bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fragility and its relationship with geriatric syndromes in a mexican population of elderly adults in a third‐level hospital
Authors: Ruiz‐Castillo Karla Paulina , Cuautle Karina Arellano , Reyes Brandon Alexis Reyes , Silva Itzel Alejandra Hernandez , Chable Adiel Eleazar Dzul 
Published: December 2023

AbstractBackgroundFrailty refers a term which describes general state of health that is characterized by an increased susceptibility or vulnerability for stressors as a consequence a deterioration of physiological reserves. Frailty have been associated to multiple Geriatric syndromes, higher rates on mortality and increased risks for poor outcomes, including Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI), which are conditions that may be common in older adults.MethodThis report is a secondary analysis from a transversal study, the inclusion criteria include adults from 60 or older, who complete evaluations at the baseline in a from a dementia clinic at a tertiary care center in Mexico. We exclude pre‐fragile and robust participants at the baseline, the analytical simple comprised 700 older adults. Frailty was established using the FRAIL criteria the presence of 3 or more remaining criteria was considered frailty. Sociodemographic variables, comorbidities, and geriatric syndromes were considered for the analysis.ResultA total of 700 older adults were evaluated and 242 (34.5%) were diagnose with Frailty. Comorbidities such as diabetes (41.7%), high blood pressure (64%) and osteoarthritis (50%) were prevalent with frailty. Female sex (63.6%) and marital status marriage (55%) were prevalent with frailty. The incidence of mild dementia was 35.1% and 28.9% for mild cognitive impairment. Multiple logistic regression was performed finding an OR (95% CI) P <.001 in the association of frail patients in the 60‐70 age group, the association of the female sex with frailty present in OR (95% CI). P .023 and being married OR (95% CI) P < .001.ConclusionIn Mexican older adults from the clinical population, the results demonstrated that frailty was associated with mild cognitive impairment and mild dementia as well as female sex, married marital status, and age. It would be necessary to compare with other groups without frailty to demonstrate the consistency of these findings as potential risk factors.
Reduction of Hippocampal Atrophy and Lateral Ventricle Enlargement Correlates with Clinical Benefit in APOE4 Carriers with Early AD: 1‐Year Results from a Phase 2 Biomarker Study with Oral Anti‐Amyloid Oligomer Inhibitor ALZ‐801
Authors: Hey John A. , Abushakra Susan , Kesslak Patrick , Yu Jeremy , Schaefer Jean , Bracoud Luc , Suhy Joyce , Power Aidan , Tolar Martin 
Published: December 2023

AbstractBackgroundALZ‐801 is an oral inhibitor of amyloid oligomer formation in development as a disease‐modifying Alzheimer’s treatment, including a Phase 3 trial in APOE4/4 homozygotes and a Phase 2 biomarker study in APOE4 carriers. We analyzed correlations between brain volume and cognitive effects of ALZ‐801 after 1 year in the Phase 2 study. We previously reported that at 1‐year timepoint, plasma p‐tau181 (primary outcome) was significantly reduced by 41% from baseline, and hippocampal volume (HV) showed ∼20% less atrophy compared to external matched controls.MethodThe study is conducted at 7 European sites and enrolled 84 APOE4 carriers (MMSE 22‐30) with positive amyloid/tau biomarkers who receive ALZ‐801 265 mg BID for 104 weeks. Primary outcome is plasma p‐tau181 at 104 weeks, and primary imaging outcome is hippocampal volume (HV) atrophy. Volumetric vMRI measures (baseline, 52 and 104 weeks) are performed by Clario, and MMSE conducted. A PK sub‐study was conducted at 65 weeks (n = 23) with bioanalysis at DDS (UK) and non‐compartmental PK analyzed by WinNonlin. Pearson correlations of MMSE changes to BSI changes of HV and lateral ventricle volume (LVV) were conducted, with two‐sided p‐values reported.ResultAt 52 and 65 weeks, changes of MMSE from baseline showed significant correlations to HV (r = 0.32 and 0.34; p<0.01, n = 66) and LVV changes (r = ‐0.42 and ‐0.44; p<0.001, n = 65). Correlations between DMMSE and DLVV were significant for both genders (range r = ‐0.54 to ‐0.42, p<0.02); correlations were observed for DHV in females (range r = 0.39‐0.47; p<0.05) and males (range r = 0.26‐0.23; p<0.18, ns). PK/PD analysis in 23 subjects showed trends (r = 0.21‐0.16, ns) between decreased HV atrophy/LVV expansion and plasma AUC24h of tramiprosate+3‐SPA (active and primary metabolite). ALZ‐801 exhibited favorable safety; main treatment‐related adverse event was mild nausea. No ARIA‐E was observed.ConclusionEarly AD subjects treated with ALZ‐801 for 65 weeks in the Phase 2 biomarker study showed strong correlations between MMSE stability, HV reduction, and decreased ventricular enlargement in overall group, and by genders. The significant correlations between cognitive and brain volume effects support the clinical benefits of ALZ‐801 in APOE4 carriers with early AD. Oral ALZ‐801 showed favorable safety and no brain edema/ARIA‐E.
Interferon regulatory factor 5 modulates microglia response to tau by interfering with phagocytosis
Authors: Giliberto Luca , d'Abramo Cristina , Cicalo Julia , Hou Jianwei , Matta Bharati , Barnes Betsy 
Published: December 2023

AbstractBackgroundThe role of the immune system in responding to neurodegenerative pathology is well established. Microglia are at the center of such response, conveying on one end a positive protective effect, but on the other end, as with senescence, contributing to the hyperinflammation that is a core feature of neurodegeneration. We have identified the transcription factor interferon regulatory factor 5 (IRF5) as a mediator of microglia activation in response to pathological tau, described its specific activation by human‐derived PHF tau and its over‐representation in AD brains. We are now proposing that IRF5 can control the phagocytic activity of microglia, hence modulating their tau‐directed activity.MethodWe utilized age‐ and sex‐matched Irf5+/+
(WT) and Irf5−
/
−
littermate mice for the analysis of ex vivo phagocytic activity of primary microglia, at steady‐state and triggered by tau. We examined microglia morphology and numbers under these conditions and with ageing. Last, we injected PHF tau intracranially to WT and Irf5−
/
−
mice, monitoring tau accumulation and IRF5 response.Result1) Irf5−
/
−
microglia have higher baseline phagocytic activity compared to WT microglia, which may be modulated by tau. 2) Microglia numbers are reduced in ageing Irf5−
/
−
3) PHF tau‐injected Irf5−
/
−
mice show significant soluble tau accumulation, but a different pattern of oligomeric and insoluble tau accumulation with age. 4) In WT mice, the PHF tau‐injected hemisphere showed significantly higher levels of IRF5 compared to the contralateral, confirming a specific response of IRF5 to tau.ConclusionTau is a specific activator of microglia and of the IRF5 pathway, which can modulate microglia response to pathology. Ageing is an active variable in the process, affecting the pattern of microglia response to tau, differentially in WT and Irf5−
/
− mice. Modulating the IRF5 pathway may be a viable therapeutic approach in tauopathies.
Multidimensional poverty increases dementia risk in South Africa, Afghanistan, and Pakistan among adults age 50 and older
Authors: Trani Jean‐Francois , Zhu Yiqi , Babulal Ganesh M. , Moodley Jacqueline , Fazal Monib Rahim , Azami Rahim , Park Soobin 
Published: December 2023

AbstractBackgroundLow‐and‐middle‐income countries (LMICs) face a crisis with a higher prevalence of dementia and cognitive impairment. It is projected that 68% of dementia cases worldwide will reside in LMICs in 2050. This differential risk is exacerbated by social and environmental determinants of health (SEDOH) and in settings with war, class division, and terrorism. There is no dementia research being conducted within these LMIC settings.MethodsData from three cross‐sectional fieldwork studies was used. In South Africa, 227 adults were from two wards of Thulani and Doornkop (11/11/19‐2/28/20). In Afghanistan, 478 adults were from 43 villages of Badakhshan and Ghazni provinces (2/15/22‐4/20/22). In Pakistan, 817 adults were from 43 villages of Punjab and Sindh provinces (4/22/22‐7/7/22). We examined the relationship between dementia and SEDOH via multidimensional poverty among adults ≥ 50 years of age adjusting for sex, marital status, age, and household size.ResultsIn South Africa, Afghanistan, and Pakistan, respectively, men were more likely to be dementia‐free (32.1%, 60.8%, 65.49%) than women (24.7%, 32.5%, 34.51%). Across all countries, a higher proportion of older adults with moderate‐to‐severe dementia lived alone without a partner. In South Africa, Afghanistan, and Pakistan, adults with moderate‐to‐severe dementia were significantly more deprived of education, health status, and employment and were more often distressed, compared to adults without dementia in each country. The risk of dementia was higher for multidimensionally poor older adults. In South Africa, the odds of dementia were 2.31X (95%CI, 1.08‐4.95) for those who were multidimensionally poor. In Afghanistan, it was 10.2X higher (95% CI,1.97‐52.62) for poor adults ≥ 70 years. In Pakistan, there was a 5.02X higher risk (95% CI, 2.07‐12.16) for poor older adults at age ≥ 50 years.ConclusionThe prevalence and depth of poverty were greater among older adults with dementia. A lack of education, poor health, and psychosocial distress are major dimensions of poverty associated with higher dementia risk. More importantly, dementia risk was significantly higher for women in all three countries compared to men. These findings support improvement in SEDOH through targeted structural policies, particularly for quality and free education and healthcare, to prevent dementia in later life.
Artificial intelligence‐driven algorithm to detect and count cerebral microbleeds on Susceptibility Weighted Imaging
Authors: Lee Kijeong , Lee Minho , Kim Regina EY , Jo Sang‐Yeong , Kim JeeYoung , Lee Kyung Mi , Lee Ji Young , Kim Donghyeon , Kim Hye Weon 
Published: December 2023

AbstractBackgroundAmyloid‐related imaging abnormalities (ARIA)‐H, characterized by cerebral microbleeds (CMB) and superficial siderosis, is an important Magnetic Resonance Imaging(MRI) finding observed in the patients with Alzheimer’s disease, especially receiving the anti‐amyloid immunotherapy. Because the severity of CMB can potentially lead to discontinuation of the therapy, the detection and counting of the CMB would be critical tasks in MRI analysis. We present an algorithm which can detect CMBs and count the number of them, automatically and accurately.MethodWe employed datasets of both SWI and phase images, developed in collaboration with Eunpyeong St. Mary’s Hospital, Kyung Hee, and HanYang University Medical Center. The data set comprises 463 participants with CMBs (N = 247) and without CMBs (N = 116). Experts denoted gold standard of each CMBs as bounding boxes. A localizer is trained by selecting 2D axial slices, including expert‐confirmed annotations. A modified recurrent layer was applied for weight‐sharing between two images. An optimized region proposal network was then applied. To reduce FP regions across entire slices, we developed a classifier with attention‐based 3D convolution blocks. From the CMB localizer, candidate 3D CMB patches were used in the classifier.ResultCMB prediction was performed on the test set including 140 participants (CMB:24; Non‐CMB:116), with 263 expert‐confirmed gold standard (Figure 1). The lesion‐wise sensitivity was 0.913 [95% Confidence interval (CI), 0.863‐0.963] and the average FP rate was 0.672 per patient [95% CI, 0.290‐1.154]. Patient‐wise sensitivity and specificity were 0.862 [95% CI, 0.792‐0.932] and 0.907 [95% CI, 0.880‐0.934], respectively. When we divided the patients into four groups according to the number of gold standard, the model predicted the groups correctly by the sensitivity of 0.879 [95% CI, 0.851‐0.907] (Table 1).ConclusionOur model outperformed the results of recent studies by reducing FP rate with comparable sensitivity. Moreover, our model may suggest additional clinical benefit, because it can automatically count the number of CMB and classify the participants into 4 groups, used in the clinical investigation of anti‐amyloid therapy, according to the number of CMB. We expect this model may improve the workflow of the time‐consuming reading task and act as a failsafe for the detection of CMBs.
White Matter Lesion Asymmetry: A Potential Indicator of Amyloid Positivity in Patients with Mild Cognitive Impairment
Authors: Kim Hye Weon , Rieu ZunHyan , Lee Hyunji , Jeong Eui Seok , Lee Min‐Woo , Lee Minho , Kim Donghyeon , Lim Hyun Kook 
Published: December 2023

AbstractBackgroundAssessing amyloid‐positivity in patients with mild cognitive impairment (MCI) is crucial as amyloid‐positive individuals have a higher risk of dementia conversion than amyloid‐negative patients. This study aimed to investigate whether the asymmetry of white matter lesions (WML) on T2‐fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), measured by artificial intelligence (AI) hyperintensity segmentation, could be a potential indicator for amyloid positron emission tomography (PET) positivity in patients with MCI.MethodThis retrospective cohort study included MCI patients who visited the memory clinic of Yeouido St. Mary’s Hospital. All participants underwent a set of clinical and neuropsychological assessments, brain MRI, and amyloid PET using [18F]‐Flutemetamol. Our in‐house AI software was utilized on paired T1 and T2‐FLAIR MRIs to process to segment and separate WML into left and right hemispheres. From the processed segmentation, we measured the subjects' individual WML differences through a volumetric assessment.ResultsTotal 122 subjects were enrolled in this study. By the amyloid‐PET positivity, 53 and 69 patients were in the amyloid‐negative and amyloid‐positive groups, respectively. The two groups were comparable with no significant differences of age (p = 0.189), sex (p = 0.057), education years (p = 0.411) and MMSE scores (p = 0.861). However, the amyloid‐positive group had a significantly higher frequency of having an e4 allele of APOE genotype (p = 0.033) and Clinical Dementia Rating scale (p = 0.024). The average volume between hemispheres significantly differed in the amyloid‐negative group (p = 0.020) but not in the amyloid‐positive group (p = 0.220). Both groups had a larger WML volume in the left hemisphere, which did not differ significantly between groups.ConclusionOur findings suggest that evaluating the asymmetry of WML rather than the total hyperintensity lesion load is necessary in MCI patients, particularly in those without amyloid pathology. In conclusion, WML asymmetry may serve as a potential indicator of amyloid positivity in MCI patients.
Revolutionizing memory improvement: KIT‐13, a novel Plasmalogen analog, inhibits neuroinflammation and boosts memory in mice
Authors: Chung Eunhee , Hossain Md Shamim , Mawatari Shiro , Honsho Masanori , Fujino Takehiko 
Published: December 2023

AbstractBackgroundA decrease in cell plasmalogens often links with an inflammatory state. Our previous study discovered that natural plasmalogens (specific types of phospholipids) extracted from scallops inhibited neuroinflammation and improved memory function in mice1. The subsequent randomized clinical trials also showed significant improvements in patients with Alzheimer’s disease by natural plasmalogens2. In order to increase the stability and achieve greater cellular plasmalogens, we developed a new plasmalogen derivative and examined if it would produce similar effects in mice.MethodIn our current study, we investigated the alkyl‐type plasmalogen analog, KIT‐13 (1‐0‐octadecyl‐2‐arachidonoyl‐sn‐glycerol‐3‐phosphoethanolamine), to evaluate its potential effect on neuroinflammation (in vitro, in vivo), neurogenesis (in vitro), and memory improvement (in vivo).In our in vitro studies, mice microglial cell lines (BV2 and MG6) were used for evaluation of the anti‐inflammatory effects, and neuronal‐like cells (SH‐SY5Y) were used to assess the effect of KIT‐13 on the regulation of brain‐derived neurotrophic factor (BDNF) and the neurogenesis marker DCX.In in vivo studies, learning and memory were assessed by Morris Water Maze (MWM) tests. The neuroinflammation was induced by LPS injection (i.p.), which increased activated glial cells and reduced memory in 12‐week‐old adult male (B6) mice.KIT‐13 (0.2 mg/kg/day) was administered orally for four weeks before LPS injection.ResultIn vitro experiments demonstrated that KIT‐13 attenuated the LPS‐induced upregulation of NOS2 expression in microglial cells and increased BDNF and DCX expression in neuronal‐like cells.Also, KIT‐13 pre‐treatment reduced LPS‐induced neuroinflammation and memory disturbance in mice, indicating that, similar to natural plasmalogens, KIT‐13 may improve memory by decreasing neuroinflammation and increasing BDNF‐mediated neurogenesis in the mouse brain.ConclusionThese findings suggested that KIT‐13 can be a therapeutic drug candidate for diseases associated with plasmalogen reduction, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and rhizomelic chondrodysplasia punctata (RCDP).
Reference:1. Ifuku et al. J Neuroinflammation 2012, 9:1972. Fujino et al. EBioMedicine 2017, 17:199‐2053. Fujino et al. J Alzheimers Dis Parkinsonism 2019, 9:44. Hossain et al. Front Cell Dev Biol 2022, 10:828282
Prevalence of Cerebral Microhemorrhages and Cortical Superficial Siderosis in APOE4/4 Homozygotes with Early Alzheimer’s disease: Baseline Findings from Phase 3 Trial of Oral ALZ‐801 in APOE4/4 Homozygotes (APOLLOE4)
Authors: Abushakra Susan , McLaine Rosalind , Barakos Jerome , Porsteinsson Anton P. , Watson David , MacSweeney Emer , Liang Earvin , Kesslak Patrick , Suhy Joyce , Power Aidan , Hey John A. , Tolar Martin 
Published: December 2023

AbstractBackgroundPlaque clearing amyloid antibodies show an increased risk of amyloid‐related imaging abnormalities with edema or hemorrhages (ARIA‐E or ARIA‐H). ARIA risk increases with number of APOE4 alleles, with APOE4/4 homozygotes showing the highest risk related to high burden of Aβ plaque in microvessels (cerebral amyloid angiopathy, CAA). To decrease the risk of ARIA, amyloid antibody trials exclude subjects with CAA‐related lesions such as >4 microhemorrhages (MH) or superficial siderosis. ALZ‐801 (valiltramiprosate), an oral drug that inhibits formation of neurotoxic Aβ oligomers, shows promising efficacy in APOE4 carriers with no observed ARIA‐E (Abushakra 2017, 2022). Two ALZ‐801 trials are currently ongoing in APOE4 carriers with Early AD. A Phase 2 study enrolled APOE4 carriers, and a Phase 3 trial enrolled APOE4/4 patients. Both studies allow >10 MH and/or some siderosis lesions at baseline.MethodThe fully‐enrolled Phase 3 trial (APOLLOE4) included 325 homozygotes with Early AD (MMSE ≥22). We evaluated prevalence of microhemorrhages (MH), macrohemorrhages and superificial siderosis (CAA lesions). Baseline MRIs acquired from 1.5T/3T scanners were centrally evaluated by Clario, and the number/location of these CAA lesions is reported.ResultSubjects had mean age 69 years, 51% female, MMSE 26, 82% white, 65% with MCI. Of 325 subjects, 313 had baseline MRIs that showed > 1 MH in 32%, including 9% with > 4 MH. A total of 9% had ≥ 1 superficial siderosis, and 2 subjects had macrohemorrahages. Occipital and frontal lobes were most common locations of CAA lesions. Most subjects had white matter disease (Fazekas = 1).ConclusionAPOE4/4 homozygotes show high prevalence of CAA lesions with 32% and 9% having lobar microhemorrhages and superificial siderosis respectively. This high burden of CAA lesions most likely underlies the high incidence of ARIA in APOE4/4 patients treated with the approved amyloid antibodies (30%‐60%). ARIA‐E is also reported in APOE4/4 patients treated with placebo in lecanemab & gantenerumab trials (4%‐6%). This background ARIA likely reflects spontaneous CAA‐related inflammation commonly reported in APOE4 carriers (CAA‐RI, Regendhardt 2020). Oral ALZ‐801 in the ongoing studies has not shown increased ARIA risk, and has safety advantage over amyloid antibodies especially for APOE4/4 homozygous patients.
Exploring needs and wishes regarding sleep support from people with dementia and their informal caregiver at home
Authors: Huisman Chantal , Huisman Emelieke , Kort Helianthe 
Published: December 2023

AbstractBackgroundMost people with dementia live in community with an informal caregiver (IC) for primary support (Greenwoord & Smith, 2019). Caring for someone with dementia can be emotionally and cognitively demanding and can influence the overall health and wellbeing negatively (Fonareva & Oken, 2014; Vasileiou et al., 2017). Behavioural and psychological symptoms of dementia (BPSD) are very common in people with dementia (PwD) and are one of the main factors that cause strain on an IC (Chiao et al., 2015). BPSD is related to sleep, for example, supporting sleep can improve cognitive function and BPSD (Shin et al., 2014). In all types of dementia sleep rhythms are changing. Sleep problems of a person with dementia can affect the sleep of an IC. Sleep disturbances can exacerbate changes in mental, physical, and cognitive health (Petrovsky et al., 2018), and may lead to nursing home admission (e.g. Livingston et al., 2017). This qualitative study explored the experiences around sleep and the wishes and needs of PwD and their IC to improve their sleep quality. This is a starting point for working toward appropriate sleep support using non‐pharmacological interventions.MethodA total of 28 interviews are performed with 31 person (PwD, IC, and professionals) comprising three duos. Thematic analysis (Braun & Clarke, 2006) is used to identify patterns within and across data in relation to participants’ lived experiences, views, perspectives, behaviour, and practices.ResultsThe first preliminary results show the following themes that are relevant: personal situation including other diseases and personal characteristics, day structure and daily activities, sleep behaviour including sleep rhythm, problems while sleeping, sleeping/naps during the day and caregiver experiences and supporting tools. The results show that these themes are related to the sleep of PwD and IC.ConclusionThe findings of this study contribute to giving insight into the experience flow and are helpful to determine the priority of subjects in order to support the IC and PwD. This study show that within the target group there are many diverse experiences and that this can vary greatly from one situation to another and from one person to another.