bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk and protective factors for dementia: epidemiological evidence and windows of opportunity
Authors: Suemoto Claudia Kimie , Nitrini Ricardo , Grinberg Lea Tenenholz , Leite Renata Elaine Paraizo , Pasquallucci Carlos Augusto , Bertola Laiss , Vidal‐Ferreira Naomi , Szlefj Claudia , Caramelli Paulo , Bensenor Isabela M , Lotufo Paulo A , Aliberti Marlon Juliano Romero , Ferri Cleusa Pinheiro , Jacob‐Filho Wilson 
Published: December 2022

AbstractBackgroundMost people with dementia already live in low‐ to middle‐income countries (LMIC). However, most evidence regarding dementia prevention comes from high‐income countries that have different socioeconomic status (SES) and risk factors prevalence than LMIC. In this session, we will present results on risk and protective factors for dementia from the Longitudinal Study of Adult Health (ELSA‐Brasil), the Brazilian Longitudinal Study of Aging (ELSI‐Brazil), and the Brazilian Biobank for Aging Studies (BAS).MethodThe ELSA‐Brasil follows 15,105 public servants since 2008‐10. The ELSI‐Brazil is a nationally representative study with 9,412 adults aged 50 years and older, who were enrolled in 2015‐16. The BAS is a neuropathology study that started in 2004 and is the largest brain bank in Latin America with a collection of 1,441 brains. The focus of this presentation will be on the associations of education, SES, and cardiovascular factors with dementia using data from these three studies.ResultIn the BAS, 77% of the sample has less than 5 years of education and 56% unskilled occupations. Compared to the group without education, those with formal education had better cognitive performance (1‐4 years: 𝛽 = ‐0.99, 95%CI = –1.85; –0.14, p = 0.02; ≥5 years: = –1.42, 95% CI = –2.47; –0.38, p = 0.008). On the other hand, occupation complexity and demands were unrelated to cognition. Similarly, we showed that education and early‐life SES were the main contributors to cognitive performance in the ELSA‐Brasil, while later SES had a lower influence on cognitive scores. Cardiovascular factors are also important contributors to brain health. Ideal vascular health was related to better cognitive function in the ELSA‐Brasil. Participants with intermediate (β = 0.064, 95%CI = 0.033; 0.096) and optimal health (β = 0.108, 95%CI = 0.052; 0.164) had better cognitive z‐scores. Moreover, carotid artery atherosclerosis evaluated by morphometric measurements was related to cognitive impairment in BAS and with cognitive decline in the ELSA‐Brasil after 8 years of follow‐up (β = ‐0.028, 95%CI = ‐0.036; ‐0.020, p<0.001). Finally, hypertension was related to worse cognition (β = ‐0.09; 95%CI = ‐0.15, ‐0.04; p = 0.001) in ELSI‐Brazil, mainly in non‐frail participants.ConclusionStudies from LMIC regarding dementia risk factors are essential to implement tailored public policies for dementia primary prevention.
eRADAR detects primary care patients at risk of having undiagnosed dementia in two real‐world healthcare systems
Authors: Coley R Yates , Smith Julia J , Karliner Leah , Lee Sei J , Fuller Sharon , Lam Rosemary , Barnes Deborah E , Dublin Sascha 
Published: December 2022

AbstractBackgroundFifty percent of people living with dementia are undiagnosed. The electronic health record (EHR) Risk of Alzheimer’s and Dementia Assessment Rule (eRADAR) was developed to identify older adults at risk of having undiagnosed dementia using routinely collected clinical data. We aimed to externally validate eRADAR in two real‐world healthcare systems, including examining performance over time and by race/ethnicity.MethodsExternal validation was conducted in Kaiser Permanente Washington (KPWA), an integrated health system providing insurance coverage and medical care, and three primary care practices at University of California San Francisco Health (UCSF), an academic medical system. This retrospective cohort study included 688,599 person‐years from 129,315 KPWA members and 42,371 person‐years from 12,567 UCSF patients aged 65 years or older without prior EHR documentation of dementia diagnosis or medication. Analyses validated performance of eRADAR scores, calculated annually from EHR data (including vital signs, diagnoses, medications, and utilization in the prior 2 years), for predicting EHR documentation of incident dementia diagnosis within 12 months.Results7,631 dementia diagnoses were observed at KPWA (11.1 per 1,000 person‐years) and 189 at UCSF (4.5 per 1,000 person‐years). AUC was 0.84 (95% confidence interval: 0.84‐0.85) at KPWA and 0.78 (0.74‐0.81) at UCSF. Using the 90th percentile as the cutpoint, sensitivity was 54% (53‐56%) at KPWA and 45% (38‐52%) at UCSF. All performance measures were similar over time, including across the transition from International Classification of Diseases, version 9 (ICD‐9) to ICD‐10 codes, and across racial/ethnic groups.ConclusionseRADAR showed strong external validity for detecting undiagnosed dementia in two health systems with different patient populations and differential availability of external health care data for risk calculations. In this study, eRADAR demonstrated generalizability from a research sample to real‐world clinical populations, transportability across health systems, robustness to temporal changes in health care, and similar performance across racial/ethnic groups.
Comparison of group‐level and individualized ROIs for predicting change in longitudinal tau‐PET in preclinical and prodromal AD
Authors: Leuzy Antoine , Binette Alexa Pichet , Vogel Jacob W , Klein Gregory , Borroni Edilio , Tonietto Matteo , Strandberg Olof , Mattsson‐Carlgren Niklas , Palmqvist Sebastian , Pontecorvo Michael J. , Stomrud Erik , Ossenkoppele Rik , Hansson Oskar 
Published: December 2022

AbstractBackgroundLongitudinal tau‐PET is increasingly used as an outcome in clinical trials evaluating disease‐modifying therapies in Alzheimer’s disease (AD). In order to quantify change in tau‐PET signal over time, regions of interest (ROIs) are used; to date, these have been based on neuropathological studies or data‐driven approaches where the same ROI is used for each subject (group‐level ROI). However, given the inter‐individual heterogeneity in spatial patterns of tau‐PET, a key question is whether the use of subject‐specific (individualized) ROIs might offer any advantages over group‐level ROIs in AD clinical trials. We aimed to address this question by comparing group‐level and individualized ROIs across several metrics using longitudinal tau‐PET in preclinical and prodromal AD.MethodsWe included 174 participants with [18F]RO948 (97 preclinical AD [Aβ‐positive cognitively unimpaired], 77 prodromal AD [Aβ‐positive MCI] from BioFINDER‐2; average follow‐up 1.90±0.50 years). Group‐level ROIs included i) Braak and ii) event‐based modelling (EBM) stages and iii) temporal and iv) whole‐brain meta‐ROIs. Individualized ROIs included i) epicenter (regions with earliest tau), ii) Q1 (quartile closest to subject‐specific epicenter based on functional connectivity) and iii) probability‐based approach (regions selected based on their probability of being tau‐positivity at baseline using Gaussian mixture modelling). Group‐level and individualized ROIs were compared using yearly percent‐change in SUVR (ΔSUVR) and required sample size in a simulated intervention that reduces tau accumulation by 20, 30 or 40%.ResultsIn preclinical AD (Figure 1A), EBM stage‐I had the greatest ΔSUVR among group‐level ROIs (4.27%). Based on 95% confidence intervals, ΔSUVR was significantly higher using the probability‐based approach (5.51%). A similar pattern was seen in prodromal AD (Figure 1B), where ΔSUVR for the best individualized ROI (probability‐based, 7.86%) was significantly greater than that for the best group‐level ROI (EBM stage‐II, 5.45%). Across interventions (20/30/40%), sample size differences were on average ∼6% lower in preclinical AD and ∼20% lower in prodromal AD using individualized ROIs, relative to group‐level ROIs (Table 1). Further analysis are ongoing using a validation cohort (n = 278) scanned with [18F]flortaucipir.ConclusionPreliminary findings using [18F]RO948 suggest that individualized ROIs carry an advantage over group‐level ROIs in AD clinical trials using longitudinal tau‐PET as outcome.
On the origin of a potential clearance marker: The contribution of enlarged perivascular fluid diffusion to an MRI derived proxy of interstitial fluid
Authors: van der Thiel Merel M. , Roos Nathalie A. , Drenthen Gerhard S. , Voorter Paulien H.M. , Feiweier Thorsten , Ramakers Inez H.G.B. , Backes Walter H. , Jansen Jacobus F.A. 
Published: December 2022

AbstractBackgroundIntraVoxel Incoherent Motion (IVIM) MRI can detect the diffusion of cerebral interstitial fluid (ISF) (Dint) and its volume fraction (fint), which has the potential as a proxy of cerebral waste clearance. fint has been suggested to both be driven by fluid diffusivity within enlarged perivascular spaces (ePVS) ‐ transporting fluid from the subarachnoid space into the parenchyma ‐ and the ISF between the parenchymal cells. Both factors play a crucial role in soluble protein clearance, e.g., Amyloid‐Beta (Aβ).This study simultaneously aims to verify the contribution of ePVS fluid diffusivity to fint and highlights the ability to specifically assess ePVS fluid diffusion in the cerebrum using a non‐invasive MR method.MethodTwenty neurotypical elderly subjects (Table 1) underwent ultra‐high field MRI (7T research system, Siemens Healthcare GmbH, Erlangen, Germany) (Table 2).The intermediate diffusion components (Dint) in the range 1.5*10‐3<Diffusivity<4.0*10‐3 mm2/s were calculated using spectral analysis (Fig.1). The relative signal contribution of Dint was quantified by fint.ePVS were segmented from the enhanced perivascular contrast images (Fig.2). Median fint values were extracted from ePVS and non‐ePVS voxels within the basal ganglia (BG).fint and Dint values from within the ePVS mask were compared with values from surrounding non‐ePVS voxels in the BG using Wilcoxon Signed Ranks Tests.ResultFigure 3 contains a graphic summary of the statistical comparison of Dint and fint values from the ePVS and non‐ePVS voxels in the BG. Higher Dint and fint values are observed in the ePVS compared to the non‐ePVS tissue.ConclusionThe current study identified a higher IVIM‐derived proxy of ISF within the ePVS compared to surrounding non‐ePVS tissue, confirming that ePVS indeed contribute to the waste clearance markerfint.ePVS are fluid‐filled spaces surrounding cerebral blood vessels, in which ISF diffusivity is less restricted. This explains the higher Dint values in ePVS compared to non‐ePVS.Furthermore, this study suggests a potential method to investigate diffusivity within the microscopic ePVS, independent of the ISF diffusivity between parenchymal cells. In patients with Alzheimer’s disease, this method could be applied to investigate alterations in ISF diffusivity which could be representative of potential Aβ blockages in ePVS.
Detection of Mild Cognitive Impairment Using In‐clinic and Remote Unsupervised Digital Cognitive Assessments
Authors: White Josh , Edgar Chris J. , Siemers Eric , Maruff Paul 
Published: December 2022

AbstractBackgroundThe Cogstate Brief Battery (CBB) is a computerized cognitive assessment validated for Alzheimer’s disease (AD) and unsupervised use. The CBB assesses processing speed, attention, visual learning, and working memory and is offered to cognitively normal (CN) and mild cognitive impairment (MCI) participants in ADNI‐3. In‐clinic visits are completed annually for MCI and every other year for CN, with both groups also able to complete unsupervised assessments at‐home within 14 days of the first in‐clinic visit and at up to 3 monthly intervals.MethodParticipants were 146 CN older adults (Mage = 72.1, SD = 6.43, age range 57–90 years, 58.2% females) and 37 older adults with MCI (Mage = 74.4, SD = 7.50, age range 61–89 years, 51.4% females). All participants underwent PET scans and confirmation of diagnosis at Baseline. Only participants with confirmed amyloid status were included in these analyses (i.e., all MCI participants were Aβ+ and all CU participants were Aβ‐). Participants completed the CBB in a supervised in‐clinic setting at Baseline, and again in an unsupervised remote setting within 90 days. Receiver Operating Characteristic analyses were conducted to ascertain whether the classification performance of the CBB in detecting MCI was similar in both settings.ResultAll CBB measures showed a significant ability to discriminate between CU Aβ‐ and MCI Aβ+ participants at both the supervised in clinic baseline (AUCs 0.63‐0.75) and initial remote visit (AUCs 0.63‐0.78). There was no significant difference for any CBB measure in classification performance (measured by AUC) between remote and supervised assessment (ps > 0.146).ConclusionThe CBB showed good ability to classify MCI‐related cognitive impairment, both supervised in clinic, and/or remotely without supervision.
Validating a set of Verbal‐Paired‐Associates word‐pair lists for Repeat, Remote, Automated Testing
Authors: Kaula Alexander J , Taptiklis Nick , Cormack Francesca K 
Published: December 2022

AbstractBackgroundVerbal‐Paired Associates (VPA) is a widely used memory task, typically administered by a trained rater, with lists of pairs of words learned over up to three attempts, followed by delayed recall. Automated scoring and administration could enable remote testing to monitor change over time but requires parallel forms of the test with equivalent psychometric properties. Here we describe the validation process and memorability characteristics of a group of 12 parallel forms of automated VPA.MethodWe generated 15 candidate VPA word‐pair lists based on prior modelling. Piloting and simulation‐based power calculations suggested a sample size of 375 would provide power of .8 to detect lists where the mean number of errors at the first attempt was more than one error different from the Grand Mean. We recruited 375 healthy participants aged 50–90 years via the Prolific online platform. We used a mixed counterbalanced design with the aim of evaluating the memorability characteristics of the candidate set of word‐pair lists. Participants were tested twice on the VPA task using different word‐pair lists, separated by a distractor task. All testing was delivered via the NeuroVocalix platform on participants’ own devices at home and was administered and scored automatically using automatic speech recognition. Automated scoring results were reviewed by a human experimenter to ensure accuracy.ResultMemory performance in individual word‐lists conformed broadly to our model‐based expectations, with significant correlations between predicted and observed performance (p < 0.05). We observed expected significant improvement in recall performance with repeated administration, showing learning of word pairs over the task. In this healthy sample there was only modest forgetting at delayed recall. Although performance was broadly equivalent across the different lists, the final selection of lists excluded three with the highest numeric difference in performance versus the overall grand mean, yielding 12 lists for repeated administration. Qualitative feedback showed good levels of acceptability and engagement with the task by participants.ConclusionWe now have a set of 12 parallel‐form word‐pair lists for use with the automated NeuroVocalix system, with consistent performance characteristics enabling long‐term repeat testing remotely and at scale.
Association of sleep quality and diffusion MRI derived interstitial fluid content – insights in cerebral waste clearance
Authors: van der Thiel Merel M. , Backes Walter H. , Drenthen Gerhard S. , Voorter Paulien H.M. , Feiweier Thorsten , Ramakers Inez H.G.B. , Jansen Jacobus F.A. 
Published: December 2022

AbstractBackgroundDisruptions in sleep are associated with Alzheimer’s disease (AD) progression. As cerebral waste clearance is most active during sleep, these reductions in sleep quality could induce impaired clearance function. Waste products are washed through the parenchyma in the interstitial fluid (ISF), its volume being regulated by the sleep‐wake cycle. A smaller ISF‐volume is found in awake states and after sleep deprivation. IntraVoxel Incoherent Motion (IVIM) MRI can detect the diffusion of cerebral ISF (Dint) and its volume fraction (fint).Using IVIM, the current exploratory study investigates whether alterations in a proxy of ISF‐volume (fint) are related to hours of sleep or self‐reported sleep quality.MethodTwenty neurotypical elderly subjects (Table 1) underwent ultra‐high field MRI (7T research system, Siemens Healthcare GmbH, Erlangen, Germany) (Table 2).The intermediate diffusion components (Dint) in the range 1.5*10‐3<Diffusivity<4.0*10‐3 mm2/s were calculated using spectral analysis (Figure 1). The relative signal contribution of Dint was quantified by the ISF‐fraction (fint). Median fint values were extracted from the white matter (WM) and gray matter (GM).Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). In addition to the clinically used total PSQI (sum of all 7 components), the PSQI1 (Subjective sleep quality) and PSQI3 (Sleep duration) components were considered.Pearson correlations were computed between the PSQI scores and fint for WM and GM. To check for potential confounding influences, partial correlations were performed adjusting for age and time of MRI‐acquisition.ResultThe sample characteristics and descriptive statistics are summarized in Table 1. Worse reported sleep quality (PSQI1) significantly relates to lower WM fint (Table 3 and Figure 2). After adjusting for potential confounding influences, a trend towards significance remained (R=‐0.437, p=0.061).ConclusionThe current explorative study identified a lower diffusion MRI‐derived proxy of ISF‐volume in the WM of subjects who reported a subjective feeling of long‐term sleep deprivation. A reduction in ISF‐volume may leave less space for waste products, such as soluble Amyloid‐beta, to be cleared from in‐between the cells. Thereby, this study puts forward a potential method for future studies to investigate impaired clearance function in relation to sleep in patients with AD pathology.
Plasma glial fibrillary acidic protein in Alzheimer’s disease and other neurodegenerative disorders: relationship to diagnosis, biomarkers, neuropathology and longitudinal progression
Authors: Shen Xue‐Ning , Huang Shu‐Yi , Yu Jin‐Tai 
Published: December 2022

AbstractBackgroundPlasma glial fibrillary acidic protein (GFAP) was associated with Alzheimer’s disease (AD), but its usefulness for diagnosis and prognosis still need validation.MethodPlasma GFAP was measured using Simoa assays in cohorts of AD, non‐AD dementia, and controls (585 participants in total and 118 with follow‐up).ResultPlasma GFAP was significantly higher in AD spectrum than in controls and non‐AD dementia, except for the dementia with Lewy bodies. It increased in a stepwise fashion from preclinical AD, through prodromal AD to AD dementia. Plasma GFAP effectively distinguished AD from controls (area under curve [AUC]>0.97), non‐AD dementia (AUC>0.80), preclinical AD (AUC>0.89), and prodromal AD (AUC>0.85). Additionally, it correlated with other AD‐related fluid and imaging markers, and displayed prognostic values for conversion to AD dementia (adjusted hazard ratio 4.49, P=0.027) and cognitive decline (standard β 0.34, P=0.002).ConclusionOur findings highlight the value of plasma GFAP as a diagnostic and prognostic biomarker for AD.
CHARACTERISTICS OF SUBJECTIVE COGNITIVE IMPAIRMENT, DEPRESSION, AND FUTURE COGNITIVE DECLINE ‐ A POPULATION BASED STUDY
Authors: Zullo Leonardo , Popp Julius , Clark Christopher 
Published: December 2022

AbstractBackgroundSubjective cognitive impairment (SCI) is common in the elderly and it is associated with increased risk of developing dementia. The aim of the present study is to investigate the relationship between SCI characteristics and cognitive and functional decline in community dwelling older people.MethodLongitudinal analysis of a cohort of 752 dementia‐free community‐dwellers aged 65 years and older from CoLaus/PsyColaus, a population‐based study from the urban area of Lausanne, Switzerland. The presence of SCI was determined using a validated 10‐item questionnaire. We used a semi‐structured interview to assess depression symptoms. A comprehensive neuropsychological test battery along with activity of daily living questionnaires were administered to assess cognitive and everyday functioning at inclusion and at follow‐up visits 5 years and 10 years later. Decline was defined as a change of the Clinical Dementia Rating (CDR) Sum of boxes > 1. Statistical analysis was based on logistic regression.ResultThe presence of SCI at inclusion predicted cognitive decline 5 years later (OR 5.44, p = 0.004). Item 1 of the questionnaire, enquiring about the feeling of getting worse at remembering recent events, was a predictor of future decline (OR 5.44, p = 0.015). Further, current depression was associated with cognitive decline at 5 years (OR 2.65, p = 0.029).ConclusionIn this population‐based study, SCI predicted cognitive decline 5 years later. The role of depression in this relationship deserves further investigation. Results considering the 10‐year follow‐up will be presented at the congress.
Memory clinic clinicians’ preferences and needs for communication with patients: A multi‐national survey study from EU‐FINGERS & LETHE projects
Authors: Hendriksen Heleen M.A. , van Gils Aniek M. , Kivipelto Miia , Mangialasche Francesca , Meester Hanneke F.M. Rhodius‐ , Smets Ellen M.A. , van der Flier Wiesje M. , Visser Leonie N.C. 
Published: December 2022

AbstractBackgroundIncreased attention to pre‐dementia stages of Alzheimer’s disease (AD) creates new challenges for clinician‐patient communication. To assist clinicians in these challenges, we aimed to: 1) identify their perspectives on communicating about diagnostic testing, biomarker test results, dementia risk, and prevention, and 2) inventory their need for communication support.MethodBetween June and November 2021, 160 memory clinic clinicians from 21 European countries (56% 31‐50yrs; 59% female, 14±10yrs of experience) completed a digital survey in which they provided their opinions based on five hypothetical patient cases: 1) AD dementia, 2) Mild Cognitive Impairment (MCI) with positive (+) AD biomarkers, 3) Subjective Cognitive Decline (SCD) with positive AD biomarkers, 4) MCI with negative (‐) AD biomarkers, and 5) SCD with negative AD biomarkers. Additionally, we asked which amount and what type of support (online tools and/or skills training) would be appreciated for 10 listed communication skills. Descriptive statistics were used to report characteristics and survey responses.ResultMost clinicians indicated they would communicate syndrome diagnosis (66‐88% of clinicians) and biomarker results (97‐100%) to all five hypothetical patients. In case of positive biomarkers, clinicians were more hesitant to explicitly mention the presence of AD in the SCD+ case (29%) than in the MCI+ case (68%). Clinicians rather emphasized that it is not yet known what biomarker positivity means for the patient (68% in SCD+ vs. 32% in MCI+). Almost all clinicians reported discussing prognosis/dementia risk (79‐98%) and prevention (90‐99%), often tailored to patient characteristics and preferences. Of note, more than half of clinicians indicated that they preferred ‘(very) much’ support regarding 9 out of 10 listed communication skills (Figure 1), via online tools (34%), training (13%), or both (32%).ConclusionEuropean clinicians have a positive attitude towards communicating about early diagnosis of AD, dementia risk, and prevention. Clinicians differ in whether and how they explain the meaning of positive AD biomarkers to patients with SCD or MCI, reflecting the current debate in the field. Moreover, we identified a need for communication support on these topics. Fulfilling clinicians’ needs might help to attune memory clinic care even better to individual patients.