bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of initial symptoms of prodromal familial Frontotemporal Lobar Degeneration: Data from the ALLFTD Consortium
Authors: Miyagawa Toji , Brushaber Danielle , Kremers Walter K. , Fields Julie A. , Forsberg Leah K. , Heuer Hilary W. , Huey Edward D. , Knopman David S. , Kornak John , Boxer Adam L. , Rosen Howard J. , Boeve Brad F. ,   ALLFTD Consortium
Published: December 2023

AbstractBackgroundThe ALLFTD Consortium aims to characterize preclinical and prodromal stage of familial Frontotemporal Lobar Degeneration (f‐FTLD) to prepare for clinical trials in FTLD.MethodWe prospectively followed 320 asymptomatic participants of the ALLFTD Consortium who are family members of f‐FTLD with a mutation in MAPT (n = 106), GRN (n = 74), or C9orf72 (n = 140), and describe the ratings on the eight domains of CDR® plus NACC FTLD (FTLD‐CDR) in those who phenoconverted to Mild Behavioral and/or Cognitive Impairment (MBCI). MBCI was diagnosed by the proposed research criteria for MBCI‐FTD (Barker MS, et al. Brain 2022). Participants who were diagnosed as MBCI but returned to asymptomatic at the following visit were excluded from the FTLD‐CDR assessment. ANOVA was used to compare continuous variables, and chi‐square test was used to compare categorical variables across the groups.ResultThirty‐six participants (15 MAPT, 9 GRN, 12 C9orf72) developed MBCI during follow‐up visits, 13 participants (5 MAPT, 3 GRN, 5 C9orf72) were diagnosed as MBCI but were characterized as asymptomatic at the following visit, and 271 participants stayed asymptomatic. Percentage of male in MBCI participants was 50% (MAPT 60%, GRN 33%, C9orf72 50%, p = 0.45). Age at phenoconversion to MBCI was 53.6±13.0 years old, the youngest in MAPT and the oldest in GRN participants (MAPT 44.3±8.3, GRN 63.1±11.3, C9orf72 56.4±10.8, p<0.001). Abnormal rating on each of the eight CDR® plus NACC FTLD domains at the initial visit of MBCI phenoconversion were observed in: “Memory” 36% (MAPT 33%, GRN 33%, C9orf72 44%, p = 0.95); “Orientation” 8% (MAPT 7%, GRN 8%, C9orf72 11%, p = 0.93); “Judgment/Problem Solving” 44% (MAPT 47%, GRN 50%, C9orf72 33%, p = 0.73); “Community Affairs” 22% (MAPT 27%, GRN 17%, C9orf72 22%, p = 0.82); “Home/Hobbies” 25% (MAPT 40%, GRN 8%, C9orf72 22%, p = 0.16); “Personal Care” 0%; “Behavior/Comportment/Personality” 44% (MAPT 60%, GRN 42%, C9orf72 22%, p = 0.19); “Language” 31% (MAPT 13%, GRN 50%, C9orf72 33%, p = 0.12).ConclusionThe three most common FTLD‐CDR domains initially disturbed in the prodromal stage of fFTLD were “Behavior/Comportment/Personality”, “Judgment/Problem Solving”, and “Memory”, while “Orientation” was intact in the majority of the individuals. Memory impairment without disorientation was seen in one‐third of the prodromal fFTLD participants.
Study Design of FINGER‐NL: a Multidomain Lifestyle Intervention in Dutch Older Adults to Maintain Optimal Cognitive Functioning
Authors: Deckers Kay , Zwan Marissa D. , Soons Lion M. , Waterink Lisa , Beers Sonja , van Houdt Sofie , Meijer‐Krommenhoek Yvonne , van Pelt Hilde , Claassen Jurgen A.H.R. , Oosterman Joukje M. , de Heus Rianne A.A. , van de Rest Ondine , Smidt Nynke , Broersen Laus M. , Counotte Danielle , Sikkes Sietske A.M. , van Boxtel Martin P.J. , Aarts Esther , Köhler Sebastian , van der Flier Wiesje M. 
Published: December 2023

AbstractBackgroundEvidence on the effectiveness of multidomain lifestyle interventions to prevent cognitive decline in non‐demented older individuals is mixed. The multidomain FINGER study1 found small positive effects on cognition among older people at risk for dementia. As part of the World‐Wide FINGERS initiative to replicate and build on these results, FINGER‐NL aims to investigate the effectiveness of a 2‐year high versus low intensive multidomain lifestyle intervention on cognitive functioning in Dutch older at‐risk individuals.MethodFINGER‐NL is a Dutch multi‐center, randomized, controlled, multidomain lifestyle intervention trial aiming to include 1,206 adults at risk for cognitive decline. Adults aged 60‐80 years with at least 3 modifiable dementia risk factors (based on ‘LIfestyle for BRAin Health’ (LIBRA))2 and either a family history of dementia or self‐reported cognitive decline are eligible for inclusion. Participants are randomized (1:1 ratio) to either a high (HI‐group) or low‐intensity (LI‐group) intervention group. The multi‐domain intervention comprises a combination of 7 lifestyle components (physical exercise, cognitive training, cardiovascular risk management, nutritional counseling (with a specific focus on the MIND diet), sleep counseling, stress management, social activities) and 1 nutritional product (Souvenaid, 125ml). The HI‐group receives a personalized, supervised and hybrid intervention consisting of group meetings and individual sessions guided by a lifestyle coach. The LI‐group receives online lifestyle‐related health education. Primary outcome is 2‐year change from baseline on the cognitive composite score covering processing speed, executive function and memory. Secondary outcomes including changes in specific cognitive domains, instrumental activities of daily living, LIBRA score, and lifestyle component specific outcomes. For recruitment, we use the Dutch Brain Research Registry.3
ResultParticipant recruitment started in January 2022. So far, 2405 people were interested, 1711 individuals have been screened for eligibility, 949 underwent baseline testing and 880 participants (73% of target sample) have been randomized and started with the intervention. The intervention is well‐accepted based on drop‐out rate (0.5%) and use of the online intervention portal. We expect to finalize randomization in Q2 of 2023 and complete the two‐year trial in 2025.ConclusionResults so far show that FINGER‐NL is well on track, the intervention is well‐accepted and the trial will reach its inclusion target.
Sex / gender bias on the Face‐Name Associative Memory Exam in clinically‐normal older adults
Authors: Lu Kirsty , Nicholas Jennifer M , Street Rebecca E , James Sarah‐Naomi , Fox Nick C , Richards Marcus , Crutch Sebastian J , Schott Jonathan M 
Published: December 2023

AbstractBackgroundMany studies of memory in older adults report a sex difference, usually with female participants scoring slightly better than males. These sex differences may be partially due to the content of the tests, with some content being more memorable to males or females (https://doi.org/10.1093/ARCLIN/ACAC102). We investigated whether male and female older adults show differences on the Face‐Name Associative Memory Exam (FNAME‐12, designed to detect subtle Alzheimer’s disease‐related memory impairment). Specifically, do they show a bias towards remembering the stimuli that match their own sex?MethodParticipants (n = 432, see Table 1) in ‘Insight 46’, a sub‐study of the MRC National Survey of Health and Development (British 1946 birth cohort), completed FNAME‐12 (version A) at age ∼73 years. Stimuli comprise six male and six female faces (presented in alternating order), with names and occupations. Recall is tested four times after various delay intervals. Four total scores were calculated across all recall trials: female names; female occupations; male names; male occupations. We fitted multivariable regression models using Generalised Estimating Equations to investigate effects of item type (name/occupation), item gender (male/female) and participant sex (male/female), and interactions between these variables, controlling for age, education, socioeconomic position and prospectively‐collected childhood cognitive ability.ResultWomen outperformed men (coefficient averaged across the four conditions = 2.2 points [95% CIs 1.3, 3.1], p<0.001) (Fig1; Fig2). This difference was exaggerated for female stimuli (interaction coefficient = 2.0 [1.4, 2.6], p<0.001), and female stimuli occupations (3‐way interaction coefficient = 0.8 [‐0.0, 1.6] p = 0.050) i.e. women scored better than men even on male names, whereas men were particularly disadvantaged at recalling information associated with female stimuli, especially their occupations (Fig2).ConclusionWe found evidence of a gender bias on FNAME‐12 among male participants, where their recall was worse for female stimuli compared to male stimuli, which may partially explain their poorer performance on this test. Such biases should be considered when interpreting sex differences on memory tests. Further analyses before the conference will investigate longitudinal FNAME‐12 performance over ∼2.4 years, to explore whether this memory bias remains constant, or whether it may be a marker of memory decline (potentially reflecting increased reliance on the relatability of test content).
Novel Increase of N‐ and O‐linked Sialylation in Alzheimer’s Disease
Authors: Fastenau Caitlyn , Wickline Jessica L , Smith Sabrina , Odfalk Kristian F , Hopp Sarah C. , Bieniek Kevin F 
Published: December 2023

AbstractBackgroundResearch shows evidence of increased sialylation in post‐mortem Alzheimer’s Disease (AD) cases. Sialylation is a form of glycosylation with the attachment of N‐acetyl‐neuraminic acid or sialic acid (SA) to glycoproteins and lipids. There are two major forms of sialylation, N‐ and O‐linked SA, modifications that regulate microglia cellular interactions and immune response. Yet it is unclear how these forms of sialylation contribute to AD pathology and modify disease progression. We hypothesize specific microglia sialylation patterns early in disease progression contribute to pathological burden and dampen immune response.MethodsWe utilized brain tissue from 10 post‐mortem human AD cases, focused on frontal, hippocampal, and cerebellar regions, and 5XFAD mouse model of amyloid pathology. To Identify N‐linked SA bonds, we focused on α‐2,6 SA which was recognized by a plant‐derived lectin. Aβ plaques, neurofibrillary tangles, microglia, and α‐2,6 SA were labelled with immunofluorescent markers in cortical brain tissue. Samples were imaged with confocal microscopy. To identify O‐linked SA bonds, Alcian Blue and Periodic Acid Schiff stains were used in novel ways to differentiate subsets of neutral and charged O‐linked SA bonds. Samples were imaged on a Aperio microscope slide scanner.Results12‐month‐old 5XFAD mice have significantly higher percent of α‐2,6 SA coverage in the plaque microenvironment compared to WT littermates (p<0.001). Pearson correlation analysis determined significantly greater α‐2,6 microglia sialylation (r = 0.522; p<0.0001) compared to plaque sialylation (r = 0.262) in the 5XFAD mouse model. Post‐mortem human AD cases displayed similar microglia sialylation patterns. Yet there was no significant correlation of between tau and α‐2,6 SA (r = ‐0.143; p<0.0001) in human AD compared to microglia sialylation (r = 0.279). Qualitatively, 5XFAD mice and human AD display similar recognition of Aβ plaque with O‐linked glycosylation patterns.ConclusionsWe observed significant α‐2,6 sialylation of microglia in 5XFAD mice and post‐mortem human AD which was independent of tau pathology. Additionally, intriguing patterns of O‐linked SA are present surrounding Aβ plaques using novel histological techniques. Next, we will closely investigate subsets of sialylated microglia to determine what forms of O‐linked SA may reduce clearance of debris by microglia while actively comparing Aβ plaque sialylation in human AD cases.
Corticobasal degeneration or hepatic encephalopathy, False positive and/or congruence between clinic and PET‐FDG imaging
Authors: Lacombe Guy , Provost Sylvain , Paquet Nancy , gosselin Sylvie , Pelletier Martin , Lariviere Mathias 
Published: December 2023

AbstractBackgroundto put into perspective the relative clinical evidence meeting the criteria of corticobasal degeneration but modified by the treatment of a metabolic diseaseMethodMultidisciplinary clinical follow‐up of a patient meeting the cognitive, speech and neurological criteria for a degenerative disease by documenting the evolution of both functional, cognitive and functional imaging during the treatment of hepatic encephalopathyResultPt of 82 y/o presents with a deterioration over 6 months of a left extrapyramidal syndrome with dystonia of this hemibody, with a dysphasia‐dysphonia spastic and ataxic documented in speech therapy compatible with corticobasal degeneration. MRI shows mild leukoaraiosis, The FDG PET‐Scan is also compatible with corticobasal degeneration. EEG done for abnormal movements is suggestive of hepatic encephalopathy in the absence of laboratory abnormality except for a very slight increase in ammonia. Ultrasound suggests the onset of liver disease. After 6 months of treatment of encephalopathy there is a slight clinical improvement. After one year of treatment the patient becomes totally autonomous with complete regression of neurological signs, dysexecutive disorders and social cognition deficits and PET‐FDG has normalized. 36 months later he is totally autonomous and is back to works as a historical tour guide.ConclusionIt is impossible for us after 36months of follow‐up to determine whether the metabolic disease has unmasked a degenerative disease early or has simulated it. We review some possible false positive situations on FDG PET‐Scan. DAT‐Scan will be done.
Glial and neuronal mechanisms contributing to differential risks in TREM2 R47H and R62H variants in Alzheimer’s Disease
Authors: Fancy Nurun N , Willumsen Nanet , Tsartsalis Stergios , Khozoie Combiz , Mcgarry Aisling , Muirhead Robert , Schneegans Eleonore , Davey Karen , Chau Vicky , Smith Amy , Thomas Michael , Scotton William J. , Hardy John A. , Huh Dann , Jackson Johanna , Matthews Paul M 
Published: December 2023

AbstractBackgroundCoding variants in the microglial TREM2 ectodomain differentially (R47H> R62H) increase the risk of Alzheimer’s disease (AD). To define mechanisms responsible in glia and neurons, we aimed to characterise neuropathology and transcriptomic responses in heterozygotes for these TREM2 variant alleles and for common allele homozygotes (CV) in non‐diseased (n = 16) and AD (n = 42) brain cortical tissue from 58 donors.MethodUsing immunohistochemistry (IHC) and imaging mass cytometry (IMC), we characterised neocortical b‐amyloid and AT8/PHF1 pTau pathology with CV (n = 30) and the R47H (n = 11) or R62H (n = 17) TREM2 carriers. We performed single nuclear RNA sequencing to test for the differential gene expression (DGE) in TREM2 and CV cortical tissues with greater 4G8+ b‐amyloid‐ or PHF1+ pTau‐immunostaining.ResultThere was a two‐fold increase in 4G8+, a three‐fold reduction in AT8+ but no change in PHF1+ immunostaining with AD in both variants versus CV. We found a reduced expression of genes associated with TREM2 function in R47H carriers relative to CV however enhanced microglial activation in R62H carriers. This was associated with an up‐regulation of pathways such as ‘neuroinflammation signalling pathway’ in R62H not seen in R47H. CV astrocytes had little DGE with increasing pathology however both variants (R47H>R62H) had an increased proportion of differentially expressed genes suggestive of a heightened activation state. R47H and R62H astrocytes impacted pathways had opposing actions such as ‘synaptogenesis signalling pathway’ and ‘PDGF signalling’ pathways downregulated in R47H but upregulated in R62H. Neuronal gene expression changes were evident in all variants, however greatly enhanced in R47H in response to 4G8+ b‐amyloid. With increasing PHF1+ pTau gene expression changes were mainly seen in R47H. Excitatory and inhibitory neurons both exhibited DGE in R47H carriers and impacted pathways centred around those involved in ‘synaptogenesis signalling pathway’, ‘SNARE signalling pathway’ and ‘synaptic long term depression’.ConclusionThis analysis identified novel disease‐associated transcriptomic differences in the glial response to TREM2 and the secondary neuronal responses that can explain differences in the genetic AD risk conferred by these two TREM2 risk variants.
Deciphering the Genomic Regulatory Architecture of iPSC Derived Oligodendrocytes from Diverse Ancestries for Alzheimer’s Disease Studies
Authors: Ramirez Aura M , Shepherd Jihanne J , Coombs Lauren , Simon Shaina A. , Moura Sofia , Rajabli Farid , DeRosa Brooke A. , Muniz Maria , Whitehead Patrice , Adams Larry D. , Mena Pedro R. , Illanes‐Manrique Maryenela Z , Starks Takiyah D. , Tejada Sergio J. , Byrd Goldie S. , Cornejo‐Olivas Mario , Feliciano‐Astacio Briseida E. , Rissman Robert A , Wang Liyong , Xu Wanying , Jin Fulai , Griswold Anthony J. , Young Juan I. , Dykxhoorn Derek M. , Vance Jeffery M. 
Published: December 2023

AbstractBackgroundThe effect of variants associated with Alzheimer’s disease (AD) can be influenced by ancestry, which determines the genomic regulatory architecture (GRA). A global understanding of GRA in the context of AD is imperative to interpret the variability associated with AD risk genes across populations. Most studies up to date have focused on studying GRA in European ancestry, in this study we aimed at determining the GRA in African, Amerindian, and European ancestries. Since GRA is cell specific, we developed a human induced pluripotent cells (hiPSC) based model for oligodendrocytes (OLs), a cell type which has limited studies focused on AD.MethodCells from AD patients or non‐cognitively impaired controls with >90% of either Amerindian, African or European global ancestry were differentiated using a modified multi‐stage protocol that promotes the development and enrichment of oligodendrocytes in neural spheroids. After terminal differentiation, cells were collected and lysed to isolate nuclei for Multiomic profiling of chromatin accessibility and transcriptome using Single Cell ATAC and Single Cell RNA‐seq. Additionally, we examined chromatin interactions using Hi‐C analyses.ResultWe identified oligodendrocyte lineage cells at different stages of development ranging from dividing cells with transcriptional profiles consistent with those of oligodendrocyte precursor cells (OPC) to mature myelinating oligodendrocytes. We compared the oligodendrocytes clusters across ancestries, cases versus controls and APOE genotypes to characterize the genomic landmarks and signatures associated with AD related GWAS loci. Astrocytes and neurons were also derived within our 3D spheroids, allowing us to study ancestry‐related cell type specific changes in GRA.ConclusionOur results provide ancestry‐specific insights into oligodendrocyte chromatin structure and gene regulation in the context of AD. These results offer an integrated view of the GRA of a previously overlooked cell lineage that constitute a large population in the central nervous system and is compromised during AD in terms of abundance and function. This will expand the available functional resources for gene identification studies in African American and Hispanic/Latino studies.
French Memory Support System: A Proof‐of‐Concept Study
Authors: Fievre Fadia Johanna , Sweet Lisa , Knoefel Frank , Santos Octavio A , Thomas Neil W. 
Published: December 2023

AbstractBackgroundMild cognitive impairment (MCI) confers a higher risk of developing dementia and may interfere with instrumental activities of daily living (IADLs). The Memory Support System (MSS) is a curriculum and calendar/note‐taking system that has proven effective to sustain independence in IADLs in individuals with MCI and protect mood among support partners. Until recently, the MSS has only been utilized among English‐ and Spanish‐speaking samples.MethodThis study investigated the use of a translated and culturally adapted MSS in four French‐speaking participants with MCI (75% female, age Mean = 69.3 [SD = 5.6], education M = 15 [SD = 2.6]) and their support partners. A within‐subject multiple baseline design (baseline, treatment end and 8‐week follow‐up) in a 10‐session, 2 to 3‐week MSS training schedule was utilized. Outcome measures included treatment adherence as well as self‐ and informant‐report questionnaires of IADLs, cognitively‐relevant everyday abilities, self‐efficacy, anxiety, depression, caregiver burden, and quality of life.ResultBy treatment end and follow‐up, participants with MCI showed improvement in adherence to the MSS calendar (Cohen’s d = ‐3.32 & ‐2.31); IADLs (d = 0.83 & 0.68); everyday abilities requiring memory (d = 0.35 & 0.43) and planning (d = 0.47 & 0.40); self‐efficacy (d = ‐1.43 & ‐1.62); symptoms of depression (d = 0.26 & 0.71) and anxiety (d = 0.09 & 0.2); and quality of life (d = ‐0.71 & ‐0.9). Support partners showed improvement in their own quality of life (d = ‐0.34 & ‐0.85) and depressive symptoms (d = 0.19 & 1.33), while their caregiver burden and anxiety symptoms generally remained unchanged.ConclusionFindings suggest that with appropriate training, French‐speaking participants with MCI can and will use the MSS. This may lead to improvement in their IADLs, some cognitively‐relevant everyday abilities, anxiety symptoms, and self‐efficacy. MSS training may also improve depressive symptoms and quality of life in both participants with MCI and their support partners. Overall, although results are generally consistent with previous studies using the MSS, further research using a larger sample of French speakers with MCI is needed to confirm current findings.
Developing Care Partner Activation Program among Filipino American Care Partners of Persons with Dementia
Authors: Ramos Mary Dioise 
Published: December 2023

AbstractBackgroundAttention must be given to Filipino‐Americans since they are a growing underrepresented population and limited research exists on their healthcare needs, priorities, and research engagement. The broad goal of this project is to address the unique challenges related to the provision of Dementia care among Filipino‐Americans.MethodMixed‐method sequential, transformative design to develop and test a program for care partners to strengthen their abilities to manage care activities, emergency department visits, and hospital admissions who experience disparities in access to care.ResultIn partnership with different Filipino‐American community‐based organizations, leaders were identified to explore capabilities and resources available to initiate the care partner activation program. Major support needed in areas related to: family dynamics and caregiving experience, spiritual and cultural values, communication and understanding of the disease process, advocacy groups, socio‐emotional support, insurance system, and financial concerns.ConclusionEducational opportunities exists for Filipino‐American families and communities related to provision of care among patients with dementia. Community‐based participatory research need to be promoted to encourage families and patients to engage and improve healthcare utilization.