bluuebunny/crossref_metadata_2025_split huggingface dataset:
Illusory responses across the Alzheimer’s disease spectrum and Lewy body disease spectrum
Authors: Shahid Marian , Rawls Ashley , Ramirez Veronica , Ryman Sephira , Santini Veronica E , Yang Laurice , Sha Sharon , Hall Jacob N , Montine Thomas J. , Lin Amy , Henderson Victor , Cholerton Brenna , Yutsis Maya , Poston Kathleen L 
Published: December 2022

AbstractBackgroundPareidolias are specific illusions of faces and objects perceived in formless visual stimuli. In studies using a noise pareidolia task in patients with clinical dementia, Dementia with Lewy Bodies patients report more illusory responses than Alzheimer’s disease patients, which correlates with severity of visual hallucinations (Yokoi et al., 2014). However, it is unknown whether illusory responses occur in earlier stages of disease or in non‐hallucinating patients across the Lewy body disease (LBD) spectrum, such as Parkinson’s Disease with and without cognitive impairment.MethodWe studied the National Alzheimer’s Coordinating Center Noise Pareidolia Task‐Short Form from the LBD Module in 300 participants from the Stanford Alzheimer’s Disease Research Center and Pacific Udall Center who completed comprehensive motor and cognitive assessments with consensus diagnostic adjudication. We included 51 Alzheimer’s disease‐spectrum (AD‐s), 38 LBD with cognitive impairment (LB‐abnlCog), 65 LBD with no cognitive impairment (LB‐nlCog), and 146 Controls. Pairwise between‐group comparisons examined the impact of diagnosis on number of illusory responses. Ordinal regression analysis compared the number of illusory responses on the Noise Pareidolia Task across diagnosis groups, adjusting for age, sex, and education. Analyses were repeated after removing participants with reported hallucinations or delusions.ResultSee Table 1 for diagnosis group demographic characteristics. LB‐abnlCog were more than 10 times more likely than Controls and about 4–5 times more likely than AD‐s and LB‐nlCog participants to endorse illusory responses. The probability of endorsing one or more illusory response was 61% in the LB‐abnlCog group, compared to 26% in AD‐s, 25% in LB‐nlCog and 12% in Control participants (Figure 1). In LBD participants without hallucinations or delusions, 52% of those with mild cognitive impairment and 67% with dementia endorsed at least one illusory response.ConclusionIllusory responses are common in cognitively impaired LBD patients, including those without any reported psychosis. The Noise Pareidolia Task does not distinguish between Alzheimer’s disease and Lewy body patients until there is measurable cognitive impairment in the LBD patients, suggesting that early, unobtrusive pareidolias might arise in conjunction with cognitive decline in LBD.
Educational Quality and Incident All‐Cause Dementia: Black‐White Differences
Authors: Soh Yenee , Mayeda Elizabeth Rose , Peterson Rachel L. , Eng Chloe W. , Quesenberry Charles P. , Whitmer Rachel A. , Glymour M. Maria , Gilsanz Paola 
Published: December 2022

AbstractBackgroundMeasurement of education via years of schooling may not be commensurate across racial and ethnic groups because of disparities in educational quality. We examine state‐level administrative school quality data and incident all‐cause dementia among Kaiser Permanente Northern California members who participated in a midlife survey and were aged 65 years or older at the start of follow‐up (1997).MethodsWe obtained educational attainment and birth state from surveys administered during 1964‐1973. We linked birth state with state‐level school quality measures (student‐teacher ratio, attendance rates, term length), categorized into tertiles using the overall sample. We obtained sex, race, and incident dementia diagnoses during follow‐up (1997‐2018) from electronic health records. Using race‐stratified Cox proportional hazards models (age as timescale), we estimated associations between each educational quality measure and dementia risk, adjusting for sex, birth region and educational attainment.ResultAmong 39,632 participants, 17% identified as Black, 44% reported less than high school education, and 7,206 individuals were diagnosed with dementia (mean follow‐up 13.5 years) (Table 1). Average educational quality was lower among Black participants (Table 1). Higher attendance rates and longer term length were associated with lower dementia risk among both racial groups (Figure 1, Table 2). Among Black participants, for example, highest versus lowest attendance rate tertile was associated with 50% lower risk (adjusted hazard ratio [HR]: 0.50, 95% confidence interval [CI]: 0.38‐0.67). Lower student‐teacher ratio was associated with lower risk only among White participants. The association between higher educational quality and lower dementia risk was stronger among Black than White participants for attendance rates and term length (race‐school quality interaction term p‐value: 0.05 and 0.03, respectively), but not significantly different for student‐teacher ratio.ConclusionIn both Black and White participants, higher school quality is associated with lower risk of incident dementia, even after adjusting for educational attainment. The associations were stronger among Black participants for attendance rates and term length. Educational disparities may partially be explained by lower average educational quality among Black participants, limiting its protective effects.
Baseline White Matter Neuroinflammation Predicts Cognitive Decline in Alzheimer Disease
Authors: Wang Qing , Wang Wenshang , Schindler Suzanne E. , McKay Nicole S. , Chen Gengsheng , Liu Jingxia , Wang Sicheng , Sun Zhexian , Hassenstab Jason J. , Fagan Anne M. , Morris John C. , Wang Yong , Benzinger Tammie L.S. 
Published: December 2022

AbstractBackgroundNeuroinflammation, an intrinsic immune response of the nervous system, is important in an early phase of Alzheimer Disease (AD) pathogenesis. However, it is largely unclear how neuroinflammation promotes the clinical progression of AD. Extracellular water edema (ECW) from Neuro‐inflammation imaging (NII), a diffusion‐based MRI approach for neuroinflammation, has been utilized to asses white matter (WM) neuroinflammation in AD. This study aims to investigate the relationship between WM neuroinflammation and longitudinal cognitive changes in AD.MethodThis study included 286 participants who were enrolled in ongoing research at the Knight ADRC at Washington University in Saint Louis. The CSF levels of Aβ42/Aβ40 and ptau181 measured with the automated Lumipulse platform were used to categorize the participants as being positive or negative amyloid (A) and tau (T), respectively (Table 1). As measures of cognitive performance, the Knight ADRC Preclinical Alzheimer Cognitive Composite (Knight ADRC‐PACC) and a Global composite score were employed for each individual. The rates of change of cognitive measures were calculated for each individual. The NII was acquired with a multi‐b value scheme (bmax =1400s/mm2 and 25 directions). The total WM neuroinflammation (NII‐ECW) was obtained using the TBSS (http://www.fmrib.ox.ac.uk/fsl) based WM skeleton. Randomise in FSL was utilized to examine voxel‐wise relationships between NII‐ECW and the rate of change of cognitive measures. Non‐parametric Kruskal‐Wallis and Chi‐square tests were employed for comparing continuous and categorical variables of the participants’ demographics, respectively. The group differences of NII‐ECW were tested using one‐way ANOVA. All statistical tests were conducted in R (R Core Team, 2020). Age, sex, and APOE ε4 carrier status were adjusted as covariates.Result
Table 1 summarizes demographic data. When compared to the A‐T‐ group, the A+T+CDR0 and A+T+CDR0.5 groups had higher NII‐ECW (Figure 1). When the A+T+CDR1 group was compared to the other groups, there was no group difference in NII‐ECW. There were substantial negative associations between the NII‐ECW and the rates of change of cognitive measures in the widespread WM regions (Figure 2).ConclusionOur data suggest that neuroinflammation increases early in preclinical AD and decreases later in the disease. Furthermore, baseline neuroinflammation as measured by NII‐ECW predicts cognitive decline in AD.
Development of retinal biomarkers for Alzheimer's disease
Authors: Leuenberger Rebecca C.T. , Verbraak Frank D. , Twisk Jos W.R. , de Ruyter Frederique J. Hart , Hoozemans Jeroen J.M. , de Boer Johannes , Bouwman Femke H. 
Published: December 2022

AbstractBackgroundThe retina has received increasing intention as possible non‐invasive diagnostic biomarker for (preclinical) Alzheimer’s disease (AD). Several studies suggest changes in retinal layer thickness or vasculature in patients with AD. Here, we aim to discriminate (preclinical) Alzheimer’s disease from controls using three retinal imaging modalities in a multimodal prediction model.MethodWe used images of 103 controls, 26 clinical AD cases, and 13 preclinical AD cases. Control subjects were cognitively healthy with a negative amyloid‐PET. Preclinical AD participants were defined as cognitively healthy subjects with a positive amyloid‐PET. The 26 clinical AD participants were recruited from the Amsterdam Dementia Cohort and fulfilled the NIA‐AA criteria with evidence of amyloid pathology based on amyloid‐PET or cerebrospinal fluid. Participants underwent three imaging modalities (Optical Coherence Tomography, Optical Coherence Tomography Angiography, fundus photography) and ophthalmological examinations to exclude ophthalmological comorbidities that could influence retinal parameters. First, we performed a multivariable logistic regression analyses per imaging modality, adjusted for age and sex, using all parameters provided by each device. Second, we created an explorative multimodal prediction model including the best performing variable per imaging modality, using the following parameters: retinal nerve fiber layer inner ring, macular vessel density outer ring and the central retinal vein equivalent (CRVE). We used Receiver Operating Characteristic (ROC) curves to test the overall predictive accuracy.ResultThe final explorative multimodal prediction model showed an acceptable predictive accuracy in discriminating AD from controls with an area under the receiving operating characteristic curve (AUC) of 0.987, and less so in the discrimination between preclinical AD and controls with an AUC of 0.775. However, with differences in the way the coefficients of identical parameters contributed to make the differentiation between AD and controls and preclinical AD and controls.ConclusionDespite of a relatively small sample size, our multimodal retinal imaging prediction model seems promising in discriminating between AD versus controls, and preclinical AD versus controls. We found that two parameters, the macular vessel density outer ring and CRVE behaved differently in AD cases compared to preclinical AD cases. More prospective studies with larger sample sizes are needed to confirm these findings.
A Million Veteran Program GWAS of Alzheimer’s Disease and Related Dementias in African Americans Identifies Multiple Genome‐Wide Significant Dementia Risk Loci
Authors: Sherva Richard , Zhang Rui , Farrer Lindsay A. , Sahelijo Nathan , Jun Gyungah R , Anglin Tori , Chanfreau Catherine , Cho Kelly , Fonda Jennifer , Gaziano J. Michael , Harrington Kelly , Ho Yuk‐Lam , Kremen William S. , Litkowski Elizabeth M , Lynch Julie , Neale Zoe , Roussos Panos , Marra David E , Mez Jesse B. , Miller Mark , Salat David H , Tsuang Debby W , Wolf Erika , Zeng Qing , Panizzon Matthew S. , Merritt Victoria , Hauger Richard L. , Logue Mark W. 
Published: December 2022

AbstractBackgroundWhile genome wide association studies (GWASs) of Alzheimer’s Disease (AD) in European ancestry cohorts (EUR) have identified >70 potentially independent AD risk loci, progress in non‐European populations has lagged. In this study, data from US Veterans of African ancestry (AFR) from the Million Veteran Program (MVP) biorepository were used to identify genetic factors associated with AD and related dementias (ADRD).MethodUsing the VA electronic medical record, 4,012 AFR ADRD cases (algorithm includes codes for AD and dementias such as vascular dementia) and 18,435 dementia‐free AFR controls were identified for inclusion in the GWAS. A GWAS was also performed using proxy dementia based on survey‐reported AFR participant parental history of AD or other dementia that included 4,385 maternal cases, 2,256 paternal cases, and 45,970 controls. Meta‐analysis of the case control and proxy results for was performed and then subsequently combined with results from a AFR AD GWAS conducted by the Alzheimer Disease Genetics Consortium (ADGC; Kunkle et al., 2021).ResultThe AFR MVP GWAS (case‐control + proxy) yielded genome‐wide significant associations with several loci including APOE (p=2.48x10‐101), ROBO1 (rs11919682, p=1.63x10‐8), and RP11‐340A13.2 (rs148433063, p=8.56x10‐9. The ROBO1 and RP11‐240A13.2 SNPs were not replicated in the ADGC sample (missing or not significant). The meta‐analysis of MVP and ADGC GWAS results (Table 1) additionally identified genome significant SNPs near known AD risk genes TREM2 (rs73427293, p=2.95x10‐9), CD2AP (rs7738720, p=1.14x10‐9), and ABCA7 (rs73505251, p=3.26x10‐10). Comparison of expression of genes near variants with suggestive evidence of association (p<5x10‐7) in the brains of EUR AD cases and controls from Framingham Heart Study, Religious Orders Study/Rush Memory and Aging Project, Mayo‐Mount Sinai Brain Bank, and Boston University Brain Bank (Panitch et al.) identified several differentially expressed genes including EML6.ConclusionThe AFR dementia GWAS presented here is the largest to date. It increased the number of genome wide significant common‐variant dementia loci reported in AFR cohorts from two to six, including genes previously implicated in EUR cohorts. Increasing representation of AFRs is an important priority in genetic studies and may lead to increased insight into AD pathophysiology and reduce health disparities.
The Association of Sleep Duration and Sleep Efficiency with Amyloid β Accumulation Among Cognitively Healthy Later Life Adults: A Systematic Review
Authors: Moon Chooza , Schneider Aaron , Zhang Meina , Cho Young‐Eun , Dang Hellen , Vu Kelly H 
Published: December 2022

AbstractBackgroundAmyloid β(Aβ) accumulation is a hallmark of the progressive neurodegenerative Alzheimer’s Disease (AD). Disruptions in sleep beyond aging are found to be risk factors of developing AD because sleep may involves in Aβ level regulations, neurotoxin clearance, or inflammation process. Sleep disruptions can be defined by shorter sleep duration and lower sleep efficiency. This systematic review examines how sleep duration and efficiency are associated with amyloid deposition in later life adults.MethodWe screened 3,122 published articles searched from electronic databases (i.e., PubMed, CINAHL, Embase, and PsycINFO) and used 14 articles for the qualitative synthesis. All articles met the eligibility criteria including published articles that contain sleep duration and efficiency measure, Aβ measure, human studies with cognitively normal older adults who are 50 and above.ResultStudies were conducted in the United States, Italy, South Korea, China, and Australia. Of the 14 studies included, 12 used a cross‐sectional design and 2 used a longitudinal design. Sample sizes ranged from 13 to 4,772. Ages of the samples ranged from 50 to 85. Studies measured Aβ using cerebrospinal fluid, serum, and Positron Emission Tomography (PET) scans with two different tracers: C‐labeled Pittsburgh compound B or fluorine 18–labeled (18F). Sleep duration and efficiency were subjectively measured using interviews and questionnaires, or objective measures, such as polysomnography or actigraphy. Studies accounted for demographic and lifestyle factors in their analyses, such as age, sex, family history, sleep, habitual alcohol consumption, slow wave sleep, apnea hypopnea index, exercise, fasting glucose, and triglycerides. Only 3 of the 14 studies indicated that sleep duration was associated with Aβ accumulation, and 4 of the studies revealed that sleep efficiency was associated with Aβ accumulation.ConclusionThis review suggests that previous studies have provided mixed evidence regarding the relationship between sleep duration and Aβ or the relationship between sleep efficiency and Aβ. Not all studies used a sufficient sample size or a comprehensive measurement of sleep. These results indicate the need for more future studies using a longitudinal design, comprehensive sleep measure, and larger sample sizes to advance understanding the relationship between sleep and Aβ.
Loss of large dendritic spines during normal aging is mediated by alterations in discrete protein networks within the precuneus
Authors: Krivinko Josh , Sui Zhiyu , Happe Cassandra , Hensler Christopher , McKinney Brandon , Newman Jason , Ding Ying , MacDonald Matthew , Sweet Robert 
Published: December 2022

AbstractBackgroundLoss of dendritic spine density in neocortical areas is a well‐known correlate of cognitive decline in Alzheimer Disease (AD), while preservation of dendritic spines in subjects containing AD‐related pathology is associated with cognitive resilience. Because normal aging is itself associated with dendritic spine loss, identifying upstream mediators of dendritic spine loss may provide an opportunity to develop targeted pharmacotherapies which enhance cognitive resilience and protect against dementia onset. We therefore quantified dendritic spine density and the abundance of over 5000 proteins in the precuneus, a cortical region that is selectively vulnerable early in AD progression.MethodThe right precuneus was isolated postmortem from 98 subjects, ages 20‐96 years, none of whom had a documented neurocognitive disorder. Quantitative immunohistochemistry and spinning disk microscopy were used to estimate dendritic spine density by detecting colocalization of spinophilin and filamentous actin. Gray matter was biochemically fractioned into cellular homogenate and synaptosome fractions, and protein abundance was quantified by liquid chromatography/tandem mass tag mass spectrometry. Proteins were assembled into correlated networks using Weighted Gene Co‐expression Network Analysis (WGCNA), and a statistical mediation analysis was used to identify protein networks which mediate the effect of age on dendritic spine density. WebGestalt was used to identify enrichment for gene ontology terms for protein networks relative to a background of all proteins detected in homogenate.ResultThe density of large dendritic spines exhibited a negative correlation with increasing age (Pearson R= ‐0.36, p<0.001) (Figure 1). A total of 1839 of 5032 proteins detected in cellular homogenate and 914 of 4754 proteins detected in synaptosomes was significantly correlated with age (q<0.05). Proteins segregated into 19 network modules, five of which significantly mediated the effect of age on dendritic spine density. The modules were enriched for gene ontology terms including “positive regulation of excitatory postsynaptic potential” (enrichment ratio=11.0, p=0.034), “neurotransmitter transport” (enrichment ratio=3.9, p=0.003) and “myelination” (enrichment ratio=21.5, p=<0.001).ConclusionDensity of large dendritic spines declines linearly with age within the precuneus. Network analysis revealed a novel role for myelination by oligodendrocytes in spine loss, identifying a potential target to increase cognitive resilience during aging.
Support for Dementia Care Partners using Telehealth: Tele‐STELLA Phase 1
Authors: Lindauer Allison , Gothard Sarah , Boardman Charles , Smith Samantha , Mattek Nora , McDaniel Delaney , Bernard Hannah , Tran Leslie , Tadesse Ruth 
Published: December 2022

AbstractBackgroundEffective interventions that reduce dementia Care Partner stress and burden are available, but access to them is impeded by barriers such as distance, cost, behavioral symptoms of dementia, stigma and social anxiety. Tele‐STELLA is a multi‐component, videoconference‐based intervention designed to provide easily‐accessible education and support for Care Partners. The goal of this intervention is to diminish the frequency of behavioral symptoms that persons with dementia experience, and Care Partner reactivity to these symptoms. Here we report on the findings of Phase 1 of Tele‐STELLA.MethodIn Tele‐STELLA interventionists meet with Care Partners, via videoconferencing, to identify specific behavioral symptoms of dementia that are distressing for them. The interventionists and Care Partners meet, first individually and then in groups, to address these symptoms using an analytic approach. Care Partners are encouraged to contact each other for support. Prior to, during, and after the 8‐week intervention we collect data on behavioral symptoms (frequency and Care Partner reactivity to the symptoms), depression, and burden using electronically‐administered surveys.ResultOf the 26 Care Partners who completed 8 weeks of the intervention 19 (70%) were female, average age of 67; 25 (96%) identified as white; 14% lived in a rural area. Burden, as assessed on the Revised Memory and Behavior Problem Checklist, did not change significantly over the 8‐week intervention, nor did scores on depression, grief or quality of life measures. There was no change in behavior frequency, but we did appreciate a significant improvement in Care Partner reactivity to the two personalized target problems they identified (Figures 1 and 2; p<0.01 and p = 0.025, respectively).ConclusionSignificant improvement was seen in Care Partner reactivity to the specific behavioral problems chosen by the Care Partners. This suggests the intervention is effective when Care Partners work on the personalized problems they identified. The lack of significant improvement on the (depersonalized) surveys may be due to unbiased reporting by Care Partners using electronically‐administered surveys, small sample size, or stabilization of affective symptoms. Phase 1 will inform revisions for the remainder of the study (total n goal = 150).