bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma metabolic profiles predict future dementia and dementia subtypes: a prospective analysis of 274,160 participants
Authors: He Xiao‐Yu , Qiang Yi‐Xuan , YOU JIA , Cheng Wei , Yu Jin‐Tai 
Published: January 2025

AbstractBackgroundBlood‐based biomarkers for dementia are gaining attention due to their non‐invasive nature and feasibility in regular healthcare settings. Here, we explored the associations between 249 metabolites with all‐cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VaD) and assessed their predictive potential.MethodThis study included 274,160 participants from the UK Biobank. Cox proportional hazard models were employed to investigate longitudinal associations between metabolites and dementia. The importance of these metabolites was quantified using machine learning algorithms, and a metabolic risk score (MetRS) was subsequently developed for each dementia type. We further investigated how MetRS stratified the risk of dementia onset and assessed its predictive performance, both alone and in combination with demographic and cognitive predictors.ResultDuring a median follow‐up of 14.01 years, 5,274 participants developed dementia. Of the 249 metabolites examined, 143 were significantly associated with incident ACD, 130 with AD, and 140 with VaD. Among metabolites significantly associated with dementia, lipoprotein lipid concentrations, linoleic acid, sphingomyelin, glucose, and branched‐chain amino acids ranked top in importance. Individuals within the top tertile of MetRS faced a significantly greater risk of developing dementia than those in the lowest tertile. When MetRS was combined with demographic and cognitive predictors, the model yielded the area under the receiver operating characteristic curve (AUC) values of 0.857 for ACD, 0.861 for AD, and 0.873 for VaD.ConclusionWe conducted the largest metabolome investigation of dementia to date, for the first time revealed the metabolite importance ranking, and highlighted the contribution of plasma metabolites for dementia prediction.
Exposure to perfluoroalkyl substances as a novel risk factor for cognitive impacts in older Asian Americans
Authors: Liu Shelley , Chen Yitong , Manz Katherine , Buckley Jessie , Parekh Ankit , Zhu Carolyn W. , Spat‐Lemus Jessica , Kukull Walter A. , Sano Mary , Li Clara 
Published: January 2025

AbstractBackgroundEnvironmental pollutants, called perfluoroalkyl substances (PFAS) have been linked to adverse cardiometabolic outcomes, immune dysfunction and cancer risk, but their associations with adult cognition are unknown. Nearly everyone in the United States has detectable levels of PFAS in their blood, but our prior work found that Asian Americans have the highest exposure burden. As Asian Americans fastest growing segment of older adults, examination of relationships between serum PFAS concentrations and cognition in Asian Americans urgently needed. Here, our study examined those associations in older Asian Americans using the National Health and Nutrition Examination Survey (NHANES), and compared findings to a non‐Hispanic White sample.MethodOur cross‐sectional study used 2011‐2014 (NHANES) data and included 57 non‐Hispanic Asian and 448 non‐Hispanic White participants who took the cognitive assessments in English, to minimize impact of assessment language on scores. Measures included the Animal Fluency test total score and word learning and recall modules from the Consortium to Establish a Registry for Alzheimer’s disease (CERAD) (immediate recall and delayed recall scores).We used linear regression to estimate impact on cognitive functioning measures per interquartile (IQR) increase in log PFOS concentrations adjusting for age, sex, education, BMI, fish consumption, and serum creatinine. To adjust for co‐pollutant confounding, we also adjusted for summed concentration of other six other PFASs. We stratified all analyses by race/ethnicity group.ResultOur sample of Asian Americans had median age of 67 [IQR: 63, 74], and 41% were female. The non‐Hispanic White sample had median age of 72 [66, 80] and 54% were female. In Asian Americans, an IQR increase in log PFOS was associated with ‐4.42 (95% CI: ‐7.02, ‐1,82, p = 0.002) fewer words listed in the animal fluency test, ‐1.30 (95% CI: ‐2.43, ‐0.18, p = 0.025) words listed in the delayed recall, and ‐1.67 (95% CI: ‐3.68, 0.33, p = 0.098) fewer words listed in the immediate recall test (Table 2 and Figure 1). All associations were null for non‐Hispanic Whites.ConclusionHigher blood levels of perfluoroalkyl substances were associated with lower animal fluency scores and delayed recall scores in Asian Americans, but these associations were null for non‐Hispanic Whites.
Poorly controlled seizures are associated with severe neuropathological changes in dementia
Authors: Zawar Ifrah , Quigg Mark S , Manning Carol A , kapur jaideep 
Published: January 2025

AbstractBackgroundSeizures maybe associated with worse neuropathology findings in people with dementia. However, the role of seizure control and how it may impact post‐mortem histopathology findings in people with dementia remains unexplored.MethodWe used the longitudinal, multicenter National Alzheimer Coordinating Center data from 9/2005 to 12/2021 to evaluate the association between seizure control and histopathological neurodegenerative changes in people with dementia. The differences between baseline demographics, cognition, mortality and neuropathology findings were investigation among three groups: 1) Recurrent seizures (over the preceding 12 months), 2) Remote seizures (history of seizures but no seizures over the preceding 12 months) and 3) No history of seizures (controls). Pearson’s Chi‐squared test, fisher’s exact test and Kruskal‐Wallis Rank sum tests were utilized for analysis as deemed appropriate.ResultOf 10,474 NACC participants who died, mortality was higher (p<0.001) among recurrent seizure (N=407, 56%) patients compared to remote (N=221, 35%) seizures and controls (N=9846,34%). Among 6085 who underwent autopsy, 294 had recurrent seizures, 151 had remote seizures and 5640 had no seizures. Recurrent seizure patients were younger than controls at death (76 vs 82 years, p<0.001). There were no group differences in education, sex, race and ethnicity. However, recurrent seizure patients had worse cognition compared to other groups. Lobar atrophy, vascular pathology, atherosclerosis of circle of willis and substantia nigra hypopigmentation were comparable among the 3 groups. However, recurrent seizure patients had more cerebral cortex atrophy (p<0.001), hippocampal atrophy (p=0.016) and locus ceruleus hypopigmentation (p=0.011). While Lewy body pathology was similarly prevalent among the groups, frontotemporal degeneration with tau pathology was less prevalent (p=0.013) among the recurrent seizures compared to other groups. Recurrent seizure patients had evidence of more severe Alzheimer’s disease pathology (AD) including thal phase for amyloid, Braak stage for neurofibrillary degeneration and density of neocortical neuritic plaque (p<0.001).ConclusionOur findings suggest that recurrent seizures compared to remote seizures prior to death are associated with postmortem evidence of more severe AD pathology and cortical and hippocampal atrophy. These findings emphasize the need for more aggressive seizure control to mitigate the potential impact of seizures on neurodegeneration.
New high throughput fully automated plasma GFAP immunoassay
Authors: Szabo Miklos , Salvati Mike , Schlichtmann Ben , Patzlaff Jason , Unruh Dusten , Curtis Kara , Mediger Laura , Nichkova‐Doseva Mikaela 
Published: January 2025

AbstractBackgroundThe analytical performance characteristics for the plasma Glial Fibrillary Acidic Protein (GFAP) immunoassay currently under development on Beckman Coulter, Inc. Access2™ and DxI9000™ analyzers is described. Blood GFAP levels may be indicative of the extent of neurologic injury in diseases such as TBI and stroke and maybe used as a marker of disease progression in other diseases such as multiple sclerosis. Plasma GFAP outperforms its CSF counterpart in detecting AD pathology and correlation to the clinical stage of the diseaseMethodThe prototype GFAP assay is a one‐step sandwich assay utilizing an anti‐GFAP mouse monoclonal (MAb) antibody/alkaline phosphatase conjugate and paramagnetic particles coated with a complementary anti‐GFAP mouse MAb. Sample and reactants are incubated, washed, then a chemiluminescent substrate is added. The light that is generated is directly proportional to the GFAP concentration in the sample. The assay time to first result is ∼30 minutes. 43 EDTA plasma samples, consisting of 19 Alzheimer’s Disease (AD) patient samples and 24 age‐matched healthy normal samples, were evaluated. A method comparison was performed between Access2™ and DxI9000™ platforms.ResultThe prototype GFAP assay has a targeted analytical measuring range of 1.0 pg/ml to approximately 700.0 pg/ml (capable of measuring analyte up to 10,000 pg/ml). 100% of normal samples were quantified (90% measuring below 20.0 pg/ml), with low dose variability (<4.0% coefficient of variation). A comparison of the prototype GFAP assay on DxI9000™ against Access2™ gave a Passing‐Bablok slope of 0.94 (R=0.992) and an intercept of 0.37 pg/ml. Concordance analysis shows excellent agreement between the Access2™ and DxI9000™ assays. The dose ratio of the median of AD over the median of normal samples for Access2™ and DxI9000™ is 2.31 and 2.41, respectively, with AD patient median dose values of 14.3 pg/ml and 14.6 pg/mL, respectively, and normal sample median dose values of 6.2 pg/ml and 6.0 pg/mL, respectively.ConclusionThe prototype GFAP assay provides fast, highly sensitive and precise results in an automated immunoassay on the Beckman Coulter Access2™ and DxI9000™ platforms. The prototype plasma GFAP assay could be used to both diagnose and monitor various neurodegenerative diseases such as AD.
Mindfulness‐Based Cognitive Defusion Training for Perceived Stress in Older Adults with Mild Cognitive Impairment: A Randomized Controlled Study
Authors: Ren Yinxia , Shi Lulu , Ge Chenxi , Gu An , Wang Lina 
Published: January 2025

AbstractBackgroundRecognizing perceived stress as a modifiable cognitive risk factor, mindfulness‐based programs emerge as promising for stress mitigation in older adults with Mild cognitive impairment (MCI). However, existing research, primarily observational and focused on chronic patients and caregivers, necessitates developing and evaluating MCI‐specific mindfulness interventions.DesignA two‐arm and assessor‐blinded randomized controlled trial.Settings and participantsCommunity‐dwelling older adults with MCI.MethodParticipants (N = 102) were randomly allocated to one of the two arms: (1) a M‐bCDT program (weekly 60‐minute supervised sessions for 8 weeks, followed by 12 weeks of unsupervised practice) or (2) health promotion classes alone, with M‐bCDT program after the follow‐up assessment. Measures of perceived stress levels, cognitive function, and mindfulness awareness levels were collected at baseline (T0), 8‐week (T1), and 20‐week (T2). Intervention effects were assessed both at a group level (Generalized Estimating Equation, GEE) and at an individual level (Reliable Change Index, RCI).ResultIn the intervention group, the M‐bCDT program demonstrated significant interaction effects compared to the waitlist control group. GEE analysis revealed showed statistically significant effects on perceived stress at both measured intervals (βT1 = ‐3.686, P<0.001; βT2 = ‐7.608, P<0.001). In cognitive functioning, significant cognitive improvements were noted in the Finger Tapping test (βT1 = 1.020, P = 0.026; βT2 = 3.000, P<0.001), Purdue Pegboard Test Assembly and Bimanual Tasks (βT1 = 0.549/0.784, P = 0.048/0.013; βT2 = 1.510/2.059, P<0.001), Auditory Verbal Learning Test (AVLT‐immediate/delayed recall: βT1 = 1.098/0.667, P<0.001/0.038; βT2 = 2.176/1.373, P<0.001), and Montreal Cognitive Assessment scores, mindfulness awareness levels in observation and non‐judgment dimension improved significantly over time. RCIs indicated improvements in the intervention group of 1.96% in perceived stress level, 70.59% and 60.78% in AVLT‐immediate/delayed recall after 8 weeks, which further increased to 31.37%, 90.20%, and 78.43% after 20 weeks.ConclusionThe M‐bCDT program effectively reduced the perceived stress levels in older adults with MCI, facilitating the improvements in cognitive function and mindfulness awareness levels, with sustained benefits for three months. It offers a standardized approach for community healthcare providers in MCI cognitive management.Trial registrationThe trial was registered at Chinese Clinical Trials Registry on 05/18/2020 (www.chictr.org.cn; Number Registry: ChiCTR2000033013).FundingNational Natural Science Foundation of China (NO. 72174061; NO. 71704053), China Scholarship Council Foundation (NO. 202308330251).
Feasibility of Training Family Caregivers of People Living with Dementia Online to Deliver Life Review Depression Intervention at Home
Authors: Miyawaki Christina E. , Bouldin Erin D. , McClellan Angela 
Published: January 2025

AbstractBackgroundDue to the high prevalence of depressive symptoms and dementia in older Americans (≥65 years), we trained unpaid family caregivers in an evidence‐based life review depression intervention virtually via Zoom and produced positive outcomes. The objective of this study was to examine the feasibility of training caregivers via online video and delivering the intervention at home.MethodWe recruited caregiver‐care recipient dyads nationwide during the COVID‐19 pandemic (N = 20 dyads). A mixed‐methods design was used to examine the results quantitatively and supported the findings with qualitative interviews with caregivers. We used fidelity scores as a measure of caregivers’ feasibility to follow the intervention protocol and conduct the life reviews. We collected the pre‐ and post‐intervention measures on care recipients’ depression as the primary outcome, and life satisfaction, caregivers’ caregiving burden, rewards of caregiving, and dyads’ relationship quality as secondary outcomes, and analyzed them using paired t‐tests.ResultCaregivers were on average 64 years old, White (65%), and female (90%). Many were married (65%), college‐educated (70%), working or retired (40% each), and in good‐excellent health (100%). Their care recipients were 80 years old (mean), and White (70%). Gender and their health conditions were equally divided into male and female (50% each), and in poor‐fair and good‐excellent health (50% each). The online‐trained caregivers’ average fidelity check‐in score was 15.86±0.268 (out of 16), which was a significant improvement from that of Zoom‐trained caregivers (14.83±0.776, p<0.001) indicating excellent adherence to the intervention protocol. The C‐PLR intervention significantly positively impacted care recipients’ depressive symptoms (p = 0.034), as well as caregivers’ rewards of caregiving (p = 0.019), especially care recipients who lived alone (p = 0.024). Caregivers’ post‐intervention qualitative interviews aligned with the quantitative results supporting that online‐trained caregivers could deliver the intervention by the protocol without adding caregiver burden.ConclusionThe outcomes of the study showed that family caregivers could learn life review skills through online videos and perform life reviews closely adhering to the study protocol. This study demonstrated that the Caregiver‐Provided Life Review, an innovative, cost‐effective intervention with a flexible delivery schedule could make a positive impact on both caregivers’ and care recipients’ mental health.
Cultural adaptation of the Savvy Caregiver program with the Native Hawaiian community
Authors: Jackson Alexandra , Dillard Adrienne , Kekauoha B. Puni , Austin Mahealani , Kia'i Lee Errol , Balaz Poki'i , Dutro Natlie , Okamoto Scott , Hepburn Kenneth , Lewis Jordan P. , O'Sullivan Kelly , Mayeda Paige , Dutro Angeliyah Kahoku , Weaver Raven 
Published: January 2025

AbstractBackgroundTo promote caregiver health and reduce burden, the Savvy Caregiver Program (SCP), an evidence‐based caregiving intervention, was adapted with a Native Hawaiian (NH) community in Hawaiʻi. The adaptation process occurred prior to pilot testing in two phases: 1) the preliminary adaptation by a community action board (CAB) and mentorship team and 2) pre‐pilot testing and expert validation with NH adults. The preliminary adaptation, titled ʻAuamo Kuleana O Nā Maʻi Poina (ʻAuamo Kuleana), aimed to include Hawaiian values, language, proverbs, and culturally relevant examples while maintaining the core components of the program. The CAB also created new videos with cultural foods, mirroring the existing training videos. To continue refining the adapted program prior to pilot testing, we pre‐piloted the curriculum and invited participants to describe their experiences and provide feedback.MethodIndividuals who participated in the 7‐week pre‐pilot of ʻAuamo Kuleana (n = 6) were asked to complete a focus group or interview to share their experiences and provide feedback. The CAB was invited to analyze the qualitative data using thematic analysis.ResultFive pre‐pilot participants attended a focus group or interview. Only one participant was actively providing care, the other participants were interested in proactive training to support their community. This was a common theme: caring as a community. Participants shared positive feedback about the program; most participants attended all sessions and read the caregiver manual. All participants preferred to meet in‐person and appreciated the revised curriculum. Two suggestions emerged: include all family members in the program to be in alignment as a ʻohana (family) in providing care; and add information about planning for their own care.ConclusionThere were high rates of satisfaction and engagement and the pilot test of ʻAuamo Kuleana proceeded without additional changes. The suggested changes from the pre‐pilot required modifications to program core components and were not incorporated at this stage. However, it may be important to consider how to incorporate cultural aspects of caring, like participants' interest in proactively learning about dementia and caregiving, caring as a community, and family‐centered caregiving (rather than dyadic caregiving), in future caregiving interventions co‐created with the NH community.
Prevalence of Cerebral Small Vessel Lesions in Mild Cognitive Impairment and Mild Alzheimer’s Disease Patients in Memory Clinic
Authors: Smitasiri Thachamai , Likitjaroen Yuttachai 
Published: January 2025

AbstractBackgroundAlzheimer's disease(AD) raises global concern with its impact on daily living. Anti‐amyloid monoclonal antibodies (mAb) serving as specific treatments used in mild cognitive impairment(MCI) and mild dementia due to AD. Severe cerebral small vessel disease(SVD) lesions such as microbleeds and white matter hyperintensities are listed as exclusions according to the recommendation for mAb treatment. In Thailand, there is no prevalence study of SVD lesions specifically in these patient grpups. The findings will provide important information for considering cost‐effectiveness of anti‐amyloid therapy, being expected to become treatment option for Thai AD patients.MethodThe cross‐sectional study was carried out at King Chulalongkorn Memorial Hospital Memory Clinic. Amnestic MCI and mild AD patients were diagnosed by clinical criteria, cognitive tests and brain MRI. Serious medical conditions and incomplete MRI were excluded. Visual rating scales were used to evaluate SVD and brain atrophy lesions (microbleeds, Fazekas score, lacunes, MTA and GCA scores). Baseline characteristics data and cognitive tests were accessed from medical records. Simple and amended SVD scores were used to determine SVD severity and analyzed correlation with cognitive tests.ResultIn the study involving 102 patients, 73.5% had MCI, and 26.5% had mild AD, with average age at diagnosis of 75.0±8.0 years. Microbleeds were present in 50% of patients, with only 17.6% had ³4 lesions. Twenty individuals (19.6%) had either ³4 microbleed lesions or Fazekas score of 3. There was no evidence of superficial siderosis or stroke involving large vessel territory. Those without microbleeds had higher TMSE score (25.4vs23.5;p=0.009). MTA score were associated with lower TMSE and MoCA scores (26.4vs22.7;p<0.001 and 22.1vs19.2;p=0.001, respectively). Weak negative correlation between simple & amended SVD scores and TMSE scores were showed (r=‐0.371 and ‐0.384, respectively;p<0.001), along with moderate negative correlation between MTA score and both TMSE & MoCA score (r=‐0.631 and ‐0.443, respectively;p<0.001).ConclusionWith MCI and mild AD, 19.6% of the samples fell within the exclusion criteria for anti‐amyloid therapy, in part of cerebrovascular imaging lesions. The results can be used to consider role of anti‐amyloid therapy in Thailand in the future.
Cognitive Reserve as a Predictor of Age of Onset and Cognitive Decline in Patients with Alzheimer’s Disease
Authors: Marmor Anat , Vakil Eli , Merhavi Shlomzion Kahana , Meiner Zeev 
Published: January 2025

AbstractBackgroundThe cognitive reserve (CR) theory seeks to explain the mismatch often reported between brain damage and its clinical expression. Unlike most previous studies that focused on individuals with memory deterioration before the diagnosis of Alzheimer’s disease (AD), the present study examined the late stages of the disease. The study sought to confirm the hypothesis that patients with higher CR are diagnosed later and decline faster than those with lower CR because their brain pathology is more severe.MethodThis is a retrospective study conducted at a memory clinic and included 642 (361 female) individuals above the age of 65 diagnosed with AD. Average age was 77.01 (range = 65‐97). Cognitive decline was evaluated using the Mini Mental State Examination (MMSE).ResultIn the entire sample, no significant correlation was found between the age of diagnosis and CR. Therefore, the sample was divided into two groups, according to years of education: (a) patients with nine years of high education or more (n = 442, with average years of education 13.93, SD = 3.00) and (b) patients with eight years of education or less (n = 141, with average years of education 5.21, SD = 3.08). Our results show that only in the group of patients with higher education, education level was significantly associated with delayed age of diagnosis. As predicted, more years of education were associated with steeper cognitive decline in both groups.ConclusionThe study examined the less studied group of individuals at late stages of AD. The study shows that the effect of education on the age of diagnosis is not linear and it is valid for those with a higher but not necessarily for those with lower education. In patients with higher education, higher CR resulted in delayed age of diagnosis but also faster deterioration; in the lower education group, the resilience factor that leads to later diagnosis is not present. The implications of the study include diagnostic and therapeutic guidelines that match the different characteristics of each group of patients.