bluuebunny/crossref_metadata_2025_split huggingface dataset:
Guidance on the use of therapeutic lying among caregivers of people with dementia by Speech and Language Pathologists
Authors: Alves Emily Viega , Lopes Isabella Amaral , Beber Bárbara Costa 
Published: December 2022

AbstractBackgroundTherapeutic lying (TL) is often used in people with dementia (PWD) who present challenging behaviors. In 2006, the creation of a guideline protocol about how to use TL, demonstrates that it requires trained professionals. Considering TL as a communication strategy, speech and language pathologists (SLPs) can play a fundamental role in guiding caregivers regarding its use. This study aims at verifying if SLPs guide caregivers of PWD to use TL to manage difficult situations and its association with their knowledge and training on the technique.MethodData collection took place through an online questionnaire that obtained sociodemographic information from Brazilian SLPs and asked them to answer the following questions: Have you ever heard about TL? Were you taught about TL in your academic education? Have you ever guided family members or caregivers of PWD to use TL? The results were presented descriptively and the association between the frequency with which the participants have guided caregivers to use TL and their knowledge about the subject was verified through Chi‐square Test with a significance level of 5%.ResultThe final sample consisted of 72 individuals. There was a predominance of female (100%), specialization (48.6%) as the highest educational level and the southern region of Brazil (45.8%). SLPs who claimed to have heard about TL comprised 23.6% of the sample, only 8.3% said they had been taught about TL during academic education and almost half of the professionals (48.6%) reported having already guided caregivers of PWD on the use of TL. There was no statistically significant association between the frequency with which the participants have guided caregivers to use TL and the fact they have already heard about the concept of TL (p = 0.07) or have already received training on it (p = 0.36).ConclusionThe study showed that many professionals guide caregivers of PWD about the use of LT, however it happens without technical knowledge to do it properly. The work highlights the importance of including this subject in the academic education of these professionals.
Efficacy and safety of Kami‐guibi‐tang for mild cognitive impairment: a pilot, randomized, double‐blind, placebo‐controlled trial
Authors: Park Jung‐Mi , Shin Hee‐Yeon , Kim Ha‐Ri , Yim Tae‐Bin , Jeon Gyu‐Ri , Jahng Geon‐Ho , Cho Seung‐Yeon , Park Seong‐Uk , Ko Chang‐Nam 
Published: December 2022

AbstractBackgroundMild cognitive impairment (MCI) is considered an intermediate phase between normal aging and dementia. As the majority of cases of amnestic MCI (aMCI) progress to Alzheimer’s disease (AD), it is considered the prodromal stage of AD, and a treatment target for prevention of further cognitive decline. However, no medications have been shown to have symptomatic or preventive benefits in MCI. Kami‐guibi‐tang (KGT) is a traditional herbal formula used in Korean medicine to treat amnesia, which is reported to increase acetylcholine levels via activation of choline acetyltransferase. The objective of this study was to evaluate the efficacy and safety of KGT in patients with aMCI.MethodThis study was designed as a single‐center, randomized, double‐blind, placebo‐controlled pilot study. Participants diagnosed with aMCI were randomized to receive either KGT or placebo granules for 24 weeks. The efficacy measure was a change in the Seoul Neuropsychological Screening Battery (SNSB) score. The safety measures included the occurrence of adverse events and abnormalities in vital signs and blood chemistry, electrocardiogram (ECG), and brain magnetic resonance imaging (MRI) findings.ResultA total of 16 patients in the KGT group and 14 patients in the placebo group were investigated in the study. The mean score of Clinical Dementia Rating‐Sum of Boxes (CDR‐SB) significantly improved from 1.53 (0.64) points to 1.13 (0.62) points in the KGT group (p = 0.010), whereas it worsened from 1.61 (0.88) points to 1.75 (0.94) points in the placebo group. There was a significant difference in the CDR‐SB scores between the two groups after the intervention (p = 0.045). The total SNSB‐D scores and the scores in the memory domain after the treatment were significantly higher than the baseline values in the KGT group, but not in the placebo group. The frequency of adverse events was not significantly different between the two groups, and there were no abnormalities in vital signs or blood test, ECG, and brain MRI findings after the intervention.ConclusionKGT may provide a safe and effective treatment option for patients with aMCI. Further studies with a larger sample size are needed to validate the findings.
Modeling functional and structural brain‐predicted age in relation to Alzheimer disease and cognition
Authors: Millar Peter R , Luckett Patrick H , Gordon Brian A. , Benzinger Tammie L.S. , Fagan Anne M. , Hassenstab Jason J. , Schindler Suzanne E. , Morris John C. , Ances Beau M 
Published: December 2022

AbstractBackgroundEstimates of “brain‐predicted age” quantify apparent brain age compared to normative trajectories of neuroimaging features. Brain‐predicted age is elevated in symptomatic Alzheimer disease (AD), but is underexplored in preclinical AD. Prior studies have typically modeled brain‐predicted age with volumetric magnetic resonance imaging (MRI), but other modalities, including resting‐state functional connectivity (FC) and multimodal MRI, have more recently been explored. In the present study, we tested the sensitivity of brain‐age predictions derived from volumetric, FC, and multimodal MRI to group differences in AD status and individual differences in cognition.MethodWe trained three Gaussian process regression models to predict age from (1) FC, (2) regional brain volumes, and (3) multimodal MRI (FC+volumetric) in 493 control participants (cognitively normal, amyloid‐negative [A‐], 18‐89 years old). We applied the trained models to independent samples staged by the presence or absence of amyloid (A+/A‐) and tau (T+/T‐) using PET (Centiloid) and CSF (amyloid β‐42/40 ratio, phosphorylated tau 181): 122 A‐T‐, 62 A+T‐, 62 A+T+, as well as 154 symptomatic AD participants. Global cognition was assessed using an established composite of cognitive tests across multiple domains.ResultAll models successfully predicted age in the control training set, with the multimodal model (mean absolute error [MAE]=5.3 years) outperforming the unimodal volumetric (MAE=6.0 years) and FC models (MAE=8.3 years) (Figure 1). In all three models, the brain age gap (BAG) was significantly elevated in symptomatic AD compared to cognitively normal controls. In the FC and multimodal models, the BAG was significantly reduced in A+T+ participants compared to T‐ controls (Figure 2). In symptomatic AD, lower global cognitive composite scores were associated with elevated volumetric and multimodal BAGs (Figure 3).ConclusionBoth FC and volumetric estimates of brain age are sensitive to symptomatic AD, consistent with previous reports. Additionally, FC‐based brain age may exhibit a biphasic response to preclinical AD pathology while volumetric brain age may be sensitive to cognitive decline in the symptomatic stage. Multimodal estimates of brain age capture each of these modality‐specific relationships, and further, improve sensitivity to healthy age differences. Hence, multimodal neuroimaging models may be useful in staging early symptomatic and preclinical AD.
β‐Lactolin Improves Mitochondrial Dysfunction in Aβ‐treated Mouse Hippocampal Neuronal Cells and a Human iPSC‐Derived Neuronal Cell Model of Alzheimer’s Disease
Authors: Ayabe Tatsuhiro , Takahashi Chika , Ohya Rena , Ano Yasuhisa 
Published: December 2022

AbstractBackgroundMitochondrial dysfunctions are a key hallmark of Alzheimer’s disease (AD). β‐Lactolin, a whey‐derived glycine–threonine–tryptophan–tyrosine tetrapeptide, has been previously reported to prevent AD‐like pathologies in an 5×FAD mouse model via regulation of microglial functions. However, the direct effect of β‐lactolin on neuronal cells and neuronal mitochondrial functions remains unknown. Here, we investigated the effects of β‐lactolin on mitochondrial dysfunctions in amyloid β (Aβ)‐treated mouse hippocampal neuronal HT22 cells and human induced‐pluripotent cell (hiPSC)‐derived AD model neurons.MethodMouse hippocampal neuronal HT22 cell line, and hiPSC‐derived AD model neuron (PSEN1 P117L mutation) and its wild‐type control were used in this study. HT22 cells were treated with β‐lactolin (1–100 nM) for 1 hr, and Aβ42 (1–10 μM) was added for the next 23 hrs. Oxygen consumption rate was measured using extracellular flux analyzer. Intracellular ATP level was determined by luciferase activity. Cells were stained with MitoTracker, JC‐1, or MitoSOX fluorescent dye, and then mitochondrial morphologies, membrane potential, and oxidative stress, respectively, were examined by high content image analysis. Cell viability was measured by MTT assay. Gene expression levels were evaluated by RT‐PCR. hiPSC‐derived wild‐type and AD neurons were cultured for 14 days under β‐lactolin treatment, and mitochondrial morphologies and membrane potentials were analyzed.ResultHT22 cells treated with both β‐lactolin and Aβ exhibited increased oxygen consumption rate and cellular ATP concentrations compared to cells treated with Aβ alone, suggesting that β‐lactolin improves mitochondrial respiration and energy production. In high content image analysis, β‐lactolin attenuated Aβ‐induced mitochondrial fragmentation, membrane potential decrease, and excess oxidative stress, eventually preventing neuronal cell death. Treatments with β‐lactolin increased gene expression of mitofusin‐2, which contribute to mitochondrial fusion events. Finally, β‐lactolin attenuated impairment in both mitochondrial morphologies and membrane potentials in hiPSC‐derived AD model neurons, suggesting β‐lactolin shows a suppressing effect on human AD pathologies.Conclusionβ‐lactolin improved AD‐related neuronal mitochondrial dysfunctions and suppressed neuronal cell death in both mouse and human AD model neuronal cells. The dual function of β‐lactolin on both neuron and microglia marks an advantage in AD prevention.
Hearing loss was associated with cognitive impairment evaluated by Bangla Adaptation of Mini‐mental State Examination in a rural Bangladeshi elderly population
Authors: Suzuki Harumitsu , Siddiquee Ali Tanweer , Sobhan Sheikh Mohammad Mahbubus , Kadota Aya , Miura Katsuyuki , Fujiyoshi Akira , Choudhury Sohel Reza 
Published: December 2022

AbstractBackgroundThe Mini Mental State Examination (MMSE) is the most commonly used, first line screening tool for dementia and cognitive decline in adults. The Bangla Adaptation of Mini‐mental State Examination (BAMSE) has been tested as a reliable instrument to assess cognitive function of the normal elderly Bangladeshi population with regards to the socio‐cultural context and low literacy rate of the country. However, there is lack of evidence regarding lifestyle and socioeconomic determinants of cognitive performance in Bangladeshi elderly population. The purpose of this study is to investigate the relationships between lifestyle and socioeconomic determinants and cognitive impairment by BAMSE among elderly Bangladeshi.MethodData was collected from an on‐going surveillance site at Tarail subdistrict in Kishorgonj district.Among the total of 410 study participants aged ≥65 years, after excluding history of stroke and Parkinson’s disease, finally 314 participants were included in this analysis. Trained interviewers assessed cognitive function using the BAMSE questionnaires and self‐reported lifestyle factors (smoking: never, past, current; hearing: normal, poor, smelling: normal, poor, lost), socioeconomic factors (marital status: married, widowed/divorced; working status: farmer, other workers, non‐workers), medication use (hypertension and diabetes) by a questionnaire, and physical measurements (weight, height and blood pressure). Hypertension was defined as either anti‐hypertensive medication use or systolic/diastolic blood pressure ≥140/90 mmHg. Literacy was defined as participants who had 1 year or more education. Cognitive impairment was defined by BAMSE score < 21. A multivariable logistic regression analysis was performed to assess the independent relationships between lifestyle and socioeconomic factors and cognitive impairment. Sex, age, hypertension, diabetes, smoking, hearing, smelling, marital and working status, and literacy were used as explanatory variables.ResultMean age (standard deviation) was 72.5(years and literacy rate was 23.6% in men and 5.9% in women. People who have hearing loss was 1.94 higher odds ratio (95% confidence interval:1.08‐3.47) for cognitive impairment compared to normal hearing in the multivariable analysis. Each 5‐year age increments was also significantly associated with cognitive impairment in the same model.ConclusionHearing loss and older age were associated with cognitive impairment in elderly Bangladeshi in this study.
The impact of Virtual Individual Cognitive Stimulation Therapy (V‐iCST) on cognition, quality of life, mood, and communication in dementia: a feasibility randomized controlled trial
Authors: Hui Esther K , Tischler Victoria , Wong Gloria HY , Gibbor Luke , Spector Aimee E 
Published: December 2022

AbstractBackgroundThe COVID‐19 pandemic has led to the suspension of community‐based dementia services worldwide, where evidence‐based interventions for dementia, like Cognitive Stimulation Therapy (CST), were delivered. Treatment access is paramount during the pandemic and beyond for people with dementia to maintain functioning and well‐being. This study aimed to evaluate the feasibility and acceptability of a virtual, 14‐session program of Individual Cognitive Stimulation Therapy (V‐iCST) in the UK.MethodA single‐blind feasibility randomized controlled trial (RCT) was conducted in the UK. Thirty‐four people with mild to moderate dementia were recruited from dementia organizations and networks. Seventeen were randomly assigned to receive V‐iCST (14, 45‐min sessions) and 17 to treatment as usual (TAU) over seven weeks. Feasibility and acceptability data, for example, recruitment, attrition, attendance, adverse effects, and fidelity, were collected. Outcome measures on cognitive function, quality of life (QoL), mood, and communication were collected pre and post‐test. Analysis of covariance was used to compare changes in V‐iCST and TAU.ResultWe have successfully completed recruitment. Results on feasibility, acceptability, and preliminary efficacy will be available at the conference.ConclusionWe hypothesize that V‐iCST is feasible and acceptable and will have positive effects on cognitive, QoL, mood, and communication. Findings will be available at the conference.
Innovative Framework to Assess the Costs of Untreated Agitation in Alzheimer’s Disease (AAD)
Authors: Michael Mary 
Published: December 2022

AbstractBackgroundIn the past decade, researchers and advocates have taken steps towards quantifying the full costs of Alzheimer’s disease and related dementias. However, our current understanding of these costs does not fully consider the behavioral symptoms of dementia, notably agitation. Agitation in Alzheimer’s disease contributes to negative social and financial outcomes for people with the condition, their care partners, and health systems. When left untreated, the negative impact of these outcomes is exacerbated, yet the scale of this impact is unknown. A review of the literature shows that there are no frameworks to help assess the true costs of agitation calling for a need for further research and assessment.MethodWe created a Markov model that investigates each stage of Alzheimer’s disease with agitation. The model utilizes five transition states with six‐month cycles. This framework assesses direct and indirect costs of disease. Direct costs include professional caregiving, non‐pharmacological intervention, nursing home costs, healthcare professional consultations, and hospitalizations. Indirect costs of disease evaluated include loss of income and value of unpaid caregiving. To establish the difference in cost to understand true costs of untreated disease, this model will allow us to compare outcomes associated with intervention with that of no intervention, from which one can derive an Incremental Cost‐Effectiveness Ratio (ICER). Additionally, we used quality‐adjusted life years to measure disease burden and health outcomes. Finally, we utilized a deterministic and probabilistic sensitivity analysis to assess the robustness of this model.ResultResults will describe a finalized Markov model with which one can assess the costs of untreated agitation in Alzheimer’s. This discussion will include perspectives and feedback from key opinion leaders in Alzheimer’s research, care, and economics from across the worldConclusionAgitation has severe consequences on individuals, families, and health systems. Oftentimes one of the first symptoms of Alzheimer’s or dementia, agitation can increase the caregiving responsibilities, trigger placement into nursing homes, and cause severe emotional and physical toll on care partners. We cannot understand the full costs of dementia or AD until we account for untreated agitation vis‐à‐vis a multi‐symptom assessment. This framework is the first step in evaluating the costs of agitation.
Shedding light on innate immune dysfunction in a mouse model of Alzheimer’s disease using a novel myeloid cell‐targeted PET imaging strategy
Authors: Chaney Aisling M , Jain Poorva , Nagy Sydney C , Cropper Haley , Reyes Samantha T. , Wu Sophia , Dwivedi Shriya , Azevedo Carmen , Jackson Isaac M , Carlson Mackenzie L , James Michelle L. 
Published: December 2022

AbstractBackgroundNon‐invasive assessment of maladaptive innate immune responses in the brains of Alzheimer’s disease (AD) patients is a critical unmet need; such techniques have the potential to not only improve diagnosis and disease monitoring, but also serve as endpoints in clinical trials of novel therapeutics. Positron emission tomography (PET) imaging of the translocator protein 18 kDa (TSPO) is a widely used experimental approach for assessing inflammation in vivo but is limited by its lack of cell specificity and inability to discriminate between beneficial and adverse immune responses. We developed the first PET probe targeting triggering receptor expressed on myeloid cells 1 (TREM1) and demonstrated its ability to specifically detect CNS‐infiltrating pathogenic peripheral myeloid cells (e.g., macrophages, monocytes, neutrophils) in the context of neurological disease. Herein, we assess the utility of TREM1‐PET compared to TSPO‐PET for detecting innate immune responses in the 5XFAD mouse model of AD.Method5XFAD and wild‐type (WT) 6–7‐month‐old mice underwent 10 min static TREM1‐ and TSPO‐PET/CT imaging. TSPO‐PET was performed 50–60 minutes post‐intravenous injection of [18F]GE‐180 (175.1±13.8 μCi). TREM1‐PET was performed 20 hours following intravenous injection of [64Cu]TREM1‐mAb (94.75±4.96 μCi). Tracer binding was quantified in the cortex, hippocampus, thalamus, and whole brain using a semi‐automated brain atlas‐based approach. CD68 immunostaining of brain tissue was performed to assess microglia/macrophage activation.ResultTREM1‐PET quantification revealed significantly increased [64Cu]TREM1‐mAb binding in the hippocampus (1.37‐vs‐1.14 %ID/g, p=0.02) and thalamus (1.00‐vs‐0.76 %ID/g, p=0.04) of 6–7‐month‐old 5XFAD compared to WT mice (Fig 1A). Elevated TREM1‐PET binding was observed in the cortex (1.77‐vs‐1.62 %ID/g, p=0.14) and whole brain (1.64‐vs‐1.46 %ID/g, p=0.08) but did not reach significance. TSPO‐PET imaging demonstrated significantly increased [18F]GE‐180 binding in all regions (cortex: 2.36‐vs‐1.48 %ID/g; p=0.0003, hippocampus: 2.59‐vs‐1.52 %ID/g, p<0.0001, thalamus: 2.18‐vs‐1.20 %ID/g, p<0.0001, whole brain: 2.55‐vs‐1.66 %ID/g, p=0.0003, Fig. 1B). CD68 staining confirmed increased microglia/macrophage activation in cortical, hippocampal, and thalamic regions (Fig 2).ConclusionDifferential regional binding patterns were observed with TREM1‐ and TSPO‐PET imaging. Notably, increased TREM1‐PET signal in 5XFAD animals suggests a role for peripheral myeloid cells in AD. Longitudinal whole‐body TREM1‐ and TSPO‐PET imaging in this model is currently underway.
Novel hydroxyl dendrimer‐based PET tracer [18F]OP‐801 detects early‐stage neuroinflammation in 5XFAD mouse model with higher sensitivity than TSPO‐PET
Authors: Carlson Mackenzie L , Reyes Samantha T. , Jackson Isaac M , Azevedo Carmen , Alam Israt S , Nagy Sydney C , Brewer Matthew , Cleland Jeffrey , Shen Bin , James Michelle L. 
Published: December 2022

AbstractBackgroundChronic activation of macrophages/microglia plays a critical role in the onset and progression of neurological diseases, including Alzheimer’s. While PET imaging could enable non‐invasive visualization and quantification of activated macrophages/microglia in vivo, most available PET tracers are nonspecific for macrophages/microglia (Lambert, 2009). To address this need, we developed [18F]OP‐801, a synthetic hydroxyl dendrimer‐based PET tracer that is selectively (>95%) taken up by reactive macrophages/microglia across the blood‐brain barrier (Alnasser, 2018). Here, we evaluated the ability of [18F]OP‐801 to detect activated macrophages/microglia in the 5XFAD murine model of Alzheimer’s compared to an established neuroinflammation imaging approach (translocator protein 18 kDa [TSPO]‐PET, using [18F]GE180).Method[18F]OP‐801 (150‐250 μCi) was injected intravenously into female 5XFAD (TG) mice (n=12) and age/sex‐matched wild types (WT, n=7) at 3.75 and 5 months old. Sensitivity of [18F]OP‐801 was compared to [18F]GE180 by assessing brain signal‐to‐background ratios. [18F]GE180 (150‐250 μCi) was administered to a subset of TG (n=5) and WT (n=4) 3.75‐months‐old mice. Static 10‐minute PET/CT images were acquired at 50‐60 minutes post‐injection for both tracers. VivoQuant brain atlas was fit to CT images and fused to PET to quantify uptake in specific brain regions.ResultIn this model, macrophage/microglial activation is associated with amyloid plaque formation and can be detected using immunohistochemistry between 2‐4 months. Image quantification revealed 3‐fold higher PET signal in 3.75‐months‐old TG compared to WT mice using [18F]OP‐801, whereas [18F]GE180 signal provided no significant difference in brain regions known to contain activated microglia: cortex and hippocampus (Figure 1, Table 1). Significant differences in [18F]OP‐801 uptake were observed between 5‐months‐old TG and WT mice in cortex (p=0.005) (TG: 0.26±0.095%ID/g, WT: 0.11±0.041%ID/g), hippocampus (p=0.017) (TG: 0.18±0.065%ID/g, WT: 0.10±0.026%ID/g) and whole brain (p=0.004) (TG: 0.20±0.082%ID/g, WT: 0.10±0.039%ID/g). TG had almost 5‐fold higher [18F]OP‐801 signal compared to WT mice (Table 2).ConclusionThese results suggest that [18F]OP‐801 can detect early stage neuroinflammation with higher sensitivity than TSPO‐PET. We are currently replicating this study in a larger cohort of 5XFAD mice to correlate PET image findings with immunohistochemistry. [18F]OP‐801 is shows promise for visualizing the progression of neuroinflammation with high specificity and sensitivity, warranting further preclinical investigation.