bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival and anti‐psychotic treatment in young onset Alzheimer’s disease
Authors: Stefanova Elka , Stojkovic Tanja , Stojmenovic Gorana Mandic , Šarčević Maksim , Obradovic Dragan , Kostic Vladimir S 
Published: December 2023

AbstractIntroductionPsychosis and agitation represent a major therapeutic problem in young onset Alzheimer’s disease (YOAD), given that these symptoms pose a great risk to the patient, but treatment options are limited. Anti‐psychotic use is connected to different side effects, but increased mortality noted in older demented population is particularly worrying. Since YOAD patients are younger we wanted to examine if anti‐psychotic use is connected to decreased survival in these patients as well.AimTo examine the association between the use of anti‐psychotics and the length of survival in YOAD.Material and methodsThis is a retrospective study on 135 patients from Memory Center of Neurology Clinic, Clinical Center of Serbia, with clinical diagnosis of YOAD. We included outpatients that had first visit to our clinic from 01.04.2012. do 01.04.2017. The need to introduce anti‐psychotics was noted during the follow‐up period and the difference in the survival of patients who at some point during the observation (from inclusion in the register until 2019) received anti‐psychotic therapy and those who did not. In this analysis we used Kaplan Meier survival analysis with log rank test with the time from the onset of symptoms to the outcome as an independent variable. Outcome was survived/died (at 2019.) and dependent variable was whether or not the patient received anti‐psychotics.ResultsDuring the period covered by this analysis, ending in 2019, among patients who received anti‐psychotics, 42 patients died while 20 remained alive. In patients who did not receive anti‐psychotics, 47 patients died while 26 remained alive. There was no statistically significant difference between the number of deaths in the group of patients who were and were not treated with anti‐psychotics (p = 0.682). Kaplan Meier analysis showed that the use of anti‐psychotics (at any point during observation) did not significantly affected survival measured as the time elapsed from the onset of symptoms to the outcome (death or 2019).ConclusionThe use of anti‐psychotics in patients with YOAD is not associated with reduced lifespan.
Sleep‐Disordered Breathing and Cognition in a Diverse Population
Authors: Peltz Carrie , Bahorik Amber L , Leng Yue , Redline Susan , O'Bryant Sid E. , Yaffe Kristine 
Published: December 2023

AbstractBackgroundSleep‐disordered breathing (SDB) in older adults is associated with worse cognitive performance and dementia risk. Few studies have examined the relationship between SDB and cognition in a diverse population.MethodsWe studied 654 non‐demented participants from the Health and Aging Brain Study‐Health Disparities (HABS‐HD)‐Dormir study, with an in‐home sleep apnea assessment, a peripheral arterial tonometry‐based system (WatchPAT‐200). SDB measurements included: the respiratory event index (REI; 3% desaturation threshold) and the oxygen desaturation index (ODI; 4% threshold), split into mild (<15 events/hour) and moderate/severe (≥15 events/hour) and assessed by REM, non‐REM, and total sleep (via WatchPat algorithm). We examined three cognitive domains, defining worse cognition as negative standardized z‐scores on the Mini‐Mental Status Exam (MMSE; general cognition); the long‐delay Logical Memory and Spanish‐English Verbal Learning Test (memory); and Trails Making Test‐B and Digit Symbol Substitution (executive function). Regression analyses determined the association between SDB and cognition, adjusting for age, race, sex, education, diabetes, and hypertension.ResultsParticipants were 42.7% Non‐Hispanic White, 35.4% Mexican‐American, and 21.9% Black, averaging 66.6 (sd = 8.2) years; 65.2% were female. The average sleep duration was 6.7 (sd = 1.3) hours; 50.4% had moderate/severe REI and 24.7% had moderate/severe ODI. Compared to mild REI, participants with moderate/severe had a trend towards worse executive function (total‐REI β = ‐0.09 (95% confidence intervals ‐0.20,0.01), p = 0.08). Moderate/severe total‐REI was not associated with global cognition (β = ‐0.02 (‐0.12,0.08), p = 0.75), but moderate/severe REM‐REI was (β = ‐0.11 (‐0.20,‐0.01), p = 0.04). Moderate/severe ODI was also associated with a trend towards worse executive function (total‐ODI β = ‐0.10 (‐0.22,0.01), p = 0.08) and global cognition (total‐ODI β = ‐0.11 (‐0.21,0.01), p = 0.06) compared to mild ODI. The association was greater in non‐REM‐ODI for global cognition (β = ‐0.14 (‐0.26,‐0.02), p = 0.02) and REM‐ODI for executive function (β = ‐0.12 (‐0.22,‐0.02), p = 0.02). There were no associations between REI/ODI and memory, and no interactions with race/ethnicity or APOE4 status. Results were similar after adjusting for body mass index.ConclusionsIn an ethnically and racially diverse population, we found that SDB was prevalent and moderate/severe SDB was associated with lower general cognition and executive function. Future studies should assess the relationship between REM/non‐REM SDB and cognition, and if SDB treatment may reduce dementia risk.
Time Together: An Intergenerational Respite, Mentorship and Training Program
Authors: Greenfield Felicia , Massimo Lauren , Kalafsky Megan , Morgan Brianna , Lynn Alison , Fein Leah 
Published: December 2023

AbstractPeople living with dementia (PLWD) and their care partners (CP) experience physical and emotional stressors that are exacerbated by social isolation. Paying for in‐home respite care can be out of reach for many; the average cost of in‐home care is $28.00 with a three‐hour minimum. Furthermore, there is a critical gap in the dementia workforce (Weiss, 2020), leaving CP without access to affordable respite care, and PLWD without access to social engagement. The Penn Memory Center’s (PMC) Time Together (TT) and Weekly Smile (WS) programs are two low‐cost intergenerational respite and engagement programs that aim to increase social engagement for PLWD, reduce CP burden, and develop a geriatric care workforce. College students are trained to provide respite care and engagement for community‐dwelling PLWD and their CP. Families pay up to $10.00 (sliding scales offered) for up to 10 hours/week of companion/respite care. The student receives $10.00 an hour for their service. The PMC launched Time Together in 2019, delivering respite services in‐person. In 2020, the pandemic forced the program to pivot to a virtual model called WS. In January 2023 we began offering TT both in‐person and virtually to maximize accessibility and flexibility. Both the in‐person and virtual component are now called Time Together (TT).To assess the impact of the WS model we used a mixed‐methods design, using qualitative and quantitative assessments. The exploratory qualitative arm used conventional content analysis methods to describe the experiences of PLWD, CP, and student participants through semi‐structured interviews. In our findings from interviews with 3 PLWD, 3 CP, and 3 student participants, PLWD cited meaningful engagement and improved mood. CPs described the importance of protected time for self‐care. Student respite workers appreciated learning about aging and dementia and especially enjoyed developing empathy and relational practice. Participation was mutually beneficial to all and created a lasting impact.We continue to collect additional qualitative and quantitative to further evaluate findings from both the virtual and in‐person arms of Time Together for this updated abstract submission. Policy implications include recommendations for respite program structure and composition.
Features of internal inconsistency in functional and organic cognitive disorders
Authors: Žunič Nina , Berlot Rok 
Published: December 2023

AbstractBackgroundMemory complaints are common in elderly and have various etiologies, including functional cognitive disorder (FCD). Diagnosis of FCD is supported by clinical evidence of incongruity with a neurodegenerative disorder and/or evidence of internal inconsistency ‐ the ability to perform a task well at certain times, but with impaired ability at other times. The prevalence of features suggesting FCD in organic disorders is unclear. We assessed the presence of clinical features of internal inconsistency and other possible discriminators of FCD from organic causes in patients with mild cognitive impairment (MCI) and subjective cognitive impairment (SCI).MethodPatients attending our tertiary memory clinic in a period of one year with SCI or MCI were included. Exclusion criteria were toxic or metabolic causes of cognitive decline, major psychiatric disorders, co‐morbid neurological conditions that could affect cognition, and uncertainty of diagnosis of organic disorder or FCD. Medical records were reviewed for evidence of internal inconsistency and other suggested discriminators between functional and organic etiology. Demographic, cognitive and clinical data were compared between groups.ResultWe evaluated 39 patients with FCD and 57 with organic disorders. MCI was more common in patients with organic disorders. However, most patients with FCD also had MCI. Patients with FCD were younger and performed better on cognitive assessments, but with significant overlap between groups (Table 1). While patients with FCD more commonly attended the appointment alone and reported greater concern about their symptoms than their supporters, these features were unspecific (Table 2). Patients with FCD reported symptoms that could represent normal experiences and provided detailed descriptions of memory lapses more commonly. While less sensitive, memory perfectionism and symptoms occurring only in specific situations were highly specific for FCD.ConclusionDifferentiation between functional and organic cognitive disorders based on history and examination can be challenging. Features suggesting internal inconsistency and incongruity with neurodegeneration may also appear in organic causes of SCI and MCI. Their varying specificity and sensitivity for FCD need to be taken into account when considering the diagnosis. Improving the identification of FCD could in turn improve identification of patients with prodromal neurodegeneration.
Systemic inflammation induced by LPS promotes insulin signaling disruption leading to Alzheimer‐like changes in wild type mice
Authors: Domańska Justyna , Więckowska‐Gacek Angelika , Wojda Urszula , Mietelska‐Porowska Anna 
Published: December 2023

AbstractBackgroundOne of the hypotheses for the ethiology of sporadic Alzheimer’s disease (AD) focuses on systemic inflammation as a driving force of aging. Another known risk factor of AD is obesity and insulin resistance, known to be associated with the activation of pro‐inflammatory cytokines.The aim of this study was to verify the hypothesis that systemic inflammation induced by lipopolysaccharides (LPS) of Gram‐negative bacteria may disrupt insulin signaling in the brain, leading to the development of neuropathological changes typical of AD. We tested this hypothesis in wild type mice by examining the LPS effect on the initiation and propagation of major neuropathological features of AD, such as amyloid‐β (Aβ) and hyperphosphorylated tau protein (p‐tau) pathologies that start from the entorhinal cortex and progresses to the hippocampus.Method3‐months old male C57BL/6J mice were injected with LPS (0.5 mg/kg) for 3 days. Mice were then analyzed at 4, 8, 12 and 16 months of age for brain markers of: insulin resistance (p‐IRS‐1(Ser616)), p‐tau pathology (p‐tau (Thr231)) and amyloid pathology (APP levels) in the entorhinal cortex and hippocampus.ResultThe results revealed an increase in p‐IRS levels from 4 months of age in both brain structures. In the entorhinal cortex an increase in p‐tau levels was observed in 8‐month‐old mice with no change in APP levels. Conversely, in the hippocampus, a decrease in levels of the full form of APP was observed in the 16‐month‐old group, with no change in p‐tau levels.ConclusionLPS, as an infectious, pro‐inflammatory agent, leads to the development of AD neuropathology. In the absence of genetic alterations typical of AD, LPS induces insulin resistance in the brain, and then leads to an increase in tau phosphorylation in the entorhinal cortex in the early stage of the disease progression, followed by the amyloidopathy in the hippocampus, with a significant delay.National Science Centre, Poland: UMO‐2014/15/D/NZ4/04361.
Assessing head muscles measured with MRI as alternative to estimate muscle mass in older persons with dementia
Authors: Borda Miguel Germán , Westman Eric , Baldera Jonathan Patricio , Duque Gustavo , Skoog Ingmar , Aarsland Dag 
Published: December 2023

AbstractBackgroundCurrent evidence suggests an association between sarcopenia and multiple negative outcomes. Traditional methods to diagnose sarcopenia are based on dual‐energy X‐ray absorptiometry (DXA) and whole body magnetic resonance imaging. These tests are complicated, time‐consuming and expensive. We aim to bring a more accessible way to diagnose sarcopenia, making its detection easier in a neurological and dementia setting where brain MRI are regularly ordered. Therefore, we aim to compare the traditional methods of muscle mass and function vs. muscle quantification using the tongue and the masseter muscle in a standard brain MRI to diagnose sarcopenia in clinical settings.MethodThe H70 study, is a longitudinal study of people born in the Gothenburg area of Sweden aged 70 at baseline. We included 791 participants with available clinical data and MRI. DXA and bioimpedance analyses were used as reference measures. Images were analyzed using 3Dslicer.(figure 1) Adjusted speermarRo coefficients were calculated to assess the correlation between the gold standard (DXA) and the muscle mass of the tongue and masseters.ResultThere was a higher prevalence of women (55,7%). When comparing the different tests to assess muscle mass, we found significant and positive coefficient between both tongue and masseter. Total lean tissue mass (DXA) & Tongue volume (Cm3) Rho = 0,375, total lean tissue mass (DXA) & Total masseter volume (Cm3) Rho = 0,326. < 0.001. (table1,2 Figure 2.)ConclusionThere is a significant positive correlation between total lean tissue mass using DXA and muscle mass calculated with MRI measuring tongue and masseter. Clinical longitudinal Implications of these measurements will be tested in further steps of this research and exposed at the conference.
The role of immunological signaling in disrupted proteostasis in the gut‐brain axis
Authors: Martin‐Peña Alfonso , Lopez‐Scarim Joshua , Gomes Beatriz , Tansey Malu Gámez 
Published: December 2023

AbstractBackgroundThe pathophysiological mechanism underlying the progressive neurodegenerative process in Alzheimer’s disease (AD) is not well understood. Hence, there is no disease‐modifying treatment. It is then imperative to identify the triggering molecular factors of the disease and the mechanisms supporting molecular spreading of toxic assemblies. Our search for these key clues in the periphery is founded on the fact that peripheral dysfunction, particularly in the gastrointestinal (GI) system, can arise decades before the onset of the classic symptoms in neurodegenerative disorders. In fact, the risk of AD increases significantly in patients with inflammatory bowel disease (IBD) when compared with the non‐IBD population. Furthermore, Tau accumulates in Crohn’s Disease guts and in sigmoid colon of AD and FTD patients. Thus, we are investigating the physiological and molecular mechanisms that support Tau spreading in the prodromal stages, particularly, along the gut‐brain axis.MethodTo test whether corrupted proteins expressed in the gut will spread their pathology to the brain, we employed the Gal4/UAS system and expressed wild‐type or mutant human Tau in selected populations of gut epithelium cells. We then monitor behavior on aging flies expressing Tau in the gut epithelium using Drosophila activity monitors and analyzed their circadian patterns of activity along with several sleep parameters.ResultWe observed that flies selectively expressing full‐length‐2N4R human Tau in enteroendocrine cells of the gut exhibited a significant impairment in their daily activity pattern that specifically affected their behavior during the light phase (day) but not during the dark period (night). Interestingly, these flies also showed an increased sleepiness during the day without affecting their nocturnal sleep pattern.ConclusionOur results support the presence of spreading mechanisms for Tau from gut epithelial cells to the brain; hence, affecting the neuronal physiology that sustain daily activity patterns. We are now investigating the pathways and mechanisms that pathological Tau in the gut employs to target these brain regions responsible for the behavioral phenotypes: transsynaptic spreading or humoral signaling via the innate immune system. We are dissecting the 3 major pathways of innate immunity in Drosophila (Imd‐Toll‐TNF) for their role in disease progression and the involvement of their target antimicrobial peptides.
Caspase‐2 Inhibition for Treatment of Alzheimer’s Disease
Authors: Rios Anna M , Chen Claire W. , Jacotot Etienne D , Troy Carol M 
Published: December 2023

AbstractBackgroundThe enzyme caspase‐2 plays a central role in cellular apoptosis and is involved in the early stages of β‐amyloid 42 and tau deposition, making it a promising therapeutic target for Alzheimer’s Disease (AD). Caspase‐2 is highly expressed in the brains of patients with AD (1, 4) and those with mild cognitive impairment, which often precedes AD. This indicates the upregulation of caspase‐2 early in disease progression, which is not observed in healthy adult brains (1‐3).MethodNew irreversible small peptidomimetics (LJ2a and LJ3a) inhibit human caspase‐2 with a remarkably high inactivation rate. (5) In primary hippocampal neurons treated with β‐amyloid oligomers, submicromolar concentrations of LJ2a and LJ3a prevent synapse loss. Using a tamoxifen‐inducible Cre system for the global removal of caspase‐2, a series of experiments were performed on mice stereotaxically injected with β‐amyloid 42. This model was used to validate caspase‐2 blockade by assessing the cellular specificity of caspase‐2 activation, the induction of downstream targets, and cell death marker expression via immunohistochemistry and western blot.ResultReplication of these experiments remains underway.ConclusionPresentation of current data can inform the rationality for using caspase‐2 inhibitors as a therapeutic treatment.
References:1. Jean, Y. Y. et al. Caspase‐2 is essential for c‐Jun transcriptional activation and Bim induction in neuron death. Biochem J 455, 15‐25, https://doi.org/10.1042/BJ20130556 (2013).2. Wang, L., Miura, M., Bergeron, L., Zhu, H. & Yuan, J. Ich‐1, an Ice/ced‐3‐related gene, encodes both positive and negative regulators of programmed cell death. Cell 78, 739‐750 (1994).3. Kumar, S., Kinoshita, M., Noda, M., Copeland, N. G. & Jenkins, N. A. Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans cell death gene ced‐3 and the mammalian IL‐1 beta‐converting enzyme. Genes & development 8, 1613‐1626 (1994).4. Liu, P. et al. A soluble truncated tau species related to cognitive dysfunction is elevated in the brain of cognitively impaired human individuals. Sci Rep 10, 3869, https://doi.org/10.1038/s41598‐020‐60777‐x (2020).5. Bosc, E., Anastasie, J., Soualmia, F. et al. Genuine selective caspase‐2 inhibition with new irreversible small peptidomimetics. Cell Death Dis 13, 959. https://doi.org/10.1038/s41419‐022‐05396‐2 (2022).
Characterization of brain metabolism, volume, and vasculature of the 5xFAD mouse model of Alzheimer’s Disease across lifespan.
Authors: Jullienne Amandine , Szu Jenny , Quan Ryan , Trinh Michelle V , Norouzi Tannoz , Noarbe Brenda P , Silvola Rebecca , Bedwell Amanda A , Eldridge Kierra , Speedy Rachael , Persohn Scott C , Territo Paul R , Obenaus Andre 
Published: December 2023

AbstractBackgroundThe MODEL‐AD Consortium seeks to develop the next generation of Alzheimer’s Disease models based on human data. A popular model of familial AD is the 5xFAD mouse, characterized by early amyloid‐β deposition and cognitive decrements. Despite numerous studies, the 5xFAD mouse has not been comprehensively phenotyped for vascular and metabolic features over its lifespan.MethodMale and female 5xFAD and WT littermates underwent in vivo 18F‐FDG‐PET imaging at 4, 6, and 12 months of age to evaluate regional glucose metabolism. A separate cohort of mice (4, 8, 12 months) underwent “vessel painting” that labels all cerebral vessels with a fluorescent dye. “Vessel painted” brains were analyzed for vascular characteristics such as vessel density, junction density, vessel length, network complexity, number of collaterals and vessel diameter.ResultsOur analyses revealed that vessel length, vessel and junction densities increased from 4 to 12 months on the cortical surface in both 5xFAD and WT mice. The number of collateral vessels between the middle cerebral artery (MCA) and the anterior and posterior cerebral arteries decreased with age but their diameters were significantly increased only in 5xFAD mice. MCA average vessel length was decreased in 5xFAD mice compared to WT. Analysis of 18F‐FDG cortical uptake found significant interactions between WT and 5xFAD mice spanning 4‐12 months of age in retrosplenial, somatosensory and visual cortices. Broadly, 5xFAD males had increased 18F‐FDG uptake at 12 months of age compared to WT mice. In most cortical regions, female 5xFAD mice had reduced FDG uptake compared to WT across the lifespan. In males these metabolic increases coincided with decreased vessel characteristics.ConclusionThe 5xFAD mouse exhibits AD‐like cognitive deficits with age that are associated with increasing amyloid‐β deposition. No significant differences were found in cortical vascular features although males and females exhibited opposite effects in 18F‐FDG uptake. The MCA supplies blood to large portions of the motor cortex and increased vessel lengths and decreased collaterals along with higher metabolic rates in 5xFAD mice may be related to increasing behavioral deficits via metabolic insufficiency or other mechanisms.