bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential Eligibility for Disease Modifying Therapies Among Individuals Referred to A Tertiary Care Memory Clinic in Calgary, Alberta, Canada: Implications for AD Biomarker Testing
Authors: Thomas Gavin , Smith Eric E. , Ismail Zahinoor , Kirkham Julia G , Roach Pamela , Goodarzi Zahra , Chowdhury Mohammad Z I , Seitz Dallas 
Published: January 2025

AbstractBackgroundPotential disease modifying therapies (DMT) for Alzheimer’s disease (AD) may become available in Canada although it is unclear what percentage of people presenting to tertiary care memory programs may require beta‐amyloid testing be eligible for these treatments. We evaluated eligibility for potential DMTs among individuals in the Prospective Registry for Persons with Memory Symptoms (PROMPT) dementia research registry, comprising patients seen in a tertiary care cognitive clinic in Calgary, Alberta, Canada, based on cognitive criteria, medical history, and potential diagnosis of AD on clinical criteria.MethodWe analyzed all individuals included in the PROMPT registry from July 2010 to May 2023 who were diagnosed with either mild cognitive impairment (MCI) or possible or probable dementia at their baseline assessment. AD biomarker testing is not routinely available in this clinic. The characteristics of PROMPT participants were then compared to the inclusion criteria used in recent trials of three DMTs. The proportions of individuals in the PROMPT registry who were potentially eligible for DMTs were then determined.ResultOf the 1,901 individuals in the PROMPT registry, 1,119 were diagnosed with MCI or dementia at their baseline visit (mean age 75 years and 54% male). Among the group with MCI or dementia, 86% (965) were diagnosed with either MCI or AD. Of the individuals diagnosed with MCI or AD, 55‐80% met cognitive test score eligibility for different DMTs at their initial clinic visit. Potential medical contraindications to treatment with DMTs were present in 27% of this sample. Of all individuals referred to the tertiary care cognitive disorders clinic diagnosed with MCI or AD, approximately 40‐58% could potentially be eligible for DMTs based on their initial clinic assessment. Of all individuals in the PROMPT dementia registry, between 20‐29% could potentially be candidates for DMTs pending neuroimaging and biomarker confirmation of eligibility.ConclusionA high proportion of memory clinic referrals are diagnosed with MCI or AD and are potentially eligible for DMTs and would require beta‐amyloid biomarker testing for eligibility confirmation. This information will help better define resource requirements for implementing AD DMTs should these become available in Canada.
Impact of Type 2 Diabetes and Hypertension on Cognition: A Propensity Score‐Matched Analysis in Mexican Americans from San Antonio
Authors: Lopez‐Alvarenga Juan C , Almeida Marcio A , Cavazos José E. , Mahaney Michael C , Maestre Gladys E. , Glahn David C , Duggirala Ravindranath , Blangero John 
Published: January 2025

AbstractBackgroundObservational studies have reported cognitive domain alterations in individuals with Type 2 diabetes mellitus (T2D), affecting cognitive domains of information‐processing speed, memory, attention, and executive function. Epidemiological observational studies have shown an association between higher blood pressure [HBP], low processing speed, short‐term memory and learning, and delayed recall. Within the US Hispanic/Latino population, specifically Mexican Americans, cognition remains insufficiently studied. This preliminary analysis aims to discern the impact of T2D and hypertension on cognition, employing propensity score matching to mitigate confounders.MethodA dataset with 650 participants without dementia (mean age 50 ± 12.6 years, BMI 29.1 ± 6.6, 63% females) from the Mexican American Family Study Cohort from low economic strata was analyzed. The effects of T2D and HBP were evaluated using propensity score matching, specifically employing nearest‐neighbor matching under a logistic model. Coefficients (95% confidence intervals) and p‐values were reported.ResultAmong the participants, 9% had T2D, 6% had HBP, and 2% had both conditions. Adjusting for sex, age, and BMI, the presence of T2D impacted face memory delay [b = 1.3 (0.1, 2.5) p = 0.032] and Continuous Performance Test (CPT) hits [b = 45.9 (24.7, 67.1) p<0.001]. Hypertension influenced California Verbal Learning Test (CVLT) learning [b = ‐11.1 (‐15.1, ‐7.4) p<0.001], CVLT recognition [b = ‐3.2 (‐6.1, ‐0.3) p = 0.03], and CPT hits [b = ‐31.1 (‐64.4, 2.3) p = 0.068)—Figure 1 CVLT score on T2D and HBP status.ConclusionThis preliminary study underscores the heightened risk of hypertension and T2D impacting cognitive function among Mexican Americans. Variations in cognitive measurements based on T2D or hypertension were observed, emphasizing the need for specific cognitive screening tools tailored to the prevalence of chronic conditions in this susceptible population.
The Bristol Brain Health Clinic
Authors: Butters Anneka F , Archer Hilary , Farouk Hannah , Coulthard Elizabeth 
Published: January 2025

AbstractBackgroundCurrently, most clinical services focus on dementia diagnosis rather than prevention, despite evidence showing benefits of preventative interventions. People often present with memory problems before having dementia, or when in the early stages and are motivated to adopt preventive lifestyle strategies to slow decline. To address gaps in clinical services we set up the Bristol Brain Health Clinic (BHC) in 2017. Here we present a clinic evaluation of diagnostic work up, interventions, and patient experience.MethodRelevant data was extracted from the medical records of patients attending The North Bristol NHS Trust BHC. Descriptive statistics were performed. Evaluation was carried out in line with European Task Force recommendations.Result110 patients were seen in clinic between 2017‐ 2023. Mean follow‐up was 2yrs (SD 1.32). All patients had access to diagnostic assessments: neurological examination, neuropsychometry, serological and cerebrospinal fluid testing (CSF). Patients were offered bespoke lifestyle information and research opportunities.Patient cohort: Mean age was 63 years (SD 11.74). 67% were male. Mean MOCA at baseline was 24 (SD 3.62).Dementia Risk Factors (prevalence): High blood pressure (49.09%), high cholesterol (47.27%), diabetic (15.45%), prediabetic (13.63%, current smoker (9.90%), ex‐smoker (39.10%), > 14 units of alcohol per week (21.81%), history of heavy drinking (14%), Mean BMI 28.01 (SD 5.85), hearing loss (40%), history of head injury (23.63%), low mood (55.45%), poor sleep quality (64%).CSF Studies: 38 subjects were tested for biomarkers of neurodegenerative disease. Twenty (52.63%) were positive, 18 (47.37%) were negative.Diagnoses at Final Review: Mild cognitive Impairment 27.27%, Dementia 20%, Subjective Cognitive Decline 18.91%, Uncertain 33.64%. Aetiologies: Alzheimer’s Disease 22.73%, Functional Cognitive Disorder 14.55%, Vascular 7.27%, Multi‐Factorial 5.45%, Parkinson’s Disease 2.73%, Lewy Body Disease 2.73, Affective Disorders 2.73%, Mixed 1.82%, Other 1.82%, Uncertain Cause 38.18%.Discharge: 37.14% of the cohort were discharged with stable/resolved symptoms.Patient Feedback: 84.21% ‘Extremely Likely’ to recommend our service. 92.31% felt possibly better able to cope with symptoms.ConclusionOur population had a high prevalence of dementia risk factors and range of diagnoses. Many patients’ symptoms were stable/resolved at follow up. This population merits further investigation and continued early targeting with preventative measures.
Differential Impact of Pulmonary Impairment Type on Cognitive Function
Authors: Mitra Sumedha , Prasad Raghav , Sahadevan Pravin , Sundarakumar Jonas S. 
Published: January 2025

AbstractBackgroundWorsening pulmonary health may be independently associated with declining cognitive function. However, the association between specific types of pulmonary impairment with cognitive function is not well understood. The present study aims to determine the differential impact of Chronic Obstructive Pulmonary Disease (COPD) and Preserved Ratio Impaired Spirometry (PRISm) in a rural Indian aging cohortMethodData from participants (n = 1223) of the Srinivaspura Aging, Neuro Senescence and COGnition (SANSCOG) cohort were analyzed. Predictive spirometry equations were derived from a similar population. Lung function was classified as normal, COPD or PRISm, based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and PRISm criteria, respectively. The Hindi Mental State Examination (HMSE) test was used to assess global cognition, while a comprehensive culturally adapted neuropsychological battery, COGNITO, was used to assess cognitive performance across five domains (visuospatial abilities, language comprehension, attention, memory and executive function). Multivariable regression models, adjusted for confounders (Table 1), were used to determine associations between spirometry parameters and cognitive performance.ResultWe found that PRISm, in comparison to normal lung function, had a significant negative association with the composite COGNITO score (β(95% CI) = ‐0.11 (‐0.18, ‐0.03), p = 0.003) as well as individual domain‐wise scores: attention (β(95%CI) = ‐0.12 (‐0.22,‐0.01), p = 0.02), memory (β(95%CI) = ‐0.12 (‐0.24,‐0.01), p = 0.02) and executive functions (β(95%CI) = ‐0.15 (‐0.28,‐0.02), p = 0.02) (Table 2). No significant associations were noted among between COPD and cognitive test scores.Forced Vital Capacity (FVC) ratio (FVC/FVC predicted) was significantly associated with HMSE score (β(95%CI) = 0.35 (0.04,0.65), p = 0.02) and the composite COGNITO score (β(95%CI) = 0.14 (0.03,0.24), p = 0.007). However, Forced Expiratory Volume (FEV1) ratio (FEV1/FEV1 predicted) was not significantly associated with HMSE score or the composite COGNITO score.ConclusionWe observed that PRISm and not COPD was associated with cognitive function, thus suggesting PRISm could be a potential risk factor for dementia (Figure 1). Correlating these findings with brain MRI, could yield findings about their differential impact on brain structure and function.
Impact of physical frailty parameters on the association between sleep quality and multimorbidity
Authors: Chatterjee Priya , Sahadevan Pravin , Pradhan Hitesh , Sundarakumar Jonas S. 
Published: January 2025

AbstractBackgroundPrevious studies have reported that poor sleep quality is associated with several adverse outcomes including multimorbidity, particularly in the aging population. Another common occurrence in the elderly is frailty. We aim to study the mediating effect of objective physical frailty parameters on the association between sleep quality and multimorbidity in an aging rural Indian population.MethodWe used baseline data (n = 3300) from the ongoing Srinivaspura Aging Neuro Senescence and Cognition (SANSCOG) cohort study, conducted in the rural areas of the state of Karnataka in India. Objective physical frailty parameters included in the study were hand grip strength (HGS), chair stand test (CST), timed up and go (TUG) tests. Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. Multimorbidity was categorized based on the presence of two or more diagnosed chronic disease conditions (self‐reported/objective measures). Multivariable logistic regression was performed to find out the association between poor sleep quality and multimorbidity. Mediation analyses [using Karlson–Holm–Breen (KHB) method] were performed separately for each of the physical frailty parameters on the association between poor sleep quality and multimorbidity and results were reported as adjusted Odds ratio (a‐OR) and 95% CI. Models were adjusted for age, gender, education, socioeconomic status, current smoking and alcohol consumption status.ResultA total of 39.09% participants had poor sleep quality (PSQI>5) and 54.12% had multimorbidity. Participants with poor sleep quality had higher odds of being multimorbid [a‐OR: 1.41, 95% CI: 1.21‐1.65]. Among the physical frailty parameters, individuals with higher TUG time had higher odds of having multimorbidity [a‐OR: 1.08, 95% CI: 1.04‐1.11]. People with higher score in the CST had lower odds of being multimorbid [aOR: 0.95, 95% CI: 0.92‐0.97]. Performance in TUG and CST significantly mediated the association between poor sleep quality and multimorbidity, although the mediated effects were small (TUG‐ 5.00% and CST‐ 6.83%). However, no association was found between HGS and multimorbidity.ConclusionOur study finds that poor sleep quality is associated with increased risk of multimorbidity and that poor performance in physical frailty parameters mediates this association.
Higher educational attainment linked with accelerated longitudinal tau accumulation in Alzheimer’s disease
Authors: Cai Yue , Zhou Xin , Fang Lili , Liu Lin , Li Anqi , Yang Jie , Sun Pan , He Zhengbo , Yu Xianfeng , Guo Tengfei ,   Alzheimer’s Disease Neuroimaging Initiative
Published: January 2025

AbstractBackgroundPrevious cross‐sectional studies have extensively documented that higher educational attainment (EA) is associated with lower β‐amyloid (Aβ) plaques and tau tangles in Alzheimer’s disease (AD). However, studies investigating the relationship between EA and longitudinal tau accumulation are strikingly lacking.MethodWe analyzed Aβ‐PET (A), tau‐PET (T), and 3D T1‐MRI images (N) from the ADNI cohort to identify 196 Aβ‐PET positive participants (A+) and 114 cognitively unimpaired participants without evidence of AD pathology and neurodegeneration (A‐/T‐/N‐/CU). A subset of 209 individuals had resting‐state functional MRI data (Rs‐fMRI), and 173 participants had at least one follow‐up tau‐PET. Participants were categorized into High‐Edu and Low‐Edu subgroups based on the median years of education of the whole cohort (16 years). Aβ‐PET SUVR of 18F‐florbetapir (FBP) or 18F‐forbetaben (FBB) were converted to Centiloids. Baseline and follow‐up tau uptakes based on the Schaefer‐200 atlas were compared between High‐Edu and Low‐Edu subgroups. The interaction of education status with baseline Aβ‐Centiloids and entorhinal tau on longitudinal tau accumulation was assessed. The voxel‐wise amplitude of low‐frequency fluctuation (ALFF) and Regional Homogeneity (ReHo) maps calculated from Rs‐fMRI data were compared between High‐Edu and Low‐Edu subgroups, and the impact of ALFF and ReHo alterations on Aβ‐Centiloids and entorhinal tau‐related longitudinal tau accumulation was also examined.ResultA+ High‐Edu individuals displayed lower baseline tau levels in temporal and parietal lobes but faster tau accumulation in medial and lateral temporal lobes (p<0.05, Figure 1). Moreover, A+ High‐Edu individuals revealed more pronounced positive associations between Aβ‐Centiloids and tau increases in bilateral visual cortices, as well as between entorhinal‐tau and tau increases in inferior parts of temporal pole and middle temporal lobe, compared to Low‐Edu individuals (p<0.05, Figure 2). Voxels with higher ALFF and ReHo in High‐Edu individuals converged in a cluster in the temporal pole, and the higher ReHo of this cluster predicted faster entorhinal tau‐related longitudinal tau accumulation in medial and lateral temporal cortices (p<0.05, Figure 3).ConclusionThese findings suggest that higher EA is associated with faster tau accumulation in medial and lateral temporal lobes in AD, and the accelerated tau accumulation of these regions may be linked to higher ReHo associated with education.
Mid‐ to late‐life changes in blood‐based biomarkers of Alzheimer’s disease pathology and neurodegeneration and associations with brain amyloid deposition: The ARIC‐PET Study
Authors: Pike James Russell , Lu Yifei , Chen Jinyu , Walker Keenan A. , Sullivan Kevin J. , Griswold Michael E. , Thyagarajan Bharat , Mielke Michelle M. , Lutsey Pamela L. , Wong Dean F. , Knopman David S. , Sharrett A. Richey , Coresh Josef , Mosley Thomas H. , Gottesman Rebecca F. , Palta Priya 
Published: January 2025

AbstractBackgroundBlood‐based biomarkers show promise as a noninvasive, inexpensive method for measuring Alzheimer’s disease pathology throughout the lifecourse. However, the predictive and classification accuracy of these biomarkers at different stages of the lifecourse and among diverse, community‐dwelling populations requires further investigation.MethodBetween 2014 and 2015, 329 dementia‐free participants from the Atherosclerosis Risk in Communities Study underwent brain magnetic resonance imaging (MRI) and florbetapir positron emission tomography (PET). Amyloid positivity was defined as a global cortex standardized uptake value ratio greater than 1.2. Stored plasma samples collected in midlife (1993‐95, mean age 58.5 years) and late‐life (2011‐13, mean age 76.2 years) from a subsample of 259 participants were assayed in 2022 using Quanterix SiMoA. The assay quantified amyloid‐β (Aβ)42/40, phosphorylated tau at threonine 181 (p‐Tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP). Unadjusted and covariate‐adjusted logistic regression models estimated the association between plasma biomarkers from midlife and late‐life and amyloid positivity in late‐life. Unadjusted receiver operating characteristic curves documented the classification accuracy of the plasma biomarkers separately and collectively.ResultThe sample (Table 1) included 151 women (58.1%), 105 Black participants (40.4%), and 136 (52.3%) participants with amyloid positivity. In models adjusted for demographics, lifestyle factors, cardiovascular factors, and the presence of APOE ε4 alleles, assays measured in midlife were not associated with amyloid positivity in late‐life (Table 2). However, late‐life measurements of Aβ42/40, p‐Tau181, and GFAP and change per decade from midlife to late‐life in p‐Tau181 and GFAP were associated with greater odds of amyloid positivity. The greatest classification accuracy (Figure 1) was achieved by using all assays measured in midlife and late‐life (AUC = 0.754), although the accuracy when using only late‐life measures was comparable (AUC = 0.737).ConclusionLate‐life plasma biomarkers of Alzheimer's disease neuropathology and astrogliosis were associated with late‐life amyloid positivity, but midlife plasma biomarkers obtained 16 to 20 years earlier did not exhibit a statistically significant association. Additional longitudinal research is needed to determine whether changes in plasma biomarkers measured before an individual is classified as amyloid positive can be used to identify individuals at risk of developing Alzheimer's disease.
The association of Diabetes Mellitus with Amyloid and Tau biomarkers
Authors: Duijkers Stephan , van der Velden Jolien , van Gils Veerle , Oomens Julie Elisabeth , Vos Stephanie J. B. , Ramakers Inez H.G.B. , Visser Pieter Jelle , Jansen Willemijn J. ,   the Amyloid Biomarker Study group
Published: January 2025

AbstractBackgroundAs global populations age, both Alzheimer’s Disease (AD) and diabetes mellitus (DM) incidence are projected to increase tremendously over the coming 20‐30 years. Studies have found that having DM is associated with increased risk of developing AD dementia. It remains unclear however whether DM impacts underlying AD pathology. In the current study we investigate associations between DM and profiles of amyloid‐β‐42 (A) and phosphorylated tau‐181 (T) pathology in cerebrospinal fluid (CSF) in participants with normal cognition (NC) and mild cognitive impairment (MCI).MethodsWe included 2890 participants with NC and 1598 participants with MCI from 21 studies of the Amyloid Biomarkers Study. Participants were classified into four AT biomarker profiles: A‐T‐, A+T‐, A+T+ and A‐T+, based on data‐driven or cohort‐specific cutoffs. All participants had data on DM diagnosis (yes/no). Bonferroni corrected chi‐square tests with pair‐wise Z‐tests were performed to compare the observed AT biomarker profile frequency across DM groups. To examine whether age‐related changes in AT biomarker profile frequencies were dependent on DM, an interaction between age and DM was entered into a Markov‐Chain‐Monte‐Carlo generalized linear mixed model.ResultsTable 1 displays sample demographics. Table 2 displays differences between participants with and without DM per AT profile. In both NC and MCI, participants with DM more often had the A‐T+ biomarker profile than participants without DM (NC: 7.6% vs. 13%; MCI: 10.2% vs. 18%; both p<0.05), while frequencies of the A‐T‐, A+T‐ and A+T+ biomarker profiles were similar among DM groups. In both NC and MCI, DM status did not impact the age‐related increase in AT biomarker frequencies (NC p = 0.34; MCI p=0.45) (Figure 1).ConclusionsThese results demonstrate that for both NC and MCI, persons with DM more often have an A‐T+ profile compared to those without diabetes, suggesting that people with DM have an increased risk of isolated tau pathology that may be independent from amyloid pathology. DM did not change frequencies of biomarker profiles across age. These findings warrant further research and could have implications for both diagnostics and clinical trial design.
A MACHINE LEARNING MODEL FOR THE PROGNOSIS OF ALZHEIMER’S DISEASE DEMENTIA AT THE MILD COGNITIVE IMPAIRMENT STAGE USING MITOCHONDRIAL METHYLCYTOSINES AS NOVEL BLOOD‐BASED BIOMARKERS
Authors: Mosquera Jose Luis , Blanch Marta , Fontal Beatriz , Martí Pau , Ferrer Paula , Trapero Carla , Rojo Nuria , Rico Inma , Campdelacreu Jaume , López Joan Bello , Lleo Alberto , Fortea Juan , Martinez‐Lage Pablo , Tort‐Merino Adrià , Sanchez‐Valle Raquel , Cruchaga Carlos , Fowler Christopher J , Laws Simon M. , Mehanian Courosh , Rene‐Ramirez Ramon , Gascon‐Bayarri Jordi , Barrachina Marta 
Published: January 2025

AbstractBackgroundPrediction of progression to Alzheimer’s Disease Dementia (ADD) at the Mild Cognitive Impairment (MCI) stage is an unmet medical need.Mitochondrial dysfunction in Alzheimer’s Disease at the brain and systemic level has been extensively described. Our previous studies showed an altered mtDNA methylation pattern throughout AD progression in human postmortem brains (Blanch et al. 2016). Similar results were found in blood samples from MCI patients (Stoccoro et al. 2022).ADmit has developed an epigenetic Next‐Generation Sequencing approach for identifying differential mtDNA methylation patterns in blood samples from MCI patients. The methylation measures, along with non‐invasive clinical features, have been integrated into a classification model that predicts the probability of progression to ADD.MethodA total of 600 subjects were recruited from longitudinal prospective clinical studies: AIBL Consortium (n=248), Hospital Universitari Bellvitge (n=125), CITA‐Alzheimer Foundation (n=75), Hospital Clínic Barcelona (n=79), Knight‐ADRC (n=64), Hospital Sant Pau (n=5), and Hospital General Hospitalet (n=4). The analysis was focused on blood samples from the baseline visit for Cognitively Normal (CN, CDR=0, n=168) and MCI subjects (CDR=0.5, n=432) with a clinical follow‐up between 3 and 16 years. The model classifies the subject as CN, MCI that does not progress to ADD, and MCI that does progress to ADD, using over 200 methylation measures and some clinical variables without including the AbPET scan. An MCI patient was considered progressed to ADD when their CDR shifted to ≥ 1, or there was a ≥ 2‐point deterioration in CDR‐SOB, or ≥ 1‐point deterioration in at least four instrumental daily life activities. The dataset was split in two subsets for training and for testing (80:20). Several methods were explored in previous analyses. Random Forest showed a superior performance through a triply replicated 10‐fold Cross‐Validation and feature selection process.ResultThe predictions on the testing data are: Accuracy=0.832 (CI95% 0.752‐0.894), Kappa=0.711, F1‐score=0.853, Sensitivity=0.951, Specificity=0.707, PPV=0.773, NPV=0.932, and an AUC=0.775.ConclusionThe present classification model performs accurate classification of ADD at MCI stage up to 14 years before the appearance of clinical signs of dementia and represents a promising minimally‐invasive prognostic tool. This is the first blood‐genomic (mitochondria) prediction model.