bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mind over memory: reducing fear and avoidance of memory loss (REFRAME) study in older adults
Authors: An Hosanna , Marquez Melissa , Regan John , O'Loughlin Patricia , Pavithra Pavithra , Taddeo Michelle , Knight Rachel , Bennett Marc P , Lenaert Bert , Griffith James W , Farina Francesca R 
Published: December 2023

AbstractBackgroundFear of Alzheimer’s disease and related dementias (ADRD) is a growing concern among older adults. High levels of fear are associated with poorer health outcomes, lower levels of psychological well‐being, and the perpetuation of harmful cognitive‐behavioral cycles that can potentially hasten cognitive decline. Interventions that disrupt these cycles could bring both immediate and long‐term benefits for reducing ADRD‐related fears. Given the projected increase in the number of people living with ADRD and accompanying fears, effective interventions are needed to address the emotional needs of older adults. We evaluated a brief psychological intervention aimed at promoting adaptive coping in older adults with heightened ADRD‐related fear and examined its effects on broader health outcomes.MethodEighty‐one older adults experiencing heightened ADRD‐related fear were recruited to participate in a 3‐week online intervention aimed at reducing fear (primary outcome) and improving secondary health‐related outcomes (i.e., anxiety, depression, social function). Participants were randomly assigned to REFRAME or active comparison group. Both groups completed psychoeducation and mindfulness activities designed to reduce fear. The REFRAME group completed an additional behavioral activation module designed to disrupt patterns of avoidant behavioral coping. Participants completed measures at baseline, weeks 1‐3 of the intervention, post‐intervention, and 4‐week follow‐up. Outcomes were analyzed using linear mixed effects models.ResultParticipants ranged from 55 to 90 years, (M = 65.4, SD = 7.1). Intervention adherence was high (>75%) across both groups. ADRD‐related fear decreased significantly over time in both groups. Anxiety, depression, and self‐reported memory failures also decreased significantly in both groups, while social function and well‐being improved. The REFRAME group exhibited a greater reduction in depression compared to the control group.ConclusionOur brief psychological intervention had positive effects on ADRD‐related fear among older adults. However, further research is needed to determine the long‐term benefits and their effectiveness in at‐risk populations (e.g., people with a family history of dementia), as well as the acceptability of this intervention in clinical settings. These findings highlight the potential benefits of disrupting harmful cognitive‐behavioral cycles, as this may encourage older adults to stay engaged in healthy behaviors for longer, ultimately improving their quality of life.
Cognitive Testing in Diverse Populations to Further the Objective and Clinical Understanding Study ‐ FOCUS
Authors: Galvin James E 
Published: December 2023

AbstractBackgroundOne of the great challenges facing clinical trial recruitment is to have a representative sample reflective of the diversity of the US population. While racial and ethnic minorities compromise 39% of the United States population, they only account for 2%‐16% of clinical trial participants.1 The aim of the FOCUS study was to collect cognitive testing data from a diverse population and develop normative ranges for Cognivue, the first FDA‐cleared computerized cognitive assessment device based on modern cognitive neuroscience. Cognivue Thrive provides a 5‐minute cognitive screen while Cognivue Clarity provides a 10‐minute comprehensive assessment, allowing both physicians and non‐physician clinicians to objectively and quantitatively access brain health beyond traditional paper and pencil cognitive tests.MethodCognivue partnered with Velocity Clinical Research to lead the recruitment efforts for the FOCUS study. The enrollment goal included an objective to enroll a group resembling the racial, ethnic, gender, and educational makeup recorded in the 2020 U.S. census data. Study subjects were recruited through local community outreach, participant referrals, and advertising. Recruitment was stopped once goals for specific sub‐groups were reached, to model real‐world outcomes. Cognivue Thrive and Clarity were administered to assess scoring and normative ranges and compared against performance on other neuropsychological test batteries within the diverse study cohort.ResultThe Cognivue/Velocity partnership resulted in recruitment of more than 1,500 subjects from 14 sites in 11 states with a mean age of 50.2±16.3y (range 18‐89), 59.2% female, and 51.8% with 12 years or less of education. Over 28% of subjects identified their race as Black or African American, American Indian or Alaska Native, Asian, Native Hawaiian or Pacific Islander, or other non‐white, and over 12% of participants identified as Hispanic or Latino.ConclusionWorking in collaboration with Velocity, a clinical research partner with study sites throughout the United States, Cognivue was able to reach a 37% research participation rate of historically underserved and underrepresented populations in the national FOCUS study.
1Clin Pharmacol Ther. 2015 Mar;97(3):263‐73. https://doi.org/10.1002/cpt.61.
Poor objective sleep quality is associated with worse cognition cross‐sectionally and longitudinally in cognitively unimpaired adults
Authors: Stankeviciute Laura , Tort‐Colet Núria , Fernández‐Arcos Ana , López‐Martos David , Sánchez‐Benavides Gonzalo , Minguillon Carolina , Fauria Karine , Holst Sebastian C , Garces Pilar , Mueggler Thomas , Arqueros Aurora , Iranzo Álex , Suarez‐Calvet Marc , Gispert Juan Domingo , Molinuevo Jose Luis , Grau‐Rivera Oriol 
Published: December 2023

AbstractBackgroundSleep disturbances are prevalent in Alzheimer’s disease (AD), with sleep quality being impaired already in the preclinical stages. Specifically, reduced sleep efficiency and sleep fragmentation have been cross‐sectionally associated with poor cognition in healthy older adults. However, there is limited knowledge of how objectively measured sleep features relate to cognitive change. We aimed to investigate the relationships of actigraphy‐measured sleep with both cross‐sectional and longitudinal cognition in a cohort of cognitively unimpaired (CU) adults at increased risk of AD.MethodThis study included 123 CU adults from the ALFASleep project (mean age 63.9 years, 60.2% females, 50.4% APOE‐ε4 carriers) without sleep medication use (Table 1). Correlates of sleep quality were measured using actigraphy (Actiwatch2®, Philips Respironics) for two weeks. We used separate multivariate linear regressions to assess the association between actigraphy‐derived sleep parameters: total sleep time (TST), sleep efficiency, sleep latency, wake after sleep onset (WASO), and cognitive composite outcomes: Preclinical Alzheimer’s Cognitive Composite (PACC), and executive, memory and attention composites. We corrected all models for age, sex, APOE‐ε4, status, education and the time difference between cognitive and sleep assessments. Furthermore, we performed analyses on cognitive change from a previous visit (performed on average 3 years before) additionally adjusting by the time difference between two cognitive assessments.ResultsIn cross‐sectional analyses, shorter TST was associated with lower PACC (p = 0.049) and executive composite (p = 0.039) scores. Also, lower sleep efficiency and higher WASO (indicating more nocturnal awakenings) were associated with lower performance on executive tasks (p = 0.015; p = 0.026) (Table 2). In longitudinal analyses, shorter TST was associated with poorer longitudinal performance in PACC and executive composite scores (p = 0.020).ConclusionsObjectively measured indicators of poorer sleep quality are associated with poorer cognitive outcomes, both cross‐sectionally and longitudinally, in middle‐aged CU adults. Importantly, the executive function seems to be the most vulnerable to sleep impairment. Further research to unravel the underlying mechanisms using multi‐modal neuroimaging and CSF biomarkers of AD pathology is undergoing.
Sleep fragmentation is associated with lower cerebral structural integrity in females
Authors: Stankeviciute Laura , Tort‐Colet Núria , Fernández‐Arcos Ana , Garcia Marina , Minguillon Carolina , Fauria Karine , Holst Sebastian C , Garces Pilar , Arqueros Aurora , Iranzo Álex , Suarez‐Calvet Marc , Mueggler Thomas , Gispert Juan Domingo , Molinuevo Jose Luis , Grau‐Rivera Oriol 
Published: December 2023

AbstractBackgroundSex is a risk factor for Alzheimer’s disease (AD), with females accounting for two‐thirds of all cases. Epidemiological evidence showcases that sleep disturbances also increase AD risk, with females reporting more disrupted sleep in ageing compared to males. However, little is understood about how objective measures of sleep are associated with brain structural integrity, especially regarding the role of sex. We explored associations between actigraphy‐measured sleep and regional cortical thickness in middle‐aged cognitively unimpaired (CU) adults at risk of AD.MethodsWe included 151 CU adults from the ALFASleep project (mean age 64.6 years, 64.2% females) (Table 1). Correlates of sleep quality were measured using actigraphy (Actiwatch2®, Philips Respironics) for two weeks. The cortical thickness (CTh) of the “Alzheimer’s disease (AD) signature” composite region of interest (ROI) was calculated using FreeSurfer v6.0. We performed separate general linear models with CTh as the dependent variable, and actigraphy‐derived sleep parameters [total sleep time (TST), sleep efficiency, sleep latency, wake after sleep onset (WASO) and sleep fragmentation] as the predictors of interest. All models were corrected for age, sex, APOE‐ε4 status, sleep medication use and the time difference between MRI and actigraphy data acquisition. To investigate whether sex modified these associations we performed interactions between each actigraphy measure and sex. Finally, we performed stratified analyses to understand which group was driving any significant effects.ResultsHigher sleep fragmentation was associated with lower CTh (p = 0.006) in the whole group (Figure 1). Results remained significant after correction for sleep medication use. Significant interactions were found between sex and sleep efficiency, WASO and sleep fragmentation (Table 2, Figure 2). Stratified analyses showed that, among females, lower sleep efficiency (p = 0.003), higher WASO and higher fragmentation were significantly associated with lower CTh (p<0.001), without any significant associations among males.ConclusionsIn CU, higher sleep fragmentation is associated with reduced cortical thickness in areas vulnerable to early AD‐related neurodegeneration. Importantly, in females, lower sleep efficiency, as well as higher WASO and sleep fragmentation are associated with lower integrity in AD‐vulnerable regions. These results suggest that females in the preclinical stages of AD are more vulnerable to the effects of sleep fragmentation.
Strategy for Creating Evidence‐based Educational Programs
Authors: Stratton Lauren 
Published: December 2023

AbstractBackgroundTo address the challenges of caregiving, the Alzheimer’s Association offers a range of educational programs, both in‐person and virtual, on a variety of topics, including understanding Alzheimer’s disease and related dementias, communication and dementia‐related behaviors, and financial literacy. The Association has a concerted effort to offer programs that meet the needs of their constituents, while also ensuring the programs are evidence‐based. The Association has developed a strategy for proving the evidence‐base of their educational programs and are systematically conducting studies on these programs.MethodThis strategy includes creating an academic collaboration with an expert researcher in the field. Additionally, collaborations are created with community partners to aid with recruitment and implementation. Recruitment is another important aspect of the strategy that must be individualized depending on the program; however we have the benefit of using our caregiving network. The methodology also is thought through carefully, including the program ‘dose’, outcomes, and the inclusion of data collection periods.ResultAdditionally, in the process of the creation and evaluation of a program, it is important to consider the generalizability and application of the program, which must then be integrated into the research design. For the Association, this approach includes developing programs that are scalable and accessible, including multiple modes of delivery, engaging diverse and underserved communities, creating Spanish versions, including all types of caregivers (including both dementia and non‐dementia caregivers). To accomplish this, caregivers are engaged throughout the entire process and the Association’s chapter network of 70 local chapters is utilized on the ground‐level to recruit and disseminate the program through community educators and community partnerships.ConclusionOverall, during this session, the strategy behind building an evidence‐base for educational programs will be discussed in‐depth and we will examine the balance that is needed to fill the need within the target population and community, ensure the program is interactive and engaging, and create a scientifically‐sound methodology.
Success and Challenges of Evaluation and Research within the Alzheimer’s Association
Authors: Clifford Kristen 
Published: December 2023

AbstractBackgroundCaregivers of people living with dementia often experience increased stress, depression, and isolation during their caregiving journey. The Alzheimer’s Association offers the live, 24/7 helpline, which provides support, resources, and information by trained staff to help offset the struggles caregivers experience. Also through the helpline, care consultations are provided, which aim to help caregivers navigate through difficult times and decisions associated with the disease.MethodTo better understand the impact of care consultations, randomized control studies were designed to be implemented in a live call center, which presented both challenges and successes.ResultA research team was established and protocols put in place to effectively manage randomization, pre‐survey, intervention, and post‐surveys.ConclusionThis presentation will discuss challenges and successes of conducting research in a live call center, as well as implications for further research.
Moderating effects of physical activity on the relationship between arterial stiffness and amyloid deposition in cognitively unimpaired older adults
Authors: Kim Geon Ha , Kim Bori.R. , Jeong Jee Hyang 
Published: December 2023

AbstractBackgroundArterial stiffness is linked to age and cardiovascular risk factors and is associated with cognitive decline and dementia in older adults. The moderating effects of physical activity (PA) on the relationship between arterial stiffness and amyloid deposition have not been established. This study investigates this interaction effect.Methods94 cognitively unimpaired older adults underwent cognitive function tests, brain MRI, and 18F‐florbetaben (FBB) PET to quantify amyloid deposition. Arterial stiffness was measured by brachial‐ankle pulse wave velocity (baPWV). PA was assessed using the International Physical Activity Questionnaire. Participants were divided into tertiles by MET‐hour/week values, and the correlation between baPWV and amyloid deposition was compared in the lowest and highest PA groups.ResultsParticipants were mostly female (76.6%) with a mean age of 72.5 and 10.6 years of education. There was a significant positive correlation between baPWV and amyloid deposition (r = 0.3, P = 0.04). In the lowest PA group, there was a significant positive correlation between baPWV and amyloid deposition (r = 0.48, P = 0.037), but not in the highest PA group (r = 0.11, P = 0.61).ConclusionPA has a moderating effect on the relationship between arterial stiffness and amyloid deposition, suggesting that higher PA may attenuate this link.
The role and mechanism of TPK‐SENP1 signaling axis in regulating Aβ deposition in Alzheimer’s disease
Authors: Zeng Yeting , Xu Yangqi , Zhong Chunjiu 
Published: December 2023

AbstractBackgroundNumerous studies have demonstrated that SUMOylation plays an important role in the development of Alzheimer’s disease (AD). However, there has been no research on how key neural signals regulate the dynamic balance of target SUMOylation/deSUMOylation in AD. Therefore, further investigation is needed to explore important SUMOylation/deSUMOylation homeostatic regulatory targets and their mechanisms in AD.MethodAlterations in neurons, glia, and apoptosis were evaluated using immunofluorescence staining. The expression of related proteins was investigated using western blotting. Aβ40 and Aβ42 levels were measured using ELISA. An AAV carrying the Syn‐eGFP‐SENP1 construct was injected into the ventricles of mice. Behavioral assessments, including the Y maze and Rotarod tests, were performed to evaluate cognitive and motor function.ResultOur findings indicate that the expression of thiamine pyrophosphokinase (TPK) is significantly diminished in the brains of AD patients. The conditional ablation of TPK in the brains of adult mice results in the emergence of a range of AD‐like pathological features. Additionally, we observed a significant decrease in the expression of SUMO‐specific protease 1 (SENP1), suggesting that TPK may play a role in regulating SENP1 expression. The overexpression of SENP1 was able to ameliorate the AD‐like pathological features observed in TPK knockout mice. Furthermore, we found that levels of APP, BACE1, and Aβ were elevated in SENP1flox/flox; Camk2α‐Cre mice relative to control mice, providing further evidence for the critical role of SENP1 in AD pathogenesis.ConclusionModulation of SENP1 expression by TPK may regulate pathological features associated with AD, suggesting that SENP1 may be an important target for the development of AD drugs.
Neuronal targeting of tau using a mRNA‐encoded tau‐specific antibody fragment
Authors: Wongsodirdjo Patricia , Caruso Alayna C , Vella Laura J , Hung Ya Hui , Götz Jürgen , Nisbet Rebecca M 
Published: December 2023

AbstractBackgroundA promising target for the treatment of Alzheimer’s disease and related tauopathies is intraneuronal tau. We have generated conventional tau‐specific monoclonal antibodies, as well as engineered antibody fragments, and demonstrated their ability to reduce tau pathology in the brains of tau transgenic mice (Nisbet et al., Brain 2017, Bajracharya, Brici et al., ANC 2021, Bajracharya et al. JCR 2022). Therapeutic efficacy is limited, however, by the inability of these antibodies to readily cross the blood‐brain barrier (BBB) and neuronal membrane to target intraneuronal tau. The SARS‐CoV‐2 pandemic revealed the potential of mRNA technology as an accessible and affordable strategy for delivering exogenous proteins, such as antibodies, to cells. The aim of this study was to explore the potential of utilizing mRNA to improve the intraneuronal delivery of our lead‐candidate tau‐specific monoclonal antibody in a single chain variable fragment (scFv) format.MethodThe cDNA encoding the tau scFv was cloned into an expression plasmid with a T7 promotor. The plasmid DNA was linearized, and in vitro transcription was conducted. The resulting mRNA was capped at the 5’ end with anti‐reverse cap analogue (ARCA), and possessed a 3’ poly (A) tail. The mRNA was then loaded into synthetic and biological nanoparticles and cellular uptake of the encapsulated mRNA and expression of the scFv was determined using mouse primary hippocampal neurons and human neuroblastoma SH‐SY5Y cells. Finally, binding of the expressed scFv to cytoplasmic tau was determined using a GFP‐pulldown assay.ResultHighly‐pure synthetic mRNA encoding a tau scFv was successfully generated and encapsulated into synthetic and biological nanocarriers. Upon treatment of cells with the encapsulated mRNA in vitro, the tau scFv was expressed and capable of engaging intracellular tau.ConclusionCollectively, our results validate the use of mRNA encoding tau‐specific antibodies as an effective and economic alternative to conventional antibodies for specific targeting of intracellular antigens such as tau.
Regulation of pro‐inflammatory cytokine release by purinergic signalling in a human monocyte‐derived microglial model
Authors: Cowley Jamie , Harrison Neale , Morano Ines , Chan Hujo , Li Zhi , Pegg Ashley , Corsi‐Zuelli Fabiana , Jinks Elizabeth , Ali Haleema , Stevens Andrew , Belli Antonio , Upthegrove Rachel , Brady Catherine , Gordon John , Qureshi Omar , Barnes Nicholas 
Published: December 2023

AbstractBackgroundNeuroinflammation is generally accepted as a major feature of Alzheimer’s disease (AD) with genetic evidence linking ‘myeloid’ associated genes (e.g. TREM2, CD33, ABCA7 and CR1) with AD risk and supporting a role for microglia (and infiltrating monocytes) in mediating pathology. The excitatory P2×7 receptor, expressed by microglia in the brain, upon activation by pathological concentrations of ATP drives a pro‐neuroinflammatory response primarily through the release of IL‐1β and IL‐18. In contrast P2Y receptor signaling has been associated with anti‐inflammatory effects such as reduction in TNFa release. The present study investigated the role of purinergic signalling in the modulation of cytokine release from human microglia derived from monocytes (iMDM).MethodHuman microglia (iMDM) were differentiated from human peripheral blood monocytes by culture in a cocktail of CNS‐associated cytokines over 5‐10 days. The immuno‐phenotype of the iMDM versus the originating monocytes were assessed by immuno‐cytochemistry. iMDM were primed with LPS before stimulation of purinergic receptors with selected agonists and antagonists to investigate cytokine release. Findings were extended using human brain slices.ResultiMDM displayed an upregulation of microglial phenotypic markers (e.g. TMEM119, IBA1, CX3CR1, P2YR12 and TREM‐2). Following priming of iMDM with LPS, the P2×7 receptor agonist, BzATP, evoked a concentration‐dependent release of pro‐inflammatory cytokines (including IL‐1α, IL‐1β and IL‐18) that was prevented in a concentration‐dependent manner by P2×7 receptor antagonists and NLRP3 inhibitors. Although the P2×7 receptor was the major driver of IL‐1β release, TNFa release (evoked by LPS) and sensitivity to NLRP3 inhibitors, was modulated by purinergic agonists suggestive of a role for P2Y receptors in this system. The importance of P2×7‐receptor in mediating IL‐1β release was further confirmed by the use of human brain slices.ConclusionModulation of purinergic signalling has the potential to regulate neuroinflammation and the ability of P2×7 receptor antagonists to suppress a pro‐inflammatory response by microglia suggests this pharmacological action may offer benefit to patients with AD.