bluuebunny/crossref_metadata_2025_split huggingface dataset:
The PACt‐MD randomized clinical trial: Prevention of Alzheimer’s dementia with Cognitive remediation plus transcranial direct current stimulation in Mild cognitive impairment and Depression
Authors: Rajji Tarek K. , Bowie Christopher R , Herrmann Nathan , Pollock Bruce G. , Lanctôt Krista L. , Kumar Sanjeev , Flint Alastair , Mah Linda , Fischer Corinne E. , Butters Meryl A. , Bikson Marom , Blumberger Daniel M. , Daskalakis Zafiris J. , Rapoport Mark J. , Verhoeff Nicolaas Paul L.G. , Golas Angela C , Graff‐Guerrero Ariel , Vieira Erica , Voineskos Aristotle N. , Brooks Heather , Melichercik Ashley , Thorpe Kevin E , Mulsant Benoit H. ,   PACt‐MD Study Group
Published: December 2023

AbstractBackgroundInterventions to prevent cognitive decline and dementia in high‐risk populations such as those with remitted Major Depressive Disorder (rMDD) or Mild Cognitive Impairment (MCI) are urgently needed.MethodPACt‐MD was a double‐blind randomized trial conducted between 2015 and 2022 comparing cognitive remediation (CR) plus transcranial Direct Current Stimulation (tDCS) vs. sham‐CR+sham‐tDCS delivered 5 days/week for 8 weeks followed by 5‐day semi‐annual boosters and at‐home daily CR, in participants with rMDD or MCI. Participants were assessed at baseline, week‐8, and yearly.The hypotheses were that compared to sham+sham, CR+tDCS would: slow cognitive decline (H1); reduce progression to MCI or dementia (H2); and acutely improve cognition (H3).The primary outcome composite score was calculated when at least half of the tests for at least four of six cognitive domains were completed. Due to COVID‐19, some participants did not complete enough tests and a second composite score using all available data was generated.Result375 participants were randomized (Active: N = 188, Mean Age = 72.1 ± 6.3; Sham: N = 187, Mean Age = 72.3 ± 6.4) and received at least one intervention session. Over up to six years, there was no time‐by‐treatment interaction using the primary composite score but there was using the all‐data score. Change in composite score differed between the two intervention groups for the primary and all‐data scores for all years except for year‐6 primary score. The year‐5 adjusted z‐score difference was ‐0.15 (95%CI [‐0.29, ‐0.005]) for the primary and ‐0.21 (95%CI [‐0.34, ‐0.067]) for all‐data score (Fig.1). Comparing active vs. sham at 8‐week (H3), the adjusted z‐score difference was ‐0.06 (95%CI: [‐0.12, 0.005]; p = 0.072); and for progression (H2), HR was 0.66 (95%CI [0.40, 1.08] p = 0.101) in a stratified Cox model. In a preplanned secondary analysis of domain scores, there was a time‐by‐treatment interaction for verbal memory with a year‐5 adjusted z‐score difference of ‐0.30 (95%CI [‐0.53, ‐0.074]) (Fig.2) but not the other domains. In another preplanned secondary analysis, the model with a randomization diagnosis‐by‐time‐by‐treatment was different from the model without this three‐way interaction (p = 0.012; Fig.3).ConclusionCR+tDCS may be effective in slowing cognitive decline (particularly verbal memory) in older patients with rMDD or MCI.
The effect of psychosocial state in patients with subjective cognitive decline, mild cognitive impairment, and Alzheimer’s disease: A cross‐sectional study
Authors: Xu Weijia , Zhao Junyu , Li Hong , Li Yulian , Luo Tingyu , Lin Rong , Yan Yuanjiao , Chen Lili , Pan Xiaodong , Xin Jiawei 
Published: December 2023

AbstractBackgroundSocial support and mental health are important issues in the context of elderly care. Social support is beneficial to both mental health and cognition. The purpose of this study was to investigate the effect of social support and mental health in patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI) and Alzheimer´s disease (AD).MethodIn this cross‐sectional, observational study, participants were 219 people between 45 and 93 (mean age = 61.82; SD = 10.13), and divided into three cognitive groups (SCD, MCI, AD). Neuropsychological assessment and psychological questionnaires were used for data collection and analysis.ResultThe SCD group and MCI group scored higher than patients with AD on the Adult Mental Health Scale (AMHS) and the Social Support Rating Scale (SSRS). The results of this study suggest that the degree of cognitive impairment of middle‐aged and old people is affected by age and education level, and is related to the level of social support and mental health status (P<0.05).ConclusionThe level of social support, mental health and cognitive decline are closely related in patients with cognitive impairments. Therefore, it is very important to give early intervention to middle‐aged and old people with poor mental health status and social support status, so as to delay the progression of cognitive impairment.
The role of synbiotics in Alzheimer`s management
Authors: Corrie Leander , Singh Sachin Kumar , Gulati Monica 
Published: December 2023

AbstractBackgroundQuercetin and Lactobacillus Brevis were used in the development of S‐SNEDDS for their antiinflammaging effect in Alzheimer`s diseaseMethodThe isotropic mixture was prepared by incorporating Capmul MCM, Tween 80 and Transcutol P as oil, surfactant and co surfactant phases respectively. Quercetin was then added. The probiotic mixture was selected as a solid carrier and drug loading was calculated. The droplet size and zeta potential was also determined. The formulation was also assessed for differential scanning colorimetry (DSC), powder x ray diffraction studies (PXRD), and field emission scanning electron microscopy studies (FESEM). Stability studies of the developed formulation was also carried out. Alzheimer’s disease was induced in rats by the use of aluminum chloride (100mg/kg) after taking necessary permission from the institution animal ethical committee. The Morris water maze (MWM) test was used to assess the animals 48 hours following the last treatment. Utilizing marketed ELISA kits, the concentrations of TNF, IL‐1, and IL‐6 were determined.ResultQuercetin was solubilized in the isotropic mixture. The drug loading was found to be 93.4±0.75% for the liquid SNEDDS (QUE‐L‐SNEDDS) formulation. The droplet size of QUE‐L‐SNEDDS was found to be 73.24±1.45nm and had a zeta potential of ‐23.21±1.34 mV. Whereas, the solid SNEDDS (QUE‐LB‐S‐SNEDDS) was found to be 74.56±1.23 nm and had a zeta potential of ‐21.43 mV, respectively. This indicated that there was no change in the L‐SNEDDS and S‐SNEDDS formulation. Further, the amorphous nature of quercetin was confirmed by the DSC, PXRD and FESEM studies. Aluminum chloride was successful in inducing Alzheimer`s disease in the rats. Impaired learning and memory impairments, increased short‐term memory loss, and decreased locomotor activity were all observed in the negative controls. The developed formulation was successful in reversing the inflammatory effects of Alzheimer’s disease.ConclusionThe present study reveals that Quercetin and Lactobacillus Brevis can be used as a symbiotic combination as well as an adjuvant therapy in the treatment of inflammation related to Alzheimer’s disease. The results reveal an interesting outcome at the preclinical level and warrants future studies aimed at other plant based polyphenolic compounds especially in neurodegenerative diseases such as Alzheimer’s disease.
Anti‐mouse CD98hc nanobodies for brain delivery of a therapeutic moiety
Authors: Rué Laura , Jaspers Tom , Degors Isabelle , De Strooper Bart , Dewilde Maarten 
Published: December 2023

AbstractBackgroundThe blood‐brain barrier (BBB) limits the therapeutic perspective for central nervous system (CNS) disorders such as Alzheimer’s disease. Interestingly, monoclonal antibodies generated against receptor‐mediated transcytosis receptors are able to transport therapeutic proteins across the BBB. Nanobodies, which are the variable domain isolated from camelid heavy‐chain only antibodies have also shown their potential to deliver therapeutics into the CNS. Here we aimed to expand the panel of nanobodies targeting other brain endothelial cell receptors.MethodCamelids were immunized with a pool of DNA encoding for several brain endothelial cell receptors. One target was chosen to validate the immunization and discovery approach, CD98hc, previously suggested to allow drug shuttling across the BBB. Nanobody libraries were selected on Chinese Hamster Ovarian (CHO) cells overexpressing the target of interest. Selected nanobodies were screened in vivo based on their potential to deliver into the CNS either a biologically active neuropeptide neurotensin to reduce body temperature, or a BACE1 inhibiting antibody that reduces the accumulation of Aβ1‐40 species.ResultDNA immunization followed by selections on CHO cells overexpressing the target of interest resulted in specific anti‐mouse CD98hc binders with affinities in the low nanomolar range. In vivo screening of mouse CD98hc nanobody binders revealed some discrepancy between the two methods used. Whereas none of the tested nanobodies fused to neurotensin was able to reduce body temperature, nanobodies fused to the anti‐BACE1 antibody 1A11 effectively reduced Aβ1‐40 levels in the brain. We suggest that the neurotensin approach, although having shown robustness with anti‐TfR nanobodies, might lack sensitivity when screening non‐TfR binders. We suggest BACE1 inhibition as a more robust model to validate CD98hc‐mediated transport across the BBB.ConclusionThis is a proof of concept study in which we have optimized our nanobody discovery approach to find nanobodies against BBB targets, and validated CD98hc as a receptor to target in order to shuttle drugs into the brain. In the future we will explore whether nanobodies raised against novel brain endothelial cell receptors could also improve brain penetration of biologics.
A risk variant in TTC3 modifies the actin cytoskeleton organization and PI3K‐Akt signaling in iPSC‐derived forebrain neurons
Authors: Cukier Holly N. , Duarte Carolina L. , Laverde‐Paz Juliana , Simon Shaina A. , Van Booven Derek , Miyares Amanda T. , Vance Jeffery M. , Pericak‐Vance Margaret A. , Griswold Anthony J. , Dykxhoorn Derek M. 
Published: December 2023

AbstractBackgroundWe identified a rare, nonsynonymous variant in the tetratricopeptide repeat domain 3 (TTC3) gene that segregated in a non‐Hispanic white late onset Alzheimer disease (LOAD) family (Kohli, et al, 2016). This missense alteration, rs377155188 (p.S1038C), is predicted to be deleterious and is extremely rare. Studies have reported that cortical TTC3 expression is reduced in LOAD patients and negatively correlated with AD neuropathology.MethodTo understand the mechanism by which the TTC3 p.S1038C may contribute to LOAD risk, CRISPR/Cas9 genome edited induced pluripotent stem cells (iPSCs) were developed that were homozygous for the variant to examine cellular and transcriptional consequences in iPSC‐derived neuronal cells (Laverde‐Paz, et al, 2021).ResultQuantitative PCR and western blot analysis demonstrated that TTC3 levels were decreased in edited compared to unedited iPSCs, as well as differentiated neurons. In growing neuronal precursor cells (NPCs), cells with the TTC3 variant recovered more quickly from a scratch wound. Since there is evidence that modulation of TTC3 affects neurite growth, morphological measures of axon formation were assessed using the Incucyte Zoom. Studies demonstrate an increase in neurite outgrowth, which phenotypically corresponds with previous studies of a decrease in TTC3 function. This phenotype was tempered by treatment with Cytochalasin D, an inhibitor of actin polymerization. Additionally, TTC3 ubiquitinates phosphorylated AKT and regulates AKT signaling. The edited cells were found to have an increase in phosphorylated AKT (pAKT) relative to total AKT. RNA‐seq of day 70 neurons identified 979 genes that were differentially expressed (FDR<0.05). This included known AD genes (BACE1) and genes in AD GWAS loci (ADAMTS1, MAF, NCK2). KEGG pathway analysis identified differential expression in PI3K‐Akt signaling pathway components, in which TTC3 has been previously implicated, as well as the axon guidance pathway, the GABAergic synapse pathway, and the Wnt signaling pathway.ConclusionCombined, these results suggest that the TTC3 p.S1038C variant causes a loss of function. Utilizing a CRISPR genome edited iPSC carrying a homozygous alteration in TTC3, we were able to identify potential mechanisms by which TTC3 may contribute to LOAD risk.
Homocysteine, vitamin B12, folic acid levels and its association with Mild Cognitive Impairment in urban and rural dwelling Indians
Authors: Mallikarjun Divya N , Malo Palash Kumar , Partha Ajith , L Abhishek M , Stezin Albert , Velavarajan Goutham , Narayanasamy Rajitha , R Meghana , M Amitha C , Menon Meenakshi , Arvind Prathima , Hameed Shafeeq K Shahul , S Sunitha H , Singh Sadhana , Kommaddi Reddy Peera , Sundarakumar Jonas S. , Issac Thomas Gregor , Diwakar Latha 
Published: December 2023

AbstractBackgroundHomocysteine (Hcy) is a sulfur containing amino acid generated in the metabolism of methionine involving co‐factors such as B vitamins and folic acid. Deficiency of these co‐factors have been associated with increased Hcy levels (Hutto, 1997). Relationship between differing levels of plasma Hcy, vitamin B12, folic acid and cognitive impairment is inconclusive.MethodCross sectional analysis was done using the baseline data from two ongoing longitudinal studies such as Tata Longitudinal Study of Ageing (TLSA, N = 984) and Srinivaspura Aging, Neuro Senescence and COGnition (SANSCOG, N = 4404), an urban and rural cohorts (Sundarakumar et al, 2020) respectively. Hcy, vitamin B12, folic acid levels were compared between the subjects of both cohorts. Comparison of these levels between healthy and MCI (Mild Cognitive Impairment) subjects within and across the cohorts were done. CDR (Clinical Dementia Rating) scale was used to classify subjects having normal cognition and MCI, considering score of 0.5 as MCI. Mann‐Whitney U test was used to compare these levels between the groups.ResultHcy, vitamin B12, folic acid levels between the two cohorts showed significant difference, with higher levels of Hcy (median (IQR)) = (17.08 (11) vs 14.63 (10); p <0.001), vitamin B12 (247 (252) vs 220 (143); p <0.001) and folic acid (8.55 (9) vs 5.55(4); p <0.05) in TLSA than SANSCOG. Significant difference seen in Hcy (17.73(11) vs 14.73 (10); p <0.001), vitamin B12 (246 (249) vs 220 (136); p <0.001) and folic acid (8.42 (9) vs 5.53 (4): p <0.001) levels for healthy subjects between cohorts, higher levels were seen in TLSA subjects. Hcy (16.08 (8) vs 14.43 (12); p <0.001) vitamin B12 (305 (341) vs 216 (174); p = 0.03) and folic acid (8.52 (9) vs 5.34 (4): p <0.001) levels were significantly high in TLSA than SANSCOG for MCI subjects. However, these levels were not significantly different between healthy and MCI subjects within cohorts.ConclusionConsistently elevated levels of Hcy was observed in urban cohort. Though elevated level of Hcy was observed with normal vitamin B12 and folic acid, it was not associated with MCI.
Knowledge and Perception of caregivers on therapeutic gardens in Elderly care homes in Lagos Nigeria
Authors: Akindejoye Funmi , Achor Micheal 
Published: December 2023

AbstractGardening can be an activity that promotes overall health and quality of life, physical strength, fitness, flexibility, cognitive ability, and socialization [1]. Horticulture therapy employs plants and gardening activities in therapeutic and rehabilitation activities and could be utilized to improve the quality of life of the worldwide aging population [2].In Nigeria families mainly provide support for their elderly ones [3], however, some families are gradually accepting the concept of care‐homes. Such care‐homes are in scarce supply and the available ones are operated by the private sector amidst limited resources. An appraisal of the availability of gardens in care‐homes showed that garden and gardening activities are mostly utilized in high‐income countries (HIC). However, the potential benefits of gardening activity are less well understood by related stakeholders in low‐ and middle‐income countries (LMICs) [4]. There is a dearth in the literature on the health impact of gardening in LMICs, thus the unavailability and lack of awareness of STH gardens in LMICs [4].This study is an aspect of a social therapeutic horticulture project in two identified care homes in Lagos Nigeria. The study accesses the knowledge of caregivers and the management of STH gardens and the perceived need for such gardens in their respective homes. Utilizing online surveys and interviews for data collection.Currently, the study is ongoing, and ethical approval is being sourced. We aim to conclude the study before the scheduled 2023 AAIC conference.
References
1. Wang, D., & MacMillan, T. (2013). The benefits of gardening for older adults: a systematic review of the literature.2. Detweiler, M. B., Sharma, T., Detweiler, J. G., Murphy, P. F., Lane, S., Carman, J., & Kim, K. Y. (2012). What is the evidence to support the use of therapeutic gardens for the elderly?3. Dokpesi, A. O. (2015). The future of elderly care in Nigeria: borrowing a leaf from a foreign land.4. Ainamani, H. E., Bamwerinde, W. M., Rukundo, G. Z., Tumwesigire, S., Kalibwani, R. M., Bikaitwaho, E. M., & Tsai, A. C. (2021). Participation in gardening activity and its association with improved mental health among family caregivers of people with dementia in rural Uganda.
Novel High‐Donepezil Loaded One‐Month Release Microspheres for Alzheimer’s Disease Treatment
Authors: Lee Jinwoo , Kim Hyemin , Lee Wonyoung , Jeong Yeojin , Lee Juhan , Seol Eunyoung , Lee Heeyong 
Published: December 2023

AbstractBackgroundDonepezil is the most commonly prescribed medication for treating Alzheimer’s disease. However, the most commonly used once daily oral formulation or recently developed once or twice weekly patch formulations have side effects such as nausea, vomiting and weight loss or skin irritation, and the patient’s compliance with these medications is very low. One month release injectable of donepezil microspheres can be a good alternative to increase patient compliance and reduce these side effects. The biggest obstacle in the development of one month donepezil microspheres is that patients tend to feel pain at the injection site due to the large volume of dosage. We have developed novel donepezil microspheres with high drug contents which can improve patient compliance and medication convenience by lowering dosage volume at the injection site.MethodMono‐dispersed and spherical shaped donepezil microspheres with different drug contents were manufactured by membrane emulsification method. The morphology of the microspheres was observed by electron microscope, and the particle size distribution was measured by laser diffraction analysis. The donepezil contents in the microspheres were analyzed using HPLC. Pharmacokinetic studies were performed after a single injection in male SD rats. The concentration of donepezil in the plasma samples was determined by LC‐MS/MS.ResultDonepezil microspheres with three different drug contents (27%, 45% and 60%) were prepared successfully with high drug encapsulation efficiency. All the donepezil microspheres regardless of high drug content have a spherical shape and smooth surface with a narrow side distribution. Despite the high content of donepezil, the initial release was well controlled to less than 5% during the first 24 hours after injection. In rat PK studies of donepezil microspheres after a single injection, plasma donepezil concentration of all three formulations was kept within the therapeutic range for more than one month.ConclusionWe have developed novel donepezil microspheres with high drug contents and without initial burst release. These high donepezil‐loaded microspheres can improve patient compliance and medication convenience by lowering dosage volume at the injection site. Currently, this novel donepezil formulation is planned for commercialization after clinical trials.
Organizational, intra‐ and interpersonal factors contributing to person‐centred care in long‐term care facilities for people with dementia
Authors: van der Kuil Milan N.A. , Hartstra Egbert , Overbeek Anouk , van der Roest Henriëtte G. , Van der Velden Claudia 
Published: December 2023

AbstractBackgroundPerson‐centred care (PCC) is seen as the golden standard for dementia care. PCC is characterized by care and support that are in line with the needs, preferences and capacities of people with dementia. Previous research showed that PCC has beneficial effects on the quality of life of people with dementia and improve healthcare professional’s working conditions. Within long‐term care PCC seems to hinge on different factors on integrated levels of care provisioning. The current study aims to provide healthcare organizations and policy makers with more insight into the modifiable factors that contribute to PCC for people with dementia living in long‐term care facilities. To this end, we aim to identify whether and which intrapersonal factors (care professional’s attitude towards dementia, attitude towards technology use, and working experience), interpersonal factors (learning potential of the workplace, vision of care, transformational leadership, emotional job demands and resources), and organizational factors (learning climate of the organization, small‐scale setting and amount of residents per care professional) contribute to higher levels of PCC.MethodData were derived from the fifth assessment of the Living Arrangements for people with Dementia (LAD)‐study, which had a cross‐sectional design. The study was performed amongst 58 long‐term care facilities providing clustered care for people with dementia under the Chronic Care Act (WLZ) in the Netherlands. Care professionals completed an adapted version of the ‘Person‐centred care questionnaire’ (PCCq) to assess the level of PCC in the participating facilities. We performed multilevel analyses, controlling for clustering effects.ResultIn total 606 care professionals participated. On the intrapersonal level, care professional’s attitude towards dementia and working experience contributed significantly to PCC. Interpersonal factors that contributed significantly to PCC were possibilities of learning during day‐to‐day work, transformational leadership, and job resources. Organizational factors were not found to significantly contribute to PCC in the model.ConclusionSeveral intra‐ and interpersonal factors, rather than organizational factors, contribute to person‐centred care.