bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hemodynamic Response Biomarkers for Aging Brain Health: Bogalusa Heart Study
Authors: Chuang Kai‐Cheng , Ramakrishnapillai Sreekrishna , Madden Kaitlyn , Amant Julia St , McKlveen Kevin , Gwizdala Kathryn L. , Dhullipudi Ramasudhakar , Bazzano Lydia , Carmichael Owen T. 
Published: December 2023

AbstractBackgroundIn functional magnetic resonance imaging (fMRI), a hemodynamic response function describes how neuron firing events are translated into a blood oxygenation response that is detected through imaging. The HRF varies between individuals and between brain regions, and its characteristics are believed to be valuable biomarkers of neurovascular aspects of brain health. However, the impact of cardiovascular risks on HRF characteristics among diverse cognitively healthy middle aged and older adults is not well studied.Method137 Bogalusa Heart Study participants performed a Stroop task during fMRI (Table.1). The HRFs of each participant within eight regions of interest (ROIs) previously identified as activated by this task [1] were calculated using a deep learning method. Each HRF was characterized by four main parameters (Figure 1): time to peak (TTP), peak magnitude (PM), trough magnitude (TM), and area under the HRF curve (AUHRF). Linear regression models related HRF parameters to demographic, cardiometabolic, and cognitive measures.ResultTable 2 shows the associations between demographic, cardiometabolic, and cognitive measures and HRF parameters. Younger age was associated with lower AUHRF in the inferior frontal gyrus (p‐value = 0.052). Whites (compared to African Americans) had lower PM in the angular gyrus and lower AUHRF in the anterior insula (maximum p‐value = 0.022). Better systolic blood pressure and diastolic blood pressure were associated with shorter TTP in the angular gyrus and cerebellum (maximum p‐value = 0.029). APOE 3‐3 genotype and better BMI were associated with shorter TTP in the middle frontal gyrus and fusiform gyrus (maximum p‐value = 0.025). Better white matter hyperintensity volume was associated with lower PM and TM in the anterior insula and cerebellum (maximum p‐value = 0.032). Better digit span backwards score, digit coding score, vocabulary score, and word reading score were associated with shorter TTP and lower AUHRF in the angular gyrus, middle frontal gyrus, and/or inferior frontal gyrus (maximum p‐value = 0.038).ConclusionIn a diverse, cognitively healthy, middle‐aged community sample, HRF parameters tracked closely with recognized indicators of brain health. Overall, lower TTP, PM, TM, and AUHRF represent better brain health, as there is no delay and alteration in neural‐vascular coupling unit. References: [1] Sheu, L. K. et al. (2012). Psychophysiology.
Age‐ and sex‐dependent differences in cognitive decline in rat models of Alzheimer’s disease
Authors: Myers Sarah J , Roseborough Austyn D , Allman Brian L , Whitehead Shawn N 
Published: December 2023

AbstractBackgroundMemory loss has been a central focus of Alzheimer’s disease (AD) research but executive dysfunction may be one of the earliest indicators of AD (Baudic et al., 2006). Executive function refers to a group of cognitive processes that are required for goal directed behaviours, such as working memory and cognitive flexibility. Amyloid‐β (Aβ) plaques and neurofibrillary tangles are considered the pathological hallmarks of AD, but evidence suggests that these are not the earliest pathologies to appear in the AD brain (Sperling et al., 2011). This highlights the importance of assessing both the prodromal and more advanced phases of AD in preclinical modelling. This study aimed to characterize age‐ and sex‐related changes in executive function, learning, and memory across normal aging in rats as well as in two aging transgenic rat strains of AD: TgAPP21 (Aβ plaque‐negative) and TgAPP/PS1 (Aβ plaque‐positive).MethodMale and female wildtype Fischer 344, TgAPP21, and TgAPP/PS1 rats were used in this study. The TgAPP21 rat overexpresses the mutant human amyloid precursor protein but does not spontaneously develop Aβ plaques, serving as an important model of prodromal AD. The TgAPP/PS1 rat overexpresses mutant human forms of both the amyloid precursor protein and Presenilin‐1 and does develop age‐dependent Aβ plaques. These strains allowed us to assess cognition under three conditions (i) normal aging, (ii) increased Aβ without plaque deposition, and (iii) age‐dependent Aβ plaque deposition. At 3, 9, or 15 months of age the rats were tested for spatial learning and memory, working memory, and cognitive flexibility using the Morris water maze, the 8‐arm radial water maze, and a T‐maze set‐shifting task.ResultAge‐dependent cognitive decline was observed across all genotypes but was exacerbated in both transgenic models. Effects of age, sex, and genotype varied across the cognitive tasks, emphasizing the importance of assessing multiple cognitive domains.ConclusionThese findings expand our understanding of the roles of sex, age and Aβ plaque‐positive/negative environments in cognitive decline in preclinical rat strains of AD. Overall, this work supports further investigation into the pathologies driving these cognitive changes and potential biomarkers for earlier detection.
Clinical Factors Associated with Cognitive Impairment and Dementia Among Patients Experiencing Homelessness
Authors: Dobbins Sarah K , Chodos Anna H 
Published: December 2023

AbstractBackgroundThe population of people experiencing homelessness (PEH) is aging; Half of PEH are now 50 years old or older. Cognitive impairment among PEH is thought to occur earlier, at higher prevalence, and progress faster than in the general population. Homelessness and associated marginalized conditions pose substantial barriers to care of people with cognitive impairment or dementia.MethodWe examined the prevalence of cognitive impairment, dementia, and clinical factors associated with these diagnoses among PEH seen between 7/1/2019‐5/31/2022 in a San Francisco safety net clinic. Medical record data for those who accessed services targeting homeless adults was retained for analysis. We analyzed the data using chi‐squared, T‐tests, and adjusted regression on select variables.ResultAmong 8,387 adults who experienced homelessness, 326 (3.9%) had a diagnosis indicating cognitive impairment or dementia. Of these, the majority (303, 92.9%) had non‐specific diagnoses, such as “cognitive impairment” (207, 2.5%), problems with “cognitive function” (19, 0.2%), or “memory issues” (77, 0.9%). 114 had specific diagnoses such as dementia (74, 0.9%), Alzheimer’s (6, 0.1%), or neurocognitive disorder (34, 0.4%). Some diagnoses overlapped (e.g. “cognitive impairment” and “dementia” were coded for one patient.) More of those with dementia or cognitive impairment had HIV, diabetes, hypertension, depression and/or anxiety, alcohol‐use disorder, and prior TBI. Those with dementia/cognitive impairment were more likely to be male and older (Table 1). More of those with dementia/cognitive impairment were white, Black, or Asian/Pacific Islander, and fewer were Latinx. Since their last clinical encounter, more of those with dementia/cognitive impairment died. In adjusted regression, the difference in hypertension, depression/anxiety, alcohol use disorder, TBI, gender, and mortality remained significant (p<0.05).ConclusionPrevalence of dementia and cognitive impairment in this patient cohort is lower than has been previously estimated in PEH (4% vs up to 25%). Non‐specific diagnoses were more commonly recorded, suggesting under‐identification and under‐diagnosis in non‐research conditions. Those with dementia or cognitive impairment diagnoses had more chronic disease and psychiatric illness, and higher mortality than those without any diagnosis. Better identification of those with cognitive impairment and dementia among PEH can help define areas of focus in the care of these marginalized individuals.
Dysregulation of UFMylation pathway in Alzheimer’s disease
Authors: Yan Tingxiang , Heckman Michael G. , Murray Melissa E. , Dickson Dennis W. , Springer Wolfdieter , Fiesel Fabienne C 
Published: December 2023

AbstractBackgroundNeuropathologically, Alzheimer’s disease (AD) is characterized by the presence of senile plaques composed of beta‐amyloid (Aβ) and neurofibrillary tangles made of hyperphosphorylated tau. Aβ and p‐tau have been shown to impact endoplasmic reticulum homeostasis, DNA damage response and autophagic functions. Intriguingly, alterations in these systems have also been connected to dysfunctions in UFMylation, a ubiquitin‐like posttranslational modification. Analogous to ubiquitin, UFM1, is conjugated to substrates via a catalytic cascade involving UFM1‐specific set of E1 (UBA5), E2 (UFC1), and a complex that consists of E3 ligase (UFL1), DDRGK1 and CDK5RAP3. UFMylation is reversible, and this is mediated by UFSP2. The UFMylation pathway is essential for brain development as complete loss of function of any of its components result in severe neurodevelopmental disorders. However, alterations in UFMylation and their role in and significance for age‐related AD remains unknown.MethodWe performed Western blot and Meso Scale Discovery based ELISA to measure the protein level of UFM1, UFSP2, tau, p‐tau and other UFMylation pathway components in human post‐mortem brain. Analyses were performed with RIPA‐ and 2% SDS‐soluble fraction from frontal cortex. To validate our finding in human tissues, we knocked out UFM1 and UFSP2 in ReN cells, a neural progenitor cell model that has already been used to study AD and that can be terminally differentiated in neurons.ResultWe found a significant reduction of RIPA UFSP2, but an increase of RIPA and SDS UFM1 in AD compared to controls. Strikingly, RIPA UFSP2 had a strong negative correlation with both RIPA and SDS UFM1. Furthermore. UFM1 was significantly increased in UFSP2‐KO neurons compared to WT, mirroring the negative correlation between UFM1 and UFSP2 observed in human brain. In addition, RIPA and SDS UFM1 had a strong positive correlation with p‐tau, indicating that dysfunctional UFMylation might play an important role for disease pathogenesis.ConclusionReduction of RIPA soluble UFSP2 in human AD frontal cortex might result in the abnormal accumulation of UFM1 and this might further facilitate the AD pathogenesis. Because of its role for several central AD‐relevant pathways, the UFMylation pathway might be a potential therapeutic target for AD.
Improvisation while Aging
Authors: Hainselin Mathieu , Krueger Kristin R , Ben‐David Boaz , Keisari Shoshi 
Published: December 2023

AbstractBackgroundArtistic interventions have potential to fundamentally improve the cognitive, emotional, and social functioning of older adults. Improvisation is based on spontaneous interaction, where individuals co‐create and interact without pre‐planning. While improvisation in cognitive and mental health interventions has become more popular, there is no review to synthesize its impact on older adults.MethodsWe reviewed the literature and summarized the effects of improvisation on the cognitive, emotional, and social well‐being of older adults.ResultsThere is now a substantial body of literature on the emotional and cognitive benefits for adults without dementia. Community‐dwelling older adults (N = 78) that participated in 12 weeks of improv combined with life review techniques demonstrated a decrease in depressive symptoms, and an increase in well‐being and meaning in life (Keisari, Palgi,et al., 2022). Older adults who participated in a 9‐min mirror‐game exercise (N = 34) had improved attentional functioning and positive affect compared to those who attended a physical activity class (Keisari, Feniger‐Schaal, et al., 2022). Two single‐group studies with older adults (N = 15, 45) showed that participation in improvisation yielded significant improvements in social isolation and perceived stress (Lindquist et al., 2021), sense of spontaneity, flow, playfulness (Bassis et al., 2022). One qualitative study suggested that the participants experienced more attentiveness, relaxation, and increased stimulation and communication following improvisation practice (Lindquist et al., 2021). Other qualitative studies showed that improvisation can help build community, increase positivity, sense of comfort and ease with the unexpected, a sense of self‐development and self‐awareness (Morse et al., 2018; Yamamoto, 2020).There is also growing evidence that older adults with dementia benefit from improv interventions. Older adults participating in improvisation interventions have experienced a reduction in depressive symptoms and increase in positive affect (N = 178; Zeisel et al., 2018). One qualitative study showed that improvisation with older adults with early stage dementia have therapeutic benefits such as improvements in learning, sociability, communication and self‐esteem (Stevens, 2012).ConclusionThere is sufficient evidence that improv as an approach to improve thecognitive, emotional, and social well‐being of older adults has strong potential and warrants further study.
Sleep disturbance associated with temporal lobe degeneration in frontotemporal dementia
Authors: Larsen Eva , Jiang Jessica , Monica Ciro Della , Hassanin Hana , Atzori Giuseppe , Dijk Derk‐Jan , Revell Victoria Louise , Eriksson Sofia , Warren Jason D 
Published: December 2023

AbstractBackgroundSleep abnormalities are increasingly recognized as markers and potential drivers of neurodegenerative proteinopathies. However, the sleep phenotype of less common dementias remains poorly characterised. In particular, clinical experience suggests that patients with focal temporal lobe degeneration in the frontotemporal dementia spectrum can experience sometimes striking sleep disruption. We recently had the opportunity to corroborate this clinical impression in a small series of representative patients participating in a larger cohort study.MethodsTo date, we have studied seven patients and three healthy age‐matched controls. The patients’ diagnoses comprise behavioural variant frontotemporal dementia associated with focal right temporal lobe atrophy (n = 3), semantic dementia associated with focal left temporal lobe atrophy (n = 2), young onset Alzheimer’s disease and logopenic aphasia (each n = 1). No participant had a past history of a clinical sleep disorder. Detailed data on sleep patterns, adapted standard sleep questionnaires (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale), overnight oximetry and neuropsychological test scores (covering domains of executive function, emotion processing, memory, and auditory perceptual learning) pre‐/post‐overnight sleep were collected with the assistance of patients’ caregivers.ResultsTwo patients with right temporal lobe atrophy and one with left temporal lobe atrophy had marked sleep fragmentation, in one right temporal case accompanied by frequent sleep attacks, with increased overall time in bed and/or attempting to sleep. Epworth and Pittsburgh indices in these patients indicated significant daytime sleepiness and reduced sleep quality; none had evidence of significant sleep apnoea on overnight oximetry. Comparatively mild clinical sleep disturbances were reported in patients with other dementia diagnoses. However, there was evidence for reduced auditory perceptual learning benefit from overnight sleep relative to healthy older controls, particularly in the patients with underlying Alzheimer pathology.ConclusionsThese preliminary findings suggest that focal temporal lobe degeneration may be associated with clinically relevant sleep disruption, as part of the more pervasive derangement of homeostasis in these syndromes. Further work is indicated to define the hypnic phenotype in detail, with sleep electrophysiology and correlative behavioural, neuroimaging and laboratory data in larger patient cohorts.
Impact of COVID‐19 in cognitively unimpaired individuals and dementia caregivers from the Peruvian Alzheimer Disease Initiative (PeADI)
Authors: Illanes‐Manrique Maryenela , Mena Pedro R. , Cubas‐Montecino Diana , Adams Larry D. , Sarapura‐Castro Elison , Castro‐Suarez Sheila , Rios‐Pinto Julia , Mejía Koni K. , Medina‐Colque Angel , Beecham Gary W. , Cornejo‐Herrera Ivan , Vance Jeffery M. , Ochoa‐Valle Edward , Cuccaro Michael L. , Cornejo‐Olivas Mario , Pericak‐Vance Margaret A. 
Published: December 2023

AbstractBackgroundThe COVID‐19 pandemic has profoundly affected people’s lives worldwide. Stress and social restriction have a negative physical and psychological effect on people with dementia and their caregivers. Peru was one of the countries that experienced social restrictions and high rates of COVID‐19 morbidity and mortality.MethodsWe assessed the NIA‐NIH COVID‐19 impact survey for unrelated cognitively unimpaired (CU) individuals and caregivers from the PeADI cohort (case‐control genetic study for Alzheimer’s disease and related dementias) from five different regions across Peru.ResultsWe analyzed 249 COVID‐19 impact surveys,65 dementia patient caregivers and 184 older CU individuals. Among caregivers,86% felt isolated and 55.3% less connected with friends and family. 87.6% felt disrupted in everyday life, and 83% could not control the important things in their life. 44.6% found more difficult to provide care. The limitations on care include:physician appointments 64.6%,respite by family or friends 36.9%,day activity programs 32.35%, and overnight or extended‐stay respite care 16.9%. About 61.5% of them significantly reduced their household income. Almost 51% negatively changed their willingness to participate in clinical research if it required in‐person visits. Among the 184 CU individuals (mean age: 69.5± 3.8 years; 58.2% women). About 40.2% had new or worsening symptoms while thinking they had COVID‐19.About 60% were tested for Covid‐19 at least once, 29.3% were diagnosed with COVID‐19, and 2.1% were hospitalized. About 70% felt worried about getting or being reinfected by COVID‐19, 68.5% felt isolated from family and friends, 84.2% felt disrupted daily life, and 68.4% felt unable to control the important things in their life. About 60% had significantly reduced household income.About 52% of the CU noticed health changes (memory and thinking 31.2%, depression 42.7%, anxiety 51%, or behavior 46.8%).About 58% changed their willingness to participate in clinical research if it required in‐person visits.ConclusionsOur results suggest that the COVID‐19 pandemic has affected dementia patient caregivers and CU individuals, both experienced variable changes in their mental health and significantly reduced household income.Caregivers have significant concerns regarding limited access to healthcare for their patients.CU individuals experienced fear of COVID‐19 reinfection.Further longitudinal surveys are required to explore changes in neuropsychiatric symptoms over time.
ABCA7 Mutations Can Present as Behavioral Variant Frontotemporal Dementia Without Amyloid Pathology
Authors: Snyder Allison , Shatz Rhonna 
Published: December 2023

AbstractBackground
ABCA7 was identified as an Alzheimer’s disease (AD) risk gene in 2011 through GWAS studies and subsequently its role in pathogenesis was confirmed via in‐vivo studies demonstrating loss of ABCA7 was sufficient to the trigger amyloid cascade. The most common presentation of ABCA7 loss of function mutations is an amnestic syndrome, however it less commonly can present with behavioral or motor symptoms. While the described clinical presentation can vary, almost all cases have been associated with AD pathology. Here we present three cases of bvFTD clinical syndromes in ABCA7 mutations carriers without evidence of AD pathology.MethodPatients underwent a comprehensive clinical assessment including neurological history, examination, neuropsychological testing, MR brain imaging, and lumbar puncture. AD biomarkers were assessed through CSF testing. Genetic testing was obtained through CLIA certified whole genome sequencing.ResultWe identified three individuals with mutations in ABCA7. Two of these individuals harbor the p.I1878M mutation and one with the p.W1214* mutation on genetic testing. They presented with behavioral variant frontotemporal dementia with no evidence of amyloid pathology on CSF biomarker testing.ConclusionWe present three cases of symptomatic ABCA7 mutation carriers without evidence of underlying AD pathology. The exact function of ABCA7 is unknown, however its purported involvement in lipid transport and immune responses are common pathways in neurodegenerative disease and raises the possibility of converging disease cascades.
The Performance of Memory Scales for Predicting Alzheimer’s Disease Biomarkers in Amnestic Mild Cognitive Impairment Patients
Authors: Sarutikriangkri Yuthachai , Hiransuthikul Akarin , Booncharoen Kittithatch , Thanapornsangsuth Poosanu , Tangnimitchoke Suchart , Likitjaroen Yuttachai 
Published: December 2023

AbstractBackgroundAnti‐amyloid‐β therapies have been approved to treat mild Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI) due to AD. Therefore, diagnosis of AD pathologies is crucial for selecting patients for treatment. Positron emission topography (PET) is used to detect biomarkers for β‐amyloid (A) and tau (T). However, the availability of PET is still limited. Neuropsychological tests may help to select patients who are likely to have AD pathologies. This study aims to select a scale with high performance for AD biomarkers in aMCI patients.MethodParticipants with aMCI were recruited from the Memory Clinic at King Chulalongkorn Memorial Hospital. PET was used to detect AD biomarkers. The Wechsler Memory Scale, Fourth Edition (WMS‐IV) and the Montreal Cognitive Assessment (MoCA) were carried out. We selected four scales which are frequently used to assess AD patients including Visual Reproduction (VR), Logical Memory (LM), and Verbal Paired Associates (VPA) from the WMS‐IV and the Memory Index Scale (MIS) from the MoCA to analyze as predictors. Patients with A+T+ were defined as aMCI with AD biomarkers (aMCI‐AD). Patients with A+T‐ and A‐T‐ were defined as aMCI with non‐pathophysiology of AD (aMCI‐npAD). Multivariable logistic regression was used to construct the predictive model. Area under receiver operating characteristic curve (AUROC) was used to identify the best model in predicting A+T+.ResultAmong 35 participants enrolled (18 aMCI‐AD and 17 aMCI‐npAD), 25 (71.4%) were female. The mean age and education were 71.3±8.1 and 13.8±4.4 years, respectively. The predictive model using LM demonstrated the highest AUROC of 0.84 (95%CI 0.70–0.93), with a sensitivity, specificity, positive predictive value, and negative predictive value of 0.83, 0.71, 0.75, and 0.80, respectively, at the cut‐point with highest accuracy of 77.1%; followed by VR (AUROC 0.78; 95%CI 0.61–0.95), MIS (0.74; 95%CI 0.57–0.91), and VPA (0.68; 95%CI 0.50–0.87).ConclusionLM has the highest performance for AD pathologies among the 4 scales to predict AD biomarkers in aMCI. We propose that before undergoing PET, LM may be an appropriate test for selected aMCI patients with a high chance of having AD pathologies.