bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychological effects of personalized dementia risk disclosure: The Barcelonaβeta Dementia Prevention Research Clinic study
Authors: Grau‐Rivera Oriol , Sánchez‐Benavides Gonzalo , Suárez‐Calvet Marc , Gispert Juan Domingo , Fauria Karine , Minguillón Carolina , Molinuevo Jose Luis 
Published: January 2025

AbstractBackgroundApproximately 35‐40% of new patients at memory clinics are cognitively intact individuals concerned about their dementia risk. The demand for personalized risk profiling and preventive strategies for those at higher dementia risk is in need of innovative infrastructures. However, disclosing dementia risk estimates raises concerns about potential negative emotional impacts. To address this challenge, the Barcelonaβeta Dementia Prevention Research Clinic, was established to evaluate the risks and benefits of novel prevention infrastructures and the potential impact of dementia risk disclosure. Here we focus on the psychological effects of personalized dementia risk disclosure on cognitively unimpaired individuals with subjective cognitive decline (SCD).MethodParticipants aged 60‐80 with cognitive complaints were pre‐selected using web‐based algorithms. Eligible participants were invited to an in‐person visit and a clinical diagnosis was established after neuropsychological, blood tests and magnetic resonance imaging assessments. Dementia risk over 5 years (%risk) was calculated and disclosed with personalized prevention plans. Impact on depression (CES‐D), anxiety (STAI), and test‐related distress (IGT‐AD) was assessed up to 12 months post‐disclosure. SCD participants were categorized into “high dementia risk” (HDR, %risk>10.8) and “low dementia risk” (LDR, %risk<3.6) groups, based on previous epidemiological evidence. Wilcoxon rank‐sum tests and Spearman’s rank correlation analyzed between‐group differences and correlations at different time points.ResultThe percentage of 5‐years dementia risk was disclosed to 192 participants with SCD. Test‐related distress (IGT‐AD) was consistently higher in HDR (N = 25) vs. LDR (N = 55), while CES‐D and STAI showed no significant differences between groups (Table 1, Figure 1). Similar results were observed in correlation analyses for the entire sample (Table 2). Median CES‐D and STAI‐S values remained below clinically relevant cutoffs for depression and anxiety across all visits.ConclusionDisclosure of dementia risk heightened test‐related distress but did not manifest clinically relevant negative effects in anxiety and depression scales. The potential impact of this psychological response on promoting engagement in preventive behaviors warrants further exploration.
Evaluation of Baseline Diffusion Tensor Imaging Biomarkers in phase 2 multi‐center PROSPECT‐ALZ study
Authors: Svaldi Diana O , Rathore Saima , Cheng Yun‐Ju , Munsie Leanne M , Fleisher Adam S , Brys Mirek , Shcherbinin Sergey 
Published: January 2025

AbstractBackgroundDiffusion Tensor Imaging (DTI) biomarkers are increasingly utilized in clinical trials of Alzheimer’s disease (AD). They have shown promise in detecting AD related changes in white‐matter (WM) integrity (Raghavan et al., 2020) and gray‐matter (GM) microstructure (Ofori et al., 2019). Moreover, DTI‐derived connectome has been shown to be related to tau progression (Vogel et al., 2020). Our study evaluated baseline GM microstructure and WM integrity measures in the PROSPECT‐ALZ trial (NCT05063539) of LY3372689, an O‐GlcNAcase (OGA) inhibitor.MethodsPROSPECT‐ALZ is a phase 2, randomized, double‐blind, multicenter, placebo‐controlled trial in participants with early symptomatic AD and presence of tau pathology measured using flortaucipir PET. Participants who received DTI scans (n = 223, age=73.40 (6.0), MMSE=25.6 (2.3), N female=124) were divided into groups based on visual assessment of flortaucipir images (Fleisher et al., 2021) (negative, n=56 vs positive, n = 144) and cognition (MMSE≤24, n = 81 vs MMSE>24 & MMSE≤29, n=133). Group differences in DTI scalars fractional‐anisotropy (FA), mean‐diffusivity (MD), and freewater‐fraction (FW) were evaluated in 16 GM regions and 9 WM tracts using ANCOVA (α = 0.05, LSmean±SE), adjusting for age and gender. FA and MD values were FW corrected (Conklin et al., CTAD 2023).ResultsVisually positive participants exhibited reduced FA in the hippocampus relative to negative participants (0.289±0.006 vs. 0.322±0.010). Positive participants exhibited increased MD in the hippocampus (1.224E‐03±2.328E‐05 vs. 1.055E‐03±3.692E‐05), isthmus cingulate (9.324E‐04±1.971E‐05 vs 8.440E‐04±3.126E‐05), medial temporal cortex (9.751E‐04±1.801E‐05 vs 8.772E‐04±2.855E‐05), and whole temporal cortex (1.050E‐03±1.707E‐05 vs 9.628E‐04±2.706E‐05). Finally, positive subjects exhibited increased FW in the hippocampus (0.554±0.006 vs 0.511±0.010), isthmus cingulate (0.457±0.006 vs 0.430±0.009), medial temporal cortex (0.475±0.005 vs 0.453±0.008), and whole temporal cortex (0.497±0.005 vs 0.472±0.008). No significant regional differences were found in WM. For MMSE, MD (1.243E‐03±3.141E‐05 vs 1.140E‐03±2.419E‐05) and FW (0.561±0.009 vs 0.529±0.007) in the hippocampus were significantly elevated in the more impaired group.ConclusionDTI was successfully implemented in phase 2 multi‐center PROSPECT‐ALZ study. Cross‐sectional analysis suggests that DTI measures can differentiate individuals based on global tau burden and cognition, presumably capturing differences in cortical microstructure. Future work will focus on multimodal evaluation of longitudinal changes in DTI, tau, and cognition.
Association of Traumatic Brain Injury with All‐cause and Dementia‐related Mortality: the Framingham Heart Study
Authors: Durape Shruti , Burton Rebecca , Joshi Prajakta S. , Chien‐Young Kurtis , Price Eden , Yhang Eukyung , Liu Yulin , Ang Ting Fang Alvin , Devine Sherral A. , Gurnani Ashita S. , Katz Douglas I , Tripodis Yorghos , Alosco Michael L. , Au Rhoda , Dams‐O'Connor Kristen , Mez Jesse 
Published: January 2025

AbstractBackgroundAlthough traumatic brain injury (TBI) is known to be associated with short term mortality, its effects on long‐term mortality remain less clear. TBI is also a well‐known risk factor for dementia. We hypothesized that TBI would be associated with long‐term mortality, particularly dementia‐related mortality.MethodsThe Framingham Heart Study (FHS) is a population‐based cohort study which recruited its original cohort between 1948‐1950, and its offspring cohort between 1971‐1975. Information on TBIs was collected across the lifespan by comprehensive review of medical records, FHS health history updates and exams and self‐report. TBI occurrence and severity were operationalized using modified American Congress of Rehabilitation Medicine and Veterans Affairs/Department of Defense criteria, respectively. Dementia diagnosis was operationalized using Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, and National Institute of Neurological and Communicative Diseases and Stroke/AD and Related Disorders Association criteria. Participants with history of TBI were matched to those without TBI for age and sex, with a 1:3 ratio. Participants who died within a year of TBI were excluded. Cox proportional hazards models assessed TBI risk for all‐cause mortality and cause‐specific competing risk models assessed risk for dementia‐related mortality.ResultsOver the course of study, 72.82% died, with 12.32% of deaths from dementia‐related mortality. 1,688 participants with TBI (Mean age at TBI = 69 (SD = 15.5) years, 59.89% women) and 5,064 age‐ and sex‐matched participants without TBI were followed for an average of 15±12 years after TBI. Hazard ratios (HRs) for all‐cause mortality were 1.09 (95%CI 1.00‐1.20) and 1.66 (95%CI 1.31‐2.09 for mild and moderate‐to‐severe TBI respectively. Hazard ratios (HRs) for dementia‐related mortality were 1.63 (95%CI 1.32–2.02) and 2.67 (95%CI 1.57–4.56) for mild and moderate‐to‐severe TBI respectively. Hazard ratios (HRs) for non‐dementia related mortality were 0.96 (95%CI 0.89–1.04) and 1.15 (95%CI 0.95–1.38) for mild and moderate‐to‐severe TBI respectively.ConclusionIn a multi‐generational community‐based sample followed since the 1940s, mild and moderate‐to‐severe TBIs were associated with all‐cause mortality with the effect driven by dementia‐related mortality.
Factors associated with dementia caregiver burden across multiple Brazilian regions
Authors: Barbosa Matheus Ghossain , de Macedo Marcos Antonio Costa Ferreira , da Mata Fabiana A. F. , Ramos Ari Alex , de Oliveira Júnior Haliton Alves , Bertola Laiss , Ferri Cleusa P. 
Published: January 2025

AbstractBackgroundThe number of people with dementia (PWD) is increasing worldwide, and especially in low‐ and middle‐income countries (LMIC). Dementia’s burden extends beyond mortality and healthcare costs. In LMIC, dementia indirect costs are proportionally higher. In Brazil two thirds of the total dementia costs come from informal caregiving, mainly provided by women who quit their jobs to act as a carer for a relative.MethodThe ReNaDe project assessed dementia’s cost, unmet needs, and investment. We recruited 140 PWD‐caregiver dyads in 17 cities across the 5 Brazilian regions. PWD were selected through their public healthcare system medical charts, we included PWD 60 years and older at any dementia severity. For this analysis we evaluated the total score of the Zarit Burden Interview (ZBI) as our main outcome and used linear regression to test potential associated factors (sociodemographic, behavioral and clinical).ResultWe included 124 participants with complete data. More neuropsychiatric symptoms in the Neuropsychiatric Inventory (β = 2.07, p = 0.000), having an insufficient income to cover all household costs (β = 10.42, p = 0.001) and quitting, but not reducing, a job (β = 6.78, p = 0.045) were associated with higher burden, while having a replacement caregiver (β = ‐9.87, p = 0.001) was associated with lower burden. The caregiver or patient’s sex, age, marital status, skin color, level of education and place of residence (urban or rural) were not associated with burden level. Furthermore, the length of the caregiving role, previous training courses, the length of the dementia diagnosis, whether the caregiver is paid, lives with the patient or reports the dyad as being a target of prejudice were not associated with level of burden. Finally, the patient’s dependence level as assessed by the Katz and the Pfeffer scales were also not associated with burden.ConclusionMost challenges to caregiving don’t appear to directly affect level of burden. More behavioral symptoms are associated with more burden, as is losing a job/income and being the only available caregiver. Caregiver support policies should focus on providing financial support and/or care alternatives to allow for free time, as well as training on how to deal with behavioral issues.
The role of risk factors in development of dementia in the Czech Republic
Authors: Kučera Matěj 
Published: January 2025

AbstractBackgroundIn 2020, the Lancet Commission introduced a meta‐analysis featuring a life course model encompassing 12 potentially modifiable risk factors for dementia: low education, hypertension, hearing impairment, smoking, obesity, depression, physical inactivity, diabetes, low social contact, alcohol consumption, traumatic brain injury, and air pollution. The aim of this study is to investigate the association of the aforementioned risk factors with the incidence of dementia with the incidence of dementia in the Czech Republic, capitalizing on a nation‐wide population‐based study.MethodThe analysis was based on data from Survey on Health, Ageing and Retirement in Europe (SHARE). Participants were included in the analytical sample if they fulfilled the following criteria: age of entry to the study of 65 years and higher, participation in at least two waves of SHARE, at least two measurements of cognitive function, and dementia‐free state at baseline. To study the association of risk factors with the incident dementia, we utilized Cox hazards models estimating hazard ratio (HR) with 95% confidence interval (CI).ResultOut of the ten risk factors, five presented an association with dementia, when adjusted for age, sex and birth cohort. The strongest hazard was found for physical inactivity, followed by low education, diabetes mellitus, depression and living alone. There was a tendency of sex being an effect modifier in the association of alcohol use, living alone and low education with incident dementia.ConclusionIn the present study, capitalizing on more than 3,500 community‐dwelling older adults, we found an association for only half of the proposed risk factors. More systematic attention should be paid to mitigating the negative effect of dementia risk factors as this could contribute to the reduction of incident dementia cases in the Czech Republic, Future studies should replicate the findings of this study in other CEE countries and ideally should have a longer follow‐up period to prevent reverse causation.
Association of markers of endothelial function with blood‐based biomarkers of Alzheimer’s Disease in individuals of admixed ancestry
Authors: Ray Nicholas R. , Kurup Jiji T. , Hamilton‐Nelson Kara L. , Griswold Anthony J. , Kunkle Brian W. , Bush William S. , Tosto Giuseppe , Ogunniyi Adesola , Akinyemi Rufus , Haines Jonathan L. , Byrd Goldie S. , Vance Jeffery M. , Pericak‐Vance Margaret A. , Beecham Gary , Reitz Christiane 
Published: January 2025

AbstractBackgroundWhile Alzheimer disease (AD) is the most common cause of dementia, it has long been recognized that cardiovascular and cerebrovascular health plays a major role in cognitive function. As such, the development of accessible biomarkers to assess vascular cognitive impairment and dementia (VCID) is a key step towards identifying effective prevention and treatment strategies. While a set of blood‐based VCID biomarkers has been under investigation, there is a critical paucity of data from genetically admixed individuals. As such, the role and impact of genetic ancestry and the validity these biomarkers in diverse populations is unknown. To address this, we assessed the associations between biomarkers of endothelial function, AD, and genetic ancestry.MethodBiomarkers include amyloid beta (Aβ)42/40 and phosphorylated tau (p‐tau)/Aβ42 ratios for AD, and vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), basic fibroblast growth factor (bFGF), vascular cell adhesion protein 1 (VCAM‐1), and intercellular adhesion molecule‐1 (ICAM‐1) for VCID. Biomarkers were collected from 256 admixed individuals sampled from Puerto Rico and Peru, and African Americans from the US. Including age and sex as covariates, mixed effects regressions were modeled separately predicting AD biomarker ratios by all VCID biomarkers, degree of African ancestry, and APOE genotype.ResultAβ42/40 ratio was associated with VEGF (β = ‐1.97×10‐5, P = .002), bFGF (β = ‐2.10×10‐4, P = .02), VCAM‐1 (β = 1.53×10‐5, P = 9.02×10‐4), ICAM‐1 (β = ‐3.72×10‐5, P = .01) and degree of African ancestry (β = 0.01, P = .04). Similarly, p‐tau/Aβ42 ratio was associated with VEGF (β = 0.01, P = .001), bFGF (β = 0.18, P = 5.21 × 10‐5), VCAM (β = ‐0.005, P = .02), and ICAM (β = 0.02, P = .02). No significant associations were observed for PlGF.ConclusionBlood‐based measures of endothelial function markers VEGF, bFGF, ICAM‐1, and VCAM‐1 are associated with both the p‐tau/Aβ42 and Aβ42/40 ratios, the latter of which is also modulated by degree of African ancestry. These observations support the notions that these CVD biomarkers may be valuable biomarkers for cognitive health in admixed individuals and inform the design of clinical trials for biomarker development across populations.
Can Routine Anti‐Inflammatory Medications Reduce Population Dementia Risk?
Authors: Richardson Connor Duncan 
Published: January 2025

AbstractBackgroundEvidence from epidemiological and clinical studies of the effect of anti‐inflammatory medication on dementia risk has been mixed. Over the past two decades there has been recurring epidemiological evidence that the use of NSAID’s for chronic inflammatory conditions is associated with a lower incidence of dementia.MethodCognitive Function and Ageing Study (CFAS) undertook baseline interviews in populations aged 65+ years in England and Wales (1989‐1994). Three areas (CFAS I) were selected for new sampling two decades later (2008‐2011) with same geographical boundaries, sampling and approach methods (CFAS II). At 2 years CFAS I interviewed 5,156 (76% response) with 5,288 interviewed in CFAS II (74% response). Data on medication use and dementia status was assessed at each wave.ResultLow dose aspirin (< 150 mg) use was associated by a reduction in dementia incidence rate (IR) in women from 60.99 (95% CI: 47.6, 78.2) per 1000 person‐years to 44.1 (95% CI: 2.0, 45.4) in 1993 and from 44.5 (33.7, 58.7) to 38.6 (27.2, 54.9) in 2013. No reduction in men was found.ConclusionThis study shows evidence that routine use of low‐dose aspirin reduces population risk of dementia in women. Mixed results in men show further analysis is needed to asses the effect over a longer follow‐up with a broader range of anti‐inflammatory medication.
Association of late‐life cognition and brain pathology with anti‐hypertensive medications
Authors: Sood Ajay , Capuano Ana W. , Mehta Rupal I. , Barnes Lisa L. , Bennett David A. , Arvanitakis Zoe 
Published: January 2025

AbstractBackgroundHypertension is a risk factor for cognitive impairment and dementia. Anti‐hypertensives (AHT) are commonly used in old age, but their association with cognition and brain pathology is not well understood.MethodTo investigate the relation of AHT with change in cognitive function and postmortem brain pathology, we evaluated 4,207 older persons without known dementia at enrollment and a subset of 1880 participants who died and came to autopsy. Participants underwent yearly clinical evaluations that included an assessment of medications and neuropsychological testing across five cognitive domains. The participants who died underwent neuropathologic evaluation of neurodegenerative (amyloid, Lewy bodies, Tar DNA binding protein ‐43, hippocampal sclerosis) and cerebrovascular pathology (infarcts, amyloid angiopathy, atherosclerosis, or arteriosclerosis).ResultOver 3,600 participants were using AHT, of which 64% were using diuretics, 55% beta‐blockers, 50% calcium channel blockers, 44% angiotensin‐converting enzyme inhibitors, and 29% angiotensin receptor blockers any time during the study. Using a linear mixed effect model adjusted for age, sex, race and education, AHT users at study entry had a higher level (estimate = 0.106, SE = 0.025, p <0.001) and a slower decline of global cognition compared to non‐users (estimate = 0.013, SE = 0.013, p = 0.013). Analyses of cognitive domains showed a similar pattern with a higher level at study entry and a slower decline of semantic memory (estimate = 0.025, SE = 0.007, p<0.001). The use of AHT was not associated with change in other domains. In a separate analysis including only participants with neuropathology, AHT use was associated with lower tau tangle density (estimate = ‐0.20, SE = 0.07, p = 0.005) after adjusting for age at death, sex, and race. The use of AHT was not associated with other neurodegenerative pathologies or cerebrovascular pathology.Conclusion: ConclusionsAHT use in old age is associated with slower cognitive decline and fewer tau tangles in the brain. Future research will need to replicate these findings and explore underlying mechanisms by which AHTs appear to have beneficial effects on cognition.This work is supported by the following NIH grants: P30AG10161, P30AG072975, R01AG15819, R01AG17917, 5R01NS084965, 1RF1AG059621, 1RF1AG074549, R01 AG22018.
Cognitive and physical activity are related to increased cognitive reserve in a large memory clinic cohort
Authors: Bocancea Diana I. , van Loenhoud Anna C. , Calandri Ismael Luis , Venkatraghavan Vikram , Groot Colin , de Boer Casper , Pijnenburg Yolande A.L. , Barkhof Frederik , van der Flier Wiesje M. , Ossenkoppele Rik 
Published: January 2025

AbstractBackgroundCognitive resilience, the ability to maintain cognitive function despite atrophy, is an important area of research in Alzheimer Disease (AD) and other neurodegenerative disorders. Life‐style factors such as participation in cognitively stimulating activity and physical activity are hypothesized to foster neural connections and enhance reserve, consequently sustaining resilience against cognitive loss. Here, we characterize cognitive and physical activity levels in a large memory clinic cohort with multiple etiologies. Further, we investigate the role of these two factors in resilience to brain atrophy across the AD continuum.MethodsWe included 4033 individuals from the memory clinic‐based Amsterdam Dementia Cohort with multiple diagnoses (Table 1). Levels of (lifetime, past and current) cognitive activity, and (current) physical activity were assessed through self‐reported questionnaires (Cognitive activity Questionnaire, CAQ and Physical Activity Scale for the Elderly, PASE). First, we tested differences in CAQ/PASE scores across the different diagnostic groups in the overall sample using linear models adjusted for age and sex. Second, zooming in on the AD continuum (i.e. amyloid‐β‐positive CU, MCI, or AD), we used linear mixed effects models adjusted for age and sex to assess whether CAQ/PASE had an interactive or additive effect on concurrent cognition and rate of decline (MMSE, memory and executive functioning domains) next to temporoparietal brain atrophy.ResultsOverall, there were differences in lifetime CAQ, current CAQ and current PASE between groups, but not in past CAQ (Figure 1). Within the AD continuum, we found that higher CAQ and higher PASE scores were associated with better cognition at baseline (Table 2). We did not find an interactive effect with brain atrophy on decline, nor an additive effect on the slope in cognition (i.e. higher activity was not associated with reduced speed of decline at similar atrophy levels).ConclusionCross‐sectional effects in the AD continuum are suggestive of a reserve effect in maintaining cognition in disease. While associations with current CAQ and PASE might be (partially) explained by reverse causality, the observed effects with past CAQ suggest that early and mid‐life participation in cognitively stimulating activities provide a cognitive benefit in AD.