bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility Study for Longitudinal Retinal Imaging in the Anti‐Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) Trial
Authors: Rissman Robert A , Ngolab Jennifer , Donohue Michael C. , Belsha Alison , Salazar Jennifer , Cohen Paula , Jaiswal Sandhya , Tan Veasna , Aggarwal Neelum T. , Alber Jessica , Johnson Ken , Jicha Gregory A , van Dyck Christopher H , Lah James J. , Salloway Stephen , Rafii Michael S , Aisen Paul S. S , Sperling Reisa A. 
Published: December 2023

AbstractBackgroundAlterations to the retina manifest in patients diagnosed with neurodegenerative diseases such as Alzheimer’s disease (AD). Retinal imaging techniques open the possibility for non‐invasive evaluation of AD pathology. Clinically AD diagnosed patients exhibit retinal spots that may be amyloid deposits. Few studies monitoring preclinical individuals exist, limiting the assessment of the feasibility of retinal imaging as a biomarker for early‐stage AD risk detection.MethodWe compared extent and distribution of retinal fluorescent spots and cerebral amyloid in clinically normal individuals who screened positive for high amyloid levels through positron emission tomography (PET) from the Anti‐Amyloid Treatment in Asymptomatic Alzheimer Disease (A4) as well as a companion cohort of individuals who exhibited low levels of amyloid PET in the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) study. We quantified the number of curcumin‐positive fluorescent retinal spots from participants from both studies to determine retinal amyloid deposition at baseline.ResultParticipants from the A4 trial exhibited a greater number of retinal spots compared to those from the LEARN study. We report a positive correlation between retinal spots and brain amyloid, as measured by the standardized uptake value ratio (SUVr).ConclusionThe results of this study support the use of retinal fundus imaging for and assessing relationships with brain amyloid PET SUVr. Further work is needed to determine the nature of retinal spots and their relationship with actual amyloid plaques cross‐sectionally and longitudinally.
Elective Surgery in People with Dementia in Northern Ireland
Authors: O'Hara Leeanne , Zafeiridi Evi , Passmore Anthony Peter , Cunningham Emma L , McGuinness Bernadette 
Published: December 2023

AbstractBackgroundElective care is defined as care that is planned in advance for those that require a procedure or treatment for an existing condition. Elective surgery aims to improve the physical or psychological quality of life for a patient and may extend the life of an individual. Evidence has shown that surgery in people with dementia (PwD) carry even more risk than those in the general ageing population particularly in terms of post‐operative complications and mortality rates. Whilst thousands of elective surgeries take place every year, it is unclear how many of these are conducted on PwD. This study explores the types and rates of elective surgery in PwD in Northern Ireland and the contributing factors to patient referral for elective surgery.MethodData was accessed through the Honest Broker Service (NI) and was retrospectively analysed. Dementia was defined in people who received one or more dementia medications (as outlined in the British National Formulary (BNF)) or when dementia was identified as a primary or secondary cause of death. Elective surgeries were identified by elective surgery referrals (Patient Administration System) (dementia cohort: n = 26,780; control: n = 24,056).ResultOverall, significantly less PwD were referred for an elective surgery compared to controls. Within the PwD group those who had higher odds to undergo an elective surgery were male, of younger age, lived in rural areas, did not transition to a care home, and were married instead of single or widowed. PwD were less likely to have an elective surgery if they received antipsychotics, but they were more likely to have a surgery if they received lipid lowering drugs, antihypertensives, hypnotics and anxiolytics, antidepressants, or antiarrhythmics. The most common surgeries from both PwD and controls were surgeries for lens, bladder and skin. Having an elective surgery was associated with lower odds of death for PwD and controls compared to people who did not undergo a surgery.ConclusionThis paper can inform health policy through insight into factors contributing to the rate and types of elective surgery referrals for PwD to ensure PwD are afforded the same care when it comes to elective surgery compared with the general population.
Validation of genetic stratification for risk of Alzheimer’s disease using UK Biobank
Authors: Escott‐Price Valentina 
Published: December 2023

AbstractUK Biobank is a very large cohort (N = 364,195) with a sufficient number of Alzheimer’s disease (AD) participants (N = 2,431) for statistical analyses. Many participants are only now reaching the age where they are at risk of developing AD and the number of AD cases is expected to grow. We have generated polygenic risk scores (PRS) in the UK Biobank data, using both standard and Bayesian approaches. These risk scores have been computed across all available SNPs (genome‐wide) and for biologically defined gene‐sets (microglia regions (Gosselin et al 2017, Science) based on GWAS signatures and transcriptomic data (Tansey et al 2018, Genome Medicine), synapse (Koopmans et al 2019, Neuron), and genome‐wide significant genes (Andrews et al 2020, Lancet Neurology)). The APOE index SNPs had prediction accuracy (AUC) of 68.6% and PRS excluding APOE region had AUC = 53.4%. The microglia gene‐set had an AUC of 59.1%, the synapse gene‐set AUC = 59.4%, and the set of genome‐wide significant genes (Andrews et al 2020, Lancet Neurology) AUC = 53.2%, increasing to 70.5%, 69.8% and 70.2%, respectively, when APOE was accounted for separately. The UK Biobank data is enriched with late onset AD cases who develop AD at a younger age compared to average age at AD onset since the cohort is, in general, younger than most AD case/control studies. Therefore, PRS including APOE have the best prediction accuracy, since APOE is associated with younger onset (Liu et al 2013, Nature Review Neurology). Gene‐sets explain a large proportion of prediction accuracy using fewer SNPs (3% and 7% SNPs for microglia and synapse gene‐sets, respectively). Enrichment of other AD related genes will be possible to observe as the UK Biobank cohort increases in age, and more individuals are diagnosed with AD.
Discovery of causal relations of risk factors using Mendelian randomisation and genetic colocalization with UK Biobank data
Authors: Dehghan Abbas , Tzoulaki Ioanna , Elliott Paul 
Published: December 2023

AbstractMany risk factors, disease traits and comorbidities have been associated with Alzheimer Disease (AD). However, given the long subclinical development of the disease it is difficult to establish temporal order or to rule out shared aetiologies in observational research. Novel analytical molecular epidemiology approaches can be used in AD to investigate potential causality. Mendelian randomisation analysis is an approach where genetic instruments are used as a proxy for the exposure and allow us to investigate the causality of the associations in an observational setting. By selecting genetic instruments MR can be extended to proxy a drug target which allows to mimic the effect of medications targeting that particular gene. Colocalization is another method that tests whether a single genetic variant is driving the association of a shared gene for two traits or disorders. The availability of large‐scale data in UK Biobank including genome‐wide association data (GWAS) and whole genome sequencing (WGS) with a range of questionnaire data, physical measurements, proteomics and other biological measurements and clinical phenotypes has the potential to develop new knowledge on AD aetiology using these new approaches. For example, we were able to study the association between features from MRI brain imaging with AD through the MR approach and show associations between genetically predicted brain iron accumulation in different brain areas with AD risk. In another approach, we were able to study pleiotropic genetic variants that affect both cardiovascular traits and AD and through colocalization identify genes that are likely to be causal for both diseases. Using the wealth of phenotypic data in UK Biobank we were able to further explore the effect of these genes across the phenome and exposome. Further molecular data is expected to be released in UK biobank including proteomics and enhance the study of molecular fingerprints of AD and to extrapolate this knowledge to medications that target them and to elucidate underlying disease pathways.
Alzheimer’s Disease genetic risk factor APoE 4 impact auditory processing in young adults
Authors: Ducos Emma Marie Madeleine , Schneefeld Felix , Igloi Kinga , Arnal Luc H. 
Published: December 2023

AbstractBackgroundRecent studies have suggested that prodromal stages of Alzheimer’s Disease (AD) are accompanied with central auditory system dysfunction, which may be used as early indicators of disease onset and progression. In AD patients of 60 years old and more and in APOE4 carriers, atypical patterns of oscillatory entrainment to repetitive sound transients have been reported and suggested as potential neuromarkers of AD. Whether such alterations of auditory functions relate to genetic risk factor of AD (APOE4) at an early age (<30) is unknown.MethodWe used EEG recordings to measure auditory responses to repetitive sounds (1 second click trains presented at various frequencies (10‐250Hz) in 32 young neurotypical participants). To test whether auditory responsivity is affected by AD risk factor, we compared auditory brain responses from 17 APOE3 (age mean = 21.6, sd = 1.8) and 17 APOE4 carriers (age mean = 23.6, sd = 4.9).ResultComparing the magnitude of auditory event related potentials (ERP) we observed that APOE4 carriers exhibit slightly attenuated P2 and P3 ERP responses as well as delayed N1 and P2 ERP responses compared to APOE3 carriers. Focusing on Auditory Steady State Response (ASSR) power across frequencies (10‐90Hz), we observed that APOE3 carriers exhibit reliably larger neural entrainment than APOE4 carriers (Cohens’ d = 0.8, ‘large’ effect size). This difference was sustained across the peristimulus time course and did vary across stimulus frequencies.ConclusionOverall, these results suggest that central auditory differences can be detected very early in at‐risk populations. Studying these signals could help identify early AD pathology and provide an entry point for therapeutic interventions against neurodegeneration.
Comparison between self‐ and informant‐rated versions of the Mild behavioral impairment checklist in patients with mild cognitive impairment
Authors: Matuskova Veronika , Krejci Monika , Horakova Hana , Ismail Zahinoor , Laczó Jan , Hort Jakub , Vyhnalek Martin 
Published: December 2023

AbstractBackgroundMild behavioral impairment (MBI) describes de novo emergent and persistent neuropsychiatric symptoms in older individuals. MBI is common in individuals with mild cognitive impairment (MCI), but self‐endorsed symptoms may not align with reports from informants. In this study, we explore the consistency between self‐ and informant‐rated versions of the Mild behavioral impairment checklist (MBI‐C), which is used to assess MBI.MethodWe included 68 individuals with MCI (MMSE 26.59±2.55) who underwent neurological, extensive neuropsychological examination and brain MRI within the Czech Brain Aging Study and had no history of prior psychiatric disorder. Both participants and their close informants completed The Czech version of the MBI‐C (MBI‐C self and MBI‐C informant, respectively). The consistency and differences between the MBI‐C self and informant total and domain scores (i.e. motivation, affect, impulse dyscontrol, social inappropriateness and psychotic symptoms), and the presence of MBI based on a cut‐off of ≥7, were examined using Wilcoxon signed‐rank test, the binomial test and Spearman´s rank correlation. Further, we explored the association between the informant‐self score difference with the MMSE as a measure of global cognition.ResultThere was no difference between MBI‐C self and informant total score (both median ratings were 5.0). Among the domain scores, we observed a difference between self and informant ratings in the impulse dyscontrol (Z = ‐2.97, p = 0.003), but not in any other score. Disagreements on the presence of MBI were observed in 19 participants (28%), but both patients and informants were equally likely to disagree on the MBI presence vs. absence. We observed weak to modest correlations between MBI‐C self and informant total and domain scores (rS = 0.34‐0.53, ps<0.01). The informant‐self score difference in MBI‐C impulse dyscontrol was negatively associated with the MMSE (rS = ‐0.39, p = 0.001).ConclusionPatients with MCI and their informants were not consistent regarding the presence of MBI, but among those who disagreed, neither informants nor patients were more likely to report MBI. The informants reported more severe impulse dyscontrol symptoms compared to the patients with MCI themselves and this difference was negatively associated with lower MMSE. The observed inconsistencies provide implications for clinical and research settings.
Interest in genetic susceptibility testing and disclosure of AD dementia risk in cognitively normal adults: A survey study
Authors: Waterink Lisa , Masselink Larissa A , van der Lee Sven J , Visser Leonie N.C. , Cleutjens Solange , van der Schaar Jetske , van Harten Argonde C. , Scheltens Philip , van der Flier Wiesje M. , Zwan Marissa D. 
Published: December 2023

AbstractBackgroundApolipoprotein‐E (APOE) genetic susceptiblity testing for Alzheimer’s disease (AD) dementia is becoming more important as clinical trials are increasingly targeting individuals carrying APOE4‐genotypes. As little is known about about the interest in knowing genetic risk for AD dementia in the general population. Our objective was to examine this in a sample of cognitively normal adults within a population‐based online research registry with the goal to implement APOEε4 status for trial recruitment.MethodAn online survey was completed by 442 cognitively normal participants between the age of 49 and 75 years (56% female) from the Dutch Brain Research Registry. The survey assessed interest in participation in research into, and disclosure of, genetic risk for dementia, and the knowing their genetic risk in different hypothetical risk scenarios (10%, 30%, and 50% genetic risk for dementia at age 85, corresponding to APOEε2/ε2 or ε2/ε3, APOEε3/ε4 or ε2ε4, and APOEε4/ε4 genotypes). All hypothetical scenarios were randomly presented to all participants. Cochran’s Q‐tests was used to analyse differences in frequencies across scenarios.ResultThe vast majority of participants was interested in participating in research and disclosure of their genetic risk (81%; Figure 1). The most reported reason was to contribute to scientific research (94%). Interest was higher in males, while lower‐educated participants more often reported to be unsure. When provided with different risk scenario’s, interest in knowing their risk was somewhat higher in the scenario’s with higher risk (50% scenario (79%) and 30% scenario (77%)) than in the 10% scenario (73%; χ2(2) = 19.91;p<.001). Most individuals expected they would share their genetic risk with close relatives (77‐89%), would participate in medication trials (79‐88%), and would make long‐term arrangements, e.g. retirement, health care, will (69‐82%), with larger proportions for scenarios with higher hypothetical genetic risk.ConclusionOur findings indicate that the vast majority of cognitively normal adults participating in a research registry is interested in AD genetic risk research participation and disclosure. Interest in genetic risk disclosure is higher in scenarios corresponding to the APOEε4 genotypes. This suggests APOEε4 screening within an online research registry is potentially a well‐received method to accelerate inclusion for preclinical trials ultimately disclosing genetic risk.
Coping and mood in carers of people with Parkinson’s disease – an anonymized online survey
Authors: Magdalena Garcia , Velayudhan Latha 
Published: December 2023

AbstractBackgroundFamily and informal carers play a substantial role in the care of patients with Parkinson’s disease (PD) especially those who develop neuropsychiatric symptoms and dementia. As PD progresses, carers are at increased risk for poor health outcomes and greater levels of stress. Furthermore, negative emotional states, such as depression and anxiety with stress, are major risk factors for the development and maintenance of poor adaptive coping strategies. However, the literature examining these in PD carers is sparse. We aimed to identify and examine relationships between mood symptomatology and coping strategies in carers of people with PD.MethodsAn anonymised self‐administered online survey was conducted for data collection within the UK (Ethics Approval Ref‐LRU‐21/22‐28386). The survey consisted of questions regarding demographics, coping strategies and mood symptoms. A snowballing sampling was used to recruit via advertising in various Parkinson’s support groups within UK. Participants who were unpaid carers (family, partner or friend) of people with PD above the age of 18 years, fluent in English and had a device to do the online survey were eligible.Results105 carers for people with PD participated online between 23rd May 2022 to 15th July 2022. 96.2% of the carers were women and most in the age range of 45‐64 years (57.1%). 93.3% of the carers were spouse or partners, lived (89.5%) and taken care of the person with PD for over 5 years (54.3%), providing care ‘most of the time’ (59%). 61.9% PD persons had dementia and 29.5% had psychosis symptoms. We found that PD carers used more of non‐adaptive than adaptive coping strategies. 91.4% of carers had anxiety and 92.4% had depressive symptoms in varying frequency. Non adaptive coping strategies were associated with increased mood symptoms.ConclusionsCarers with adaptive coping strategies had lower frequency of mood symptoms. Further research in larger samples is needed not only to understand the relationships of coping strategies and mood symptoms in carers of people with PD but also important to devise interventions to support these carers to improve their well‐being.
Microtubule‐binding region tau fragment tau368 as a biomarker of Alzheimer’s disease
Authors: Simrén Joel , Janelidze Shorena , Kac Przemyslaw Radoslaw , Karikari Thomas K , Smirnov Denis , Kvartsberg Hlin , Gonzalez‐Ortiz Fernando , Sjons Emma , Mattsson‐Carlgren Niklas , Brum Wagner Scheeren , Palmqvist Sebastian , Ashton Nicholas J. , Zetterberg Henrik , Galasko Douglas R. , Hansson Oskar , Blennow Kaj 
Published: December 2023

AbstractBackgroundRecent studies suggest that microtubule‐binding region (MTBR) tau fragments may be markers of tau tangles in Alzheimer’s disease (AD) when used in ratio with total tau (MTBR‐tau/T‐tau) to normalize for T‐tau secretion. One such candidate marker is MTBR‐tau containing residue 368 (MTBR‐tau368). In this study, it was cross‐sectionally evaluated in participants from a memory clinic cohort and an autopsy series.MethodsWe included Aβ‐negative cognitively unimpaired (CU) individuals, individuals in the AD continuum (Aβ‐positive CU, mild cognitive impairment (MCI) and AD dementia), and with non‐AD dementia from the BioFINDER‐1 study, who all underwent [18F]‐flortaucipir‐PET. Further, we included CU and CI participants from UCSD Alzheimer’s disease research center (UCSD‐ADRC) who underwent lumbar puncture (LP) antemortem and then donated their brain for autopsy, examining AD neuropathologic change (ADNC) and non‐AD pathologies. All participants had immunoassay‐based CSF measures of T‐tau and MTBR‐tau368 by commercial immunoassays (Euroimmun [BioFINDER‐1] and Lumipulse [UCSD‐ADRC] T‐tau) and an in‐house Single molecule array (Simoa) assay, respectively. Statistical analyses were performed using linear models (covarying for age and sex) and Pearson correlations.ResultsSixty‐seven individuals from UCSD‐ADRC (mean [SD] age at LP 74.3 [8.4] years, 4.3 [2.1] years before death) and 181 from BioFINDER‐1 (72.5 [7.4] years) were included for this study. There were no group‐level differences in MTBR‐tau368 levels alone in any of the cohorts. In the UCSD‐ADRC cohort, MTBR‐tau368/T‐tau was decreased in participants with high (estimated marginal mean [EM = 0.06) vs. low (EM = 0.09, P = 0.01) or no (EM = 0.1, P = 0.001) ADNC and with higher Braak stage (V‐VI; EM = 0.06 vs. III‐IV; EM = 0.08, P<0.05, and I‐II; EM = 0.09, P<0.001). In BioFINDER‐1, Aβ‐positive MCI and AD dementia had lower MTBR‐tau368/T‐tau (EM∼0.04) compared with all other groups (EM = 0.06‐0.07, P<0.05‐<0.001). Further, MTBR‐tau368/T‐tau inversely correlated with tau‐PET in Braak‐like regions III‐IV and V‐VI (r = ‐0.35 and ‐0.42, P<0.001). MTBR‐tau368/T‐tau was unchanged in individuals in the frontotemporal dementia (FTD) spectrum (behavioral variant FTD/semantic dementia, and corticobasal syndrome/progressive supranuclear palsy).ConclusionConcordant with recent data, MTBR‐tau fragments alone do not change in AD or other neurodegenerative disorders. However, when normalizing MTBR fragments to T‐tau secretion, their capability of reflecting the extent of tau pathology provides opportunities of staging AD using CSF biomarkers.