bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact on End‐of‐life Planning of a Care Coordination Program for persons living with dementia
Authors: Tan Zaldy S. , Qureshi Nabeel , Kremen Sarah , Rhinehart Deana , Gatmaitan Dyane , Spivack Erica , Guinto Augustine , Sicotte Nancy 
Published: December 2023

AbstractBackgroundAlzheimer’s disease and related dementias (ADRD) afflict over five million persons in the U.S., and persons living with dementia (PLWD) have been shown to receive poor quality care and have worse health outcomes compared to those without ADRD. We developed a population‐based dementia care management program to support the care of PWLD in a large U.S. healthcare system.MethodsIn a large multi‐specialty medical group practice, we identified patients enrolled in a value‐based insurance program (Medicare Advantage) using the EPIC electronic health record (EHR), and eligible patients were invited to enroll in the CARES dementia care program. Patients were eligible if they had an ICD‐10 diagnosis of ADRD in the EHR problem list and/or past medical history, or currently taking an FDA‐approved medication for ADRD. We additionally included patients with ADRD who have a primary care provider in the affiliated academic health system. During an in‐person intake visit, a study‐assigned nurse practitioner (NP) engaged in advance care planning discussion with patients and caregivers and completed advance directives (AD) and Physician Order for Life Sustaining Treatment (POLST). We assessed the rate of completion of the AD and POLST pre‐program and post‐enrollment.ResultsWe enrolled 195 patients in the CARES dementia care program. After enrollment, participants increased completion of advanced directives from 27.7% to 30.8% (p = 0.25) and the POLST from 13.3% to 23.1% (p = 0.006). Of the POLST forms completed, 70.7% indicated that the patient was ‘do not attempt resuscitation’ (DNAR) (65.2% of those who completed the POLST pre‐program, 77.8% for those who completed after enrollment, p = 0.19). Among those who completed the POLST, 55.0% indicated selective medical interventions (63.6% pre‐program, 47.1% post‐enrollment, p = 0.15), 40.0% wanted full medical interventions (31.8% pre‐program, 52.9% post‐enrollment, p = 0.10), and 5.0% wanted comfort‐focused interventions (4.5% pre‐program, 5.9% post‐enrollment, p = 0.43). Trial period of nutritional supports was indicated by 69.2% (72.7% pre‐program, 64.7% post‐enrollment, p = 0.28), while 28.2% wanted no artificial treatment (27.2% pre‐program, 29.4% post‐enrollment, p = 0.45), and 2.6% wanted long‐term nutritional support (0% pre‐program, 5.9% post‐enrollment, p = 0.13).ConclusionA dementia care coordination program shows signs of increased completion of end‐of‐life planning, with the majority choosing ‘do not attempt resuscitation’ (DNAR).
Validated, unified theory of Alzheimer Disease illuminates two essential research questions
Authors: Kennedy Alison Ruth 
Published: December 2023

AbstractBackgroundA 2001 unified theory of thiamine deficiency (TD) in Alzheimer Disease (AD) (1‐p.85) was validated in 2015 (2), and published in 2017 (3). Update?MethodScientific literature review on topic of thiamine and/or AD. PUBMED, elibrary.wiley.com, mspace.lib.umanitoba.caResult1. Thiamine supplementation can potentially correct key AD abnormalities: the cholinergic deficit (1‐p.64, 4), B‐Amyloid (1‐p. 77, 3), tau (5), neuroinflammation (4, 5,6, 7) and memory (1‐p59).2. Limited oral thiamine supplementation trials in AD have had mixed results (1‐p49, 6).ConclusionEssential research questions:a. What causes TD in AD? (altered thiamine requirements, excretion, absorption, transport, metabolism, or diet and other factors*?) (1)b. What is the optimal treatment of TD in AD? (control for medications*, medical conditions* and dietary components affecting thiamine intake and utilization* (1‐p. 52, 1‐p.53,9). Consider advantages of intramuscular injections vs. oral treatments (8), need for other nutrients (1‐p.52), proven thiamine treatments in TD diseases.
References:1. Kennedy, A.R. (2001). The potential role of thiamine in the pathogenesis and treatment of Alzheimer’s Disease. M.Sc. dissertation. University of Manitoba, Winnipeg. http://mspace.lib.umanitoba.ca/handle/1993/19635
2. Pan, X. (2015). Measurement of brain thiamine metabolites for Alzheimer Disease diagnosis. 2015 Nov 26. doi: 1016/j.ebiom.2015.11.0393. Kennedy, A.R. (2017). Scientific evidence supporting a unified theory of Alzheimer Disease. Alzheimers Dement,13(7S)_ Part_31/p.P1478‐P1478 https://doi.org/10.1016/j.jalz.2017.07.551
4. Lu’o’ng, K., Nguyen, LT (2011). Role of thiamine in Alzheimer’s Disease. Am J Alzheimer’s Dis Other Demen., 26(8):588‐598. https://doi.org/10.1177/1533317511432736
5. Tapias, V. et al. (2018). Benfotiamine treatment activates the Nrf2/ARE pathway and is neuroprotective in a transgenic mouse model of taupathy. Hum Mol Genet Aug 15; 27(16): 2874‐2892. https://doi.org.10.1093/hmg/ddy201
6. Fessell, J. (2021). Supplemental thiamine as a practical, potential way to prevent Alzheimer’s disease from commencing. Alzheimers Dement: Translational Research and Clinical Interventions. 7 (1)/e12199. https://doi.org/10.1002/trc2.12199
7. Sambon, M. et al. (2021). Neuroprotective effects of thiamine and precursors with higher bioavailability: Focus on benfotiamine and dibenzoylthiamine. Int. J. Mol. Sci. 22(11):5418. https://doi.org/10.3390/ijms22115418
8. Baker, H., et al. (1980). Oral versus intramuscular vitamin supplementation for hypovitaminosis in the elderly. J Am Geriatr Soc., 28(1):42‐45. https://doi.org/10.1111/j.1532-5415.1980.tb00123.x.9. Vora, B. et al. (2020). Drug‐nutrient interactions; discovering prescription drug inhibitors of the thiamine transporter ThTF‐2 (SLC19A3). Am J Clin Nutr., 111(1), 110‐121. https://doi.org/10.1093/ajcn/nqr255
TMS and imaging correlates of spasticity in persons at‐risk for the A431E PSEN1 mutation
Authors: Iyer Pooja , Shi Yonggang , Ringman John M 
Published: December 2023

AbstractBackgroundSpastic paraparesis (SP) occurs in approximately 45% of carriers of the A431E PSEN1 mutation (MCs), sometimes preceding cognitive decline. SP is typically caused by reduced cortical excitatory output to spinal motor neurons resulting from delayed cortical conduction time or increased inhibitory output from cortex. Previous studies have observed that people with spasticity have increased corticospinal inhibition at rest and altered interhemispheric inhibitory control (amount of inhibition and conduction time) during isometric contraction. Hence, in this study, we sought to identify transcranial magnetic stimulation (TMS) and diffusion MRI and flortaucipir PET imaging predictors of SP using these inhibitory measures captured using TMS.MethodWe included 19 persons known to be at‐risk for the A431E PSEN1 mutation (15 MCs, 3 NCs) and one person affected by the F388S PSEN1 mutation who participated in a comprehensive study of autosomal dominant AD including TMS, diffusion MRI, and flortaucipir PET. We measured cosrticospinal inhibition for lower limbs at rest by targeting tibialis anterior muscle representation at primary motor cortex. For inter‐hemispheric inhbition (extent of inhibition and transcallosal conduction time), we stimulated the hemisphere ipsilateral to the limb performing isometric contraction. We ran a non‐parametric regression model for prediction using the gsm function from the npreg package in R© because several variables were not normally distributed (Shapiro‐Wilk test, p<0.05).ResultSpasticity score (Ashworth scale) was positively associated with interhemispheric inhibition, transcallosal conduction time, and DTI measures of the corticospinal tract and pre‐post‐para central lobes of both hemispheres (Spearman rank correlation, p< 0.05). Among all inhibitory TMS measures and DTI variables, the transcallosal conduction time for the lower limbs (β = 2.87) and suvr_rh_paracentral (β = ‐25.92) independently predicted increased spasticity scores. The interaction effect between these measures was insignificant. The prediction model had an adjusted R2 value of 0.89.ConclusionWe show increased transcallosal conduction time and decreased white matter integrity around the right‐hemisphere paracentral lobule is associated with increased mean spasticity scores in people with A431E PSEN1 mutations. This is consistent with other studies showing altered interhemispheric control in SP. Delay in transcallosal conduction time in A431E PSEN1 MCs may compromise inter‐hemispheric control limiting smooth movement control.
The relation between adverse childhood experiences and fostering health behaviors in adult women
Authors: Tsotsoros Cindy E , Tavares Karina L. 
Published: December 2023

AbstractBackgroundAdversity in early childhood plays a central role in health outcomes later in life. Social determinants of health, such as environment, play a role in lifestyle habits developed and possessed throughout adulthood. The more adverse childhood experiences (ACEs) an individual has, the more likely they are to have negative physical and mental health outcomes (Sacks & Murphey, 2018).MethodData was collected in a larger cohort study assessing biomarkers in women between the age of 65‐85. Among the 232 women, two groups were recruited: individuals with 0 ACEs and individuals with 3 or more ACEs. Survey data was collected from participants and analyzed using SPSS Version 28. Health lifestyle was measured using the Health‐Promoting Lifestyle Profile (HPLP‐II; Walker, et al., 1987). The HPLP‐II has six subscales: health responsibility, nutrition, spiritual growth, physical activity, stress management, and interpersonal relations. ACEs were measured with the Adverse Childhood Experiences Questionnaire (Felitti et al., 1998) and addressed three categories of adversity: abuse, neglect, and household dysfunction (HD).ResultThe 87 participants who had zero ACEs (M = 2.56, SD = 0.46) compared to the 145 participants with three or more ACEs (M = 2.18, SD = 0.41) demonstrated significantly higher HPLP‐II scores indicating that healthier behaviors are performed more frequently for those with zero ACEs, t(230) = 6.65, p<.001. All of the multiple linear regressions were overall statistically significant (HPLP‐II (R2 = .17, F(3, 228) = 16.44, p<.001); health responsibility (R2 = .07, p< 001); physical activity (R2 = .05, p = .002); nutrition (R2 = .07, p<.001); spiritual growth (R2 = .17, p<.001); interpersonal relationships (R2 = .13, p<.001); stress management (R2 = .12, p<.001)). Neglect and HD significantly predicted overall HPLP‐II ((β = ‐.21, p = .012); (β = ‐.19, p = .008)) and interpersonal relationships ((β = ‐.23, p = .008); (β = ‐.23, p = .003)). HD significantly predicted health responsibility (β = ‐.18, p = .022) and nutrition (β = ‐.22, p = .005). Neglect significantly predicted spiritual growth (β = ‐.25, p = .003). Abuse significantly predicted stress management (β = ‐.17, p = .05), and was trending in predicting physical activity (β = ‐.16, p = .078).ConclusionACEs play a significant role in future health behaviors, with household dysfunction being the largest predictor.
Plasma biomarker and neuroimaging changes in a Chinese community aging cohort: The Greater‐Bay‐Area Healthy Aging Brain Study (GHABS)
Authors: Guo Tengfei , Zhang Mingkai , Shi Dai , Li Yuxia , Chen Xuhui , Zhao Ruiyue , Lan Guoyu , Cai Yue , Sun Pan , Li Anqi , Zhu Yalin , Liu Lin , Guo Lizhi , Zhou Yajing , Liu Zhen , Sun Kun , Wang Xinlu , Xu Linsen , Wang Qingyong , Han Ying 
Published: December 2023

AbstractBackgroundTo investigate the alternations of β‐amyloid (Aβ), tau, neurodegeneration, and cognition in different stages of Alzheimer’s disease (AD) in the Chinese community aging population is important for early diagnosis and intervention of AD in China.MethodWe recruited 422 Greater‐Bay‐Area Healthy Aging Brain Study (GHABS) participants from the community and completed cognitive assessments, including 100 cognitively unimpaired (CU), 189 subjective cognitive decline (SCD), 82 mild cognitive impairment (MCI) and 51 AD dementia individuals. Among them, 343 individuals had plasma Aβ42/Aβ40, p‐Tau181, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) data measured by the Simoa platform. Furthermore, 159 and 96 individuals had concurrent MRI and 18F‐D3‐FSP Aβ PET scans, respectively. Generalized linear models were used to compare plasma biomarkers, AD typical cortical FSP Aβ standard uptake value ratio (SUVR), residual hippocampal volume (rHCV), and cognitive scores between different clinical and A/T (A: plasma Aβ42/Aβ40, T: plasma p‐Tau181) groups, controlling for age and sex. Multiple comparison corrections were conducted (Benjamini‐Hochberg, p<0.05). The association of plasma Aβ42/Aβ40 and p‐Tau181 with plasma NfL, GFAP, Aβ PET, rHCV, MoCa, and SCD‐Q were also investigated, including age, sex, and diagnosis as the covariates.ResultSCD individuals had higher plasma p‐Tau181 (standardized β (βstd) = 0.251[95% confidence interval (ci): 0.031, 0.472], p = 0.038) and GFAP (βstd = 0.259[95% ci: 0.035, 0.483], p = 0.023) than the CU individuals (Figure 1). Compared to the A‐/T‐ group, A+/T+ individuals had more (p<0.001) abnormal changes in all the plasma biomarkers, Aβ PET, rHCV, and MoCa, and A‐/T+ individuals had more hippocampal atrophy (p = 0.012) and marginal higher plasma NfL (p = 0.074) (Figure 2). Continuously, lower plasma Aβ42/Aβ40 was only related to higher plasma GFAP (p<0.001), whereas plasma p‐Tau181showed significant association with plasma NfL (p<0.001), plasma GFAP (p = 0.026), Aβ PET (p = 0.028), and MoCA (p = 0.023) (Figure 3).ConclusionThis study summarizes the characteristics of plasma biomarkers and brain imaging of AD and provides novel insights into the alternations of Aβ, tau, neurodegeneration, neuroinflammation, and cognition in different stages of AD in Southern China’s aging population. These findings are critical for using plasma biomarkers and neuroimaging to detect early AD changes in China.
The AβpE 3‐42 peptide is associated with a higher degree of inflammation than Aβ1‐40 in brains with Alzheimer’s disease.
Authors: Soto‐Rojas Luis Oskar , Harrington Charles R , Carmen Cardenas‐Aguayo Maria , Cruz‐López Fidel , Viramontes‐Pintos Amparo , Gevorkian Goar , Luna‐Muñoz José 
Published: December 2023

AbstractBackgroundAlzheimer’s Disease (AD) is the most common neurodegenerative disease histopathologically characterized by the presence of neuritic plaques (NPs), extracellular deposits composed of amyloid beta peptide (Aβ) and neurofibrillary tangles (NFTs) composed of tau protein. It has been hypothesized that Aβ promotes synthesis and secretes proinflammatory proteins causing neuronal and endothelial damage in the AD brain. In this context, it is not clear if the truncated Aβ species can be more toxic than the full‐length ones. Therefore, this work aimed to explore the association of the Aβ1‐40 peptide (full length) and AβpE3‐42 (truncated species) with inflammation in the brains of AD patients.MethodWe used postmortem tissue from the temporal cortex of patients with AD and it was analyzed by confocal microscopy using antibodies against the peptide Aβ 1‐40 and AβpE 3‐42, phospho tau and caspase‐5 (inflammatory type caspase). The amyloidogenic plaques AB1‐40 and AβpE3‐42 and their association with the inflammation marker caspase 5 were quantified. In addition, caspase 5 was quantified by western blot (WB) in control brains and those with AD.ResultWe found high caspase‐5 immunoreactivity specifically associated with extracellular Aβ peptide deposits. Interestingly, this caspase 5 is associated preferentially with the truncated Aβ pE 3‐42 peptide. Likewise, caspase‐5 was expressed mainly in brain blood vessels which had Aβ peptide deposits. We did not detect the colocalization of this enzyme with the tau protein. WB assays show increased caspase 5 in AD brains compared to controls.ConclusionIn conclusion, our findings show that the truncated AβpE3‐42 peptide is closely associated with caspase 5, a key enzyme in the inflammation process. This latter may be a specific biomarker of inflammation in AD brains.
Predictive analysis between cytokine profile and Aβ42, p‐Tau, and p‐Tau/Aβ42 levels in the cerebrospinal fluid of older adults with and without cognitive impairment
Authors: Bolaños Burgos Ivonne Carolina , Aquino Pedro Henrique Oliveira , Ribeiro Julia Mendes , de Andrade Rafael Souza , Engelmann Gabriela Tomé Oliveira , Hansen Erika de Oliveira , Dias Natália Silva , Carvalho Andréa Teixeira , Miranda Debora , Romano‐Silva Marco Aurelo , de Marco Luiz Armando Cunha , Viana Bernardo de Mattos , Bicalho Maria Aparecida Camargos 
Published: December 2023

AbstractBackgroundThe immune system activation observed in Alzheimer’s disease (AD) pathology contributes to its pathogenesis. It is proposed that ongoing interactions between β‐amyloid plaques, Tau protein, and neuroinflammatory mediators such as cytokines contribute to the maintenance of the inflammatory state in the brain. The aim was to evaluate whether cytokine profiles can predict variations in Aβ42, pTau, and pTau/Aβ42 cerebrospinal fluid (CSF) levels in older adults with and without objective cognitive impairment.MethodsEighty older adults were recruited, with a clinical diagnosis of AD dementia (36), with Mild Cognitive Impairment (MCI) (24), and without objective cognitive impairment (20). CSF levels of Aβ42, pTau, and 27 cytokines were assessed by the Luminex xMAP technique. Significant associations between Aβ42, p‐Tau, and p‐Tau/Aβ42 CSF levels and cytokines were explored in multiple linear regression analyses adjusted for age, education, and APOE ε4 carrier status.ResultsWe found that Granulocyte and Macrophage colony‐stimulating factors (GM‐CSF) (β = ‐.375; p = .010) and IL‐6 (β = ‐.370; p = .014) had a negative significant association with Aβ42, while IL‐8 (β = .452; p = .002) and IL‐4 (β = .488; p = .001) had positive significant association and higher magnitude of effect on Aβ42. For pTau, age (β = .240; p = .029), IL‐2 (β = .314; p = .012) and ε4 allele (β = 0.349; p = .002) had a positive significant association. The variable with the greatest magnitude of the effect was the presence of the ε4 allele. For the p‐Tau/Aβ42 ratio, G‐CSF (β = .423; p = .003) and GM‐CSF (β = .317; p = .019) had a significant positive association, while for IL‐8 (β = ‐.554; p = .001) and IL‐12 (β = ‐.334; p = .019) the association was significantly negative. IL‐8 had the greatest magnitude of effect on p‐Tau/Aβ42 ratio values.ConclusionThe higher levels of IL‐4 and the IL‐8 associated to a higher Aβ42 suggest their role at the beginning of the disease. On the other hand, the lower level of IL‐8 associated with a higher p‐Tau/Aβ42 suggests its inactivation as the disease progresses. Conversely, the higher levels of GM‐CSF associated with higher p‐Tau/Aβ42 suggests a more robust recruitment of the immune cell system at later stages.Reference: Aksnes, M., et al., (2021). Associations of cerebrospinal fluid amyloidogenic nanoplaques with cytokines in Alzheimer’s disease. Translational Neurodegeneration.
A CenTauR scale based on 18F‐MK6240
Authors: Dore Vincent , Bourgeat Pierrick , Leuzy Antoine , Huang Kun , Krishnadas Natasha , Feizpour Azadeh , Fripp Jurgen , Villemagne Victor L , Rowe Christopher C 
Published: December 2023

AbstractBackgroundA standardized scale for the quantification of tau PET imaging would allow comparison and combination of data across tracers and sites resulting in large meta‐analysis and the application of universal cut‐offs. The proposed approach called CenTauR (CTR) was evaluated on 18F‐MK6240 using both global and regional anchoring.Method375 18F‐MK6240 PET & T1w scan pairs (HC Aβ‐ = 179/MCI Aβ+ = 98/AD Aβ+ = 98) from AIBL&ADNeT were spatially normalised using SPM8 and SUVR normalised using the cerebellar cortex. PET scans were then quantified in 4 composite ROIs [Mesial‐Temporal (Me), Meta‐Temporal (MT), Temporo‐Parietal (TP) and Frontal (FT)] from a previously defined “universal” cortical mask. To anchor the 0 and 100 CTR, we only included HC Aβ‐ (<10CL) and AD Aβ+ (>25CL) individuals younger than 75y, with MMSE ≥20, we also excluded HC participants with a quantification higher than the 75%tile in the Me and AD patients with a quantification lower than the 25%tile in the MT, resulting in 68 HC Aβ‐ and 29 AD Aβ+. We investigated two CTR scaling approaches using either a single transform based on the TP anchors to transform SUVR into CTR for all composites or using region‐based equations scaled with regional anchors.ResultThe mean and standard deviation (std) for the HC and AD groups are reported in Table 1.Using a single transformation resulted in the following equation:Ct = 100x(SUVR‐0.97)/2.26Region‐based equations can be extrapolated from Table 1. Figures 1 and 2 show that regional CTR overstretches quantification in FT compared to single equation‐derived CTR. Thresholds set at 2 std above the HC were 2.38, 9.43, 7.66, 1.82, and 6.16 CTR for Me, MT, TP, FT and Global respectively, and were 7.05, 7.48, 7.66, 10.20, 7.68 CTR when using regional equation‐derived CTR.ConclusionThe region‐based approach provided slightly more consistent CTR distributions in the HC across the ROIs however, this approach tends to over‐stretch the CTR values in the frontal region.
Comparison of plasma and cerebrospinal fluid protein markers and their significance for the characterization of dementia disease status
Authors: Rehman Habbiburr , Ang Ting Fang Alvin , Tao Qiushan , Zhang Xiaoling , Qiu Wei Qiao 
Published: December 2023

AbstractBackgroundAlthough Aβ42 and phosphorylated tau (p‐tau) in cerebrospinal fluid (CSF) are valuable to diagnose Alzheimer’s disease (AD), many patients are reluctant to accept lumbar puncture. In addition, there is lack of biomarkers for the different stages of AD dementia. This study sought to compare the plasma and CSF protein markers to characterize dementia status.MethodThis cohort study included Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants who had baseline levels of 73 proteins measured in plasma (566 total, 58 cognitively normal (CN), 396 mild cognitive impairment (MCI), and 112 AD) and in CSF (310 total, 92 CN, 149 MCI, and 69 AD). Univariate/multivariate logistic regression and least absolute shrinkage and selection operator (LASSO) were used to identify the protein candidates for the disease classification. The following three models were examined for CN vs. MCI and MCI vs. AD; model 1: proteins only, model 2: proteins adjusted for age, sex, education, and model 3: model 2 plus APOE4 status.ResultNine proteins in plasma and CSF were chosen based on their importance from LASSO. The area under the curve (AUC) for the final multivariate logistic regression including the 9 proteins was calculated for each disease group in plasma [CN vs. MCI: 0.895 (model 1), 0.899 (model 2), 0.921 (model 3), and MCI vs. AD: 0.828 (model 1), 0.842 (model 2), 0.856 (model 3)]. In addition, AUC in CSF [CN vs. MCI: 0.678 (model 1), 0.726 (model 2), 0.770 (model 3) and MCI vs. AD: 0.711 (model 1), 0.738 (model 2), 0.765 (model 3)] was also estimated. We observed that plasma proteins outperformed the CSF proteins to be associated with MCI and AD. Also, plasma proteins were significantly better than the established AD markers, namely CSF Aβ42 and p‐tau in CN vs. MCI [AUC: 0.836 (model 1), 0.842 (model 2), 0.862 (model 3)] and MCI vs. AD [AUC: 0.665 (model 1), 0.673 (model 2), 0.680 (model 3)].ConclusionThis study demonstrates that the combination of plasma proteins could be considered an effective marker for diagnosing AD and its early‐stage symptoms with better performance than the other markers.