bluuebunny/crossref_metadata_2025_split huggingface dataset:
Family Caregiving in a Great Lakes Native American Community: A Mixed Methods Study of Service Utilization
Authors: Wyman Mary F. , Lambrou Nickolas H. , Lewis Jordan P. , Buerger‐Cole Haley M. , Hammock Colin , Klammer Kristianna , Lawrence Sacheen L. , Miller Debra A. , Petri Florence , Perzynski Joseph D. , Johnson Adrienne L. , Zuelsdorff Megan , Gleason Carey E. 
Published: December 2023

AbstractBackgroundNative Americans are disproportionately impacted by ADRD, and family caregiving is uniquely significant within Indigenous communities. Caregiving services can improve outcomes but are underutilized, and increasing use of caregiver services is key to addressing the dementia care crisis. Indigenous populations are underrepresented in the ADRD caregiving literature, resulting in a significant gap in understanding of how to improve engagement with services. We examine perspectives on service utilization among caregivers in a large tribal nation in the US Great Lakes region.MethodWithin a community‐based research partnership between the Wisconsin ADRC and the Oneida Nation of Wisconsin, N = 481 completed a survey on use of seven common caregiver resources, including support groups, respite, caregiver training, household help, transportation for care recipient, nursing home, and financial assistance. Drawing on the Andersen model of utilization, multiple regression models examined correlates of positive attitudes toward use of services among caregivers (N = 207), defined as past, current, or intended future use of services. Follow‐up in‐depth interviews with 10 caregivers of elders with ADRD (Table 3) explored decision‐making regarding service utilization using qualitative content analysis.ResultThere were few demographic differences between caregivers and non‐caregivers in the sample (Mage = 52 and 54 yrs; 75% female; Table 1). Over half (54.6%) of caregivers were employed; most (64%) cared for someone with ADRD. In the final regression model in the caregiver subsample, only level of belief that traditional Oneida values and practices support caregivers in using caregiver services predicted positive attitudes toward service utilization (p<.001; Table 2). Interviews revealed barriers to service use include low awareness, complexities of service funding structures, and Elder preferences. Perceptions of alignment of traditional cultural values with service use were complex and nuanced.ConclusionUsing mixed methods in a Native American community sample, we identified unique barriers to access resources to support elders with ADRD and their families, including perceived cultural support for service use. Our findings contribute to the scant literature on ADRD caregiving among Native Americans and provide support for tailored interventions (e.g., Savvy Caregiver in Indian Country). Results can inform public health initiatives to address ADRD disparities and improve outcomes for Indigenous persons with ADRD.
Utility of accessible neuroimaging markers of cerebrovascular disease in identifying cerebral amyloidosis across the Alzheimer’s disease spectrum
Authors: Howe Matthew D. , Emrani Sheina , Kunicki Zachary J. , Britton Karysa J. , Salloway Stephen , Oh Hwamee ,   Alzheimer’s Disease Neuroimaging Initiative
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is defined by the presence of cognitive impairment and cerebral amyloidosis and is associated with several cerebrovascular disease (CVD) risk factors including age, apolipoprotein‐E ε4 (APOE‐ε4) genotype, hypertension, diabetes and hyperlipidemia. Despite this association, the clinical utility of individual CVD biomarkers in screening for AD pathology is understudied. Therefore, we sought to examine the relationship between cerebral amyloidosis and magnetic resonance imaging (MRI)‐based CVD measures, including cerebral microbleeds, ischemic infarction, and white matter hyperintensities (WMH). We hypothesized that CVD biomarker burden would be positively associated with amyloidosis. Given recent studies have shown plasma phospho‐tau181 (P‐tau181) is a promising early biomarker of amyloidosis, we further hypothesized that combining P‐tau181 with CVD biomarkers would predict amyloid status in cognitively unimpaired and impaired persons.MethodParticipant data were extracted from the Alzheimer’s Disease Neuroimaging Initiative database (N = 1,430). Volumetric data (WMH volume [WMHv], medial temporal lobe volume [MTLv]) were normalized and log‐transformed. Adjusted odds ratio (OR) was calculated using logistic regression with dichotomized amyloid‐PET status as the outcome. Area under the curve (AUC) was compared by the likelihood ratio test.ResultAfter adjustment for age, sex, APOE‐ε4 status, MTLv, cognition (MoCA), and other CVD biomarkers of interest, we found that WMHv alone was significantly associated with amyloidosis in both cognitively impaired (OR = 1.21) and unimpaired (OR = 1.25) persons. We then developed an accessible diagnostic model incorporating WMHv, significant covariates and plasma P‐tau181. Addition of P‐tau181 to the model improved diagnostic accuracy in cognitively impaired persons (AUC = 0.85 to 0.87, p < 0.001), and did not attenuate the relationship between WMHv and amyloidosis.ConclusionWe newly identify WMH, but not other CVD lesions, as predictive of amyloidosis in both preclinical and symptomatic AD. The current study adds to the literature regarding which CVD biomarkers are most predictive of AD pathology. Measurement of WMH alongside P‐tau181 and other biomarkers may produce an accessible screening algorithm for AD. Study generalizability is limited by ascertainment bias and lack of diversity. Future research will compare the performance of WMH to standard AD biomarkers in a more diverse, community‐based sample.
Comparison of longitudinal rates of atrophy and tau accumulation between posterior cortical atrophy and logopenic progressive aphasia
Authors: Sintini Irene , Radford Jonathan Graff , Machulda Mary M. , Singh Neha Atulkumar , Carlos Arenn Faye , Schwarz Christopher G. , Senjem Matthew L. , Jack Clifford R. , Lowe Val J. , Josephs Keith A , Whitwell Jennifer L 
Published: December 2023

AbstractBackgroundPosterior cortical atrophy (PCA) and logopenic progressive aphasia (LPA) are atypical variants of Alzheimer’s disease which typically show different cross‐sectional patterns of atrophy and tau deposition. Patterns of atrophy remain distinct longitudinally. A direct comparison of rates of atrophy and tau accumulation between these syndromes has not yet been reported.MethodWe evaluated 20 PCA and 20 LPA patients; all were amyloid‐positive on [11C]PiB‐PET. Structural MRI and tau‐PET were performed at baseline and one‐year follow‐up. Annualized rates of change in grey matter volume (log Jacobians from tensor‐based morphometry) and flortaucipir‐PET SUVRs were calculated at the lobar level. A global tau SUVR was calculated using parietal, temporal, and occipital regions. Lobar rates were compared between PCA and LPA with linear models, accounting for education, sex, age, baseline global tau SUVR (for tau‐PET), with significance set at p = 0.05. SPM voxel‐level comparisons were performed, with the same covariates, with significance set at p = 0.001.ResultGroups did not differ in age, Apoe status, baseline global tau SUVR or whole brain volume, or their annualized rates of change. LPA had shorter disease duration. In the lobar models, PCA had faster rates of atrophy in the occipital lobe and there were no significant differences on rates of tau accumulation, but a trend for LPA having faster rates of tau accumulation in all lobes. Baseline global tau SUVR was negatively associated with rate of tau accumulation in parietal and temporal lobes. Age was negatively associated with rates of tau accumulation in frontal, temporal and occipital lobes and with rates of atrophy in frontal and parietal lobes. Voxel‐level analysis confirmed these results, with PCA showing faster rates of occipital atrophy, and LPA showing subtle evidence for diffuse faster rates of tau accumulation (Figure 1).ConclusionLongitudinal patterns of neuroimaging abnormalities differ between PCA and LPA, although with divergent results for tau accumulation and atrophy that may reflect differences in disease stage. Rates of change are strongly influenced by age and severity of baseline tau, with faster rates of tau accumulation in patients with younger age and lower baseline tau deposition.
The Mobile Toolbox for monitoring cognitive change
Authors: Gershon Richard C. 
Published: December 2023

AbstractBackgroundThe NIH Mobile Toolbox (MTB) includes adapted self‐administered versions of the NIH Toolbox® measures in an expanding library of other brief, sensitive, and easy‐to‐use tasks. Investigators can use the MTB to design smartphone‐based test batteries, develop custom surveys, deploy and manage data collection, and aggregate results. Ease of deployment enables use of the measures in targeted studies, as well as for use in large‐scale surveillance of adults ages 18+ (e.g., to track cognitive functioning across many ages to better understand the life‐course development of Alzheimer’s Disease and ADRD). We describe MTB and demonstrate use of the platform.MethodMTB was created through an NIA‐funded, multi‐institutional effort led by teams based at Northwestern University, Sage Bionetworks, UCSF, and Penn State. All MTB measures were developed for use on Apple and Android smartphones, and then fully validated and then normed in a large national sample.ResultThe MTB library includes eight core cognitive tests assessing language (Spelling; Word Meaning), executive functioning (Arrow Matching; Shape‐Color Sorting), associative memory (Faces and Names), episodic memory (Arranging Pictures), working memory (Sequences) and processing speed (Numbers and Symbols). The system can also passively collect contextual factors that might influence performance. Additional cognitive and non‐cognitive assessments from the International Cognitive Ability Resource (ICAR), Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia (CNTRACS), Test My Brain, NIH Toolbox Emotion and the Patient‐Reported Outcomes Measurement Information System (PROMIS) will be available later this yearConclusionThe MTB addresses many scientific, practical, and technical challenges to cognitive assessment by capitalizing on advances in technology, measurement, and cognitive research. Additional clinical validation is underway in clinical and healthy populations, including those at risk for or diagnosed with cognitive impairment or AD/ADRD. MTB is suitable for use in research incorporating point‐in‐time and burst designs as well as ecological momentary assessment (EMA). Guided by the principles of open science, the platform supports data sharing and many components are open source to allow researchers and developers to integrate externally‐developed measures. The MTB is available for use in clinical research and pharmaceutical studies.
Association between G‐Protein Coupled Receptor 55 (GPR55) Single Nucleotide Polymorphisms and Alzheimer’s Disease
Authors: Mori‐Fegan Daniel K , Noor Shiropa , Wong Yuen Yan , Wu Che‐Yuan , Black Sandra E. , Ross Ruth A , Swardfager Walter ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: December 2023

AbstractBackgroundG‐protein‐coupled receptor 55 (GPR55) is a lysophosphatidylinositol and novel cannabinoid receptor. GPR55 signalling and single nucleotide polymorphisms (SNPs) have been implicated as a potential therapeutic target for neurodegenerative diseases such as Alzheimer’s Disease (AD); however, foundational knowledge on the role of GPR55 in AD progression remains lacking. We hypothesised GPR55 SNP minor allele carriers would have greater brain atrophy, cognitive decline, and AD‐related biomarker changes.MethodThis retrospective, longitudinal, observational study used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We selected participants with clinically normal cognition, mild cognitive impairment (MCI) or mild AD from ADNI2 and ADNIGO phases as a discovery sample. Exploratory screening of GPR55 SNPs identified rs2969126G/C associated with brain volume. Cerebrospinal fluid amyloid beta‐42 (CSF‐Aβ42), total and phosphorylated‐tau (t/p‐tau) were considered. Mini‐Mental State Exam and the Logical Memory Delayed Recall Test were also selected to evaluate overall cognitive status, executive function, and memory. ANCOVA models evaluated baseline differences between SNP carriers and major allele homozygotes (dominant model), controlling for sex, age, baseline cognitive status and APOE e4 across AD biomarkers, brain volumetrics and cognitive measures. Longitudinal associations were assessed as interactions between SNP and visit (baseline, 12 and 24 months) in mixed models.ResultIn ADNI2/GO (n = 755), minor allele carriers represented 15% of the sample. Significantly greater decline in CSF‐Aβ42 levels was observed in Aβ42‐positive clinically normal minor allele carriers (F(1,45.2) = 6.35, p = 0.015). Carriers with MCI had significantly higher t‐tau (F(1,126) = 4.303, p = 0.04) and p‐tau concentrations (F(1,129) = 6.98, p = 0.009) longitudinally. Significantly smaller hippocampal volumes over time were seen in minor allele carriers in the whole group (F(1,444) = 5.74, p = 0.017), with a trend in the AD/MCI subgroup (F(1,325) = 3.364, p = 0.06). Clinically normal minor allele carriers had significantly poorer baseline logical memory scores (F(1,285) = 6.92, p = 0.009). These results did not replicate in the ADNI3 cohort.ConclusionCarriers of the GPR55 SNP rs2969126G/C minor allele had greater Aβ42 and tau biomarker abnormalities, smaller brain volumes and poorer memory scores over time in different stages of AD. This preliminary study prompts replication studies in different stages of AD progression to implicate GPR55 as a potential therapeutic target for AD.
Dopamine‐enriched functional connectivity alterations associated with neuropsychiatric symptoms in people with mild cognitive impairment and mild Alzheimer’s disease
Authors: Manca Riccardo , Venneri Annalena 
Published: December 2023

AbstractBackgroundAlterations in neurotransmission and brain functioning are likely to be among the first neuropathological changes occurring in Alzheimer’ disease (AD). However, how such alterations are associated with neuropsychiatric symptoms still remain elusive. The aim of this study is to investigate resting‐state functional connectivity based on a priori knowledge of dopamine receptor distribution in the brain as a potential marker of AD‐related behavioural problems.MethodClinical, Neuropsychiatric Inventory (NPI) and structural and resting‐state functional MRI data were collected for people with either mild cognitive impairment or mild dementia due to AD. Functional MRI data were pre‐processed by using the Receptor‐Enriched Analysis of functional connectivity by targets (REACT) procedure to obtain functional connectivity (FC) maps informed by dopamine D1 (D1r) and D2 receptor (D2r) PET atlases. The association between NPI total scores and dopamine‐enriched FC was tested with multiple regression models in SPM12 by including age, education, sex, MMSE scores and total intracranial volume as covariates. An exploratory analysis was carried out to compare dopamine‐enriched FC maps between 10 patients with and 10 without psychotic symptoms.ResultThe total NPI score was negatively correlated with D1r‐enriched FC in the brainstem, thalamus, medial and inferior temporal cortices and in the precuneus and with D2r‐enriched FC in fronto‐parietal and superior temporal areas. Psychotic patients showed primarily lower D1r‐enriched FC than non‐psychotic patients in occipito‐ and medio‐temporal areas and lateral fronto‐parietal areas and lower D2r‐enriched FC in occipito‐parietal areas. However, psychotic patients also had higher D1r‐enriched FC in dorsolateral prefrontal cortices and D2r‐enriched FC in the basal ganglia, thalamus and hypothalamus than non‐psychotic patients.ConclusionA widespread decrease in FC influenced by the distribution density of different dopamine receptors, especially in fronto‐parietal, occipito‐temporal and brainstem areas, may represent the neural process driving behavioural alterations in people with mild AD. Such alterations may be particularly predisposing to psychotic symptoms, although a combination of both downregulation and upregulations in specific dopamine‐informed FC pathways may play a pivotal role.
Sleep Patterns and Prospective Diffusion Weighted Imaging Biomarkers: the Sleep and Dementia Consortium (SDC)
Authors: Baril Andree‐Ann , Misialek Jeffrey , Cavuoto Marina G. , Yiallourou Stephanie , Himali Dibya , Sanchez Erlan , Kline Christopher , Redline Susan , Purcell Shaun , Beiser Alexa S. , Seshadri Sudha , Gottesman Rebecca F , Lutsey Pamela L. , Pase Matthew P. , Himali Jayandra Jung ,   Sleep and Dementia Consortium
Published: December 2023

AbstractBackgroundAdequate sleep is necessary to maintain brain health, with sleep disturbances associated with higher Alzheimer’s disease (AD) risk. Diffusion‐weighted imaging (DWI) metrics are increasingly recognized as useful neuroimaging biomarkers to detect AD‐related white matter degeneration. We assessed the relationship between sleep patterns and prospective DWI metrics in the Sleep and Dementia Consortium (SDC). The SDC studies associations between polysomnography (PSG)‐derived sleep with dementia risk and cognitive and MRI endophenotypes.MethodThe SDC includes five community‐based cohorts, two of which have DWI acquisitions: The Framingham Heart Study (FHS) and the Atherosclerosis Risk in Communities study (ARIC). Dementia‐free participants who underwent both PSG and DWI‐MRI were selected, including 354 FHS participants (56.6±7.1y, 57%W), and 184 ARIC participants (61.6±5.0y, 52%W). The MRI session was approximately 15 years after the PSG on average (FHS:17.0±1.3y; ARIC:15.8±0.8y). Fractional anisotropy (FA) and mean diffusivity (MD) were considered for both cohorts, in addition to free‐water (FW) in the FHS. Sleep metrics were harmonized centrally, distributed for cohort‐specific linear regressions, and study‐level estimates were pooled in random effects meta‐analyses. Analyses were adjusted for demographics, obesity, time between PSG and MRI, antidepressants and sedative medication usage. An interaction term by APOE4 allele carrier status in regression models was used to test its moderating effect.ResultIn the FHS, sleep fragmentation was associated with DWI measures in the expected direction: Higher Wake After Sleep Onset and lower Sleep Maintenance Efficiency were associated with lower FA (β±SE = ‐0.17±0.09,p = 0.04; β±SE = 0.23±0.10,p = 0.03), higher MD (β±SE = 0.15±0.07,p = 0.04; β±SE = ‐0.20±0.09,p = 0.03), and higher FW (β±SE = 0.17±0.07,p = 0.02; β±SE = ‐0.22±0.08,p = 0.008). Meta‐analysis of FHS and ARIC revealed significant pooled effects between lower Sleep Maintenance Efficiency and lower FA (β±SE = 0.17±0.08,p = 0.04). In the FHS, APOE4 allele significantly moderated the association between REM sleep proportion with FA and MD, where lower REM sleep percentage was associated with higher MD (β±SE = ‐4.89±1.95,p = 0.02) and lower FA (β±SE = 4.93±2.26,p = 0.03) in APOE4 carriers only.ConclusionIn the SDC, sleep fragmentation was associated with MRI markers of poorer white matter integrity 15 years later. Less REM sleep was associated with poorer white matter integrity in APOE4 allele carriers only, suggesting that disrupted sleep architecture may contribute and interact with neurodegenerative processes to affect brain integrity.
ConnectShareCare builds connections among care partners of people with serious illness
Authors: O'Donnell Elizabeth A. , Buccelleto Andrea C. , Van Citters Aricca D. , Nelson Eugene C. , King Joel , Holthoff Megan , Kirkland Kathryn B. 
Published: December 2023

AbstractPeople living with chronic illnesses naturally turn to peers and community members to address the need for emotional support, practical advice, and quick help with emergent problems. Health systems have been slower to incorporate the expertise that comes from patients and caregivers/ care partners’ lived experience into the design and delivery of care.A coproduction learning health system model aims to draw on the expertise of all to deliver optimal “whole person” care and to capture learning for improvement in the process of care delivery. This model harnesses naturally occurring peer‐to‐peer connections outside the traditional healthcare system into facilitated support networks, which extend the scope of services offered by the health system to support lay care partners, thereby improving their resiliency and inviting them to share their expertise with others.With patients and care partners, we co‐designed and piloted an online facilitated support network, connectsharecare.org, to help persons providing care or support to an adult with a serious illness better prepare to cope with surprises that arise post diagnosis and/or during bereavement. The team prioritized two network functions (1) connecting care partners to information and (2) facilitating emotional support.Between its launch in April 2021 and January 2023 the network has grown to more than 200 members with more than 3,500 posts over 21‐months. Most members report satisfaction with the support and information received, and say that the network helps them find meaning and purpose by supporting others. The most frequently used discussion threads focus on well‐being, emotions, and sources of joy and hope. The network is being adapted and improved as we learn from the data generated.It is feasible to engage a multi‐stakeholder team to co‐design an online peer‐to‐peer facilitated support network for care partners of people with serious illness. ConnectShareCare is valued by care partners. This work has the potential to contribute to a coproduction learning health system for people living with Alzheimer’s disease and other dementias by (1) prioritizing and addressing potentially unique needs of their care partners, (2) generating data for continuous quality improvement, and (3) contributing to scientific knowledge.