bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction between Oligomeric Amyloid‐β and Cardiovascular Risk Factors is Associated with Executive and Dorsal Attention Network Dysfunction in Pre‐dementia
Authors: Kumar Dilip , Soo See Ann , Sandhu Gurveen Kaur , Zailan Fatin Zahra , Leow Yi Jin , Vipin Ashwati , Koh Chen Ling , Lee Faith Phemie Hui En , Ghildiyal Smriti , Kandiah Nagaendran 
Published: December 2023

AbstractBackgroundOligomeric amyloid‐β(OAβ) accumulation within brain tissue has been shown to be associated with major AD neuropathological features including tau pathology, synaptic loss, inflammation and oxidative damage; as well as cognitive impairment in dementia cohorts (Celine.E.N et.al.,2018). However, association of OAβ with functional connectivity (FC) and cardiovascular risk factors is not clearly known in the pre‐dementia stage. We aimed to examine association of FC with OAβ and other dementia risk factors in a pre‐dementia cohort to understand the underlying mechanisms related to OAβ.MethodsWe included 98 age and sex matched participants and classified them into OAβ+(28) and OAβ‐(70) subgroups using a OAβ cut‐off ratio of ≥ 0.9 (MDS‐ OAβ Test Kit, PeopleBio Inc, South Korea). Participants completed resting‐state functional MRI, clinical and lifestyle history questionnaires, blood, and neuropsychological assessments for global cognition on Montreal cognitive assessment and Visual Cognitive Assessment at Dementia Research Centre (Singapore). The Cardiovascular Risk Factors, Aging and Dementia (CAIDE) risk score was computed, and independent sample or chi‐squared analysis were performed to evaluate group‐level participant characteristics. Region‐of‐interest based FC analysis for 19 seeds from executive control (ECN), default‐mode, salience and dorsal‐attention networks (DAN) was performed to examine the network‐based FC differences in OAβ+ and OAβ‐ groups in association with CAIDE using ANCOVA model.ResultsMean age of OAβ+ and OAβ‐ were 62.04±8.84, and 62.05±8.07 (Table‐1). No significant FC differences were observed between OAβ+ vs OAβ‐ subjects. There were no significant FC differences related to CAIDE score in OAβ+ and OAβ‐ groups. Nonetheless, the OAβ*CAIDE interaction showed significant FC changes. The OAβ+*CAIDE interaction analyses showed reduced FC within ECN and DAN (Figure‐1a). Whereas OAβ‐*CAIDE interaction showed reduced FC only within ECN (Figure‐1b). Furthermore, OAβ interaction with apolipoprotein‐ε4 (OAβ*APOE4) was found to further influence FC trends in ECN and DAN (Figure‐1c,1d).ConclusionWhile no FC differences were observed between OAβ+ vs OAβ‐ subjects, the interaction between CAIDE and APOE4 moderated FC changes within the ECN and DAN. These observations in a pre‐dementia cohort suggest that the presence of cerebrovascular risk factors may result in differential FC dysfunction in ECN and DAN depending on APOE4 status.
Results from the Australian PITCH study: a national stepped‐wedge cluster RCT evaluating a dementia training program for home care workers
Authors: Dow Briony , Dang Christa , Doyle Colleen , Savvas Steven , Batchelor Frances , Ames David , Winbolt Margaret , Malta Susan , Clarke Philip , Panayiotou Anita , Cooper Claudia , Livingston Gill , Lyketsos Constantine G. , Burton Jason , Loi Samantha M , Low Lee‐Fay , Wise Erica , Scherer Sam , Fairhall Anne , Goh Anita M Y 
Published: December 2023

AbstractBackgroundThe NHMRC‐funded Promoting Independence Through quality Care at Home (PITCH) project aimed to improve outcomes for people living with dementia and their paid and family carers via an evidence‐based dementia specialist training program for home care workers (HCWs). PITCH training was co‐designed with HCWs, family carers and people with dementia, consisting of 2×3.5 hour sessions, delivered face to face (F2F) or on‐line.MethodsStepped‐wedge cluster RCT including 18 home care services in rural and urban VIC, NSW, and SA cluster‐randomised into one of two arms. Data collection from 18 July 2019 to 12 May 2022. Analyses included linear mixed models with intention to treat.ResultsN = 213 HCWs completed baseline measures, N = 144 completed 6‐month follow‐ups, and N = 120 completed 12‐month follow‐ups. 172 HCWs completed the training program. N = 148 (86%) completed all training sessions; N = 81 F2F and 67 online.Primary outcome measureHCWs' Sense of Competency in Dementia Care Staff (SCIDS) was higher after training (p = 0.04). This was driven by F2F training: SCIDS for HCWs completing F2F training was higher vs no training (p = 0.003) and online training (p = 0.015). There was no difference between online training and no training (control condition).Secondary outcome measuresOverall, HCW scores on the Dementia Attitudes Scale (DAS) showed no difference between training and no training. However, F2F training was associated with higher DAS compared to no training (p = 0.05) and online training (p = 0.05).Training improved scores on the Dementia Knowledge Assessment Scale (DKAS, p = 0.03). This was also driven by F2F training (F2F vs no training p = 0.024; F2F vs online p = 0.026).There was no difference between online training and no training for DAS and DKAS. Training had no effect on Strain in Dementia Care Scale (SDCS) scores.Discussion/ConclusionReceiving F2F PITCH training improved dementia attitudes, dementia knowledge, and sense of competence in delivering dementia care for HCWs versus no training and online training.The HCW workforce has unique challenges to accessing and completing training and education to deliver evidence‐based dementia care. Minimising these challenges is critical to the delivery of quality home care. PITCH training now has evidence for its efficacy but only when delivered face‐to‐face.
Diagnostic of Novel Plasma Biomarkers in Controls, SCD and MCI Subjects
Authors: Boutajangout Allal , Masurkar Arjun V. , Ahmed Wajiha , Debure Ludovic , Vedvyas Alok , Links Jon , Faustin Arline , Osorio Ricardo S , Marsh Karyn , Wisniewski Thomas 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is the most common cause of dementia, and a challenging disease for the development of plasma biomarkers. Blood samples are the most easily collectable samples for medical diagnosis. This study evaluates the potential of plasma biomarkers in identifying early stages of AD.Method189 participants were recruited at the NYU Alzheimer Disease Research Center. This cohort includes n = 75 with normal cognition (NL), n = 77 with subjective cognitive decline (SCD), n = 37 with mild cognitive impairment (MCI). Comprehensive neuropsychological and magnetic resonance imaging evaluations were conducted for all patients. Plasma biomarkers assays (total tau [t‐tau], neurofilament light [NfL], glial fibrillary acid protein [GFAP], ubiquitin carboxyl‐terminal hydrolase L1 [UCH‐L1], Aβ1‐42, Aβ1‐40 and pTau181) were measured using the SIMOA SR‐X, a novel technology that employs highly sensitive immunoassays with a limit of detection (LOD) under 100 fg/ml.ResultThe levels of NfL, t‐Tau, GFAP and UCH‐L1 were measured using the Neurology 4‐plex A. NfL levels showed a significant difference between NL and SCD (one tailed t‐ test p = 0.0459). GFAP showed statistically significant differences between NL and MCI, (one tailed t‐test p = 0.0369). Aβ1‐42 showed a significant difference between SCD and MCI (one tailed t‐test p = 0.0493). pTau181 levels showed a significant difference between NL, SCD and NL, MCI (p = 0.0447 and p = 0.0439, respectively). The ratio of pTau181/Aβ1‐42 shows a significant difference between NL and MCI (one tailed t‐test p = 0.0187). Correlation of these biomarkers with brain imaging and cognitive measures is underway.ConclusionBiomarker levels of NfL, GFAP, Aβ1‐42, pTau181 and Ratio pTau181/Aβ1‐42 in plasma samples showed several significant differences between the three groups of subjects. Plasma biomarkers can be useful for the diagnosis of AD related pathology at early stages.
Plasma phosphorylated tau 181 in relation to Alzheimer’s prevalence and cognition in the Thai community
Authors: Hemachudha Pasin , Thanapornsangsuth Poosanu , Saraya Abhinbhen Wasontiwong , Luechaipanit Watayuth , Hemachudha Thiravat 
Published: December 2023

AbstractBackgroundThe identification of biomarkers for Alzheimer’s disease (AD) in blood samples has the potential to facilitate early diagnosis and improve the accuracy of AD diagnosis. Plasma phosphorylated tau (p‐tau) is a promising biomarker for AD; however, its utility in estimating the prevalence of AD and screening for cognitive impairment in non‐demented populations has yet to be explored in Thailand.MethodThe study recruited 110 non‐demented participants over the age of 40 from the family members of patients attending a neurology clinic. Plasma p‐tau 181 levels were measured, and AD prevalence was estimated using a pre‐defined cut‐off derived from an independent cohort with biomarker‐defined AD status according to the current framework (Jack et. al., 2018). The correlation between plasma p‐tau 181 levels and. neuropsychological data were also evaluated.ResultThe median age of participants was 66 years, and the median mini‐mental state examination score was 29. The estimated prevalence of AD was 20.0% (95% CI 13.6‐28.4) in preclinical and mild cognitive impairment patients when using p‐tau as a biomarker, which was lower than the prevalence estimated using amyloid abnormalities of 30.1% (95% CI 29.2‐31.1)(Jansen et. al., 2022) (X
2 [N = 8944] = 5.28, p = .022). Plasma p‐tau 181 levels also showed a negative correlation with neurocognitive test scores (Rho = ‐0.24, P .013).ConclusionThe results of this study suggest that plasma p‐tau 181 is a promising biomarker for the estimation of AD prevalence in non‐demented populations in Thailand and may represent those at risk of clinical onset. However, further studies are needed to investigate its utility in risk stratification, public health preparedness, and cognitive performance assessment.
Tau pathology is associated with neuropsychiatric symptoms in a cohort of individuals of predominantly Mexican descent at risk for autosomal‐dominant Alzheimer’s disease
Authors: Ortega Nancy E , Pa Judy , Shi Yonggang , Sagare Abhay P , Zlokovic Berislav V , Chui Helena C , Ringman John M 
Published: December 2023

AbstractBackgroundNeuropsychiatric symptoms are common in Alzheimer’s disease (AD), causing significant suffering and diminished quality of life for both individuals and caregivers. The goal of this study was to investigate the relationship between tau pathology in vivo and neuropsychiatric symptoms within a cohort of individuals of predominantly Mexican ancestry at risk for fully penetrant autosomal dominant AD (ADAD) caused by mutations in PSEN1 and APP genes (Figure 1).MethodParticipants from the Estudio de la Enfermedad de Alzheimer en Jalisciences (EEAJ) cohort were selected based on availability of demographic variables, mutation carrier status, tau PET scans (flortaucipir), and completion of the neuropsychiatric inventory (NPI). Linear regression models were used to investigate whether regional tau PET standard uptake value ratio (SUVR) predicted total score on the NPI. Models were adjusted for age, sex, and mutation carrier status. Participants were characterized as carriers if they possessed one of the following ADAD mutations: PSEN1 A431E, PSEN1 I180F, or APP V717I. Analyses were done with and without outliers. The 12‐item total NPI score was used for all analyses. The primary brain regions of interest (i.e., medial orbitofrontal, caudal anterior cingulate, rostral anterior cingulate, parahippocampal, precuneus, and lateral occipital) were selected based on previous findings. Additional analyses were conducted only on individuals who were carriers of 1 of the ADAD mutations.ResultThe sample consisted of 31 participants (45% women, mean age±SD = 37.1±11.7 years, 71% ADAD mutation carriers [81% PSEN1 A431E, 16% PSEN1 I180F, and 3% APP V717I carriers]). A significant relationship was found between regional tau pathology and neuropsychiatric symptoms for all six brain regions (Table 1), all p’s < 0.01. Within all regression models, regional tau pathology explained between 24% to 49% of the variance in neuropsychiatric symptoms. Sub‐set analyses completed on the ADAD mutation carriers sample exhibited similar results (Table 2). No significant results were found for non‐carriers.ConclusionRegional tau pathology within six distinct brain regions is strongly associated with neuropsychiatric symptoms in a cohort of individuals of predominantly Mexican ancestry at risk for fully penetrant ADAD caused by mutations in PSEN1 and APP genes.
Biomarkers of Alzheimer’s disease pathology in atypical non‐amnestic clinical phenotypes
Authors: Nevzorova Kseniya , Shpilyukova Yuliya , Shabalina Alla , Fedotova Ekaterina , Illarioshkin Sergey 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is most commonly presented with memory loss features. However, there are atypical clinical phenotypes including predominant visual, language, executive, behavioural, or motor dysfunction. The goal of our study was to estimate the prevalence of Alzheimer’s pathology in non‐amnestic clinical variants.MethodWe examined 40 patients (17 males, 23 females, 66.1±8.3 yrs) with atypical phenotypes of AD (Table 1). Seven patients had the phenotype of logopenic variant of primary progressive aphasia (lvPPA), 3 patients had the diagnosis of posterior cortical atrophy (PCA), 19 had corticobasal syndrome (CBS), and 11 cases met research criteria of clinical behavioral variant of AD (bvAD). All patients underwent lumbar puncture. CSF biomarkers Abeta‐42 (cutoff 150 pg/mL) and p‐tau181 (cutoff 600 pg/mL) were analyzed. According to the recommendations of International Working Group (2021) we defined probable and possible AD based on clinical phenotype and studied CSF biomarkers.ResultThe overall prevalence of AD pathology in the studied groups was 42.5% (20% for probable diagnosis and 22.5% for possible). All results are presented in Table 1. The highest prevalence of AD pathology in atypical clinical phenotypes was found in the group of PCA (66.7%), the lowest ‐ in the group of bvAD (36.4%). Almost a half of patients in both lvPPA and CBS groups had AD pathology based on biomarkers – 42.9% and 42.2%, respectively.ConclusionThe results showed the importance of verifying AD pathology biomarkers in common (PCA, lvPPA) and uncommon (CBS) phenotypes. Behavioral variant, considered as a rare AD phenotype, in our studied cohort was characterized by relatively high occurrence of positive AD biomarkers. Increasing the use of AD biomarkers in clinical practice and greater recognition of atypical phenotypes can ensure early diagnosis, treatment and care for these patients.
Metformin use and stroke risk in Hispanic and non‐Hispanic veteran men with type 2 diabetes
Authors: Imran Noor , Vasquez Eliana A , MacCarthy Daniel , Jacob Mini Elizabeth , Espinoza Sara , Hazuda Helen , Seshadri Sudha , Satizabal Claudia L. , Wang Chen‐Pin 
Published: December 2023

AbstractBackgroundStroke is a strong risk factor for dementia in the elderly. Traditional stroke risk factors such as hypertension and diabetes are also associated with the incidence and progression of dementia. There is a lack of data characterizing the effect of metformin use on stroke in racially/ethnically diverse cohorts. We sought to evaluate the impact of metformin as a preventative treatment in reducing the incidence of stroke risk in a cohort of older US veteran men with type 2 diabetes (T2D).MethodOur cohort included men with T2D, ≥65 years old, insulin/thiazolidinediones naïve, and without stroke history. Metformin use was defined as ≥180 days of prescription during 2002‐2003. Stroke incidence was identified by ICD9 codes 430‐438 (excluding TIA, 435) from inpatient/outpatient visits every year during 2004‐2012. Generalized estimating equations were used to estimate the odds ratios (OR) of stroke diagnosis over time associated with metformin use, where inverse propensity score weights (IPSW) for metformin use were incorporated to minimize confounding. Furthermore, the generalizability method was used to compare IPSW adjusted ORs between race/ethnicity groups after calibrating covariates between groups. Finally, inverse probability weights for survival were incorporated to project the adjusted ORs among the survivors.ResultAmong 19,705 men with T2D, 81.3% were non‐Hispanic White, 5.3% Hispanic White, and 13.4% were non‐Hispanic Black. Overall, 26.7% used metformin (35.2% of Hispanic Whites, 27% of non‐Hispanic Whites, and 21.4% of non‐Hispanic Blacks). Metformin use was associated with attenuating the temporal increase in stroke risk during 2009‐2012 (vs. 2004‐2008) among Hispanic White (log(aOR) = ‐0.05, p‐value = 0.02), This stroke risk attenuation effect by metformin use was marginally different between Hispanic White with non‐Hispanic Black (p = 0.056) and significantly different between Hispanic White and non‐Hispanic White (p = 0.02). The stroke risk attenuation effect of metformin was not significant conditioned on survival.ConclusionOur study suggests that metformin use is associated with a reduced distal stroke risk amongst men of Hispanic ethnicity compared to non‐Hispanics. Further studies are needed to elucidate the putative biological or pharmacological mechanism for this difference and to uncover the impact on dementia risk.
A Study on the effects of seasonal variations in cognitive function on driving behaviour.
Authors: Suzuki Mio 
Published: December 2023

AbstractBackgroundThe population in Japan is ageing, and approximately 30% of the elderly are said to have Alzheimer’s disease. On the other hand, however, there are areas with insufficient transport services due to the declining birth rate, and the elderly have to drive cars. In order to reduce accidents caused by drivers with dementia, it is necessary to know the relationship between cognitive function and driving, but cognitive function is said to fluctuate daily. The aim of this study is to obtain knowledge that contributes to the prediction of accidents by observing the seasonal variation in cognitive function and driving using the same subjects.MethodA cognitive function test, a driving skill test at a driving school and an observation 1‐month survey of driving behaviour on public open roads were conducted on 40 drivers aged 70 years or older who drive their cars daily. The survey was conducted twice on the same subjects, once between April and June and once between October and December. From the data obtained, seasonal differences were verified.ResultIt is said that elderly drivers often drive short distances in their neighbourhood, but in reality they also make long trips. Comparing spring/summer and autumn/winter, autumn/winter drivers are more likely to be in a state of cognitive decline and drive more unevenly.ConclusionCognitive function and driving behaviour of older drivers differ depending on the season. As the passage of time and more short‐term fluctuations may have an impact, it is important to systematise the fluctuating changes in various cycles and link them to safe driving support.
Ameliorative effect of β‐pinene targeting mitochondrial dysfunction and oxidative stress in Alzheimer’s disease
Authors: Dahiya Mini , Kumar Anil , Yadav Monu 
Published: December 2023

AbstractBackgroundSporadic Alzheimer’s disease (sAD) is the most common type of dementia, characterized by the deposition of extracellular senile plaques, neurofibrillary tangles (NFTs), and neurodegeneration, leading to memory impairment and dementia. Intracerebroventricular (ICV) streptozotocin (STZ) mimics sporadic Alzheimer’s disease (sAD) characterized by neurodegeneration arising from oxidative stress, and mitochondrial dysfunction. β‐pinene is a monoterpene having antioxidant properties interlinked with mitochondrial functioning. To study the neuroprotective and cognitive enhancement properties of β‐pinene on mitochondrial dysfunction, oxidative stress, and histological changes in an animal model of Alzheimer’s disease induced by ICV‐STZ.MethodTo establish the sAD model, intracerebroventricular (ICV) streptozotocin (STZ) at a dose of 3 mg/kg was administered bilaterally in rats on a stereotaxic apparatus. Behavioral tests such as Morris water maze (MWM), novel object recognition (NOR) and Actophotometer were performed to evaluate spatial & recognition memory and locomotor functions. Three treatment doses (50mg/kg, 100 mg/kg and 200mg/kg) of Beta pinene (β‐pinene) and Galantamine (2 mg/kg) as a reference drug were given orally to ICV‐STZ induced rats for 21 days. Cortical and hippocampal tissues were dissected. Estimation of oxidative stress, mitochondrial dysfunction as complex I, II, III, IV activity and acetylcholinesterase activity were performed for cholinergic function. Moreover, histopathology was evaluated by hematoxylin and eosin (H&E) staining.Resultβ‐pinene treatment attenuated ICV‐STZ‐induced cognitive impairment in MWM and NOR. There is no significant effect revealed on locomotor activities. Moreover, in the cortex and hippocampal area of the brain, Mitochondrial enzyme complex I, II, III, and IV, and acetylcholinesterase (AchE) activities were normalized. Furthermore, reduced glutathione (GSH), catalase, superoxide dismutase (SOD), and (Lipid peroxidation) LPO were also reversed. β‐pinene prevents neurodegeneration as examined in histopathology.ConclusionIn the ICV‐STZ rat model, β‐pinene was found to be neuroprotective by reducing oxidative stress and mitochondrial dysfunction, consequently enhancing cognitive functions indicated in the behavioral outcomes.