantly recruited from 2/5 clinical sites and may not represent the final imaging cohort. FBB quantification (N=20) revealed a mean cortical summary SUVR of 1.09±0.12 (19.6±18.4 centiloids) (whole cerebellum normalization; previously validated positivity threshold=1.08), and 8/20 (40%) of these participants were Aβ+ (Fig. 1A). MK‐6240 quantification (N=23) showed predominantly no/minimal binding with a few exceptions in medial and lateral temporal lobes (Fig. 1B&C).ConclusionThe POINTER imaging study is meeting the target URG enrollment and representative of the main U.S. POINTER trial. Higher frequency of Aβ positivity than published in population cohorts coupled with greater cardiovascular risk factors among POINTER participants highlights our success in recruiting individuals at increased risk of cognitive decline.