bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges of recruitment and biomarkers collection in Caribbean Hispanics
Authors: Reyes‐Dumeyer Dolly , Piriz Angel , Soriano Belisa , Franco Yahaira , Coronado Zoraida Dominguez , Recio Patricia , Mejia Diones Rivera , Medrano Martin , Lantigua Rafael A. , Vardarajan Badri N , Honig Lawrence S. , Mayeux Richard 
Published: December 2023

AbstractBackgroundGenetic Studies of Alzheimer’s Disease in Caribbean Hispanics (CH) has been ongoing for over 20 years. Our primary goal was to identify genes in large well‐phenotyped, multiplex families, and sporadic cases and controls. This longitudinal collection of data represents a unique resource for the scientific community. The project is led by collaborators in the United States (US) and the Dominican Republic (DR). For the past three years, our efforts have been centered on the collection of cerebrospinal fluid (CSF), plasma, serum and Paxgene tubes for RNA to study core biomarkers. Collection of blood samples for DNA to conduct genetic analyses is also ongoing.MethodThe cohort consisted of participants aged 50 and older from the DR, including those living in the New York City area, willing and able to provide a blood and CSF samples. Interviewers in the DR were trained to collect data, blood samples and CSF. DNA samples were sent overnight to Columbia university (CU) for processing. CSF, Paxgene tubes, serum and plasma samples were processed in the DR and stored at ‐80F for batch shipping to CU. APOE genotyping was conducted in the US. Biomarkers, metabolomics, and proteomics data was generated at Columbia University. Methylation assays from Paxgene was conducted at Uniformed Services University (USUHS).ResultWe have databased a total of 1899 individuals with plasma samples, 1707 with Paxgene, 1731 with serum and 203 with CSF. Blood samples from 1079 participants have genome wide arra, whole genome sequencing and APOE genotyping. 192 CSF samples have proteomics completed, 153 CSF samples have metabolomics data and 742 have plasma biomarkers (Ab40, Ab42, T‐tau, P‐tau181, NFL and GFAP)).ConclusionSample collection for genetic studies in developing countries present important logistical challenges. Despite these challenges, sample quality is comparable to those collected in New York. Biomarkers from CSF, serum and plasma can give us a closer look into underrepresented populations such as Caribbean Hispanics. Results suggest that similar protocols can be successful in Latin America. Future work will augment the biosample collection of the cohort by collecting samples from additional subjects.
Promoting Dementia Prevention in African Americans: Qualitative Findings from Developing a Smoking Cessation Messaging Campaign
Authors: Johnson Adrienne L. , Gleason Carey E. , Lathen Lorraine 
Published: December 2023

AbstractBackgroundAfrican Americans (AA) are twice as likely to develop dementia compared to White counterparts. Cigarette smoking is a known modifiable risk factor for dementia and harder to quit with worse health outcomes for AA versus White adults. Because age is the strongest predictor of dementia onset, and older adults are half as likely to quit smoking compared to younger counterparts, older AA adults who smoke may be at higher risk for dementia compared to older non‐Hispanic whites. Culturally‐specific interventions for AA smokers are beneficial in terms of intentions to quit, utilization of quit‐smoking resources, and quitting success. However, there has yet to be a culturally‐specific message for older adult AA smokers to motivate cessation attempts and increase the use of evidence‐based quitting treatments.Method8 focus groups and key informant interviews were conducted with current and former AA smokers between 50‐80 years old with no history of dementia or MCI. Interviews lasted 60 minutes, used a semi‐structured interview guide, and were completed in person or virtually and led by a trained moderator knowledgeable of smoking in AA communities.ResultDirected content analyses using a combination of deductive/inductive coding identified themes in 5 domains: concerns about aging, previous tobacco prevention advertisements, recommendations for future tobacco prevention advertisements, smoking and health risks, and smoking cessation treatments. Participants reported multiple concerns about aging; most were related to their smoking. Contrary to previous research with primarily White older adults who smoke, AA participants indicated dementia was no more important than any other health condition in motivating quitting. Most participants reported a strong existing motivation to quit, but multiple barriers impeded their success. One key barrier to quitting was access to cessation resources, and participants reported a strong desire for support groups with similarly aged and race‐concordant peers trying to quit smoking. Participants felt existing cessation advertisements were not made for them and did not include enough information to be helpful.ConclusionFindings highlight a need for increased resources to support cessation efforts in older adult AA communities, utility of developing culturally‐specific messages, and importance of discussing priorities with communities prior to developing dementia prevention messaging.
TREM2‐related Polygenic Risk Score predicts defect Innate Immune Activation in Alzheimer’s Disease
Authors: Dijkstra Janna I.R. , Tijms Betty M. , Vermunt Lisa , Teunissen Charlotte E. , Flier Wiesje M. , Holstege Henne , Visser Pieter Jelle , Lee Sven J 
Published: December 2023

AbstractBackgroundTREM2 plays a central role in immune response which, in turn, is strongly related to Alzheimer’s disease (AD) pathology. We previously found an AD‐subtype with and without innate immune activation based on CSF proteomics. Possibly, genes associated with TREM2 pathways could explain differences between these two subtypes since R47H and R62H mutations are associated with decreased microglial activation. We tested this hypothesis in a large single site cohort, and compared them on PRS including previously reported GWAS genes associated with TREM2 pathways.MethodWe included participants from the Amsterdam Dementia Cohort who had AD subtyping based on CSF proteomics available (n = 466). Based on literature, we labelled 19 of 83 known AD risk genes as belonging to TREM2 pathways and used these to construct a TREM2‐PRS. We studied associations between a standard AD‐PRS with 83 SNPs, TREM2‐PRS with 19 SNPs and non‐TREM2‐PRS with 64 SNPs between two AD‐subtypes being (1) without innate immune activation and (2) with innate immune activation, using logistic regression models (correcting for sex, age and 5 principal components).ResultThe cohort involved 146 controls (mean age 61 years, 34% female) and 195 AD cases: 97 without immune activation subtype (mean age 64 years, 52% female) and 98 with immune activation subtype (mean age 68 years, 54% female). Both subtypes showed comparable increased risk on the standard AD‐PRS compared to controls (OR 1.65, 95%CI 1.2‐2.3, p = 0.002 and OR 1.7, 95%CI 1.1‐2.5, p = 0.006) (Table 1). A higher TREM2‐PRS was associated with no immune activation subtype (OR 1.5, 95%CI 1.1‐2.1, p = 0.008). The PRS of the other 64 risk variants, which were not labelled as belonging to TREM2 pathways, was associated with immune activation subtype (OR 1.5, 95%CI 1.1‐2.1, p = 0.02).ConclusionAD individuals with a CSF proteomic‐based subtype without immune activation show more genetic variants in TREM2 pathways, whereas these SNPs are not related to the subtype with innate immune activation. These findings provide evidence for genetic differences underlying AD‐subtypes, and suggest that therapies targeting immune functioning may need to tailor therapies to AD‐subtype (i.e., additional activation vs. decreasing activation).
Common neurobiological mechanisms underlying anosognosia and neuropsychiatric symptoms across the Alzheimer’s disease spectrum
Authors: Gagliardi Geoffroy Pierre , Mimmack Kayden J. , Wang Sharon , Fawzy Michael Elnemais , Cacciamani Federica , Munro Catherine E , Gatchel Jennifer , Marshall Gad A , Vannini Patrizia 
Published: December 2023

AbstractBackgroundBoth loss of awareness for cognitive decline (a.k.a. anosognosia) and neuropsychiatric symptoms (NPS) are common symptoms in Alzheimer’s disease (AD) and have been associated with AD pathology. Recent studies have shown a co‐occurrence between these symptoms across the AD spectrum, suggesting shared underlying neurophysiological processes, especially within the default mode network (DMN). Here, we investigated the relationship between NPS and altered awareness and the structural integrity (as assessed with diffusion tensor imaging, DTI) of brain regions supporting the DMN in participants with and without amyloid pathology.MethodsThree‐hundred participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) underwent an amyloid positron emission tomography (PET), using 18F‐AV45 (florbetapir), and were classified into two groups: amyloid‐positive (A+) and negative (A‐). Individual mean fractional anisotropy (FA) was calculated from tracts overlapping the DMN regions. An awareness index was computed using the discrepancy between Everyday Cognition questionnaire scores from participants and informants. The Neuropsychiatric Inventory Total Score was used to assess the informant‐reported NPS. We compared amyloid groups on demographics and our different measures of interest. Pearson correlations were used to determine associations between measures of interest in each amyloid group. A multivariate multiple regression (MMR) model was performed to determine whether structural brain integrity predicts altered awareness and NPS jointly.ResultsA+ participants were significantly older (74 ± 7 vs. 72 ± 7 for A‐), more impaired (CDR global), and showed lower awareness and diffusion, and greater NPS (all p<0.001, see Table 1). Significant correlations were found between the FA, NPS, and awareness measures in A+ participants, with decreased FA associated with decreased awareness and more NPS. The MMR confirmed these associations between FA, awareness and NPS (p<0.02, see Table 2). The Pillai test revealed that the DTI effect jointly contributed to both models. No significant relationships were observed in the A‐ group.ConclusionOur results show that, in amyloid‐positive individuals across the AD spectrum, decreased awareness and increased NPS were related to decreased structural integrity of the DMN. This supports the hypothesis of common neurobiological mechanisms underlying anosognosia and NPS in AD.
Instant diagnosis of dementia in older patients who were admitted with forgetfulness to a single geriatric memory clinic
Authors: DOST Fatma Sena , ONTAN Mehmet Selman , Mutlay Feyza , KAYA Derya , ISIK Ahmet Turan 
Published: December 2023

AbstractBackgroundAging is a process associated with progressive and predictable changes that can cause many diseases. As in other systems, structural changes occur in the brain, behavior, and cognitive functions with age. Older people often complain about the decrease in cognitive skills, especially in the memory area and forgetfulness is one of the most common cognitive complaints. In this study, we evaluated the diagnosis of major and minor cognitive impairment in older people who were admitted with forgetfulness to our clinicMethodThis cross‐sectional study, retrospectively desgned, was conducted between January 2018 and January 2022 on a total of 1440 participants who applied to the Geriatrics department with the complaint of forgetfulness, without any acute health problems and with a complete geriatric assessment, including activities of daily living, evaluation of cognitive functions and mood, and blood tests. Dementia diagnosis was made according to the DSM‐V and related specific diagnostic criteria. All demented patients had brain imaging, and cerebrospinal fluid biomarkers, if possible.ResultThe mean age and female frequency were higher in patients with major and minor cognitive impairment while estimated glomerular filtration, folate, and TSH levels were lower. The prevalence of major and minor cognitive impairment was 7.70% and 21.30% respectively. Most of the 3 major neurocognitive impairment diagnoses were Alzheimer’s Disease (7.40%), dementia with Lewy body (3.50%), and Parkinson’s Disease Dementia (1.70%).ConclusionConsidering the risk of dementia in older adults, evaluating the memory complaints has of great importance. This study shows that the majority of the older adults who applied with the complaint of forgetfulness do not have dementia. It is remarkable that the rate of major and minor cognitive impairment was too high to be ruled out in our study population.
Determinants of dementia phenotype in North African & Mid‐eastern Israelis
Authors: Keret Ophir , Rabinovici Gil D. , Rosen Howard J. , Goldberg Ilan , Beninger Felix , Glik Amir 
Published: December 2023

AbstractBackgroundDiverse ethnic ancestry and adverse social health determinants are increasingly recognized to impact dementia on multiple dimensions: genetically and environmentally determined risk, clinical presentation, detection, and the utility of cognitive testing and management. Most evidence originates from ethnically diverse cohorts in North America, with little representation of other world regions. We aimed to assess dementia clinical and neuroimaging phenotype in individuals of Middle Eastern and Northern African (MENA) descent, a population severely underrepresented in brain health research.MethodsThe Alzheimer’s and atypical dementias in Israelis of diverse ancestry and disparate social health determinants (ADIDAS) project started on January 1st, 2022, and will prospectively recruit 200 individuals aged 40‐80 years reporting a new cognitive decline. The ADIDAS protocol includes APOE genotyping, structured assessment of early‐to‐late life social determinants, Israeli neighbourhood disadvantage index, medical history, vascular risk factors, cognitive testing, plasma Alzheimer’s biomarkers (Aβ40, Aβ42, total‐tau, p‐tau181, and NfL), and brain MRI. Ancestry was defined using participants and paternal country of birth. Countries were grouped into MENA, European, or neither, as defined by the World Bank. The project aims to assess the relationship between ethnic ancestry and associated social health determinants as predictors of brain neurodegeneration evident on neuroimaging and plasma biomarkers.Preliminary ResultsAs of January 1st, 2023, the ADIDAS cohort recruited 51 participants (55% female, mean age 65.8±8.4 years) of MENA (n = 24), European (n = 23), and neither (n = 3) ancestry. A preliminary comparison of MENA and European groups reveals MENA in our cohort are on average younger (63.87±8.9 vs. 68.3±8.2 years), have fewer years of schooling(11.7±2.5 vs. 16.2±3.4 years), and more likely to obtain only elementary or vocational education (75% vs. 13%). MENA were more likely to score poor results on cognitive testing‐ MMSE (21.6±4.9 vs. 24.8±5.5), receive a higher clinical dementia rating sum of boxes (3.4±2.5 vs. 1.45±1.4), and a lower carriage rate of apoE4 allele (11% vs. 30%).ConclusionPreliminary non‐matched comparison suggests MENA with early‐stage cognitive impairment have a different social, cognitive, and genetic risk profile than individuals of European ancestry. Results of plasma biomarkers profile and MRI‐related structural changes will be shared at AAIC2023.
Influence of visible white matter lesions on volumes from automated parcellations.
Authors: Sudre Carole H , Carrasco Ferran Prados , James Sarah‐Naomi , Wong Andrew , Malone Ian B , Cash David M , Fox Nick C , Cardoso M Jorge , Schott Jonathan M , Barnes Jo 
Published: December 2023

AbstractBackgroundWhite matter hyperintensities (WMH) are a common occurrence in ageing populations. Their hypointense appearance on T1‐weighted scans is known to affect automated processing and subsequent extraction of volumetric measurements. While lesion infilling with healthy appearing tissue is a common practice in the context of multiple sclerosis, this is not yet the case in studies of neurodegenerative diseases. We investigated the impact of WMH infilling on the volumetric outputs of two automated parcellation pipelines.MethodT1‐weighted and T2‐FLAIR scans were acquired for 462 individuals in the Insight46 neuroimaging substudy of the MRC National Survey for health and Development (NSHD). WMH were automatically segmented and T1‐weighted scans were subsequently infilled over the lesion masks. Two automated parcellation methods Geodesic Information Flows (GIF) and FastSurfer (FS) were run on the two T1‐weighted scans (original and infilled). Cortex, lateral ventricles, basal ganglia (BG), whole brain and total intracranial volumes (TIV) were derived from the four resulting parcellations. Spearman correlation was used to assess the relationship within and across methods according to infilling status. Correlations were also calculated between the observed volumes or percentage difference (original vs infilled volumes) and the WMH burden expressed as percentage of TIV.ResultThe relationship between parcellated volumes and WMH burden varied across methods and tissues/brain areas. While there was little observable relationship for GIF between brain volume or TIV difference and WMH, this relationship was positive for FS. The relationship with cortical volume difference was in opposite directions for GIF (negative relationship) and FS (positive relationship), indicating a tendency to decrease the estimated volume when WMH were visible for GIF and increase it for FS. For lateral ventricles and basal ganglia, volumetric measurements were higher in the presence of visible WMH for GIF and FS (Figure1). Correlations between FS and GIF were slightly stronger after infilling but correlation with WMH burden were attenuated (Table2).ConclusionThe impact of presence of visible WMH on T1‐weighted scan varies according to the chosen technique of analysis and strong correlations were observed between the difference in measured volumes and the WMH burden. Infilling should be considered when T1‐weighted derived volumes are studied.
Inflammation and working memory performance in everyday life: Gender differences among older adults with and without cognitive impairment
Authors: Harrington Erin E , Graham‐Engeland Jennifer E , Lipton Richard B. , Roque Nelson A , Sliwinski Martin J. , Engeland Christopher G. 
Published: December 2023

AbstractBackgroundInflammation is a risk factor for cognitive decline, mild cognitive impairment (MCI), and Alzheimer’s disease (AD). Past research suggests that inflammation relates to cognitive performance and MCI status in laboratory settings, but it remains unclear how inflammation relates to everyday cognitive performance. The present work addressed this gap by examining inflammatory biomarkers in association with working memory measured via ecological momentary assessments (EMA) among those with and without MCI. Gender differences in these links were also examined.MethodOlder adults (n = 270, Mage = 76.97, 68% female) enrolled in the Einstein Aging Study were classified as MCI (n = 78) or no MCI using Jak Bondi criteria. Participants completed a two‐week EMA protocol which included daily periodic assessments of spatial working memory and provided two blood samples (one before and one following EMA), from which circulating (basal) and lipopolysaccharide (LPS)‐stimulated cytokines were quantified. Analyses examined correlations between inflammatory markers and working memory performance (i.e., accuracy – mean error distance) stratified by MCI status and by gender.ResultsAmong those with MCI, higher levels of circulating cytokines (interleukin [IL]‐1b, IL‐6, IL‐10) correlated with worse working memory performance. In the MCI group, higher levels of stimulated cytokines (IL‐4, IL‐6, IL‐8, IL‐10, tumor necrosis factor‐alpha [TNF‐ α]) were associated with better performance. When examined by gender, it was men with MCI who appeared to drive these effects, as higher levels of circulating IL‐1b correlated with worse performance and higher levels of stimulated cytokines (IL‐1b, IL‐6, IL‐8, IL‐10, TNF‐α) correlated with better performance. No significant associations were observed among men without MCI, or among women regardless of MCI status. Findings held when controlling for BMI, age, and education.ConclusionKeeping with past work, the present study suggests that higher levels of circulating inflammation relate to worse working memory in everyday settings. Further, exhibiting a more robust response to immunological challenge (i.e., higher stimulated cytokines) may relate to better everyday working memory. However, these associations were observed only in men with MCI. Future longitudinal research is needed to better understand the links between circulating inflammation, inflammatory responses, and MCI; ultimately, this might inform early risk detection for MCI and AD.
Variability in Sleep is Associated with Inflammatory Biomarkers: Results from the Einstein Aging Study
Authors: Ji Linying , Shen Yuqi , Harrington Erin E , Van Bogart Karina , Graham‐Engeland Jennifer E , Derby Carol A. , Engeland Christopher G. , Buxton Orfeu M. 
Published: December 2023

AbstractBackgroundPrior research links poor subjective sleep and higher systemic inflammation, both of which are risk factors for cognitive decline in older adults. To expand upon previous findings, we investigated associations between multiple objective aspects of sleep health (including sleep variability) and inflammation (including stimulated inflammatory markers) among a diverse sample of older adults.MethodParticipants free of dementia (N = 218, mean age = 77.5 years, 66% females; 46% White, 38% Black, 14% Hispanic/other, MCI positive = 61) enrolled in The Einstein Aging Study were included. Wrist actigraphy (Spectrum Plus) over 16 days yielded measures of sleep disturbance by wake after sleep onset (WASO), sleep duration as total night sleep time (TST), sleep timing (midpoint of night sleep), and variability of each sleep measure. Inflammatory markers included circulating CRP and interleukin (IL)‐1β, IL‐4, IL‐6, IL‐8, IL‐10, and tumor necrosis factor (TNF)‐𝛼 plus lipopolysaccharide (LPS)‐stimulated levels of these same cytokines. Separate linear regression models evaluated the association of each inflammatory marker and the average level and variability of each sleep measure. Models controlled for BMI, gender, age, education, and race/ethnicity.ResultCirculating inflammatory markers were generally not associated with objective sleep measures. However, after controlling for covariates, associations were observed between shorter average WASO and higher IL‐4, later average night sleep midpoint and higher IL‐6, and more variability in TST with higher IL‐1β. For stimulated cytokines, more WASO variability was associated with higher levels of all stimulated cytokines except IL‐6 and IL‐1β. More variability in sleep duration (TST) was associated with higher IL‐8 (but not other cytokines). Mean and variability of sleep timing, and mean WASO and TST were not significantly associated with any of the stimulated cytokines.ConclusionThe present findings add substantially to research suggesting that sleep patterns are related to inflammation in older adults. Stimulated cytokines [IL‐4, IL‐10, IL‐8, TNF𝛼] were more strongly related to variability measures than mean sleep measures. Since stimulated cytokine levels reflect inflammatory reactivity to immune challenge, the present findings suggest future work should explore underlying relationships between poor sleep and central disruption, and possibly neurodegeneration, in older adults. Specifically, poor sleep (greater sleep variability) might contribute to higher reactivity of neuroinflammation pathways.