bluuebunny/crossref_metadata_2025_split huggingface dataset:
A PROSPECTIVE STUDY OF ALZHEIMER’S DISEASE DIAGNOSIS AND PROGNOSIS (VALCODIS COHORT)
Authors: Cháfer‐Pericás Consuelo , Baquero Miguel , Álvarez Lourdes , Ferré‐González Laura , Peña‐Bautista Carmen , García‐Vallés Lorena , Ferrer Inés 
Published: December 2023

AbstractBackgroundThe Valencian Cognitive Diseases Study (VALCODIS) provides a large cohort of cases suffering from neurodegenerative diseases causing cognitive problems in their initial phases. This cohort is being obtained from admitted patients at Cognitive Disorders Unit Hospital Universitari i Politècnic La Fe (Valencia, Spain), as a basis to contribute on the Alzheimer’s disease (AD) diagnosis and prognosis research.MethodPatients who come to the Cognitive Disorders Unit at Neurology Department of Hospital La Fe can be recruited to the VALCODIS cohort after their informed consent have been obtained. Patients with moderate and severe dementia are not proposed to participate. Included patients were studied with standard analytical and neuroimaging procedures, commonly brain MR, and CSF biomarkers determination (β‐amyloid‐42, β‐amyloid‐40, p‐Tau, t‐Tau, neurofilament light chain). Patients on anticoagulation, other contraindications or not suitable for LP can be included if an amyloid brain PET can be obtained. In some patients, brain PET with FDG is also obtained. After amyloid status is assured, a detailed neuropsychological evaluation is obtained in every patient using at least MMSE, CDR, RBANS and GDS scales. Finally, blood samples were taken to determine some potential biomarkers (lipid peroxidation, lipids, proteins, microRNAs) and stored simultaneously with CSF samples.ResultA total of 1100 participants aged 50 to 80 years, who were on follow up from January 2017 to August 2022 have been included in the VALCODIS cohort. This cohort is composed by early AD patients (mild cognitive impairment (MCI), mild dementia), other dementias in their initial phases (frontotemporal dementia, Lewy body dementia, vascular dementia) and cognitively healthy persons. Also, some of MCI‐AD patients were followed‐up at 2 years to carry out a prognosis study, by means of neuropsychological evaluation and blood biomarkers.ConclusionThe VALCODIS cohort represents a valuable infrastructure describing 6‐year experience about early and specific AD diagnosis, and prognosis. This cohort will provide a large number of patients, biologically diagnosed by CSF biomarkers, as well as their demographical, clinical and biochemical data. In addition, the biological samples (blood, plasma, urine, saliva, CSF) were stored to carry out further biomarkers studies.
Retinal microvasculature and risk of incident dementia over a 10‐year period: results from the 3C‐Alienor population‐based study
Authors: Rebouças Sara Cristina Lima , Cougnard‐Gregoire Audrey , Arnould Louis , Delyfer Marie‐Noëlle , Schweitzer Cédric , Korobelnik Jean‐François , Foubert‐Samier Alexandra , Cheung Carol Y , Wong Tien Yin , Delcourt Cécile , Helmer Catherine 
Published: December 2023

AbstractBackgroundThe retina and the brain microvasculatures share many anatomical and physiological similarities; thus, retinal microvasculature could represent a potential screening tool for cerebrovascular and neurodegenerative diseases. Changes in retinal microvasculature have been associated with dementia in previous studies. However, all the previous studies analyzing retinal vascular network features in relation to dementia or Alzheimer Disease (AD) were cross‐sectional. This study aimed to explore the longitudinal relationship between retinal microvascular features and dementia incidence over a 10‐year follow‐up period.MethodWe included 617 participants from the Three‐City (3C) population‐based cohort and its ancillary ophthalmological study, the Alienor study. Quantitative retinal vascular features (caliber, tortuosity, fractal dimension) were assessed at baseline in the Alienor study using the semi‐automated Singapore I Vessel Assessment (SIVA) software; dementia was actively screened and diagnosed over a 10‐year period. Cox proportional‐hazards models were used to estimate the risk of incident dementia and its main etiologies (i.e., probable or possible AD and mixed or vascular dementia) associated with retinal vascular features.ResultThe mean age of the participants was 79.5 years (SD 4.4) and 66.6% were women. During the follow‐up (median of 7.2 years), 134 participants developed dementia (87 probable or possible AD and 38 mixed or vascular dementia). In multivariate models adjusted for the main potential confounders (socio‐demographic factors, vascular co‐morbidities and Apolipoprotein ε4 allele), increased arteriolar tortuosity was associated with increased risk of dementia (HR per SD increase = 1.26, 95%CI: 1.07; 1.50). Despite some trends, retinal calibers were not significantly associated with dementia all‐cause. When considering the different etiologies of dementia, wider retinal venular calibers were associated with mixed or vascular dementia, but not with Alzheimer’s disease. Fractal dimensions were not associated with dementia.ConclusionChanges in retinal microvasculature were associated with risk of incident dementia. More works are needed to replicate and determine which features could help identifying persons at risk of future dementia at an early stage, and to examine the specific processes that might be involved according to dementia etiology.
Vascular and extravascular localization of Aβ in Alzheimer’s retina
Authors: Lee Sieun , Whitney Dylan , Liu Alice , Schwab Katerina , Jiang Kailun , Hirsch‐Reinshagen Veronica , MacKenzie Ian R , Hsiung Ging‐Yuek Robin , Sarunic Marinko , Beg Mirza Faisal , To Eleanor , Cui Jing , Pham Wellington , Matsubara Joanne A 
Published: December 2023

AbstractBackgroundRecent in vivo and ex vivo studies have demonstrated retinal vasculopathy may be associated with Alzheimer’s disease (AD). We investigated amyloid beta (Ab) localization relative to vessels in wholemount retinas from AD and control donors. We specifically tested whether extravascular retinal Ab aggregated toward vessels and whether the Ab localization pattern differed between the AD and control retinas.MethodFrom 15 AD donors and 10 age‐matched controls, free‐floating punches were taken in the foveal, peri‐foveal, and mid‐peripheral temporal, superior, and inferior neuro‐retina. Immunohistochemistry was performed for Ab (6F/3D, 12F4) with secondary antibodies tagged with Cy3. The punches were imaged at 543‐nm using Zeiss LSM 510 confocal microscope focused at the ganglion cell layer in four non‐overlapping 450mm x 450mm images. Blind raters segmented the images into intravascular and extravascular regions excluding cell bodies and artefacts. Quantitative analysis was performed as follows: Ab reactivity was detected pixel‐wise by intensity thresholding, and the total vessel area, raw and normalized intra‐ and extravascular Ab load, and vessel proximity of extravascular Ab were computed.ResultOut of 452 images 272 contained visible vessels. Total vessel area was lower in the AD retinas in the superior region (p = 0.004). There was no group difference in Ab load except in the temporal intravascular region (p = 0.007); however, intravascular Ab signal may be due to blood artefacts and requires caution in interpretation. Aggregation of Ab near vessels was tested by comparing the vessel proximity of extravascular Ab‐positive pixels against that of all other pixels in the extravascular region. Extravascular Ab were located significantly closer to the vessels than the background in the control retinas in the peri‐fovea (p = 0.0023) and temporal (p = 0.001) regions, but this was not observed in AD retinas.ConclusionWith our previous study on intracellular retinal Ab, the current study suggests that Ab deposition pattern in the retina is specific in spatial regions (eg. temporal, superior) and anatomical regions (eg. intracellular, intravascular). The non‐specificity of Ab localization relative to the vessels in AD may indicate compromised Ab clearance via retinal vasculature.
ABOARD Cohort; a national initiative to involve citizens in AD research
Authors: Rhodius‐Meester Hanneke F.M. , de Boer Casper , Handgraaf Dédé , Claassen Jurgen A.H.R. , de Haan Romy , Hempenius Liesbeth , van Munster Barbara C. , van Strien Astrid M , de Vugt Marjolein , Arts Derk , Kooistra Minke , de Rijke Tanja J. , Beusink Miriam , Pijnenburg Yolande A.L. , van der Flier Wiesje M. 
Published: December 2023

AbstractBackgroundMany research cohorts consist of selected research populations, and their outcomes may not translate directly to daily life. Patient Reported Outcomes (PROs) provide this information, but data across the entire disease trajectory, from ‘at risk’ to dementia, are lacking. To address this gap, paving the way for value‐based health care, we have set up a Dutch national data collection infrastructure. This initiative called the ABOARD Cohort aims to (i) study the AD disease trajectory using both PROs and medical data, (ii) link to available registry data, and (iii) serve as central platform to initiate additional studies.MethodThe ABOARD Cohort (www.aboard‐cohort.nl) is part of the ABOARD project, a national public‐private partnership with >30 partners. The cohort is an ongoing, participant‐centered data‐collection, focused on PROs, a minimal CRF with relevant medical data, and linkage to existing data sources. Eligible participants with or at‐risk of AD and their care‐partners are recruited directly‐to‐participant, via (social) media and leaflets. Informed consent and annual collection of PROs through questionnaires are facilitated online, on separate platforms. Governance is based on the principle of data‐portability, the participant being owner of their own data. Participants optionally consent for their study data to be linked to e.g. health insurance and medical record data. We ensure active public‐involvement through a dedicated participant panel.ResultIn September 2022, the ABOARD Cohort was launched. In the first 4 months, n = 82participants (mean age 56±16, female 53(65%)) signed up via the study portal. 60(73%) gave consent to link their data to registries. The ABOARD Cohort Panel, consisting of 57 participants recruited via social media, provided input on the (consent) procedure, via surveys and panel discussions. The early phase experiences are now used to optimize procedures prior to a large social media campaign inviting participants in Spring 2023. The narrative of this campaign is that participants can contribute an hour of their time to help Alzheimer’s research (Figure).ConclusionThe ABOARD Cohort lays the foundation for a future with personalized medicine for AD. With this large scale societal initiative, we attempt to involve a large number of Dutch citizens in Alzheimer’s research.
Assessing posttraumatic stress disorder with patients suffering from neurocognitive disorder: development of the PTSD with NCD Inventory (PNI)
Authors: Coeur Estelle , Derreumaux Alexandre , Robert Philippe , Corveleyn Xavier 
Published: December 2023

AbstractBackgroundPTSD and NCD have common symptoms such as mood disorders (depressive symptoms, aggressivity, etc.) or cognitive disorders (executive dysfunctionning, amnesia, etc.). Due to these similarities, and because existing tools are not suitable for this population specificities, PTSD diagnosis may be difficult. Based on the existing literature, a new screening tool was created, allowing a hetero assessment of PTSD for this population. This study consists in explaining the development and the pre‐testing of our new tool, following specific scale development guidelines.MethodA research was conducted to analyze the inventory construct which allowed us to analyze over 50 tools and create our items. An expert panel assessed the first version, which was used in a protocol conducted with 44 participants suffering from NCD.ResultFirst, the tool was modified consequently to the expert panel’s review, for a total of 15 domains with 4 at 8 items. Cronbach’s alpha and Pearson’s correlation enlightened good reliability when tested with the 44 participants (inventory’s Cronbach’s alpha = 0.75). By the end of the pilot testing, 13 domains composed of 70 items were kept.ConclusionThe different validation steps lead to the creation of a new hetero‐assessing tool with specific PTSD items and suitable to a population with NCD. Domains will gauge both the symptoms frequency and impact. According to literature, this tool will focus on DSM‐5 criteria A, B and E. The next step will be to analyze the PTSD with NCD Inventory’s psychometric properties.
Longitudinal age effects in microstructures of the hippocampal subfields.
Authors: Zia Ghina , Shahid Syed Salman , Risacher Shannon L , Saykin Andrew J. , Wu Yu‐Chien 
Published: December 2023

AbstractBackgroundThe human brain undergoes considerable morphologic change with age, which is one of the primary risk‐factors for Alzheimer’s disease (AD). Age‐related microstructural changes in the brain may be quantified by advanced diffusion MRI (dMRI) with compartment modeling. In this longitudinal study, we aimed to investigate the effects of age on the hippocampal subfields, one of the brain regions vulnerable to the early stages of AD.MethodThirty‐seven cognitively normal older adults (70.6 ± 6.7 years) were recruited from the Indiana ADRC. Participants received a baseline and a follow‐up MRI scan over 24 ± 11.7 months with a Siemens 3T Prisma scanner using a 64‐channel head coil. We applied grey‐matter‐specific multi‐compartment diffusion model (cortical‐neurite orientation dispersion and density imaging) to derive diffusion microstructural metrics, namely orientation dispersion index (ODI), volume fractions of fast isotropic diffusion (VFISO), and intracellular‐space (VFIC) in the hippocampal‐subfields (CA1‐3, CA4 and dentate gyrus (CA4‐DG), and subiculum) [1]. To study the longitudinal age effects, we investigated the rate of change in the diffusion metrics and the association between the rate of change and age. Linear regression analysis was performed using SPSS software and adjusted for sex, education, APoE e4 status, and subfield volumes (Table 1).ResultAll subjects had normal cognition (i.e., MoCA and MMSE, Table 1). The volumes of CA1‐3 and subiculum significantly decreased between the baseline and follow‐up MRI scans, (p<0.05, Table 1). During this period, while significantly increased ODI within subject was observed in CA4‐DG, significantly decreased VFISO in all the subfields and increased VFIC in the subiculum were noted (Figure 1). The decreasing rate of VFISO in CA4‐DG was significantly associated with age (Table 2), suggesting the reduction in VFISO accelerated over age.ConclusionWe demonstrated that diffusion metrics are sensitive to microstructural alterations in the hippocampal subfields of cognitively normal older adults. The cornu ammonis region 4 and dentate gyrus is the most vulnerable region affected by aging with increased tissue dispersion and age‐accelerated reduction in fast isotropic diffusion. Future studies will focus on the effects of the initial microstructural condition to its rate of change with aging.
References: 1. Shahid, et al., Brain,2022
Use of plasma P‐tau217 for enrichment in the Phase 2 PROSPECT‐ALZ study of LY3372689 in early symptomatic Alzheimer’s disease: Cohort selection and baseline characteristics
Authors: Munsie Leanne M , Fleisher Adam S , Cheng Yun‐Ju , Stauffer Marianne L , Schade Andrew E. , Page Todd J , Mergott Dustin J. , Brys Mirek 
Published: December 2023

AbstractBackgroundInhibition of O‐linked N‐acetyl glucosaminidase (OGA) is hypothesized to impede the formation of hyperphosphorylated, insoluble tau aggregates and neurofibrillary tangles. LY3372689 is an orally available, potent inhibitor of OGA being tested in the ongoing PROSPECT‐ALZ study. This is the first study assessing the safety and efficacy of an OGA inhibitor in individuals with early symptomatic Alzheimer’s Disease (AD). To improve efficiencies in identifying individuals with desired levels of tau pathology, PROSPECT‐ALZ implemented a gated screening approach using plasma P‐tau217 as an enrichment step prior to tau PET. We present the study design, findings from the screening process, and baseline characteristics of the PROSPECT‐ALZ study cohort.MethodWith 68 sites across Australia, Canada, Japan, Poland, and the US, PROSPECT‐ALZ is an ongoing multicenter, double‐blind, placebo‐controlled Phase 2 study with 1:1:1 randomization of daily LY3372689 low dose, LY3372689 high dose, or placebo. The primary objective is to evaluate the effect of LY3372689 on AD clinical progression, as assessed by the change from baseline to endpoint (76‐124 weeks with common close design) on the integrated AD Ratings Scale (iADRS).Pre‐screening procedures include the Mini‐Mental State Examination (MMSE, scores of 22‐30) and a plasma P‐tau217 test to determine eligibility for further screening. Subsequent key inclusion requirements to meet were age 60‐85 years, a CDR global score of 0.5 or 1 with a memory box score of ≥ 0.5, and a PET (18F‐flortaucipir) scan demonstrating an intermediate or high level of aggregated brain tau by combined visual and quantitative assessment.ResultAfter consent, 2180 participants entered screening. The top reason for screen failure was a P‐tau217 result below the eligibility threshold. Performance of the P‐tau217 test for pre‐screening patient selection as well as characteristics and demographics of the screening and randomized cohorts will be presented.ConclusionAs blood‐based biomarkers become more accessible, their use in selecting participants for clinical research is desirable. The PROSPECT‐ALZ study successfully implemented plasma P‐tau217 in sequence with tau PET to improve efficiency in identifying trial participants. This study of LY3372689, the first orally administered OGA inhibitor to be investigated in AD, has topline trial results anticipated in 2024.
Suicide ideation, attempts and deaths in people living with dementia (PLWD): A systematic review and meta‐analysis of prevalence and risk factors
Authors: Stott Joshua , Tsipa Anastasia , Fearn Caroline , Baou Celine El , Charlesworth Georgina , Flanagan Katie , Brotherhood Emilie V , Crutch Sebastian J , John Amber , Desai Roopal 
Published: December 2023

AbstractBackgroundSuicide is a major public health concern. However, little is known about whether dementia is associated with suicide outcomes, and if so what the risk factors for suicide are in this group. This study aimed to conduct meta‐analyses to examine pooled associations between dementia and suicide outcomes (ideation, attempts, death by suicide) as well as pooled associations between risk factors (sex, dementia subtype) and suicidality in people living with dementia (PLWD).MethodSystematic searches were conducted in Medline, Embase, Psycinfo, Cinahl Plus, and Web of Science for keywords related to dementia and suicide. Quantitative studies with a sample of PLWD and suicidality as an outcome and that were available in English were included. Experimental studies, case reports and studies with a focus on euthanasia/assisted suicide, or self‐harm without suicidal intentionality were excluded. Relevant effect sizes were extracted and inverse variance weighted meta‐analyses were run using a random‐effects model.Result55 studies were included. Meta analyses showed that compared to people without dementia, having dementia was significantly associated with death by suicide (OR = 2.48, 95% CI:1.82;3.38), and suicidal ideation (OR = 2.29, 95% CI:1.75‐2.99), but not suicide attempts. Men with dementia were more at risk of attempting (OR = 1.28, 95% CI:1.25;1.31) and death by suicide (OR = 2.84, 95% CI:1.51;5.37) than women with dementia, but there was no difference in suicidal ideation. Compared with Alzheimer’s disease, people with vascular dementia (VaD), frontotemporal dementia (FTD), and other dementia (OD) types were significantly more likely to attempt suicide. People with Lewy body dementia (LBD) were significantly more likely to report suicidal ideation.ConclusionPLWD are at higher risk of suicidal ideation and death by suicide than those without dementia, but not suicide attempts. This could suggest that PLWD are not more likely to attempt suicide but are more likely to be successful when an attempt is made. Key risk factors for suicide attempts amongst PLWD are being male, sub‐type of dementia diagnosis (VaD, FTD and OD), while having a diagnosis of LBD is a risk factor for suicidal ideation. These results are important for understanding and managing risk in PLWD.
White matter hyperintensity volume changes are associated with progressive hippocampal atrophy in Insight 46: the neuroscience sub‐study of the MRC National Survey of Health and Development, the British 1946 birth cohort
Authors: Brown Thomas M. , Sudre Carole H , Keuss Sarah E , Coath William , Prosser Lloyd , Nicholas Jennifer M , Malone Ian B , James Sarah‐Naomi , Murray‐Smith Heidi , Cash David M , Richards Marcus , Barnes Jo , Schott Jonathan M 
Published: December 2023

AbstractBackgroundWhite matter hyperintensity volume (WMHV) is a presumed marker of cerebrovascular disease associated with ageing, Alzheimer’s disease (AD) and vascular dementia. Higher baseline WMHV is associated with increased brain atrophy rate, with disproportionate effects in the hippocampus – a region affected early in AD. Understanding the relationships between longitudinal change in WMHV and hippocampal atrophy, while accounting for AD and cardiovascular risk factors, will increase our understanding of the multifactorial disease processes occurring during the early stages of AD.MethodRate of change in WMHV was calculated using Bayesian Model Selection (BaMoS) and total hippocampal atrophy rate was calculated using the Boundary Shift Integral (BSI), measured concurrently between two time‐points. Participants with major neurological disorders were excluded. Linear regression was used to test whether rates of WMHV change predicted rates of hippocampal atrophy while adjusting for total intracranial volume (TIV), sex and age. Further models adjusted for baseline PET amyloid‐β (Aβ) standard uptake value ratio (SUVR), ApoE‐e4 carrier status, and Framingham heart study cardiovascular risk (FHS‐CVS) aged 69, and tested for interactions with rate of WMHV change.Result308 individuals with high‐resolution isotropic MRI data at two time‐points were analysed in this study (Table 1). For every 1ml/year increase in WMHV there was an associated 0.013ml/year decrease in total hippocampal volume (Table 2, Model 1). This association remained when adjusting for Aβ SUVR (Table 2, Model 2), ApoE‐e4 status (Table 2, Model 3), and FHS‐CVS (Table 2, Model 4). A separate semi‐partial correlation analysis showed 4.6% of variance in rate of hippocampal atrophy was uniquely explained by rate of WMHV change when accounting for TIV, sex and age. There were no significant interactions between rate of WMHV change and Aβ, ApoE‐e4 or FHS‐CVS in relation to hippocampal atrophy rate.ConclusionIncreases in WMHV were significantly associated with progressive hippocampal atrophy accounting for head size, age and sex. These associations were not materially changed when adjusting for amyloid deposition, ApoE‐e4 or cardiovascular risk factors. These results suggest systemic processes that contribute to WMH development also contribute to hippocampal atrophy. Further work is required to determine the processes that drive this relationship.