bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and neuroimaging predictors of Alzheimer’s Dementia Conversion in patients with mild cognitive impairment using 18F‐Florapronol amyloid PET by quantitative analysis over 2 years
Authors: Kim Seon Jeong , Chung Hye‐in , Yoon Daye , Jeong Young Jin , Kang Do‐Young , Park Kyung Won 
Published: December 2023

AbstractBackgroundPatients with mild cognitive impairment(MCI) are a clinically important group because of the increased risk for the progression to Alzheimer’s dementia(AD). Amyloid positron emission tomography(PET) was useful as a predictor for identifying AD pathology in the pre‐dementia stage. We determined the rates of conversion to AD in MCI patients based on amyloid positivity by visual and quantitative analysis over 2 years. We also investigated the clinical and neuroimaging predictors for conversion to AD.MethodIndividuals aged 50 and above with MCI according to Petersen’s criteria were eligible. Subjects underwent laboratory tests including APOE genotyping, neuropsychological tests, brain magnetic resonance imaging(MRI), and amyloid PET assessed by 18F‐FC119S. Amyloid positivity was determined in each lobe of the brain and quantitatively analyzed. The follow‐up period was at least 2 years. Cox regression analysis was performed to identify prognostic factors which are independently related to time to AD conversion.ResultWe recruited 50 patients and 39 subjects were enrolled. 5 patients dropped out at 2 years, so 34 subjects were finally included. 13 of 34(38.2%) by visual analysis and 12 of 34(35.3%) by quantitative analysis of 18F‐FC119S PET showed amyloid positive. The basic demographics were not significantly different between the groups except for Korea‐Instrumental Activities of Daily Living(K‐IADL) at baseline(p = 0.004) and 1 year(p = 0.001), Mini‐mental State Examination(MMSE) at 2 years(p = 0.047) and Global Deterioration Scale(GDS) at 2 years(p = 0.029). 4 of 13(30.8%) by visual analysis, 4 of 12(66.7%) by quantitative analysis amyloid‐positive MCI patients converted to AD. Amyloid positive in posterior cingulate was marginally significant(p = 0.066). AD conversion group had a higher Clinical Dementia Rating‐Sum of box(CDR‐SOB) at baseline(p = 0.002) compared with remained MCI group. In multivariate cox regression, CDR‐SOB at baseline, MMSE at 1 year and K‐IADL at 2 years were included.ConclusionAmyloid‐positive MCI group was more likely to progress to AD. But long‐term follow‐up was required. By quantitative analysis of 18F‐FC119S PET, amyloid deposition in posterior cingulate was highly associated with the AD conversion group. CDR‐SOB at baseline, MMSE at 1 year and K‐IADL at 2 years were considered as clinically valuable prognostic predictors of disease progression. Especially, CDR‐SOB is important as a predictive biomarker in the pre‐dementia stage.
Influence of APOE ε4/ε4 on Fluid Biomarkers in Patients from the PUMCH Dementia Cohort
Authors: Shang Li , Dong Liling , Huang Xinying , Wang Tianyi , Mao Chenhui , Li Jie , Wang Jie , Liu Caiyan , Gao Jing 
Published: December 2023

AbstractBackgroundApolipoprotein‐E (APOE) ε4 is a major genetic risk factor for Alzheimer’s disease (AD). Current studies, which mainly based on the clinical diagnosis rather than biomarkers, come to inconsistent conclusions regarding the effect of APOE ε4 homozygotes (APOE ε4/ε4) on cerebrospinal fluid (CSF) biomarkers of AD. Additionally, few studies have explored the effect of APOE ε4/ε4 on plasma biomarkers. Therefore, we aimed to investigate the effect of APOE ε4/ε4 on CSF and plasma biomarkers in dementia and biomarker diagnosed AD.MethodA total of 297 patients were enrolled. They were classified into Alzheimer’s continuum, AD and non‐AD according to CSF biomarkers and/or β amyloid PET results. Plasma Aβ40, Aβ42, glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL) and P‐tau181 were quantified in 144 of the total population using an ultra‐sensitive Simoa technology. We analyzed the effect of APOE ε4/ε4 on CSF and plasma biomarkers in dementia and biomarker‐diagnosed AD.ResultBased on the biomarker diagnostic criteria, 169 participants were diagnosed with Alzheimer’s continuum, 120 patients with AD and 128 individuals with non‐AD. The APOE ε4/ε4 frequencies were 14.2% (17/120) in AD, 11.8% (20/169) in Alzheimer’s continuum and 0.8% (1/128) in non‐AD. Only CSF Aβ42 was shown to be decreased in APOE ε4/ε4 carriers than in non‐carriers for patients with AD (P = 0.024). As well, we did not find any effect of APOE ε4 on plasma biomarkers of AD and non‐AD. Interestingly, we found that in non‐AD patients, APOE ε4 carriers had lower CSF Aβ42 (P = 0.018) and higher T‐tau/Aβ42 ratios (P<0.001) and P‐tau181/Aβ42 ratios (P = 0.002) than non‐carriers.ConclusionOur data confirmed APOE ɛ4/ɛ4 was most common in biomarker diagnosed AD. The APOE ɛ4/ɛ4 had an effect on CSF levels of Aβ42 but not tau for AD and non‐AD, suggesting that APOE ɛ4/ɛ4 affected the Aβ metabolism of both. APOE ε4/ɛ4 had no effect on plasma biomarkers of AD and non‐AD.
Views Of Experienced Physiotherapists About Excellence In Dementia Care: A Qualitative Study
Authors: Quick Stephen M , Lawler Katherine , Shannon Michelle M , Soh Sze_Ee , McGinley Jennifer L , Snowdon David A , Callisaya Michele L 
Published: December 2023

AbstractBackgroundPhysiotherapy interventions can improve mobility and prevent falls in people with dementia. However, physiotherapists have been found to have low knowledge and confidence in working with people with dementia. Excellence in dementia physiotherapy has not been described in the literature, and it is important to establish with dementia considered a global health priority. Therefore, the aims of this study were to determine 1) what is excellence in physiotherapy dementia care and 2) how can excellence be achieved.MethodsThis was a qualitative study using an interpretive description approach. Participants were 16 physiotherapists from around Australia considered to be experienced in the field of dementia care. Snowball sampling was utilised from the starting group of physiotherapists practicing in Australia, who were recognised by the National Gerontology Committee of the Australian Physiotherapy Association as experienced experts in dementia care. Physiotherapists participated in semi‐structured interviews. Thematic analysis was undertaken, with themes/subthemes derived and a qualitative thematic framework generated.ResultsThe four themes (and subthemes) were: 1) engaging the person with dementia (knowing the person, using knowledge to adapt the approach to successfully deliver physiotherapy interventions, optimising the physical environment), 2) collaborative care (working with care partners, working as an interdisciplinary team), 3) development of clinical skills and expertise on the job and 4) advocating for the role of physiotherapy in dementia care.Discussion/ConclusionPhysiotherapists believe that excellence in dementia care involves being able to effectively engage the person with dementia in therapy, training and supporting care partners, and providing interdisciplinary care. Excellence in care was less about the application of evidence‐based practice, but more about providing patient‐centred care, achieved mainly through on‐the‐job learning from both physiotherapy and other health professional peers.
Visual scanning of faces with neutral expression in patients with Alzheimer’s disease and amnestic mild cognitive impairment
Authors: Boz Hatice Eraslan , Koçoğlu Koray , Akkoyun Müge , Tüfekci Işıl Yağmur , Ekin Merve , Akdal Gülden 
Published: December 2023

AbstractBackgroundDeficits in face perception and face processing have been reported in Alzheimer’s disease (AD) (Kawagoe et al., 2017). However, conflicting findings were presented in these functions in amnestic mild cognitive impairment (aMCI) compared to older adults (Lim et al., 2011). This study aimed to examine eye movement patterns during visual scanning of faces with neutral expressions in AD, aMCI, and healthy controls (HC).MethodNinety‐five participants, including 29 patients with AD (mean age 72.5±7.9), 34 patients with aMCI (mean age 70.6±6.7 years), and 32 HC (mean age 68.5±6.2 years) were participated in the study. Eye movements were recorded from the right eye with the EyeLink 1000 Plus video‐based eye tracker. In the face scanning task, neutral face images without emotional expressions produced by artificial intelligence were used. In this task, which consists of a practical trial and 20 trials, each stimulus was shown for 3000 ms. Participants were instructed to examine the neutral face images presented. Number of saccade, fixation counts, mean fixation duration, and first fixation duration were analysed separately on the regions of eyes, mouth, nose, and face.ResultThe mean number of fixation, the number of saccades, and mean fixation duration across the face were significantly reduced in AD patients compared to HC. The mean number of fixation and fixation durations in the eye were significantly reduced in AD compared to HC. No significant difference was observed in all groups in eye movements in the nose and mouth. In addition, aMCI and HC exhibited similar eye movement patterns in the face‐scanning task.ConclusionStudies with healthy individuals have reported typical eye movement patterns focusing primarily on the eyes, but also on the nose and mouth regions. It is stated that the decrease in the gaze towards the face and eye region in AD patients may be related to face processing difficulties. To our knowledge, this is the first study to examine eye movement patterns during neutral face scanning in AD and aMCI.This work was supported by the TUBITAK project number 119S560.
GM1 modulates amyloid‐beta activation of NLRP3 inflammasome in microglia through Akt/mTOR‐mediated regulation of autophagy
Authors: Wang Wenxuan , Zhao Lin , Whitehead Shawn N 
Published: December 2023

AbstractBackgroundMicroglia are cellular players underlying neuroinflammation, a major driver of Alzheimer’s Disease (AD) pathogenesis. In the AD brain, microglia are observed surrounding beta‐amyloid (Aβ) plaque and are responsible for amyloid clearance. However, chronic microglia activation by amyloid leads to microglia dysfunction, including autophagy dysregulation, degradative impairment, and a prominent pro‐inflammatory response that exacerbates plaque deposition and neurodegeneration (Hickman et al., 2008). The key to targeting neuroinflammation may be GM1 ganglioside. Gangliosides are glycosphingolipids highly enriched in the central nervous system and play a critical role in membrane organization and signal transduction. Notably, Ganglioside dysregulation has been observed in pre‐clinical and clinical models of AD (Svennerholm et al., 2008). GM1, the most abundant ganglioside in the adult brain, serves a neuroprotective and anti‐inflammatory role, but the mechanism remains unknown (Galleguillos et al., 2022). This study aims to interrogate the cell‐specific mechanism and therapeutic potential of GM1 to alleviate microglia inflammation in response to amyloid. We hypothesize that GM1 ganglioside is protective against neuroinflammation by upregulating microglia autophagy in AD.MethodBV‐2 microglia culture was activated by oligomeric Aβ (Aβo) exposure with or without GM1 pre‐treatment. Cells were treated with rapamycin, an mTORC1 inhibitor and autophagy modulation. NLRP3 inflammasome activation was assessed by pro‐inflammatory gene transcription and cleaved caspase‐1 and IL1β release. Autophagy was assessed by p62 and LC3 II/I protein expression. Microglia ganglioside abundance was measured using electrospray‐ionization mass spectrometry.ResultAβo significantly increased microglial NLRP3 inflammasome priming, suppressed autophagy flux, and increased GM1 degradation compared to control. GM1 pre‐treatment attenuated Aβo inflammasome activation and promoted autophagy initiation by downregulating Akt and mTOR phosphorylation. The protective effect of GM1 involves membrane signalling receptors such as Trem2.ConclusionGM1 ganglioside is protective against amyloid‐mediated microglia inflammation by suppressing NLRP3 inflammasome priming and restoring autophagy via Akt/mTOR signalling pathways. GM1 upregulation of autophagy demonstrates a promising therapeutic target to resolve neuroinflammation and halt the accelerated progression of AD.
The impact of gender‐specific survival on the incidence of dementia in Parkinson’s disease ‐ A cohort analysis of Parkinson’s disease patients in German health claims data for the years 2006 to 2017
Authors: Fink Anne , Dodel Richard , Georges Danieal , Doblhammer Gabriele 
Published: December 2023

AbstractBackgroundThe aim of our study is to analyze gender‐specific patterns of Parkinson’s disease dementia (PDD) incidence. In addition, we are investigating the extent to which gender differences in survival after initial Parkinson’s disease (PD) diagnosis influence differences in PDD risk among PD patients.MethodWe used a random sample of German longitudinal health claims data of persons at ages 65 years or older (2006‐2017). We identified incident PD cases who were followed‐up for a PDD diagnosis or death. We computed age‐ and gender‐specific PDD incidence rates, death rates, and cumulative PDD incidence functions with death as competing risk. In addition, we performed Cox regression models and Fine and Gray competing‐risk regression models, considering death as a competing event, to calculate PDD hazard ratios (HR), adjusted for important risk factors such as age at PD onset, PD severity in terms of modified Hoehn&Yahr (HY) scale, comorbidities, and medications.ResultOf 2,195 incident PD cases, 602 people died and 750 people received a dementia diagnosis by the end of 2017. 44% of PD men and 45% of PD women had received a dementia diagnosis, 45% of PD men and 32% of PD women had died, and only 11% of PD men but 23% of PD women had survived without a PDD diagnosis. PDD risk among PD patients differs by gender when controlled for age at onset, severity of PD, comorbidities and medications, with men having a higher PDD risk than women (HR = 1.18, p = 0.029). When accounting for death, men and women do not differ regarding their PDD risk (HR = 1.02, p = 0.770). Gender‐specific analyses showed significant age and severity effects in women (Age: HR = 1.05, p<0.001, HY 0‐2.5: reference, HY 3‐5: HR = 1.46, p = 0.011), but not in men.ConclusionWe found that older age at first PD diagnosis and higher disease severity increase PDD risk, but this association is attenuated for PD men when we consider death as a competing risk. This implies that the most frail PD men die rapidly before receiving a dementia diagnosis, whereas women with PD survive at higher rates than men, regardless of their age at onset and disease severity.
Transcriptomic profile across different brain areas in Alzheimer’s disease
Authors: Ferrari Riccardo Rocco , Fantini Valentina , Garofalo Maria , Francesca Dragoni , Gerlando Rosalinda Di , Cattaneo Valentina , Davin Annalisa , Profka Xhulja , Medici Valentina , Guaita Antonio , Gagliardi Stella , Poloni Tino Emanuele 
Published: December 2023

AbstractBackgroundAging is often characterized by a progressive loss of cognitive abilities due to the onset of Alzheimer Disease (AD). In recent years, ‐omic sciences have allowed us to begin to shed light on its molecular pathways in order to speculate about new and attractive hypothesis on AD pathogenesis.MethodIn this study, a whole transcriptome analysis and a Gene Set Enrichment Analysis (GSEA) have been carried out on brain samples from hippocampus (HI), temporal and parietal cortex (TC, PC), cingulate cortex (CG), and substantia nigra (SN) from the Abbiategrasso Brain Bank (ABB) of 6 subjects with clinical and neuropathological diagnosis of AD and 3 healthy age‐matched controls in duplicate. Clinical and neuropsychological profile were obtained through serial evaluations, made at the baseline and in the following years. According to the ABB protocol, the neuropathological diagnosis was based on a complete histological characterization, including all the main proteinopathies and vascular scoring.ResultTranscriptomic results showed a greater number of differentially expressed genes (DEGs) in TC (1571) and CG (1210) and a least amount of DEGs in HI (206), PC (109) and SN (60). Furthermore, the GSEA showed a difference between the group of early affected brain areas (HI, TC) and the group of the subsequently involved areas (PC, CG, SN). Notably, in HI and TC there was a significant down‐regulation of shared DEGs primarily involved in the synaptic transmission and in the development of the central nervous system (CDK5R1, KCNC1, KCNC2, BSN), while in PC, CG and SN there was a significant down‐regulation of genes primarily involved in the proper protein folding and trafficking and inflammation (HSPA1B, HSPA1A, DNAJB1, FKBP4, CHORDC1, STIP1).ConclusionThe course of AD could follow a definite time and severity‐related pattern that arises from inflammatory processes and protein misfolding, observed in PC, CG and SN, and leads to synaptic impairment, observed in HI and TC. Therefore, we can relate neurobiological processes to clinical manifestations and outline a clearer picture of AD neuropathology and pathogenesis. This could help to discover novel biological targets in order to develop effective and well‐timed therapeutical approaches.
Voice Quality Monitoring in Dementia Households
Authors: Jouaiti Melanie , Vaidyanathan Ravi 
Published: December 2023

AbstractBackgroundVoice disorders are common in People Living with Dementia (PLwD) and a decrease in voice quality can be an indicator of cognitive deterioration. Previous computational works have successfully employed voice to detect or predict dementia. Voice quality can be assessed by a speech therapist, or computationally when subjects periodically repeat the same sentences. There is, however, to our knowledge, no research on monitoring voice to track dementia progress from unconstrained data collected in the wild.MethodIn this work, we employ a dataset containing audio recordings of 14 households (a carer, a PLwD and visitors) interacting with Alexa. We identify several voice features, such as speech rate and OpenSmile features that differ between healthy users and PLwD. We create a voice footprint for each PLwD using a Gaussian distribution and identify audio recordings that significantly differ from this baseline over time by combining Expectation‐Minimisation and Mahalanolis distance outliers detection.ResultThe voice features selected are significantly different between our two user groups (p‐value < 0.0001). Training a classifier on those features, allows us to identify healthy subjects and PLwD with over 90% accuracy. We are also able to quality how much the voice differs from its baseline over time.ConclusionWhile we can computationally identify voice variations that are out the ordinary, in the future, we will compare our results to a clinical assessment of voice quality. We will also integrate a semantics analysis to identify grammar errors or the use of wrong words. This will allow us to design an objective index measure for monitoring of speech quality.
POORANA CHANDROTHAYA CHENTHURAM (PCC), A SIDDHA SYSTEM OF MEDICINE PROTECTS AGAINST SCOPOLAMINE‐INDUCED COGNITIVE IMPAIRMENTS IN EXPERIMENTAL RATS
Authors: George Sugin Lal Jabaris Sobhana , B Chitra , Pullaiah Chitikela P , Krishnamoorthy Bhavani , A Manoj 
Published: December 2023

AbstractBackgroundIndian Systems of Medicine (ISM) are considered to be of native medical systems which were assimilated into Indian culture. ISM comprising of Ayurveda, Yoga, and Naturopathy, Unani and Siddha which are in practice since time immemorial much before the recognized health system came into existence. In Siddha system, higher order pharmaceutical forms of medicine called PCC are predominantly prepared with metals and minerals through well‐coined pharmaceutical procedures and techniques that have been inscribed in the Siddha literature. The methods which convert the toxic metals/ minerals into compatible form that fits for human consumption. It has the privilege that these drug forms can cure many chronic diseases, in precise dosage. PCC is an imperative medicine which contains gold, mercury and sulphur in defined quantity. As given in Siddha vaithiyathirattu PCC is prepared from Gold, Mercury, and Sulphur in a ratio of 1:8:16 and processed with the required amount of red cotton flower juice and plantain stem pith juice. It is well known for its effectiveness in respiratory disorders especially bronchitis, hepatic disorders, renal diseases, neurological disorders, and skin diseases. However, there are no reports on whether PCC may improve cognitive dysfunction.MethodsWe used RAM and NORT models to evaluate cognitive improvement. In addition, the acetylcholinesterase enzyme was assessed in the brain tissues. Further, protein expression of BDNF was also assessed in hippocampus tissues after the behavioral tasks.ResultRepeated administration of PCC (2.5, 5 and 10 mg/kg., p.o) before the acquisition trial (T1) explored the object significantly more than the familiar one during the discrimination trial (T2) respectively, showing an increase in memory retention. In the radial arm‐maze task, scopolamine‐treated rats with PCC showed decreased working memory errors as compared to scopolamine‐alone treated rats. Treatment with different doses of PCC showed up‐regulation of BDNF with a significant effect by inhibiting the elevation of acetylcholinesterase activity when compared to the vehicle‐treated group.ConclusionsThese results suggest that the PCC ameliorates scopolamine‐induced impairment of cognitive functions in rats. These data further support that the anti‐amnestic effect of PCC recommends it as a promising candidate for clinical trials in patients with cognitive impairment.