bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are social network and nativity status associated with neurocognitive functioning in a sample of middle/older adults from the “Study of African Americans and Latinas/os to Understand Dementia”‐SALUD?
Authors: Oleas Denise S. , Arentoft Alyssa , Cham Heining , Slaughter Alexander W. , Breen Elizabeth Anne , Schuck Lauren A , Camuy Alicia M , Talavera Sandra , Mindt Monica Rivera 
Published: December 2023

AbstractBackgroundOlder adults may experience decreased social support, which has been linked to cognitive decline and increased risk of dementia. Immigrants may also experience more social isolation due to discrimination and fear of deportation. This study examined social networks, nativity status, and neurocognitive functioning(NC) in an ethnoculturally diverse sample of middle/older adults.MethodParticipants included 26 immigrants (Mage= 64.12, SD = 5.64) and 109 U.S.‐born adults (Mage= 65.37, SD = 7.10). Participants completed a comprehensive NC battery and the Berkman‐Syne Social Network Index(SNI; a well‐validated self‐reported questionnaire assessing close social support, where higher scores represent more social support). Demographically‐adjusted norms were used to compute average global NC and domain T‐scores. A series of hierarchical multiple regressions were computed to predict global and domain NC T‐scores. SNI and age were entered at Step‐One, the interaction term(age*SNI) was entered at Step‐Two, and nativity status was entered at Step‐Three.ResultResults revealed that the omnibus model was significantly associated with Attention/Working Memory(A/WM) (R² = .13; ps = .009) and Processing Speed(PS) (R² = .20; ps = .002). Notably Step‐Three of the model significantly contributed to the association of AWM (R²Δ= .11; ps<.05) and PS (R²Δ= .09; ps<.05) beyond Step‐One and Step‐Two. For A/WM, the interaction term, and nativity status (𝛽s = .04‐6.96, respectively; ps<.05) were significantly associated with A/WM. For PS, SNI, the interaction term, and nativity status (𝛽s = ‐3.91‐8.17; ps<.05) were significantly associated with PS. Such that, there is a main effect of nativity status with immigrants scoring lower on measures of A/WM by 6.96 and PS by 8.17 units. Overall, there is a negative association between age and A/WM and PS but as SNI increases the relation between age and NC becomes positive. Only nativity status (𝛽s = 5.99‐8.23; ps<.05) significantly predicted Memory, Verbal Fluency, and Global NC functioning scores.ConclusionFindings show that among middle/older adults, both SNI and nativity status are associated with A/WM and PS, suggesting that a larger SNI can serve as a protective factor against the effects of aging on NC functioning. Importantly, even when SNI and age were not significantly related to NC T‐scores, nativity status was. Nativity status likely serves as a proxy for other risk factors (e.g., healthcare access), which should be explored in future studies.
Higher baseline cerebrospinal fluid platelet‐derived growth factor receptor‐β levels are associated with slower reductions in longitudinal cerebral blood flow among cognitively unimpaired individuals
Authors: Moore Elizabeth E. , Zhang Panpan , Pechman Kimberly R. , Liu Dandan , Houston Michelle L , Shashikumar Niranjana , Davis L. Taylor , Archer Derek B. , Gifford Katherine A. , Landman Bennett A. , Blennow Kaj , Zetterberg Henrik , Hohman Timothy J. , Jefferson Angela L. 
Published: December 2023

AbstractBackgroundCerebrospinal fluid (CSF) platelet‐derived growth factor receptor‐β (PDGFR‐β) is an emerging biomarker hypothesized to reflect pericyte damage. CSF PDGFR‐β levels are increased in Alzheimer’s disease (AD), but it is unknown if pericyte injury contributes to cerebrovascular changes common in AD. We examined if PDGFR‐β relates to changes in cerebral blood flow (CBF) and white matter injury in older adults.MethodVanderbilt Memory and Aging Project participants (n = 152, baseline age 73±7 years, 43% mild cognitive impairment [MCI]) underwent baseline lumbar puncture and serial brain MRI over a 7‐year (5.5±2.3) follow‐up period. CSF PDGFR‐β concentrated was measured by immunoassay. MRI included pseudo‐continuous arterial spin‐labeling to quantify CBF, T2‐FLAIR to quantify white matter hyperintensities (WMHs), and diffusion tensor imaging (DTI) to quantify white matter microstructural integrity. Ordinary least squares regression and linear mixed‐effects models related baseline CSF PDGFR‐β to baseline and longitudinal whole brain and regional CBF, WMH, and DTI metrics, adjusting for baseline demographic variables, modified Framingham Stroke Risk Profile, cognitive status, apolipoprotein‐ε4 status, and regional tissue volume. Longitudinal models adjusted for follow‐up time. Follow‐up models tested a CSF PDGFR‐β x cognitive status interaction.ResultIn main models, higher CSF PDGFR‐β levels were cross‐sectionally associated with lower mean diffusivity (indicating better microstructural integrity) in white matter tracts in the frontal, temporal, parietal, and occipital lobes (p‐values<0.03) but were unrelated to WMHs (p‐values>0.18). Models investigating associations with longitudinal white matter variables were null (p‐values>0.35). CSF PDGFR‐β cross‐sectionally interacted with diagnosis on temporal lobe CBF, such that higher CSF PDGFR‐β related to higher CBF in MCI participants (p = 0.01). In longitudinal models, baseline CSF PDGFR‐β interacted with cognitive status on whole brain and occipital lobe CBF (p‐values<0.04). Stratified models showed higher baseline CSF PDGFR‐β related slower reductions in longitudinal CBF in whole brain (p = 0.02), frontal (p = 0.04), temporal (p = 0.02), parietal (p = 0.01), and occipital lobes (p = 0.008) in cognitively unimpaired participants only.ConclusionAmong older adults, higher CSF PDGFR‐β levels are associated with better white matter integrity at study entry and predict slower reductions in longitudinal CBF among cognitively unimpaired individuals. Results suggest that higher PDGFR‐β levels may reflect subclinical vascular remodeling that provides protection to future cerebrovascular compromise.
Investigating the effect of neuropsychiatric symptoms on Alzheimer’s diagnosis using multi‐modal brain networks
Authors: Guo Lei , Zhang Yanfu , Tang Haoteng , Mackin Scott R , Thompson Paul M , Huang Heng , Zhan Liang 
Published: December 2023

AbstractBackgroundStudies suggested that the comorbidity between Neuropsychiatric Symptoms (NPS) and dementia highlights the prognostic value in prodromal phases. Our central hypothesis is that the accurate prediction of NPS can improve the Alzheimer’s diagnosis. We adopt deep learning techniques to simultaneously predict MCI and depression, one of the most frequently observed NPS and measured by GDS score.MethodWe analyzed 114 subjects from the ADNI‐D project, including 77 NC (70.91±5.3, 19 males) and 37 MCI (70.51±4.66,17 males). (No difference in age or GDS between groups). 85×85 brain structural and functional networks were reconstructed for each subject. We propose a multi‐view graph neural network (GNN) (Figure 1) to predict cognitive status (classification) and NPS score (regression) simultaneously. To verify our method and hypothesis, we selected five baselines, including three non‐deep methods (logistic regression, random forest, and SVM) and two deep methods (two‐layer MLP and GNN which uses the same model as ours but only considers the classification task).ResultWe firstly conducted traditional regression analyses (Y ∼ Age + Sex + GDS) and Y can be brain functional or structural network edges or the derived network measures. Our results show that none of these measures are survived after applying the Bonferroni correction to account for multiple comparisons, which indicates that the GDS and brain network may not predict each other using a linear model. Then, we tested the deep learning approach, and our proposed framework achieves the best performance among all three evaluation matrices (Acc, F1 score, and AUC) in comparison with other baseline methods. (Figure 2)ConclusionThese results demonstrate that the depression score can be used to improve the MCI diagnosis, apparently favoring our central hypothesis. Our future work will focus on conducting more analyses on different NPS and different stages of dementia.Figure 1. Proposed multi‐view GNN. The first layer considers both node features (red) and edge features (blue) to compute the hidden representations for the next layer. The second layer only considers node representations (brown). The node‐level embeddings are then max‐pooled and concatenated to yield the final multi‐view graph‐level embedding.Figure 2. The comparison of prediction results.
Neuroimaging Correlates of Alzheimer’s Disease biomarkers in a mid‐life, racially diverse high‐risk cohort
Authors: Munkombwe Chinkuli , Misiura Maria , Igwe Kay C. , Likos Kelly D. S. , Verble Danielle D , Zetterberg Henrik , Brickman Adam M. , Hu William T. , Dotson Vonetta M , Wharton Whitney 
Published: December 2023

AbstractBackgroundClinicians and researchers utilize neuroimaging (NI) biomarkers of Alzheimer’s disease (AD) at an increasing rate. It is crucial that we determine whether these biomarkers generalize to underrepresented populations, particularly Black Americans (BAs), as they are 64% more likely as white individuals to develop AD. BAs may exhibit unique AD biomarker profiles across disease states, including NI biomarkers. Investigating biomarkers in at‐risk individuals may allow for early identification and intervention. Here we analyze comprehensive NI biomarkers including resting state fMRI, white matter lesions, and hippocampal volumes in conjunction with cerebrospinal fluid (CSF) markers in a midlife, racially diverse, cognitively normal cohort with a parental history of AD.MethodData included 57 cognitively normal, middle‐aged individuals, 14 BAs and 43 white. CSF was acquired via lumbar puncture to determine CSF t‐tau and Aβ1‐42 concentrations. Using resting state fMRI data, we analyzed default mode network connectivity between the posterior cingulate & precuneus, parrahippocampal gyrus (PHG), temporal pole, hippocampus, and lateral temporal cortex. We obtained regional WMH data from FLAIR images using an in‐house algorithm, and hippocampal volumes from Freesurfer. In our multivariate model, outcome variables were connectivity values, regional WMH and hippocampal volumes, with race and CSF t‐tau and Aβ1‐42 as our independent variables with a race X CSF interaction term.ResultWe identified a significant race X t‐tau and race X Aβ1‐42 interaction term for temporal and parietal WMH volumes and connectivity between PHG and temporal pole. Higher AD CSF biomarkers negatively correlated with brain connectivity (p = 0.01), and positively with WMH volume (p<0.001) in BAs.ConclusionWe extend our previous work to a middle‐aged cohort to show that DMN connectivity may be a predictor of AD risk in middle‐age, particularly for BAs, and that BAs may exhibit earlier vulnerability to vascular lesions. We support previous work that the temporal lobe is the first region to experience AD‐related connectivity changes, and that WMHs may predispose this region to AD vulnerability. This study emphasizes the need for recruitment of diverse cohorts in NI studies of AD.
Subcortical deformation is uniquely related to cortical thickness among FTLD mutation carriers
Authors: Stocks Jane K , Heywood Ashley , Beg Mirza Faisal , Cobigo Yann , Rosen Howard J. , Wang Lei 
Published: December 2023

AbstractBackgroundFrontotemporal lobar degeneration (FTLD) due to familial mutations results in heterogenous clinical phenotypes for which there are no specific biomarkers. Here, we test whether subcortical deformation differs in FTLD genetic mutation carriers, and if deformation was uniquely related to cortical thickness.Method317 participants from ALLFTD with familial FTLD (C9orf72 (n = 139), GRN (n = 77), and MAPT (n = 101)) and 27 controls without mutations (NCC) were evaluated. MRI data underwent FreeSurfer processing to estimate cortical thickness (CT). High‐dimensional, large‐deformation diffeomorphic metric mapping was used to model surfaces of the caudate and putamen. Regression analyses investigated the effect of mutation on CT and subcortical surface deformation, after controlling for age, sex, and education. Finally, linear models were constructed in each mutation group to explore the association between areas of significant surface deformity and CT, corrected for age and multiple comparisons.ResultFigure 1 shows significant (corrected p<.05) T‐scores where mutation carrier groups differ in CT from NCC (red = greater atrophy in mutation). Figure 2 shows greater outward local deformation in the caudate body among C9 and MAPT compared to NCC. Significant relationships between deformation and CT (corrected p<.05) were observed in bilateral temporoparietal, frontal and cingulate cortex in both C9 and MAPT carriers. C9 and MAPT mutation carriers have greater outward deformation in postero‐lateral putamen. Deformation was associated with CT in C9 within the left temporal and prefrontal lobes, and in the right temporoparietal, occipital and cingulate cortices for MAPT (Figure 3). No significant deformation was observed in GRN compared to NCC.ConclusionFamilial FTLD mutations are associated with subtle subcortical shape variations that show unique relationships to cortical atrophy.
Multi‐cohort genome‐wide association study on flortaucipir PET identifies novel risk loci associated with tau deposition and its role in AD pathology
Authors: Gunasekaran Tamil Iniyan , Lee Annie J , Dumitrescu Logan C , Mormino Elizabeth C. , Sperling Reisa A. , Saykin Andrew J. , Hohman Timothy J. , Vardarajan Badri N ,   Alzheimer’s Disease Neuroimaging Initiative
Published: December 2023

AbstractBackgroundAmyloid‐β plaques and tau neurofibrillary tangles are the pathological hallmarks of Alzheimer’s disease (AD). Previously, genetic studies on amyloid‐β mediated AD pathogenesis dominated the field, and genetic studies on tau pathology are limited by comparison. Prior studies suggest that the spread of tau neurofibrillary tangles within the medial temporal lobe occurs following abnormal deposition of amyloid‐β, leading to cognitive impairment. Although amyloid‐β and tau both play a role in AD pathogenesis, exact genetic pathways associated with them are still unknown.MethodWe performed genome‐wide association study (GWAS) with brain Tau standard uptake value ratios (SUVRs) measured from positron emission tomography (PET) images from the A4 ((N = 311 with preclinical AD;female = 62%;tau mean‐SUVR = 1.076±0.06) and ADNI studies (N = 375‐280 cognitively normal, 76 mild cognitively impaired and 19 AD;female = 53%;tau mean‐SUVR = 1.12±0.13). Models were adjusted for age, sex and APOE‐ε4 dosage. Additionally, we evaluated the association of amyloid‐β and tau SUVRs with AD polygenic risk scores (PRS). PRS was calculated using genome‐wide variants, excluding 1MB region flanking APOE, and effect sizes from Kunkle et al GWAS study of clinical AD.ResultAnalysis of tau‐SUVR in 686 participants, identified five genome‐wide significant loci: rs78636169 (P = 1.37×10−9) in JARID2, rs114272033 (P = 7.87×10−9) in ISCA1P2, rs7292124 (P = 1.73×10−8) in RP1‐272J12.1, rs114742337 (P = 2.85×10−8) in RP4‐771M4.2, and rs138338441 (P = 3.91×10−8) in AC092684.1. Rs13412014 in AC007364.1 and rs9393067 in RP11‐314C16.1 were also associated with amyloid‐SUVR in a previous large GWAS. Two loci previously associated with clinical AD in a recent large GWA study, INPP5D (rs10933431) and SEC61G (rs76928645), were also nominally associated (P<0.05) with tau deposition in our study. Genes associated with Tau‐SUVR are enriched in the Schaffer axonal collaterals (P<1×10−05) that form synapses in hippocampus. Genome‐wide PRS of AD (excluding APOE region) was strongly associated with amyloid‐SUVR (P = 3.21×10−11;R2 = 0.077) but only weakly associated with tau‐SUVR (P = 1.38×10−04;R2 = 0.027). We are in the process of replicating our results in an independent cohort of 700 participants with measurements of tau deposition.ConclusionWe identified five novel genetic loci associated with tau pathology. Several genes involved in tau deposition were also associated with amyloid load in the brain. Taken together, our findings will clarify the genetic pathways that effect both amyloid and tau pathology in AD.
Tau and amyloid PET associations with impaired sleep and 24‐hour rhythms across aging and neurodegenerative disease
Authors: Winer Joseph R. , Romero America , Lok Renske , Vossler Hillary , Young Christina B. , Anders David , Shen Bin , Morales Aimara Pacheco , Davidzon Guido , Henderson Victor , Poston Kathleen L. , Zeitzer Jamie M , Mormino Elizabeth C. 
Published: December 2023

AbstractBackgroundDisrupted sleep and fragmentation of sleep‐wake rhythms are common in the context of healthy aging as well as in neurodegenerative disease. As wearable devices become increasingly popular among older adults, there is a growing need to understand how metrics of sleep‐wake behavior might be able to identify neurodegenerative disease and differentiate disease etiology and severity.MethodParticipants (n = 145) from the Stanford Alzheimer’s Disease Center (ADRC) and the Stanford Aging and Memory Study (SAMS) were recruited for 14 days of at‐home actigraphy (wrist‐worn accelerometry) data collection. A subset of participants received 18F‐PI‐2620 and 18F‐florbetaben PET scans to assess tau and amyloid burden. The cohort included cognitively normal older adults (healthy controls, HC), patients with Alzheimer’s disease (AD) spectrum, and patients on the Lewy body (LB) disease spectrum. Actigraphy analyses focused on nocturnal sleep efficiency, 24‐hour diurnal amplitude, and 24‐hour activity fragmentation (intradaily variability, IV). Amyloid burden was quantified in centiloids and tau burden was quantified as 18F‐PI‐2620 SUVR within bilateral inferior temporal cortex. The Neuropsychiatric Inventory Questionnaire (NPI‐Q) was used as a measure of neuropsychiatric symptom severity.ResultLB patients had lower 24‐hour activity levels relative to AD and HC participants, as measured by diurnal amplitude (W’s≥650, p’s<0.01; Fig 1A & B). AD patients had marginally higher IV relative to HC (W = 1084.5, p<0.1; Fig 2A & B), whereas sleep efficiency was comparable across etiologies and cognitive status (Fig 1C). Higher IV was associated with higher NPI‐Q scores in cognitively impaired patients (rho = 0.31, p = 0.03; Fig 2C). Greater amyloid burden was associated with lower diurnal amplitude in HC and AD (rho = ‐0.29, p = 0.02; Fig 3A). Inferior temporal tau was associated with sleep efficiency both within HC and AD (rho = ‐0.28, p = 0.07; Fig 3B) and in all amyloid‐positive participants (rho = ‐0.41, p = 0.02; Fig 3C).ConclusionThese findings suggest that sleep and 24‐hour rhythms show meaningful variation across individuals and are associated with AD and LB disease severity. While sleep efficiency and IV did not robustly differ between AD and LB groups, the measures were associated with disease‐related features such as biomarkers of amyloid and tau pathology and neuropsychiatric symptoms.
The Ethics of Past and Future Memory Care Models: Perspectives from the Dutch and Danish Dementia Villages
Authors: Roberts Emily 
Published: December 2023

AbstractDementia care organizations face a range of daunting environmental changes and challenges. Internationally, there is a long history of efforts to improve quality of care and life for individuals with dementia. In a time of particular attention to the images of older adults confined to a single or shared room in a care facility due to COVID‐19, autonomy becomes the overarching problem, not only because in general institutions limit the freedom of frail elders, but because the existential conditions that create the need for long term care such as chronic disease, cognitive decline, and the need for general support with activities of daily living (ADLs) rail against the autonomy of independent self‐sufficiency. Additionally, these environments are institutional in design and size, with little access to outdoor spaces and other amenities. This perspective manuscript addresses the ethics of past and future memory care models, looking specifically at the European Dementia Village model. This model allows for autonomy and continuation of patterns of daily living through housing integrated with large exterior walks and gardens, restaurants shops and amenities within familiar and normal surroundings, reducing resident anxiety and fear. This pioneering health care experiment negotiates rivaling discourses of intimacy, professionalization and medicalization. In order to get a deeper understanding of the culture and ethics of the model, the first two dementia village sites were visited which included meetings with care staff and administrators. Those conversations and observations led to a series of aligned themes relating to the ethics of the DV model which include: the strength of the social approach, clinical support, resident/staff collaborations and advocating for ethical dementia care.
Serum Arachidonic Acid Oxylipins Indicate Small Vessel Injury And the Related Executive Function Decline In Stroke Patients
Authors: Yu Di , Liang Nuanyi , Xiong Lisa Y. , Shen Qing , Lin William Z. , Ozzoude Miracle , Goubran Maged , Rabin Jennifer S. , Ramirez Joel , Symons Sean , Haddad Seyyed MH , Tan Brian , Nanayakkara Nuwan D. , Dilliott Allison Ann , Binns Malcolm , Beaton Derek , Arnott Stephen R. , Lawrenece‐Dewar Jane M , Sahlas Demetrios J. , Casaubon Leanne , Otoki Yurika , Lanctôt Krista L. , Masellis Mario , Swartz Richard H. , Taha Ameer Y. , Swardfager Walter ,   The ONDRI Investigators
Published: December 2023

AbstractBackgroundCerebral small vessel disease (SVD) frequently co‐occurs with other neurodegenerative pathologies and collectively lead to cognitive deficits. Previously, we found that the ratios of soluble epoxide hydrolase (sEH)‐ derived diols to the parent epoxides (generated by CYP2J/2Cs) linoleic acids were associated with greater white matter hyperintensities (WMH) and poorer executive function in patients with transient ischemic attack. However, the associations with the diol and epoxide species derived from arachidonic acid (AA) have not been explored.MethodsThe study cohort is comprised of 159 stroke patients (mean age = 69.2, 32.1% female) from the Ontario Neurodegenerative Degenerative Research Initiative. EpETrEs (AA epoxides) and DiHETrEs (AA diols) were quantified by a targeted ultrahigh pressure liquid chromatography mass spectrometry (UPLC‐MS/MS). Executive function was assessed using a composite score that included Digit Symbol Substitution Test (DSST), Trial‐Making Test Part B, Stroop Color‐Word Interference Test, and FAS Verbal Fluency Test. WMHs were quantified from T2‐Fluid‐Attenuated‐Inversion‐Recovery MRI through Lesion Explorer (https://imaging.brainlab.ca/lesion‐explorer.html).In linear models controlling for age, sex, education or age, sex, glucose, cholesterol, and waist circumferences were used for cognitive and imaging out comes, respectively.Results11(12)‐EpETrE was found to be associated with less WHM (ρ = ‐0.175, p = 0.040) and better executive function (ρ = 0.166, p = 0.039). In a sub‐cohort of patients with small vessel stroke (n = 50), the relationship between WMH and 11(12)‐EpETrE became stronger (ρ = ‐0.390, p = 0.014). 14(15)‐EpETrE was also associated with less WMH (ρ = ‐0.416, p = 0.009). Similar relationships were not seen with the diols or diol to epoxide ratios.ConclusionsOxylipins derived from sEH activity may be potential biomarkers of vascular cognitive impairment and small vessel disease in stroke patients.