bluuebunny/crossref_metadata_2025_split huggingface dataset:
Striatal Amyloid deposition in sporadic Alzheimer’s Disease
Authors: Arena Julieta , Urrutia Leandro , de Leon Magdalena Ponce , Seminara Emiliana , Falasco German , Bérgamo Yanina , Allegri Ricardo Francisco , Sevlever Gustavo , Vazquez Silvia 
Published: December 2023

AbstractBackgroundIt has been shown that disorders associated with early‐life alterations in amyloid production or processing such as in autosomal dominant Alzheimer’s disease (AD) and down syndrome‐associated dementia have a different pattern of Aβ deposition, with early striatal accumulation, as compared to sporadic late‐onset cases, in which striatal deposition has been suggested to be a marker of late and advanced amyloidosis. It is not clear, however, if the pattern of amyloid accumulation is related to any other factors or if it has any impact on brain metabolism. We aimed to determine if there are any clinical or demographic predictors of striatal tau accumulation in sporadic AD and whether its presence affects the subjects´ brain metabolism.MethodSubjects that underwent positron emission tomography (PET) scans with 18F‐FDG and 11C‐PIB were analyzed retrospectively. Only those with clinical diagnosis of AD and mild cognitive impairment (MCI) due to AD were considered for the analysis. Visual analyses were performed to exclude subjects without cortical amyloid accumulation. Mean values from cortical volumes of interest (VOIs) and striatum were obtained. Amyloid deposition was correlated with age and disease duration via Pearson’s correlations. Amyloid deposition was also correlated to brain metabolism as assessed by FDG PET.Result150 subjects were included in this study. Neither age nor disease duration was correlated with striatal amyloid accumulation. Subjects with striatal Pib accumulation showed higher cortical amyloid burden. Moreover, higher striatal amyloid burden was positively correlated with higher frontal amyloid burden specifically. Amyloid burden in the striatum did not seem to have an impact on the glucose metabolism in the striatum itself. However, variations in cortical glucose metabolism could be observed. A higher striatal amyloid burden was correlated with cortical glucose hypometabolism, specifically in the precuneus and temporal areas (Figure 1).ConclusionThere seems to be a stage of sporadic Alzheimer’s disease in which amyloid accumulates in the striatum. This, in turn, appears to have an impact on brain functioning. Whether this has a real impact on cognitive performance remains to be elucidated.
MRI‐Based Water Exchange Rate Across the Blood‐Brain‐Barrier is Associated with Diffusion MRI Free Water in Older Adults
Authors: Bauer Christopher E. , Pappas Colleen , Zachariou Valentinos , Maillard Pauline , Arvind Caprihan , Shao Xingfeng , Wang Danny J.J. , Gold Brian T. 
Published: December 2023

AbstractBackgroundThe blood brain barrier (BBB) tightly regulates the clearance of waste from the central nervous system. Changes in BBB function may disrupt such clearance mechanisms, resulting in increased waste and unrestricted fluid, or free water (FW), which can be measured using diffusion‐weighted imaging. Here, we explored whether MRI‐based BBB water exchange rate (kw; measure of BBB function) is associated with FW within white matter tracts connecting the executive control network (ECN). We further explored whether FW within the ECN would likewise be associated with executive function performance.MethodFifty‐three older adults (ages 65‐85) without dementia were scanned using a 3‐Tesla MRI Siemens Magnetom Prisma with a 64‐channel head coil. A 3D gradient‐and‐spin‐echo diffusion‐prepared arterial spin labeling (DP‐ASL) sequence and a 126‐direction main diffusion MRI sequence using 4 b‐values (0, 500, 1000, and 2000 s/mm2) were acquired. Each participant’s mean kw values averaged over the entire brain were calculated from the DP‐ASL data. FW maps were calculated, registered to FMRIB space, and skeletonized using FSL’s tract‐based spatial statistics (TBSS). Skeletonized FW values were averaged across the white matter tracts connecting the ECN using a previously defined fMRI template. All participants completed the cognitive assessment from the Uniform Data Set Version 3 within one year of the scan date. Executive function was assessed for each participant based on a composite measure including digit span backwards and trails making part B test minus part A. A multivariate linear regression model first tested the association between whole brain kw values (predictor) and FW in the ECN as the dependent variable. A second multivariate linear regression model then tested the association between FW in the ECN (predictor) and EF performance as the dependent variable. Models controlled for age and sex.ResultsWhole brain kw values were negatively associated with FW in the ECN (r = ‐0.338, p = 0.031). FW in the ECN was negatively associated with EF performance (r = ‐0.318, p = 0.024).ConclusionOur results suggest that BBB dysfunction is associated with free water in large‐scale cognitive networks. Subsequent free water changes in these networks are linked with associated decreases in cognitive performance.
Population attributable fractions for risk factors for dementia in Argentina: sex and socioeconomic differences during ten years
Authors: Calandri Ismael Luis , Elgani Sofía Alejandra , Crivelli Lucía , Allegri Ricardo Francisco , Suemoto Claudia Kimie 
Published: December 2023

AbstractBackgroundThe twelve potentially modifiable risk factors(RF) for dementia are estimated to account for 40% of dementia cases worldwide based on data from high‐income countries. However, population attributable fraction (PAF) distribution and impact may be affected by the socioeconomic context. We aimed: a) to calculate PAFsin Argentina (a low‐income country) using census data, b) to compare differences between sex and socioeconomic strata, and c) their evolution across a ten‐year period.MethodWe collected cross‐sectional data from three Argentinian census between 2009 and 2018 to estimate risk factor prevalences. We calculated PAFs for each risk factor using relative risk estimates from previous meta‐analyses. Next, we adjusted PAF for communality between risk factors, and used these values to calculate overall weighted PAFs. Finally, we analyzed the differences in PAFs for sex and socioeconomic strata defined as income quintiles and compared the overall PAFs between years.ResultWe could identify 8 of the 12 RF in census data; the rest were estimated using other sources. We estimated an overall weighted PAF of 39.9% 95%CI [38.29%‐39.89%] (Table 1). We found no significant differences between the overall PAF of women and men (p = 0.12) (Figure 2). However, women presented more social isolation (4.9% CI95%[4.2%,5.7%]) than men (2.2% CI95%[2.1%,4.1%]), and greater smoking PAF (p = .027). Significant differences were found in the overall PAF of the two lower economic strata (Q1 37.4% CI95% [35.3%,39.5%]; Q2 40.3% CI95% [38.6%,42.1%]) compared with the upper stratum (Q5 29.8% CI95% [28.2%,31.5%]) (Figure 3). There were no significant changes in weight PAF over the course of 10 years. However, while some factors, such as education, improved, alcohol use and social isolation worsened.ConclusionWe found a higher prevalence of risk factors, even though not all of them could be assessed. Also, the distribution of risk factors varied according to sex and socioeconomic level, suggesting that public policies should consider working on the most important RF.
Physical activity attenuates the effect of poor sleep quality on cognitive function in adults with chronic stroke
Authors: Stein Ryan G , Falck Ryan S , Tai Daria , Best John R. , Davis Jennifer C , Hsiung Ging‐Yuek Robin , Eng Janice J , Middleton Laura E , Hall Peter A , Liu‐Ambrose Teresa 
Published: December 2023

AbstractBackgroundGood sleep quality is important for cognitive health. Individuals with chronic stroke are at an increased risk for dementia and about half have insomnia. Stroke survivors are a target population in need of intervention strategies to promote sleep quality to preserve cognitive function. Physical activity is a promising approach. Hence, in this cross‐sectional analysis, we examined whether physical activity moderates the effect of poor sleep quality on cognitive function in adults with chronic stroke.MethodThis is a cross‐sectional analysis of baseline data acquired from 121 community‐dwelling older adults with chronic stroke (age: 70.73 ± 8.56 years; 38.30% female) enrolled in a 6‐month randomized control trial. Sleep quality was assessed with the MotionWatch8 (MW8) and physical activity was measured with the Life Space Questionnaire (LSQ; 0‐120). Participants were split into higher or lower physical activity by the median LSQ score (median = 64.00). Cognitive performance was measured with the 13‐item Alzheimer’s Disease Assessment Scale (ADAS‐Cog; 0‐85), with higher scores indicating worse cognitive performance. A linear regression was performed to first assess the independent association of MW8‐measures of sleep quality (i.e., sleep duration, fragmentation, efficiency, latency, and awakenings) and ADAS‐Cog score, after accounting for age and Montreal Cognitive Assessment score (MoCA) score. Based on the results of this linear regression, we performed a second linear regression with ADAS‐Cog score as the dependent variable, and sleep latency (minutes), physical activity level, and the interaction of sleep latency * physical activity level as independent variables, controlling for age and MoCA score.ResultGreater sleep latency (β1 = 0.22, p = 0.017) was significantly associated with greater ADAS‐Cog score, after controlling for age and MoCA (R2 = .50, F(3, 105) = 34.74, p<.01). Physical activity significantly moderated the association between sleep latency (β1 = 0.38, p = 0.033) and ADAS‐Cog score (R2 = .53, F(5, 103) = 22.93, p<.01). Specifically, those in the higher physical activity group showed lower ADAS‐Cog scores with higher sleep latency (r = .67, p = .627) and those in the lower physical activity group showed higher ADAS‐Cog scores with higher sleep latency (r = .75, p = .007).ConclusionPhysical activity attenuates the effect of poor sleep quality on cognitive function in adults with chronic stroke.
Indexing the Predictive Utility of Real‐World Sleep to Discriminate Early Alzheimer’s Disease
Authors: Chang Jun Ha , Wu Ruiqian , Zhang Ying , Rizzo Matthew , Merickel Jennifer 
Published: December 2023

AbstractBackgroundSleep dysfunction is one of earliest symptoms of Alzheimer’s disease (AD) and can accelerate cognitive decline, increasing risk of AD. Emerging technologies, like actigraphy, allow for continuous monitoring of real‐world sleep. Our goal is to determine the predictive utility of real‐world sleep dysfunction features for indexing warning signs of incipient dementia like mild cognitive impairment (MCI).MethodSubjects were classed as cognitively neurotypical (N = 31) or impaired: MCI (n = 51) or AD (N = 7) based on NIA‐AA diagnostic criteria, as evaluated by a neurologist from clinical exam, neuropsychological, and demographic assessments. (Table 1) Each subject was tracked for 3 months with wrist‐worn actigraphy. Self‐reported sleep diaries validated real‐world sleep data. Sleep duration and quality were estimated across means and standard deviations (SD) of: Total Sleep Time (TST), Sleep Latency (SL), Sleep Efficiency (SE), Wakefulness After Sleep Onset (WASO), and Awakening Count (AC). An optimal logistic regression model, adjusting for demographics (age, gender, education), was quantified and used to rank the explanatory value of sleep covariates to discriminate impaired vs. typical aging using stepwise selection.ResultAcross 6,530 validated, nightly sleep periods (mean = 73.4 ± 17.0 sleep periods per subject), we found best discrimination of impaired vs. typical aging, ranked from best to least discrimination (Table 2), for average sleep efficiency [SE] (b = 3.58, p = 0.03), nightly wakefulness [WASO] (b = 3.42, p = 0.04), variability of daily sleep quality [SE] (b = 1.65, p = 0.001), and awakening frequency [AC] (b = ‐0.79, p = .03). TST did not discriminate impaired from typical aging.ConclusionResults align with prior literature, demonstrating that sleep quality is an optimal feature to track early warning signs of dementia from real‐world sleep. Critically, SE shows the most promise for discriminating early decline while TST did not show predictive utility in this study. Digital fingerprints of sleep behavior in the real world offer unique added value to neurobiological biomarker evidence of preclinical disease, improving early detection of AD risk to bolster interventions aimed at treating AD—‐even its earliest stages.
Utilizing Respondent Driven Sampling to assess neurocognitive functioning in the indigenous American Samoa population 60 years or older.
Authors: Tofaeono Vaatausili 
Published: December 2023

AbstractBackgroundRespondent Driven Sampling (RDS) is a cost‐efficient, chain referral sampling method, where respondent seeds recruit others who are eligible within their social networks; those recruited by the seeds then recruit others (Heckathorn, 1997). In American Samoa recruitment of a random population‐based sample is difficult due to systematic error and biases in sample characteristics arising from the hierarchical relationships prominent in American Samoan society (Aitaoto, et al. 2007; Cassel 2010; Cassel, 2014). The INdigenous Samoan Partnership to Initiate Research Excellence (INSPIRE) program recruited 718 participants age 45 and over during a 51‐day period with 20% age 60 or higher. For this reason, RDS methods were utilized to assess neurocognitive functioning in the Samoan population age 60 or over.MethodINSPIRE program staff recruited 60 participants as RDS seeds (30 men and 30 women). Once the seeds completed the data collection process, they were given coupons to recruit a maximum of 3 community members. In addition, they were provided a printed reminder of the eligibility criteria. The patterned continued to create consecutive recruitment waves (Wave 1, n = 60; Wave 2, n = 180; Wave 3, n = 540) until the sample size was reached. Participants received a total $25 incentive for participating in the survey. Additionally, participants will be compensated as RDS recruiters and receive an additional $15 for each recruit who participates, up to a maximum of 3. The RDS recruitment proposed to yield 780 participants, with 390 women and 390 men with a 12% loss to follow up.ResultPreliminary data analysis reveals target sample size was collected in 126 days (41% Male, 59% Female). Referral chain analysis reports only 25% of seeds recruited 80% of participants although social networking sizes varied for the seeds. Some participants with higher social networks did not participate in recruiting.ConclusionIntercept promotions complimented the use of RDS to help identify seeds and include faith‐based institutions (churches), senior centers, civics clubs, village‐based and other networks to recruit men and women, ages 60 and over. Maintaining a central location for study implementation and coupon payment supported ease of access for the study population.
Greater sensitivity of the hippocampus than the entorhinal cortex in response to western diet, manifested by accelerated neuroinflammation and neurodegeneration in the progression of Alzheimer’s disease
Authors: Więckowska‐Gacek Angelika , Mietelska‐Porowska Anna , Domańska Justyna Marta , Wojda Urszula 
Published: December 2023

AbstractBackgroundThe western diet (WD), characterized by a combination of simple carbohydrates, saturated fatty acids and cholesterol, is known to induce metabolic syndrome and systemic inflammation. These peripheral disorders induce neuroinflammation and affect brain function, suggesting that WD may have a significant impact on Alzheimer’s disease (AD) progression (Więckowska‐Gacek et al., 2021). In this study we aimed to verify the hypothesis that WD feeding accelerates neuroinflammation, resulting in accelerated deposition of Aβ plaques, accelerated appearance of neurodegeneration markers and destabilization of neuronal cytoskeleton.MethodsTransgenic male mice expressing human APP with the Swedish mutation (APPswe) were divided into three age groups: 4‐ and 8‐month old animals (4M, 8M) represent early pre‐symptomatic stages of AD, while 12‐month old animals (12M) represent later stages of AD with visible amyloid pathology. The APPswe mice were fed standard or western diet from the 3rd month of age. The effect of WD on selected markers was analyzed in the hippocampus and entorhinal cortex by Western blotting and immunohistochemistry.ResultsCompared to control mice fed standard diet, WD feeding induced astrogliosis (GFAP) in the hippocampus as early as in 4M, followed by several changes in 8M such as activation of the pro‐inflammatory microglia (↑Iba1, ↓CD68, ↓P2RY12), a decrease in the level of TLR4, and the fluctuations of levels of pro‐inflammatory cytokines (IL‐1β, IL‐6). These changes in the hippocampus at 8M co‐occurred with enhanced production of Aβ plaques. Moreover, WD accelerated the processes associated with age‐related neurodegeneration (lower levels of PSD95 in 8M, and of NeuN in 12M). In the entorhinal cortex, the examined molecular changes appeared with a delay in time or not at all.ConclusionThese results indicate that the westernized pattern of nourishment is an important modifiable risk factor of AD which can accelerate development of AD pathology. Furthermore, the data demonstrate that, compared to the entorhinal cortex, the hippocampus is a brain structure that is generally more sensitive to the macronutrient composition characteristic of WD, manifested by accelerated neuroinflammation, amyloidopathy and neurodegeneration.Polish National Science Center grants: 2018/29/N/NZ7/01724, 2014/15/D/NZ4/04361
Design of a Bilingual and Bicultural Dementia Screening Toolkit Integrated in the Electronic Health Record
Authors: Shah Samantha , Diaz‐Santos Mirella , Eliseo Stephanie G Ovalle , Moreno Gerado , Bholat Michelle , Vossel Keith , Chang Timothy S 
Published: December 2023

AbstractBackgroundBased predominantly on longitudinal cohort studies, the prevalence of Alzheimer’ disease (AD) is estimated to be 3‐10% in individuals over 65 years old and has increased risk (1.5‐2.0 times) in Black and Hispanic/Latinx individuals. In our prior analyses of the University of California Los Angeles (UCLA) electronic health record (EHR), we found that only 1% of patients over 65 years old are diagnosed with AD, and AD is less likely to be diagnosed in Black and Hispanic/Latinx patients compared to white patients (relative risk 0.86‐0.9). One solution to the underdiagnosis of AD in real‐world clinical care, is to screen for dementia.MethodsRecent work by several University California AD Centers and the California Department of Public Health developed a short (<5 min) dementia screening tool (DST). The DST includes a three‐question questionnaire for the patient and an informant if present, followed by the Mini‐Cog if applicable (Figure 1). The questions ask about changes in language, memory, and personality (Figure 2). The DST is considered positive if any question is answered “Yes” by the patient or informant, or if the Mini‐Cog score is <3 out of 5 points. To improve care for non‐English speaking patients, we developed the questionnaire in Spanish, which was adapted to Hispanic/Latinx culture.ResultsThe DST is integrated in the EHR. The questionnaires are sent to patients prior to the visit via the messaging system. Answers to the questionnaire and the Mini‐Cog are entered into a flowsheet in an easily accessible EHR tab. We also created a documentation link that automatically loads the DST results, final score, and recommendation into provider notes. The DST is live at a diverse UCLA family medicine clinic, which sees HL and Black patients. In the first three weeks, 178 patients were screened with the toolkit and eight patients were referred for specialty care.ConclusionsWe have developed a cultural and linguistic responsive DST that is integrated in the EHR. We will continue evaluating its ability to increase appropriate diagnosis of dementia in diverse racial and ethnic groups, and share our DST including EHR integration so it can be implemented elsewhere.
pTau181 plasma biomarker performance as an inclusion criterion for Alzheimer’s Disease clinical trials
Authors: Mammel Anna , Kumar Pankaj , Fortna Ryan , Biehl Donald , Cruz Anna , Encarnacion Mary , Burns Lindsay H , Kupiec James , Hsiung Ging‐Yuek Robin , Mousavi Ali , MacKenzie Ian R , Hirsch‐Reinshagen Veronica , Frykman Hans 
Published: December 2023

AbstractBackgroundAdvances in ultrasensitive detection techniques for blood biomarkers allow the quantification of AD‐specific phosphorylated Tau proteins, including Tau phosphorylated at threonine 181 (pTau181) in patient plasma. pTau blood‐based biomarker have shown great promise as inclusion criteria and secondary endpoint evaluation in clinical trials.MethodThe University of British Columbia (UBC) CARD biobank plasma samples from clinically diagnosed AD and non‐AD patients were used to establish clinical and analytical validity of the pTau181 plasma assay per FDA fit‐for‐purpose guildelines (Neurcode USA, Inc.). We assessed the analytical measurement interval, clinical reportable range, linearity, intra‐laboratory precision, specimen stability, interference, and clinical performance.ResultThe pTau181 plasma assay provides a robust and accurate biomarker approach for independent determination of AD, with an AUC of 0.9 in our validation study cohort. The cut‐point (≥ 30 ng/L) had 100% sensitivity and 88% specificity for AD diagnosis in autopsy‐confirmed samples. The plasma pTau181 assay appears to be performing well as additional screening metric for inclusion of mild‐to‐moderate AD subjects in Phase 3 clinical trials (i.e. RETHINK‐ALZ and REFOCUS‐ALZ). 89% of the clinical sites participating in the REFOCUS‐ALZ study and 80% of sites participating in the RETHINK‐ALZ had at least 70% of screened subjects meeting this criterion.ConclusionAD plasma biomarker (pTau181) quantified using an RUO assay has great potential both as a diagnostic tool and to streamline clinical trials in AD.