bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hippocampal Enlargement and White Matter Hyperintensities in Obstructive Sleep Apnea Patients
Authors: Mula Manasa , Mathew Alex , Das Sandhitsu R. , Nasrallah Ilya M. , Bryan R N , Detre John A. , Benzinger Tammie L.S. , Wolk David A. , Hanlon Alexandra , Lozano Alicia , Moelter Steven , Chi Luqi , Davis Eric M , Cheng Cindy , Bhamidipati Abhinav , Gooneratne Nalaka , Richards Kathy C 
Published: December 2023

AbstractBackgroundObstructive sleep apnea (OSA), which results from recurrent collapses of the upper airway system, affects around 27% of the geriatric population with mild cognitive impairment (MCI) and causes intermittent hypoxia and sleep fragmentation (Mubashir et al., 2019). Prior research suggests that OSA results in brain ischemic preconditioning, causing hippocampal enlargement due to adaptive hippocampal neurogenesis (Rosenzweig et al., 2013). OSA has also been linked to increased white matter hyperintensities (WMHs) through hypoxic‐ ischemic injury, which contribute to cognitive decline in dementias such as Alzheimer’s disease (Zacharias et al., 2021). Previous research necessitates studying the effects of apnea in an elderly population with MCI.MethodIn the Memories2 study, subjects aged 55‐85 underwent a polysomnography and were assigned to the no OSA (OSA‐) group if their apnea‐hypopnea index (AHI) was <5 events/hour or to the OSA (OSA+) group if their AHI was ≥15. Amnestic MCI status was determined with a neuropsychological battery using standard criteria. The subjects received an optional MRI, in which hippocampal and WMH volumetry were derived from a T1‐weighted structural scan and a whole‐brain fluid‐attenuated inversion recovery (FLAIR) scan, respectively. Statistical analyses (two‐sample t‐tests and Wilcoxon‐Mann‐Whitney test) were performed to understand group differences in hippocampal volume and WMH at baseline. Hippocampal volume data (N = 131) was obtained for 67 OSA+ and 64 OSA‐ subjects. WMH data (N = 129) was obtained for 66 OSA+ and 63 OSA‐ subjects.ResultOSA+ subjects had significantly greater right hippocampal volume (p = 0.0374) and left hippocampal volume (0.0336) than the OSA‐ subjects. OSA+ subjects also had higher levels of white matter hyperintensities as compared to the OSA‐ subjects (p = 0.0340) (Table 1).ConclusionIncreased WMH burden is suggestive of hypoxic‐ischemic injury and supports the hypothesis that hippocampal enlargement may be a response to intermittent hypoxia in OSA. These findings reveal the need for early evaluation for sleep apnea. The future direction of this work includes analyzing the group differences adjusting for covariates, detecting and verifying outliers, and rerunning analyses with the complete baseline data. Future data from the Memories2 study will examine the effects of OSA treatment in MCI patients using continuous positive airway pressure (CPAP).
Associations of antipsychotic medication use with mortality, stroke, and myocardial infarction among long‐term nursing home Medicare beneficiaries
Authors: Okhravi Hamid , Fang Fang , Sheehan Brynn E 
Published: December 2023

AbstractBackgroundIn 2005, the Food and Drug Administration issued a black box warning regarding increased mortality and cardiovascular accidents with the off‐label use of antipsychotic medication (APM) in patients with dementia. To improve the quality of care for patients with dementia in nursing homes (NH), in early 2012, the Centers for Medicare & Medicaid Services launched the National Partnership (NP) aimed at combatting the excessive use of APM. Within five years of the partnership, the number of antipsychotic prescriptions in NHs decreased by 34%. The objective of the present study was to examine how APM use has impacted other outcomes, including mortality and major cardiovascular events such as stroke and myocardial infarction (MI) among NH residents with dementia.MethodWe analyzed Medicare data on a sample of 611,773 long‐term NH residents with dementia, aged 50 years and older, from 2011 through 2016. Residents who had received hospice care during the time period were excluded. Cross‐sectional (by year) logistic regressions were conducted to examine the associations of APM use with death, stroke, and MI in the years 2011‐2016. Regression models were adjusted for demographic and co‐morbidity indicators.ResultLogistic regressions (see results in Table 1) revealed that NH residents prescribed APM had a significantly higher probability of death compared to non‐users from 2011 through 2015. However, in 2016, the probability of death was lower among APM users than non‐users, although the association was weak. Additionally, NH residents who were on APM were less likely to have a stroke or MI than non‐users from 2011 through 2016.ConclusionCurrent study findings suggest that APM use is likely associated with a heightened probability of death among long‐term NH residents, which is consistent with previous literature. The finding that APM use is negatively associated with stroke and MI is inconsistent with prevailing understandings that APM use would lead to higher risks of these outcomes. The shift in the likelihood of death in 2016, and negative associations with stroke and MI warrant further investigation as to the possible contributing factors of death and cardiovascular events in NH residents on antipsychotic medications.
Online abridged behavioral neurology training for specialists in Latin America: EduBrainLat
Authors: Escudero Stefanie Danielle Pina , Franco Teresita Ramos , Archila Oscar Robles , Renteria Miguel E. , Ibanez Agustin , Slachevsky Andrea , Yokoyama Jennifer S. 
Published: December 2023

AbstractBackgroundCurrently, dementia training is only offered in a few large medical centers in a handful of Latin America ́s biggest cities. Reduced access and the heterogeneous quality of dementia education for clinicians hinder the diagnosis and treatment of neurodegeneration in Latin America.AimThis project aims to fill the education gaps and increase specialist´s diagnostic and therapeutic skills in neurodegenerative diseases through an interactive online Spanish‐language pilot program tailored for Latin America.MethodsWe put together a 108 hour curriculum formed by four modules: basic aspects of behavioral neurology, neurobehavioral and neuropsychiatric syndromes,treatment, and other aspects of neurodegenerative diseases. It was delivered by 35 brain health experts and reviewers that coolaborate with the Global Brain Health Institute in at the University of California, San Francisco to a pilot group formed by 35 geriatricians, neurologists and psychiatrists from six Latin American Countries (Peru, Mexico, Chile, Colombia, Ecuador, and Venezuela). An initial and final evaluations were performed with the Spanish‐dementia knowledge assessment scale (Carnes et al, 2021), the Frontotemporal Dementia Knowledge Scale (Magrath et al 2021) and clinical cases. In addition, short evaluations submitted by professor were answered before and after each class. Separately, we requested feedback from the students about the course.ResultsComparing the overall scores between the initial and final evaluation, there was a 7% increase in the Geriatrician´s score, 4% in Neurologists´ score and 9% in the Psychiatrist’s score. The greatest increase was in Frontotemporal Dementia Knowledge. (Figures 1 and 2). The topics with the worse baseline scores were clinical evaluation attention, executive functions, and atypical Alzheimer´s Disease. We observed an increase in knowledge after every class. Most of the feedback brought to light that there were many topics that specialists had not had the opportunity to learn before such as sleep in neurodegeneration, traumatic encephalopathy, and atypical dementia syndromes.ConclusionIt is imperative to find ways of bringing education to regions where dementia prevalence is increasing, and specialist do not have enough knowledge. Online programs are feasible and effective strategies to close educational gaps.
Mitigating chronic neuroinflammation in Alzheimer mice by novel immunomodulatory imide drugs (IMiDs) conserves neuroplasticity and cognitive function and also alleviates neurodegeneration‐behavioral impairments in TBI‐challenged mice
Authors: Greig Nigel H , Lecca Daniela , Hsueh Shih Chang , Tweedie David , Scerba Michael T , Hoffer Barry , Wang Jia‐Yi , Sambamurti Kumar , Lahiri Debomoy K. , Kim Dong Seok 
Published: December 2023

AbstractBackgroundNeuroinflammation is an invariable characteristic of chronic neurodegenerative disorders, such as Alzheimer’s disease (AD), and acute ones, epitomized by traumatic brain injury (TBI). However, whether neuroinflammation development drives disease progression or is an epiphenomenon remains unknown.MethodsTo test the hypothesis that, once initiated, AD‐associated chronic neuroinflammation directly drives progressive synaptic/neuronal loss and cognitive decline irrespective of changes in amyloid‐β (Aβ) peptide generation, a new class of immunomodulatory imide drugs (IMiDs) was developed on the backbone of thalidomide/pomalidomide to reduce proinflammatory cytokine generation and resulting inflammation, but lacking action on SALL4 – a key protein implicated in thalidomide teratogenicity. (i) 5xFAD mice, known to develop neuroinflammation consequent to excessive Ab generation, were evaluated over a 4‐month period during which cognitive deficits develop, and (ii) wild type mice subjected to TBI and impacted with motor and cognitive impairments were evaluated to assess whether selective resolution of neuroinflammation by novel IMiDs could mitigate behavioral declines.ResultsPomalidomide (Pom) and the more potent novel analog, 3,6’‐dithioPom (3,6’‐DP), which does not impact SALL4 levels, were administered to reduce microglial cell activation ‐ as confirmed in primary cortical cultures challenged with Aβ and RAW 264.7 cells challenged with lipopolysaccharide (LPS). 3,6’‐DP, in particular, decreased microglial and astrocyte activation in hippocampus and cerebral cortex of 5xFAD mice. This was accompanied by reductions in synaptic and neuronal cell loss, and behavioral impairment in the absence of changes in Aβ plaque or peptide generation. In TBI challenged mice, 3,6’‐DP, likewise, mitigated neuroinflammation and resulted in reduced neuronal loss and behavioral impairments.ConclusionsAD‐associated chronic neuroinflammation directly drives progressive synaptic/neuronal loss and cognitive decline. Pharmacologically mitigating microglial/astrocyte activation without altering Aβ generation provides a means to mitigate AD‐associated cognitive/behavioral impairments, and provides a new drug candidate to alleviate other neurodegenerative disorders, such as TBI.
Education, wealth, and survival after dementia diagnosis
Authors: Chen Yi , Crimmins Eileen M. , Zissimopoulos Julie M 
Published: December 2023

AbstractBackgroundThe relationship between socio‐economic status (SES) and length of life after dementia diagnosis may vary by specific aspects of SES. Education and wealth, two widely used measures of SES, may extend life expectancy via greater efficiency of health investment and better access to care. However, according to the cognitive reserve hypothesis, education protects against dementia pathology and thus when dementia symptoms manifest, individuals with higher education have more advanced atrophy, likely shortening their post‐dementia life expectancy. This paper examined education and wealth disparities in 1) timing of dementia diagnosis, 2) length of life after diagnosis, and 3) use of healthcare after diagnosis as a potential mechanism through which education and wealth differentially influence survival.MethodData was extracted from the Health and Retirement Study (HRS) linked to Medicare claims. From claims we identified 2,377 individuals with incident dementia diagnosis between 2000 and 2016 and followed them for up to 18 years. Using Cox proportional hazard models, we estimated relationships between education, household wealth, and mortality, adjusting for demographics, comorbidity, function, and cognition at the time of dementia diagnosis. To test whether SES disparities were driven by healthcare utilization, we ran linear regressions on the number of emergency room (ER) visits, inpatient admissions, and office visits after diagnosis with the same set of predictors.ResultIndividuals with higher education and wealth exhibited less functional and cognitive impairment at dementia diagnosis. The protective effect of higher education on mortality was absorbed by controlling for wealth. In the fully adjusted model, ranking in the top quartile of wealth was associated with a 17% reduction in mortality risk (HR = 0.83, 95% CI: 0.72‐0.96), relative to the bottom quartile. Wealth was not associated with ER visits, hospitalization, or office visits.ConclusionMore intact function and cognition at incident diagnosis did not confer longer survival for the highly educated. In contrast, the most affluent experienced a lower mortality risk, which was unrelated to healthcare utilization. While more research is warranted to understand pathways, these disparities inform opportunities for achieving health equities among persons living with dementia, by targeting at those with limited financial resources.
Characterizing cerebral microhemorrhage associations in dementia subtypes in the UK Biobank
Authors: Haddad Elizabeth , Sheikh‐Bahaei Nasim , Jahanshad Neda 
Published: December 2023

AbstractBackgroundCerebral microbleeds (CMBs) are associated with neurodegenerative diseases (Charidimou, 2011) and have been identified as an adverse amyloid‐related imaging abnormality event (ARIA‐H) related to amyloid clearing medications (Sperling, 2011). Identifying risk factors for CMBs can help refine inclusion criteria for clinical trials and mitigate the risk of ARIA‐H. CMBs are readily detected on T2*‐GRE MRI sequences, including susceptibility weighted imaging (SWI) – a modality used to detect magnetic field distortions caused by paramagnetic products like iron (Haacke, 2004, Liu, 2017). We explore CMB associations with demographic, disease, and imaging markers in a subset of participants with varying dementia subtypes and complaints in the UK Biobank (Miller, 2016).MethodA total of 75 participants who had clinically diagnosed or self‐reported dementia and SWI imaging were selected; 4 participants were excluded due to extreme motion. We used MARS criteria (Gregoire, 2009) to identify CMBs on SWI and validated our findings using other sequences to exclude CMB ‘mimics’ (Figure 1A). The number, classification, and position of CMBs were recorded. Logistic regressions modeling the outcome of at least one ‘definite’ or ‘total’ (‘definite’ + ‘possible’) CMB were performed and effect sizes were calculated across hippocampal volume, white matter hyperintensity load (WMH), and global WM diffusion MRI (dMRI) microstructural measures.ResultParticipants were predominantly male (65%) with a mean age of 69.8 (± 7.1) years. 9 participants had at least one ‘definite’ CMB and 8 more had at least one ‘possible’ CMB for a ‘total’ of 17 individuals with CMBs. Individuals with CMB(s) were significantly older than those without. CMBs were mostly ‘strictly lobar’ for both definite (78%) and total (71%) classifications (Table 1). The presence of CMBs were found across a spectrum of dementia diagnoses (Figure 1B). Microstructural dMRI measures including global WM FA, MD, and ISOVF were significantly associated with presence of total CMBs (q<0.05) (Figure 2).ConclusionMeasures reflecting WM organization were sensitive to the pathophysiology of CMBs in those with dementia. Future work should investigate whether WM microstructure can predict the development of CMBs in those with dementia, particularly in individuals undergoing amyloid clearing treatments.
[18F]MK6240 and [18F]PI2620 autoradiography on postmortem human brain tissue in AD
Authors: Aliaga Antonio , Therriault Joseph , Socualaya Kely Quispialaya , Aliaga Arturo Aliaga , Hopewell Robert , Tissot Cécile , Rahmouni Nesrine , Macedo Arthur C. , Massarweh Gassan , Pascoal Tharick A. , Soucy Jean‐Paul , Rosa‐Neto Pedro , Zimmer Eduardo R 
Published: December 2023

AbstractBackgroundTo compare the post mortem uptake of [18F]MK6240 and [18F]PI2620 in the brain hemisphere, of A‐T‐ (CN) and A+T+ tissueMethodAutoradiography (ARG) imaging using [18F]MK6240 and [18F]PI2620 was used to assess uptake of CN and AD tissues. One study used sections of whole‐hemisphere of one CN tissue and one AD tissue. The uptake value of [18F]MK6240 was calculated from a regions of interest (ROI) drawn manually from the area of cortex gray matter (GM), cortex white matter (WM), and background (BG).Other study was 24 tissues from the prefrontal cortex (Pfc) (12CN, 12AD), hippocampus (Hip) (12 CN, 12 AD) and cerebellum (Cer) (12 CN, 12 AD) were evaluated with [18F]MK6240, and [18F]PI2620. The uptake value of [18F]MK6240 and [18F]PI2620 was calculated from ROI drawn manually from the area of pfc GM, hip GM and cer GM.ResultThe ARG showed greater [18F]MK6240 uptake in AD than in CN tissue. There were significant differences between CN and AD tissue in terms of cortex gray GM distribution and cortex WM, but no significant differences in BG. These results also, there is no correlation between the specific activity of [18F]MK6240 and the uptake value in CN and AD tissues. In a second experiment, based on our findings there was a significant difference between CN and AD groups when assessed by [18F]MK6240 as well as [18F]PI2620 in the pfc_GM and hip_GM. Furthermore, we found no difference between AD and CN tissues when assessed by [18F]MK6240 and [18F]PI2620 in cerebellum GM. Ratio values Pfc/Cer and Hip/Cer assessed by [18F]MK6240 as well as there were significant differences between CN and AD. [18F]MK6240 and [18F]PI2620 were highly correlated in AD but not in CN brain tissues.ConclusionWe also found that [18F]PI2620 and [18F]MK6240 have similar brain uptake in post‐mortem tissue.
Trajectory of depressive symptoms prior to dementia diagnosis
Authors: Werhane Madeleine L , Shofer Jane , Todd Kaitlin , Crane Paul K , Li Ge 
Published: December 2023

AbstractBackgroundDepression has been repeatedly linked to increased risk for dementia. While there is some research to suggest that an individual’s trajectory of depression symptoms over time may inform dementia risk above and beyond depression symptoms at a single time point, this has yet to be demonstrated in a dataset specifically designed to capture longitudinal brain aging and dementia outcomes.MethodA cohort study of 4,171 community‐dwelling older adults (65+ years) who were enrolled in the Adult Changes in Thought (ACT) study. Participants were initially non‐demented at baseline, and underwent biannual assessment of cognitive status (Cognitive Abilities Screening Instrument, diagnostic consensus) and self‐reported depression symptoms (via 20‐item Centers for Epidemiological Studies‐Depression [CESD]) for up to 24 years. We used Item Response Theory (CESD‐IRT) scores to address limited sensitivity to lower depressive symptom level in the general population and nonlinear measurement properties of the CESD. Diagnosis of dementia was made at consensus meeting based on history and clinical examination.ResultSample characteristics are summarized in Table 1. Linear mixed effects modeling, adjusted for covariates (age, sex, education, race), revealed that there was greater increase of depressive symptoms prior to diagnosis of dementia compared to those who did not receive diagnosis of dementia at end of study (p<.0001). This finding was consistent when depression symptom trajectories were estimated using CESD‐20 raw vs. CES‐IRT scores (Fig. 1 & 2, respectively). The difference in depression symptom trajectories by dementia outcome did not differ as a function of sex. Significant differences (p<0.001) in mean depression symptom total scores were observed by dementia outcome as early as 10 years prior to diagnosis/censoring for both the CESD‐20 raw score (1.0 ± 0.2) and the CESD‐IRT scores (0.16 ± 0.03).ConclusionThe pattern of increasing depression symptoms many years prior to dementia diagnosis reinforces the notion that the association between depressive symptoms and dementia in older adults may be primarily due to a shared common cause, or that depressive symptoms represent an early sign of dementia in the preclinical phase. Changes in specific depressive symptoms prior to dementia diagnosis will also be examined.
Association of sarcopenia with cognitive impairment in older adults in the open population
Authors: Cervantes Maria Elena Alvarez 
Published: December 2023

AbstractBackgroundSarcopenia is a progressive and generalised skeletal muscle condition where there is a loss of muscle mass and function, while cognitive impairment is a clinical syndrome characterised by impairment in different cognitive and neuropsychological domains. Cognitive impairment has been studied as a risk factor for sarcopenia, however, it has not been established whether sarcopenia is a risk factor for cognitive impairment.MethodThis is a secondary analysis of 2,158 adults aged 65 and over assessed within the Dementia Research Group 10/66 protocols. In which grip strength, calf circumference and physical performance were measured to establish a diagnosis of sarcopenia. In addition, they were divided into groups depending on cognitive status.ResultOf all the older adults assessed, those with cognitive impairment or dementia had worse indicators in anthropometric measurements and in sarcopenia‐related measurements.ConclusionIn older Mexican adults, the presence of sarcopenia was not found to be associated with mild cognitive impairment, but was associated with the presence of dementia, even after controlling for other risk factors widely documented in the literature.