bluuebunny/crossref_metadata_2025_split huggingface dataset:
The electronic Person‐Specific Outcome Measure (ePSOM) in the US population: What matters to individuals the most about their brain health
Authors: Saunders Stina , Jannati Ali , Gomes‐Osman Joyce Rios , Pobst Jeff , Morrow William Isaiah , Tobyne Sean , Showalter John , Pascual‐Leone Alvaro 
Published: January 2025

AbstractBackgroundIt is essential that both drug and lifestyle‐based interventions aimed at delaying the functional decline in conditions like Alzheimer’s disease and related dementias (ADRDs) capture change in functioning that incorporates the person’s voice. Such brain health priorities can vary across populations and it is unclear to what degree findings from the ePSOM program in the UK might apply to the US.MethodsWe conducted an online nationwide study to understand what matters to people aged 50 and older about their brain health in the US. The ePSOM US survey (May 2023‐Jan 2024) collected primarily free‐text responses, alongside sociodemographic information, self‐reported neurodegenerative disease diagnosis, and self‐reported confidence in managing personal priorities. We examined [1] the difference in relative frequency of specific words for key sociodemographic groups and comparable UK/US populations, and [2] compared the differences in confidence scores between the diagnosis and non‐diagnosis groups (gender and age controlled) using the Mann–Whitney U test.ResultsA total of 764 participants provided over 11,522 free text responses. Most were female (69%), married (63%), had higher education (64%) and did not report neurodegenerative disease diagnosis (93%); mean age 63.17 (SD = 8.52) in women, 62.99 (SD = 8.30) in men. There were statistically significant differences (p<0.05) in the pattern of responses between sub‐groups: younger/older; male/female; higher/lower education and UK/US populations but not between those with and without a diagnosis. Individuals with a diagnosis rated their confidence significantly lower (median score 20/25, IQR = [17,23]) than those without a diagnosis (median score 24/25, IQR = [22,25]; U = 8908, p<0.05).ConclusionOur study demonstrates that there is heterogeneity in the outcomes that matter to individuals about their brain health across sociodemographic groups and UK/US populations. These findings support the notion that emerging treatments in ADRD should be developed with a person‐centred approach that accounts for sociodemographic factors, and that confidence may be an appropriate construct to measure self‐perceived ability. Efforts such as the ePSOM program offer an evidence‐based method to capture and monitor personally meaningful treatment targets.
Can a picture description differentiate the nonfluent/agrammatic and logopenic variants of primary progressive aphasia?: Evidence from Catalan‐Spanish bilinguals
Authors: Pugalenthi Lokesha , Montagut Núria , Marques‐Kiderle Sonia Karin , Rodriguez Camille Wagner , Iyer Ami , Chaires Jan Christian Holst , Motta Whendy Avila , Filella‐Merce Júlia , Zhu Nuole , Rubio‐Guerra Sara , Illán‐Gala Ignacio , Borrego‐Écija Sergi , Lladó Albert , Fortea Juan , Lleo Alberto , Sanchez‐Valle Raquel , Santos‐Santos Miguel A , Grasso Stephanie M 
Published: January 2025

AbstractBackgroundPrimary progressive aphasia (PPA) is a language‐based dementia linked with underlying Alzheimer’s disease (AD) or frontotemporal dementia. Clinicians often report difficulty differentiating between the logopenic (lv) and nonfluent/agrammatic (nfv) subtypes, as both variants present with disruptions to “fluency” yet for different underlying reasons. In English, acoustic and linguistic markers from connected speech samples have shown promise in machine learning (ML)‐based differentiation of nfv from lv. To our knowledge, this approach has not been evaluated in other languages nor in the context of bilingualism.MethodTwenty‐four Spanish‐Catalan bilingual patients (lv = 15, nfv = 9) were asked to describe a picture (WAB Picnic Scene) in both their dominant and non‐dominant language. From the participant’s recorded response, 10 acoustic features were derived with PRAAT and 15 linguistic features were derived with the Natural Language Processing (NLP) tools SpaCy and CLAN. A similarity score between the image and patient’s transcription was derived with the Vision‐Language model CLIP. The acoustic features, linguistic features, and CLIP scores, were separately fed into ML classification algorithms for differentiating nfv from lv in participants' dominant and non‐dominant samples.ResultThe acoustic‐based classifiers achieved classification accuracy (F1 score) of 59% in the dominant and 86% in the non‐dominant language, respectively. The linguistic‐based classifiers achieved F1 scores of 73% in the dominant and 77% in the non‐dominant language, respectively. The CLIP‐based classifier achieved F1 scores of 82% in the dominant and 82% in the nondominant language, respectively. The acoustic and linguistic classifier performed 25% (p = 0.077) and 4% (p = 0.18) better given only non‐dominant samples compared to only dominant samples.ConclusionTaking advantage of recent advances in multilingual NLP, we achieved promising and effective differentiation of nfv from lv for Spanish‐Catalan bilingual patients using a nearly automated pipeline. Interestingly, our acoustic and linguistic‐based classifiers performed better given responses from a patient’s non‐dominant language, and the acoustic feature set was more accurate in discriminating between nfv and lv compared to the linguistic model. Future directions include examining patterns in a larger sample size and comparison of performance on different types of connected speech tasks.
Remote Cognitive Assessment for Preoperative Evaluation in Older Adults: Feasibility and Associations with Subjective Cognitive Concerns
Authors: Wise Amy B. , Dhanam Sreya , Zhou Sara , Sinha Anika , Hernandez Kaylee , Pawar Niti , Boxer Adam L. , Chang Odmara L Barreto , Staffaroni Adam M. 
Published: January 2025

AbstractBackgroundPostoperative complications of major surgical interventions include delirium. Delirium is a risk factor for dementia, and in some cases, may signal underlying neuropathological processes. Cognitive tests that accurately predict post‐operative outcomes could identify patients with cognitive vulnerabilities who may benefit from preoperative counseling and postoperative interventions. Unfortunately, in‐person presurgical cognitive evaluations are often not available, but digital technologies may improve access. In this pilot study, we evaluate the feasibility of utilizing a smartphone app to conduct preoperative remote cognitive assessment in patients undergoing spine surgery. We also evaluate the relationship of app‐based assessments with subjective cognitive concerns.MethodWe enrolled 30 older adults ( = 65 years old) who were scheduled for elective spinal surgery anticipated to last at least three hours. On the ALLFTD Mobile App, participants completed a battery of cognitive tests, a measure of subjective cognitive concerns (12‐item self‐reported everyday cognition scale, Ecog‐12), and a user experience survey. A subset (N = 12) had a study partner complete the 41‐item Ecog, reporting on observed changes in cognitive function over a 10‐year period prior to the surgery. Linear regressions adjusted for age evaluated the associations between subjective cognitive concerns and the objective app‐based outcomes (Flanker task and a composite of several measures).ResultAverage age of participants was 71.2 years (SD = 4.4); 46.1% were women and 75% identified as White. Most (96%) participants indicated that the time required to complete the app assessments was acceptable, 77% indicated that the app instructions were clear, and all participants indicated that the text on the app was large enough to read comfortably. Participants' subjective cognitive concerns (ECog‐12) were significantly associated with a composite of app tasks (ß = ‐0.48, p = 0.01). The executive functioning domain of the study partner Ecog was significantly associated with patient performance on an app‐based executive functioning task (ß = 0.75, p = 0.007).ConclusionThese findings support the feasibility of remote preoperative assessments in older adults using smartphones. The study also provides preliminary support that these measures can objectively quantify self‐ and partner‐reported cognitive concerns. Future work will explore associations with postoperative outcomes.
Association between medial temporal and neocortical Tau SUVR across tau imaging agents: HEAD Study
Authors: Rahmouni Nesrine , Tissot Cécile , Hosseini Seyyed Ali , Macedo Arthur C. , Servaes Stijn , Therriault Joseph , Lussier Firoza Z , Arias Jaime Fernandez , Wang Yi‐Ting , Stevenson Jenna , Trudel Lydia , Gauthier Serge , Baker Suzanne L. , Pascoal Tharick Ali , Rosa‐Neto Pedro 
Published: January 2025

AbstractBackgroundThe association between medial temporal and neocortical SUVR depends on availability of cortical tau. However, tracer differences in affinity and off‐target binding might interfere in these associations. Here, we examined the association between medial temporal and neocortical SUVR using voxel‐based approach.MethodWe included 92 individuals (46 Cognitively Unimpaired and 46 Cognitively Impaired) from the HEAD Study recruited at McGill University. All individuals were assessed for amyloid‐ß (Aß) deposition using [18F]AZD4694‐PET and at least two tau‐PET ligands ([18F]MK6240 and [18F]Flortaucipir). A subset of 25 individuals had 2 additional tau‐PETs scans: [18F]RO948 and [18F]PI‐2620. Voxel‐based regression models evaluated the relationship between PET tracers’ uptake in the entorhinal cortex (EC) and its association with the tracer’s uptake in later Braak regions. All models include Aß‐PET, age, and sex as covariates and RFT was used to account for multiple comparisons. Additionally, we extracted the number of significant voxels in the associations within each Braak regions.ResultPositive associations were observed between tau‐PET SUVR in the EC (Figure 1). [18F]MK6240 EC was correlated with tracer uptake in the whole cortex. [18F] Flortaucipir was associated with tracer uptake in similar regions, albeit showing a lower t‐value. [18F]PI2620 EC uptake correlated with binding in regions Braak II‐V. Finally, [18F]RO948 was associated with uptake in regions Braak II‐IV. We further validated our results by extracting the number of significant voxels in each Braak regions. [18F]MK6240 showed the highest percentage of spatial extent of tau spreading in all Braak regions, followed by [18F]Flortaucipir and [18F]RO948. [18F]PI2620 demonstrated the lowest spatial extent.Conclusion[18F]MK6240 SUVR better predicted the spatial extent of tau spreading in the whole cortex. Results were concordant at the voxel and region‐on‐interested levels. [18F]Flortaucipir showed similar results, in lower magnitude. Finally, [18F]PI2620 and [18F]RO948 were further lower. Nevertheless, the later analyses were conducted in a smaller sample. Our results support the concept that MK6240 affinity possibly explain these results.
Driving Tau Pathogenicity Seeding ‐ How Fibril Structure and Post‐Translational Modifications Alter Seeding Capacity
Authors: Kasen Alysa , Breton Libby , Meyerdirk Lindsay , Lövestam Sofia , McPhail Jacob , Louwrier Ariel , Scheres Sjors , Henderson Michael 
Published: January 2025

AbstractBackgroundThe accumulation of hyperphosphorylated, aggregated tau in neurons is one of the hallmarks of Alzheimer’s disease (AD). Recent work in structural biology has solved the structure of tau fibrils in several tauopathies and found that the structure of the tau fibrils varies between diseases, but fibril structure is conserved among patients within the same disease, suggesting fibril structure relates to its pathogenicity. Tau fibrils derived from AD brain (AD PHFs) seed AD‐like pathology in wild‐type mice, yet efforts to recapitulate this seeding with recombinant fibrils have failed. The differential capacity of tau fibrils to seed pathology also supports the relevance of tau structure to its pathogenicity. We hypothesized that recombinant fibrils that recapitulate the core region structure of AD tau will show similar seeding capacity to AD tau, with PTMs playing a modulatory role.MethodsWe took advantage of recently developed recombinant tau fibrils with diverse structures to investigate how tau fibril structure and PTMS are related to tau seeding capacity in primary cortical neurons. Fibrils of interest from the screen were then assessed through hippocampal injection into wild‐type and MAPT knock‐in mice.ResultsIn‐vitro screening showed that fibrils more closely resembling the core structure of an AD PHF had a higher seeding capacity than other fibrils. However, the replication of the core structure alone in truncated fibrils is not sufficient to fully replicate the seeding capacity of AD PHFs, indicating that the region outside of the core structure, containing PTMs, likely plays an essential role in pathology seeding. This finding was replicated in the seeding model into wild‐type and MAPT KI mice. We also found that tau fibrils containing PTMs had a higher seeding capacity than full length fibrils without PTMs. However, the presence of PTMs alone was not enough to fully replicate the seeding capacity of AD PHFs.ConclusionsThe structure and PTM patterns of tau fibrils appear to be closely tied to fibril pathogenicity, with recombinant fibrils more closely resembling AD PHFs having a more similar seeding capacity. We believe that the generation of fibrils closely resembling AD PHFs can lead to improved model systems of tau pathology in AD.
APOEε4, blood glucose levels, peripheral inflammation, and cognitive change among postmenopausal women in the Women’s Health Initiative
Authors: Klinger Hannah M , Coughlan Gillian T , Hayden Kathleen M. , Manson JoAnn E. , Wild Robert A , Jung Su Yon , Casanova Ramon , Liu Longjian , Shadyab Aladdin H. , Wactawski‐Wende Jean , Schembre Susan M , Liu Simin , Rapp Stephen R. , Resnick Susan M. , Baker Suzanne L. , Buckley Rachel F 
Published: January 2025

AbstractBackgroundOlder women have a higher prevalence of Alzheimer’s disease relative to comparably aged men. Although the biological mechanisms driving this sex difference remain elusive, emerging data suggest that longevity, APOEε4, inflammation, and blood glucose levels may play roles. Our objective was to examine the associations of APOEε4, high sensitivity‐C‐reactive protein (hs‐CRP), and fasting blood glucose levels with cognitive changes over time among women enrolled in two ancillary studies of the Women’s Health Initiative (WHI).MethodWe identified 2,534 women from WHIMS‐ECHO (Enrollment agemean(SD) = 70(4) years) and 400 women from WHIMS‐Y (Enrollment agemean(SD) = 52(1) years) with baseline data available for APOEε4 carriage, plasma hs‐CRP, and serum‐measured fasting blood glucose, and longitudinal cognitive measures, including the TICSm, EBMT, EBMT‐recall, verbal fluency, Digit Span Backwards, and CVLT scores. A series of linear mixed‐effects models were used to examine these three predictors’ main and interactive effects on longitudinal cognition changes, adjusting for age, education level, body mass index, diabetes status, WHI randomization arm, and cohort (including random intercepts and slopes). Hs‐CRP levels were log transformed and glucose levels were inverse transformed. All data were z‐scored.ResultAPOEε4 carriage was associated with steeper cognitive decline on the TICSm, EMBT, EBMT‐recall, verbal fluency, Digit Span Backwards, and CVLT‐correct scores compared to non‐carriers (Table 1). APOEε4 carriers with lower blood glucose levels showed steeper cognitive decline on TICSm and EBMT‐recall scores but less intrusions on the CVLT compared to APOEε4 carriers with higher glucose levels. Additionally, APOEε4 carriers with higher levels of hs‐CRP demonstrated a steeper decline on CVLT‐correct scores relative to APOEε4 carriers with lower hs‐CRP levels. Women with higher levels of hs‐CRP alone exhibited steeper cognitive decline on the EBMT and Digit Span Backwards test compared to women with lower hs‐CRP. Women with higher levels of both hs‐CRP and blood glucose also showed significantly faster rates of decline on TICSm and verbal fluency scores relative to women with higher hs‐CRP who had lower blood glucose levels. Three‐way interaction tests (APOEε4*CRP*glucose) did not yield significant results.ConclusionThese findings underscore the complex interplay between genetic risk, metabolic and inflammatory health, and their associations with cognitive decline among older women.
A polygenic score for executive function correlates with differential rates of cognitive decline
Authors: Dehghani Nadia , Massimo Lauren , Rhodes Emma , Cousins Katheryn A Q , Boyle Rory , Emrani Sheina , Phillips Jeffrey S , Ohm Daniel T , Matyi Melanie A , Van Deerlin Vivianna M , Irwin David J , McMillan Corey T 
Published: January 2025

AbstractBackgroundExecutive dysfunction is a hallmark clinical feature of frontotemporal degeneration (FTD). Genome‐wide association studies have identified genetic variants, and resulting polygenic scores (PGS), related to executive function (EF) in population studies. We evaluated whether EF‐PGS correlates with differential rates of cognitive decline in FTD.MethodWe computed an EF‐PGS based on a prior EF‐GWAS for 375 individuals genotyped in the Penn Integrated Neurodegenerative Disease Database with a diagnosis consistent with FTD including bvFTD, naPPA, svPPA or cognitively normal. We investigated the association between EF‐PGS tertiles and cognitive decline over time (letter‐guided fluency, n = 257; semantic fluency, n = 185 with animals, n = 171 with vegetables; backwards digit span, n = 140; Boston Naming Test, n = 179) in linear mixed effects models adjusting for age at baseline, sex, education years and baseline cognitive score.ResultOverall, the low‐PGS tertile exhibited faster decline over time in letter‐guided fluency assessed by the number of correct words beginning with the letter “F” produced in 1‐minute (t = −2.77, df = 96, p = 0.007 compared to the intermediate‐PGS tertile; t = −2.41, df = 99, p = 0.018 compared to the high‐PGS tertile). There was no significant differential rate of decline between EF‐PGS tertiles in measures of semantic fluency, confrontation naming (Boston Naming Test) or working memory (backwards digit span), with the caveat that fewer participants in our cohort had these measures.ConclusionOur results suggest that lower EF‐PGS correlates with faster cognitive decline over time, particularly specific to letter‐guided fluency. This PGS, based on genetic variants associated with EF, may reflect the domain‐specific decline in cognitive performance observed across FTD syndromes.
Associations of Vision Impairment with Cognitive Impairment Among Stroke Survivors in the Atherosclerosis Risk in Communities Study
Authors: Hreha Kimberly , Ashner Marissa , Peskoe Sarah , Downer Brian , Reistetter Timothy , Whitson Heather 
Published: January 2025

AbstractBackgroundVision impairment is a common complication of stroke, which has been linked to cognitive decline in stroke survivors. Little is known about how specific types of vision impairment influence the relationship between stroke and dementia. The aims of this project were: (1) to characterize the prevalence of both pre‐stroke and stroke‐related vision impairment(s) among stroke survivors with and without mild cognitive impairment (MCI) or dementia, and (2) to determine associations of vision impairment with cognitive impairment, depression, and physical performance.MethodsData from the Atherosclerosis Risk in Communities Study (ARIC) were studied. Our analytic cohort included ARIC participants who had both a stroke hospitalization captured via surveillance prior to dementia and cognitive measures from Visits 5‐6. Participants without a retinal exam prior to their stroke were excluded. We determined the prevalence of specific types of vision impairments and ocular conditions as well as patient‐level demographics, stratified by cognitive status. Multivariable linear and logistic regressions, controlling for age, sex, and education, modelled the relationship between types of vision impairment and each outcome.ResultsOur final cohort contained n = 227 individuals, with mean (standard deviation [SD]) age of 78.5 (5.56) years. Participants were primarily male (54.2%) and white (73.6%), with a mean of 14.5 (SD = 4.24) years of education. 15.9% had a pre‐existing vision impairment (e.g., glaucoma), and 18.5% developed a stroke‐related vision impairment (e.g., diplopia). Vision impairment (all types) was significantly associated with dementia (adjusted odds ratio (OR) = 2.17, 95% confidence interval (CI) = 1.07‐4.41), but not MCI (OR = 1.23, 95% CI = 0.07‐2.20). In assessing pre‐stroke vision impairment and stroke‐related vision impairment separately, there were no statistically significant associations with any outcomes.ConclusionsThis study informs the rates of types of well‐characterized vision impairments in a group of stroke survivors. There is a 2‐fold increase in the likelihood of dementia among stroke survivors with vision impairment as compared to those without vision impairment, defined as either pre‐stroke or stroke‐related impairment. Future data collection in larger, more diverse populations is needed to determine how specific types of vision impairments in stroke survivors associate with cognitive impairment as well the likelihood of depression or worse functional status.
The impact of dementia medications on medical outcomes in older adults
Authors: DeMercy Haylie M. , Brenner Colleen A. 
Published: January 2025

AbstractBackgroundDementia often includes behavioral and psychological symptoms such as behavioral excitement, mood disorders and psychosis. Antipsychotic drugs are often prescribed alone or in conjunction with cognitive enhancers, however, these drugs can increase risk for adverse cardiovascular/cerebrovascular events (MACCE) and mortality. This study investigated whether those prescribed antipsychotics and/or cognitive enhancers experienced a MACCE more quickly and if medication dosage impacts survival time.MethodsData from 1,126 patients aged ≥ 50 or older, with a diagnosis of dementia and behavioral symptoms were studied. We compared four different models of BPSD treatment using Cox Regression Analyses.ResultsResults indicated that there was a significant effect of type of medication on duration until MACCE, (p < .001). The odds of experiencing a MACCE were 96.3% higher for individuals treated with both antipsychotics and cognitive enhancers (p < .001), 78.7% higher for those treated with only antipsychotics (p < .001), and 31.9% higher for those treated with only cognitive enhancers (p = .003). There was also a significant effect of dosage on duration until MACCE, p < .001. The odds of experiencing a MACCE sooner were 238% higher for those on high doses of antipsychotics (p < .001), and 48% higher for individuals on a medium dose (p < .001) compared to low doses. There was also a significant effect of cognitive enhancer dosage on duration until a MACCE, (p < .001). The odds of experiencing a MACCE were 76% higher for individuals on high doses of cognitive enhancers (p < .01) and 38% higher for those on a medium dose (p < .05) compared to low doses.ConclusionThere is a clear increased risk of adverse medical outcomes when using antipsychotic and cognitive enhancing drugs in the treatment of dementia with behavioral symptoms. The use of antipsychotic medication, particularly at high doses, was associated with the greatest risk of an adverse medical outcome. Use of antipsychotic medications in this population should include close monitoring for cardiovascular/cerebrovascular events.