bluuebunny/crossref_metadata_2025_split huggingface dataset:
Piloting a Mediterranean Ketogenic Nutrition Program to Address Pain in Older Adults with Mild Cognitive Impairment
Authors: Sheffler Julia L , Klejc Kamelia , Cruz‐Almeida Yenisel 
Published: December 2023

AbstractBackgroundPain is a persistent problem in older adults associated with poorer quality of life, greater risk of falls, functional impairment, and risk for cognitive impairment. Psychosocial and lifestyle interventions may be especially important to consider in older populations who may be more susceptible to negative side effects of pain medications. Ketogenic nutrition (KN) is one promising option that may offer a nonpharmacologic pathway for treating pain; however, KN is also a relatively strict and complex diet associated with challenges in dissemination and long‐term adherence, especially in older adults with memory impairments.MethodThis pilot clinical trial (N = 58) evaluated a 6‐week Mediterranean KN program designed to evaluate adherence and preliminary effects of the program on pain in individuals with possible mild cognitive impairment (aged 60‐85). Participants completed daily at‐home urine ketone testing during the program, weekly evaluations of psychosocial and health characteristics, and three in‐person assessments of health, ketones, pain, and other relevant measures.ResultsAnalyses demonstrated significant improvement in pain intensity across the assessment period. Average daily urine ketone level and average self‐reported adherence across the 6‐week program were both positively correlated with improvements in pain‐related quality of life (ps<.05).ConclusionFindings offer preliminary evidence that a group, Mediterranean KN program and adherence to this type of nutrition may reduce the experience of pain and pain‐related outcomes for older adults.
Classifying Memory Clinic Patients Using the Digital Clock Drawing TestTM, Mini‐Mental State Examination, and Philadelphia (repeatable) Verbal Learning Test
Authors: Libon David J , Swenson Rodney , Jannati Ali , Bates David , Tobyne Sean , Pascual‐Leone Alvaro , Gomes‐Osman Joyce Rios 
Published: December 2023

AbstractBackgroundDigital cognitive assessments (DCA) enable quick, sensitive, and reliable assessment of neurocognitive operations that underlie dementia and mild cognitive impairment (MCI). We examined how well the DCTclockTM DCA, Mini‐Mental State Examination (MMSE), and Philadelphia (repeatable) Veral Learning Test (PrVLT) can classify memory clinic patients by cognitive impairment profile.Method106 serial referrals to an outpatient memory clinic were assessed with the DCTclock, MMSE, and P(r)VLT. Using statistical criteria for subtle cognitive impairment (SCI, Edmonds et al., 2015) and MCI (Jak et al., 2008), patients were classified into cognitively normal (CN, n = 21), SCI (n = 33), amnestic MCI (aMCI, n = 22), and dysexecutive/mixed MCI (d/mMCI, n = 30) groups. A series of stepwise logistic regression analyses were conducted with CN participants as the criterion group.ResultIn the first analysis (Table 1), P(r)VLT‐recognition (X2= 24.39, p<0.001) entered the model first followed by the DCTclock Score (X2= 16.68, p<0.001). P(r)VLT‐recognition classified aMCI patients (Wald = 11.21, p<0.001). DCTclock (Wald = 8.97, p<0.001) and P(r)VLT‐recognition (Wald = 4.06, p<0.001) classified d/mMCI patients. In the second analysis the four command DCTclock composites were analyzed, excluding the MMSE and P(r)VLT‐recognition scores, Spatial Reasoning classified patients into their respective groups (SCI, Wald = 3.68, p<0.055; aMCI, Wald = 8.84, p<0.003; d/mMCI, Wald = 19.12 p<0.001). Third, analyzing DCTclock command Spatial Reasoning, MMSE, and P(r)VLT‐recognition, the P(r)VLT score, again, entered first (X2= 24.39, p<0.001) followed by DCTclock Spatial Reasoning (X2= 18.95, p<0.001). DCTclock Spatial Reasoning classified SCI patients (Wald = 4.66, p<0.031), P(r)VLT‐recognition classified aMCI patients (Wald = 9.11, p<0.003), and both DCTclock command Spatial Reasoning (Wald = 10.56, p<0.001) and P(r)VLT‐recognition (Wald = 3.32, p<.068) classified d/mMCI patients.ConclusionUnlike the MMSE that takes 10‐15 minutes to administer and is scored subjectively, all DCTclock data are digitally obtained and automatically scored, requiring no examiner interface for administration and interpretation, thus obviating clinical judgment, ensuring inter‐rater reliability, and enabling more efficient cognitive assessments. In this series of logistic regression analyses, a combination of DCTclock and P(r)VLT clearly outperformed the MMSE in classifying non‐demented memory clinic patients into cognitively normal, subtle cognitive impairment, and MCI subtypes. These results support the efficacy of DCAs in clinical trials and to screen for emergent cognitive impairment in primary care and specialty medical practices.
Optimising remote sampling of NfL and GFAP using blood cards in the Genetic Frontotemporal Dementia Initiative (GENFI) cohort
Authors: Goldsmith Sophie E , Swift Imogen J , Oh Lara , Laban Rhiannon , Zetterberg Henrik , Esteve Aitana Sogorb , Rohrer Jonathan D. 
Published: December 2023

AbstractBackgroundIn recent years, blood‐based biomarkers have become key measures in the study of dementia, including frontotemporal dementia (FTD), with use in diagnosis and clinical trial outcomes. Remote collection of blood samples provides a more accessible and cost‐effective alternative to regular clinic visits and allows for more frequent measures to be taken. This is particularly relevant as we progress into an era of clinical trials in FTD. The aim of this current study was to assess whether neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), markers previously shown be increased in genetic forms of FTD, can be measured using dried blood cards and to optimise the protocol for this.Method10 participants from the University College London GENFI study (three C9orf72 mutation carriers, four GRN mutation carriers and three mutation negative controls) were included in this pilot study. Blood samples were collected by venepuncture from each participant: one sample for plasma analysis and one sample which was used to pipette whole blood on to a blood card. NfL and GFAP concentrations were subsequently quantified using the Simoa multiplex Neurology 4‐Plex A (N4PA) assay in both plasma and the dried blood card. Total protein concentration was measured with the Bradford protein assay and used to correct for variable concentrations of blood card spots. The effect of incubation temperature and time as well as freeze thaw cycles were also assessed as part of the optimisation process.ResultIn this pilot cohort, blood card GFAP concentration (BSA corrected) very strongly correlated with matched plasma GFAP (r = 0.897, p = 0.0004), whilst blood card NfL concentration (BSA corrected) strongly correlated with matched plasma NfL (r = 0.721, p = 0.0234). Incubation temperature impacted total protein concentration in the blood cards, but freeze‐thaw and incubation time did not.ConclusionThis pilot study shows that NfL and GFAP concentrations can be successfully quantified using dried blood cards and results strongly correlate with plasma measures. Future work will involve investigating whether these biomarkers can be measured in blood cards obtained with capillary blood through lancet‐based fingerprick collection and assessing the feasibility of home collection.
Relationships between excessive daytime sleepiness and arterial stiffness with cognitive function in a racially diverse high‐risk cohort
Authors: Butts Brittany , Hu William T. , Verble Danielle D , Likos Kelly D. S. , Bliwise Donald , Trotti Lynn Marie , Benameur Karima , McCart Alisha W , Cook Jordan A , Hammerschlag Bruno L , Nimmagadda Nivi , Russ Amber , Wharton Whitney 
Published: December 2023

AbstractBackgroundAs pathologic processes leading to Alzheimer’s disease (AD) begin many years before clinical diagnosis, assessment of pre‐clinical AD risk factors in high‐risk individuals is needed. Excessive daytime sleepiness (EDS) is associated with increased cardiovascular dysfunction, neuroinflammation, and neurodegeneration, leading to cognitive impairment. We tested the hypothesis that EDS and increased arterial stiffness are related to worse cognitive function in a cohort of Black or African American (B/AA) and non‐Hispanic White (NHW) participants.MethodA community‐based racially diverse sample of cognitively unimpaired adults (47‐83 years), most (87%) with a family history of AD, were enrolled. Cognitive testing took one hour and included domains of executive function, working memory, and verbal and visuospatial ability and language. Daytime sleepiness was measured with Epworth Sleepiness Scale (ESS); EDS was defined as ESS≥10. Arterial stiffness was measured using pulse wave velocity (PWV).ResultParticipants (N = 85) were 64±8 years of age, 75% female, 48% B/AA, and highly educated (81% ≥college). Mean central blood pressures were 126±18 mmHg (systolic) and 80±10 mmHg (diastolic), with no differences by race or sex. Scores were lower among B/AA versus NHW participants for Judgement of Line of Orientation (17.71±6.0 versus 23.53±6.0, p<.001, Cohen’s d = .083) and Multilingual Naming Test (28.25±2.7 versus 30.57±2.0, p = .005, d = .950). EDS was present among 15% of participants and associated with lower scores on Digit Symbol (p = .004, d = .917), and Multilingual Naming Test (p = .006, d = 1.455). Total time on Trails A was higher among those with EDS (36s versus 30s, p = .040, d = .575). Higher PWV values were associated with lower scores on Digit Symbol Substitution (r = ‐.259, p = .029), Buschke Selective Reminding Test (‐.298, p = .012), CERAD Word List (‐.306, p = .009), F‐A‐S (r = ‐.253, p = .033), and Animal Fluency (r = ‐.326, p = .006).ConclusionIn a racially diverse cohort at risk for AD, we found that excessive self‐reported daytime sleepiness and increased arterial stiffness were associated with worse scores across multiple cognitive domains. Poor sleep and vascular dysfunction are known contributors to AD pathology, providing potential modifiable targets of intervention to reduce or delay the development of AD in cognitively normal, but high‐risk individuals. Further work is needed for a better understanding of modifiable AD risk factors in diverse populations
Cerebral perfusion is elevated in a novel model of aged hAβKI APOE4 mice
Authors: Obenaus Andre , Singh Aditya , Pad Rojina , Iyer Anika , Ketsan Tia , Jullienne Amandine 
Published: December 2023

AbstractBackgroundThe Model Organism Development and Evaluation for Late‐Onset Alzheimer’s Disease (MODEL‐AD) Consortium is developing the next generation of Alzheimer’s disease (AD) models based on human genomic and imaging data. Recently, MODEL‐AD has generated a new human Aβ Knock‐In (hAβKI) mouse carrying the APOE4 allele. APOE4 carriers are at increased risk for AD. Previous studies have demonstrated altered cerebrovascular integrity and function. We examined the cerebrovascular function in the hAβKI APOE4 mice at 18mo of age using perfusion‐weighted magnetic resonance imaging (PWI). We investigated brain‐wide perfusion alterations in conjunction with histopathological vessel painting.MethodsContrast‐enhanced PWI MRI (9.4T) was undertaken from hAβKI APOE4 (n = 6) and WT (n = 5) mice at 18mo of age following tail vein cannulation for Gadolinium infusion. Imaging sequences included: T1‐pre and post‐infusion, PWI (10min) and susceptibility‐weighted imaging (SWI) for blood extravasation and iron content. All data were processed using JIM v9 software for maps of cerebral blood flow (CBF), volumes (CBV), time to peak, mean transit time and dynamic susceptibility measures for blood‐brain barrier dysfunction. Manual regions of interest (ROI) were performed for cortex, temporal lobe cortex, dorsal hippocampus and thalamus, and semi‐automatic 30+ regions based on the Allen mouse brain atlas. At the end of the in vivo experiments all mice underwent vessel painting followed by microscopic analyses.ResultsCompared to WT mice at 18mo of age, hAβKI APOE4 mice exhibited elevated CBF in virtually all regions examined. CBF was elevated approx. 16%, 11%, 4% and 23% in the cortex, hippocampus, thalamus and temporal lobe cortex, respectively. CBF was significantly elevated in the retrosplenial and temporal lobe cortices (p<0.05). CBV was also significantly increased in temporal lobe. Ongoing analyses will correlate vascular network measures (density, junctions, length) to PWI metrics as well as to hAβKI only mice.ConclusionsThe 18mo hAβKI APOE4 mouse compared to WT exhibited consistent brain‐wide elevations in cerebrovascular measures. This increase may represent a compensatory mechanism to maintain decreased metabolism that occurs with aging. The MODEL‐AD consortium (UCI/IUSM/JAX) continues to develop new and novel AD mouse models. All data will be made available to AD researchers via the Sage Knowledge Network (https://adknowledgeportal.synapse.org/).
Functionally Informed Polygenic Risk Scores for Alzheimer’s Disease
Authors: Sale Rebecca L , Betti Michael J , Kaas Garrett , Gamazon Eric R 
Published: December 2023

AbstractBackgroundAlzheimer’s Disease (AD) is a heritable, neurodegenerative disease. Most AD cases can be categorized as Late Onset Alzheimer’s Disease (LOAD) cases, which are polygenic. Genome Wide Association Studies (GWAS) of LOAD have identified several associated single nucleotide polymorphisms (SNPs). These variants are in 75 genetic loci, and have implicated a diverse array of genes, cell types, and biological pathways in LOAD. Additionally, many associated variants are not in protein coding regions of the genome. However, it is difficult to determine if all associated variants are functionally relevant and contribute to the etiology or progression of the disease. Here, we present CoRE‐BED, a variant annotation tool that can categorize SNPs into functional classes, such as promoters or enhancers, for a given cell type. These functional variants in each cell type are subsequently used to determine functional variant contributions to LOAD heritability and risk.MethodWe annotated a recently published GWAS of AD (Bellenguez et al 2022) using CoRE‐BED. CoRE‐BED leverages 19 functional assays across 33 distinct cell types from EpiMap to classify variants into functional categories for each supported cell type. Annotated variants were used to estimate cell type specific partitioned heritability using LD Score Regression. Finally, annotated variants were used to build cell type specific Polygenic Risk Scores (PRS). PRS was tested using multiple PRS software and utilized the annotated GWAS as a training dataset and independent cases and controls derived from Vanderbilt University’s biobank, BioVU.ResultCoRE‐BED provided functional classifications for all variants in the GWAS for individual tissue types. Variants that pass genome wide significance (P < 5×10−8) are enriched for functional annotations. Immune related cell types contribute the greatest proportion of partitioned heritability. Standard PRS methods outperform cell type informed PRS measures.ConclusionCoRE‐BED is a robust annotation tool that can determine functional annotations at the SNP level. AD GWAS significant associations overlap with functionally annotated SNPs in multiple cell types. Partitioned heritability indicates that immune related cell types may play an important role in the heritability of AD. However, conventional methods for PRS still provide the most robust means to predict AD risk.
Are There Differences in Screening MMSE Interview Durations Between Subjects Who Maintain Severity and Subjects Who Drop Below Screening Inclusionary MMSE Thresholds at Baseline? An Exploratory Analysis.
Authors: Kott Alan , Wang Xingmei , Miller David S. 
Published: December 2023

AbstractBackgroundWe have previously identified a large proportion of subjects (> 10%) entering clinical trials in early Alzheimer’s disease to possibly suffer from Baseline inflation (Kott, 2023). Without useful predictive markers, the identification of these subjects happens only when these subjects are already randomized into the trial. Our prior analyses showed an almost linear relationship between MMSE interview duration and MMSE total score (Kott, 2022). To be able to identify possible subjects with MMSE score inflation at Screening, we wanted to test the hypothesis that those subjects with likely inflated MMSE scores had significantly longer scale administration times, possibly corresponding to increased symptom severity below the MMSE inclusionary threshold.MethodData from 6,922 subjects were pooled from 6 early AD clinical trials. We restricted the analysis to interviews between 3 and 30 minutes long, shorter interviews are technically not possible and longer interviews likely indicate user error. This decreased the sample to 6,717 subjects. Subjects were dichotomized into subjects meeting Screening MMSE criteria at Baseline and subjects who dropped below the Screening MMSE criteria at Baseline. A generalized linear model was fitted to the data with the Screening MMSE duration used as the predicted variable and type of subject (drops below criteria yes/no) as the predictor variable correcting for the MMSE score at Screening.Result937 subjects no longer met MMSE inclusion criteria at Baseline. For those subjects, MMSE interview duration increased significantly (∼40 seconds).ConclusionOur post‐hoc analysis found significantly longer Screening MMSE interview durations in subjects who no longer met MMSE inclusion cutoffs at Baseline. The increase was consistent with our hypothesis and likely reflects that these subjects had their Screening MMSE scores inflated in order to meet inclusion criteria. We suggest including prolonged MMSE durations in analytical programs as a marker of possible MMSE score inflation alongside other markers, like MMSE vs ADAS‐Cog discordance. We plan additional analyses to better understand this problem.
Do Caregivers of Alzheimer’s Disease Have Adequate Levels of Physical Activity?
Authors: Menengiç Kübra Nur , Bülbül Nazlı Gamze , Doğan İdil Arasan , Kendirli Sude , Çınar Nilgün 
Published: December 2023

AbstractBackgroundThe care of individuals with Alzheimer’s disease is mostly provided by their spouses and children. It is stated that an average of 18 billion hours is spent annually on informal care provided by family members. It is known that caregiving affects both physical and mental health. The burden of care that arises in this process increases the stress and burnout levels of caregivers, causing psychological symptoms, especially depression and anxiety. However, it has been shown in many studies that the incidence of chronic diseases in caregivers is high. The level of physical activity, which is one of the most important determinants of living a healthy life, has an impact on the physical and mental health of individuals. In this study, we aimed to examine the physical activity levels of family members who care for individuals with Alzheimer’s disease.MethodThe sociodemographic information of the caregivers and the functional levels of the patients they care for were recorded in the forms we prepared. Physical activity level was evaluated with the ‘Quick Assessment of Physical Activity Scale’.ResultOf the caregivers participating in the study, 88.4% were female and 11.6% were male. The mean age was 53.89±11.9 years. 79.7% of them were not working actively. 40.6% of caregivers diagnosed with Alzheimer’s disease were completely dependent on their caregivers in daily life. It was found that 6.7% of the participants were physically inactive and 66.7% had insufficient physical activity.ConclusionIt was observed that the percentage of physically inactive Alzheimer’s disease caregivers was above the average of individuals in the same age group living in Turkey. In this context, we think that it is important to investigate the economic, social and psychological factors that cause a sedentary lifestyle in caregivers. Considering the positive effects of physical activity on physical and mental health, it is important to provide conditions that support caregivers to be more active. In order to reduce the economic and social burden of Alzheimer’s disease in society, public health policies should not only be formed to cover individuals with Alzheimer’s disease, but also strategies should be included for the needs of caregivers.
Comparison of Functional Mobility Performances of People with Alzheimer’s Disease, Mild Cognitive Impairment, and Cognitively Healthy Individuals
Authors: Menengiç Kübra Nur , Ovacık Uğur , Güngör Feray , Bülbül Nazlı Gamze , Çınar Nilgün , Yeldan İpek 
Published: December 2023

AbstractBackgroundOne of the important factors that make it difficult to carry out activities of daily living independently is the decrease in functional mobility. Mobility‐related disability is a major public health issue that reduces the quality of life and increases the need for care, the burden, and the cost of care. However, in the early stages of dementia, the deterioration in motor skills is often overlooked. This study aimed to compare the mobility performance of healthy individuals and people with Mild Cognitive Impairment (pwMCI) and Alzheimer’s disease (pwAD).MethodCognitive level was measured with Montreal Cognitive Assessment (MoCA) and mobility performance was measured using Timed Up and Go Test (TUG) and 5 Times Sit to Stand Test (5XSTST). Statistical analysis was performed using One Way ANOVA in SPSS v.26 and the level of significance was accepted as p<0.05.Results36 pwAD (Age: 74.90±9.25, 53.12% Female), 14 pwMCI (Age: 63.82±12.55 years, 52.6% Female), and 10 cognitively healthy individuals (Age: 60.25±10.23 years, 82% Female) were included the study. The mean of MoCA scores were 12.62±6.36, 22.25±3.04 and 28.5±0.5; TUG results were 15.34±11.83 sec, 7.47±1.41 sec and 6.86±1.98 sec; 5XSTST results were 16,31±7.75 sec, 11.06±1.98 sec and 9.34±2.37 sec. A significant difference was found between the three groups in terms of TUG and 5XSTST results (p = 0.027, p = 0.015, respectively).ConclusionIn pwAD and pwMCI, the decrease in cognition appears to be accompanied by impairment in functional mobility. Motor skills should be evaluated not only in AD diagnosis but also during the prodromal stage to provide early intervention for loss of motor function. Improving motor function should be added to rehabilitation goals before impaired functional mobility begins to affect activities of daily living.
Cognitive Training with Neurofeedback using fNIRS is Associated with Improved Cognition in Older Adults
Authors: Acevedo Bianca P , Collins Nancy , Ageiwa Kota , Kinoshita Mika 
Published: December 2023

AbstractBackgroundThis study examined the effects of a 4‐week cognitive training program with neurofeedback (CT‐NF) using fNIRS among 86 healthy, older adults.MethodParticipants were randomized to either a treatment (app‐based ABC games) or control (Tetris) group, and they all completed seven cognitive assessments, pre‐ and post‐intervention. Also participants received live feedback of their brain activity (neurofeedback using fNIRS) while doing their exercises.ResultThe treatment (ABC) group showed significant improvements in memory and composite cognitive function, while the control group did not. Cortical brain activity (measured during CT‐NF) was associated with both cognitive and game performance.ConclusionThese findings suggest that CT‐NF and specifically ABC exercises, confer improved cognition in the domains of memory and overall cognitive function in healthy, older adults.