bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapidly Progressive Dementias: Case series in a South American hospital
Authors: Santajuliana Franco , Berrios Waleska , Deschle Florencia , Caporale Sofia , Pozo Juan , Marroquin Maria Veronica , Grecco Martin , Ayarza Ana , Povedano Guillermo 
Published: December 2023

AbstractBackgroundRapidly Progressive Dementias‐RPDs include patients with cognitive decline that evolve to dementia or death faster than expected within 1 to 2 years, although typically seen progress during weeks to months in the clinical practice.RPDs constitute 3‐4% of all dementias. It comprises an extensive spectrum of clinical disorders such as immune‐mediated, infectious, metabolic, and prionic diseases, as well as neurodegenerative dementias. So, it remains significant to identify this clinical syndrome and its eventual reversible causes.We report a case series of patients with RPDs that were admitted to our hospital.MethodRetrospective study. We selected patients with RPDs assessed during June 2018 and June 2022. We collected: demographic data, time of evolution, comorbidities, radiological and laboratory findings, treatment and response, and mortality.ResultWe included 19 patients with a median age of 74 years, and 52.6% were female (N = 8). The median time of evolution was 2 months. 26.3% (N = 5) patients had a history of oncological disease and 10.5% (N = 2) of psychiatric disorders. Diagnostic work‐up showed abnormalities: 47.4% on MRI (N = 9; 2 cortical diffusion restriction, 1 global cortical atrophy, 1 meningioma, 1 glioma, 1 hydrocephalus, 3 vascular lesions), 10.5% in the laboratory (N = 2; hypothalamic‐pituitary‐thyroid axis alterations), 21.1% epileptic discharges on electroencephalogram (N = 4). Autoimmune panels in CSF and serum were positive for GAD‐65 in one case amongst 8 patients studied (12.5%). We arrived at an etiology in 52.6% (N = 10) of patients: 1 Creutzfeldt‐Jakob disease, 1 hypothyroidism, 1 steroid‐responsive encephalopathy associated with autoimmune thyroiditis‐SREAT, 1 Hakim‐Adams syndrome, 2 brain tumors, 2 neurodegenerative dementias, 3 vascular dementias). 47.4% (N = 9) patients received treatment with IV methylprednisolone, with a good response in 44.4% (N = 4). Mortality was 36.8% (N = 7).ConclusionIn our case series, we identified 21.1% of patients with potentially reversible etiologies. However, we observed 47.4% of cases without a definitive diagnosis. It could be associated with immune‐mediated entities without a specified antibody at the time of evaluation. We also report a death rate close to that described in the literature.
Target prioritization using human genetics – anchored protein – protein interactions network for Parkinson’s Disease
Authors: Chaurasia Shilpi , Srivastava Gyan P , Xu Dong 
Published: December 2023

AbstractBackgroundAdvancements in genome‐wide association studies (GWAS) have provided pivotal information about genes that are genetically associated to disease conditions. For example, Parkinson’s Disease GWAS studies and GWAS meta‐analysis has provided many candidate genes representing various pathways associated with Parkinson’s Disease, e.g., Lysosomes, mitochondrial dysfunction, Syn‐aggregation, etc. Amongst them, Leucine‐rich repeat kinase 2 (LRRK2) is one of the strongest candidates for PD therapeutic and many compounds targeting LRRK2 are already under clinical trials. To optimize therapeutic effects, protein interactors of LRRK2 could be targeted. We hypothesized that instead of selecting GWAS candidate itself, e.g., LRRK2, exploring a network of interacting proteins to GWAS candidates could give us better understanding of the genetic link to disease biology and hence better targets for therapeutic success.MethodWe created genetically anchored protein‐protein interaction network for Parkinson’s Disease from genes having strong genetic link to PD (seed genes) and all proteins interacting with any of the seed genes. These networks were uploaded and visualized on our in‐house tool – PDNet, a network‐based visual analytics prototype to analyze the network modules and propose candidates for potential therapeutic target prioritization in PD. Published and internally generated gene expression data is used to identify differentially expressed genes that fit in pathways implicated in PD.ResultPathway crosstalk were observed amongst different pathways and hub‐genes were identified that could be potential key drivers of the network in the disease progression and help in understanding the disease pathology. Multiple parameters were computed for the prioritization of the candidate genes, that have the highest score of an indirect genetic link to PD and could be good target for consideration based on other OMICS evidence. The experimental target evaluation of these candidates has narrowed down targets for further screening for drug discovery.ConclusionOur GWAS‐based network analysis framework provides a new way of identifying targets that are genetically involved in the disease but doesn’t show strong signal in GWAS analysis.
Nucleus basalis of Meynert degeneration starts in the earliest stages of Alzheimer’s disease: A deformation‐based morphometry analysis
Authors: Shafiee Neda , Dadar Mahsa , Spreng R. Nathan , Collins D Louis 
Published: December 2023

AbstractBackgroundOne of the earliest pathological events in the course of AD is thought to be the degeneration of cholinergic neurons in the basal forebrain (Grothe et al. 2012). The largest cluster of cholinergic cells within the basal forebrain are found in the Nucleus basalis of Meynert (NbM) (Hampel et al. 2020). Studies show that loss of cholinergic projections due to cholinergic degeneration in NbM, is associated with the decline in cognitive abilities, specifically in memory and attention processing (Mesulam et al. 2013). However, identifying the NbM region on MR images is difficult due to limitations in the resolution and contrast of T1w images.MethodData included the baseline MRI scans of 677 amyloid‐positive subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset from ADNI1, 2, and GO. Scan resolution was increased to 0.5 mm isotropic voxel size by super‐sampling (Manjón et al. 2010) before non‐linear registration to an ADNI‐based unbiased template. The resulting deformation fields were used to compute the Jacobian determinant map for each subject as a proxy for local volume. A voxel‐wise linear regression model analysis was performed on Jacobian maps to assess the pattern of volumetric change within an NbM mask according to diagnosis: DBM ∼ 1+Dx+AGE+Dx:AGE+SEX; where DBM are the Jacobian values for subjects, Dx is the categorical variable for disease stage (NC, eMCI, lMCI, AD) and Dx:AGE is an interaction term between diagnosis and age of each subject.ResultFigure 1 shows the statistically significant differences in local volume, comparing successive disease stages, within the NbM mask, after FDR correction (coronal section, A) NC vs eMCI, B) eMCI vs lMCI, C) lMCI vs AD). As it has been shown here, the Jacobian map (as a proxy for atrophy) becomes more pronounced as the disease advances.ConclusionOur results show that NbM degeneration starts as early as the preliminary stages of mild cognitive impairment, and this change accelerates as the disease progresses. This points to MRI‐based measurements of NbM as potential biomarkers for early AD detection and as a marker of disease burden.
The effect of fasting status on Alzheimer’s disease plasma biomarkers AB40, AB42, GFAP, NfL, CD‐14, and YKL‐40
Authors: Vasquez Erin Livia , Kautz Tiffany F , Kivisäkk Pia , Satizabal Claudia L. , Bernal Rebecca , Seshadri Sudha , Cruchaga Carlos , Yiallourou Stephanie , Gonzales Mitzi M. , Himali Jayandra Jung , Pase Matthew P. 
Published: December 2023

AbstractBackgroundPrior research has shown that Alzheimer’s disease (AD) blood biomarkers may be altered by fasting status, but this is poorly studied.1 For accurate diagnosis, it is essential to have controlled protocols. To examine the effect of fasting on AD biomarkers, we compared levels of amyloid‐beta (AB) 40, AB‐42, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), YKL‐40, and CD‐14 in fasting and non‐fasting samples.MethodMarkVCID consortium2 plasma (n = 10) was used to determine the effect of fasting for AB‐40, AB‐42, GFAP, and NfL using the Quanterix Neuro 4‐plex E kit. Blood samples were collected in the morning and again 2‐hours post‐breakfast.Knight Alzheimer’s disease research center (ADRC) plasma (n = 16) was used to determine the effect of fasting on YKL‐40 (MSD) and CD‐14 (ELISA, R&D system). Blood collections occurred within a 1‐year span.Biomarker results were normalized as required and paired t‐tests or Wilcoxon signed‐rank tests were used to compare values between fasting and non‐fasting results. ICC was used to correlate fasting and non‐fasting results.ResultThere were significant differences between fasting and non‐fasting levels for NfL (p = 0.0137), GFAP (p = 0.0137), and AB42:40 (p = 0.0020), but no significant changes for AB42 (p = 0.4316) and AB40 (p = 0.1815) (Figure 1). Strong correlations between fasting and non‐fasting results were observed for all four biomarkers (ICC = 0.873‐0.964) (Figure 3).There was no significant difference between fasting and non‐fasting concentrations for YKL‐40 (p = 0.86) or CD‐14 (p = 0.43) (Figure 2). There was poor correlations between fasting and non‐fasting YKL‐40 (ICC = 0.472) and CD‐14 (ICC = 0.254) (Figure 3). This was not due to the length of time between the two blood draws (YKL‐40, r2 = 0.067; CD‐14, r2 = 0.024) or the collection time of day (YKL‐40, r2 = 0.076; CD‐14, r2 = 0.001) (Figure 1).ConclusionAlthough significant changes in NfL, GFAP, and AB40:42 were observed, these values correlated well, suggesting that fasting might not alter diagnostic categorization. Additionally, while no significant differences were measured for YKL‐40 or CD‐14, there was poor correlation between fasting and non‐fasting values that were not related to the length of time between the draws or the time the draw occurred. We are working to determine the variable(s) responsible for these results.
TSH levels versus impairment of cognitive and affective domains in older adults: A secondary analysis of MHAS
Authors: Pinilla Thalia , Parra Mauren , Salazar Salomon , Borda Miguel Germán 
Published: December 2023

AbstractBackgroundTSH levels are associated to symptoms such as bradypsychia, bradylalia, hypoprosexia, decreased learning ability, memory impairment and even depressive symptoms, affecting cognitive domains.MethodA secondary analysis of National Study of Health and Aging in Mexico (MHAS) from population interviewed in 2012 with TSH levels (1.948) regarding people with (1287) and without (661) congnitive impairment, in comparison to a follow‐up in 2018 (849 people) based on the same cognitive domains and TSH levels.ResultCognitive impairments were higher in women than men, specially around 60 years. The most affected impairment was no amnesic unidomain. People included have mostly normal thyroid function, but people with worst THS levels, commit more than one cognitive domain.ConclusionTSH levels control reduce the progression of cognitive impairment.
Absence of higher order association based mnemonic percepts in Alzheimer’s disease
Authors: Singh Aditya , Das Nirupam , Kundu Sankhanava , Saha Titli , Jayaprakash Balaji 
Published: December 2023

AbstractBackgroundEveryday learning involves higher order associations (HOA) across new and old experiences when a response is encoded without reinforcement. However, the neural and behavioral mechanisms of HOA‐based learning during remote memory retrieval are unknown.MethodWe implement novel behavior to test the neural and behavioral mechanisms of HOA during remote memory retrieval. We train the animals in context A and sequentially test these animals for remote retrieval in same (A), similar(B), or novel (C) context, while invoking HOA‐based learning to investigate the neural correlates of HOA using hippocampal lesions, chemo genetics, and 2‐photon in vivo imaging.ResultCohorts of AD mice show overall differences in freezing vs. controls (1‐w ANOVA, P>F = 1.48E‐11, n = 5). Subgroups of AD (n = 12) and control (n = 14) mice during remote retrieval in BAC show overall difference (1‐w ANOVA, P>F = 4.59E‐6), with AD mice showing similar freezing in B and A (t = ‐0.70). Freezing in C is different for control mice in ABC vs. BAC order (P>F = 1.84E‐8, n = 5,14) whereas, interestingly, AD mice show similar increase in C freezing on Day3 of remote testing for ABC vs. BAC testing orders (P>F = n.s, n = 5, 12). AD (n = 3) and WT (n = 4) mice were trained with tone and tested after 70 days. Freezing before and during the tone was significantly different for WT mice (1‐t Paired‐sample‐t‐test, P<t = 0.015). Discrimination‐index indicates better discrimination ability for WT as compared to AD mice (1‐t two‐sample‐t‐test, P<t = 0.026). We further evaluate the neural correlates of such behavior in WT mice by timed‐hippocampus lesions, chemogenetic inhibition of PVcre interneurons in dorsal CA1, and longitudinal 2p‐in vivo imaging.ConclusionWe find that PVcre neurons are necessary for HOA during remote learning in WT mice and there is a loss of specificity in HOA‐based new learning during remote memory retrieval with AD mice. Our novel findings establish a basis for early behavioral and neural markers for predicting AD diagnosis to assist with early medical interventions.
Sex differences of cerebrospinal fluid biomarkers in Alzheimer’s disease
Authors: Kanemaru Kazutomi , Kanemaru Akiko , Kurihara Masanori , Hatano Keiko , Ihara Ryoko , Higashihara Mana , Nishina Yasushi , Iwata Atsushi , Saito Yuko , Murayama Shigeo 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is more common in women than in men. Thus, to investigate the sex‐specific mechanism is important to understand the pathogenesis of AD. We examined the sex differences in levels of CSF biomarkers (tau, ptau‐181, Aβ42, HVA and 5HIAA) in AD.MethodThe subjects of this study consisted of clinically diagnosed 386 patients with AD (age 75.9±8.4 years, 237 women and 149 men). The clinical diagnosis was made based on the AD diagnostic criteria (NIA/AA, McKhann GM, et al., Alzheimers Dement 2011; 7: 263‐269). The CSF samples were obtained by lumbar puncture after informed consent was obtained. The levels of CSF tau, ptau‐181 and Aβ42 were measured by ELISA (Fujirebio, Belgium) according to the manufacturer’s protocol. The levels of CSF HVA and 5HIAA were measured by HPLC. We compared the levels of CSF biomarkers between women and men.ResultAge, the levels of CSF tau, ptau‐181 and Aβ42 showed no sex differences. The levels of CSF HVA (ng/ml) were 32.6±19.3 in women and 25.9±14.4 in men. The levels of 5HIAA were 19.1±11.7 in women and 14.8±7.7 in men. The levels of CSF HVA and 5HIAA were significantly higher in women than those in men (t‐test, HVA: p<0.001, 5HIAA: p<0.001).It has been reported that women have higher values of HVA and 5HIAA among normal subjects, due to higher monoamine oxidase (MAO) activity in women. The MAO‐A and MAO‐B genes are located on the X chromosome, and are controlled by XCI (X‐chromosome inactivation). However, the MAO genes may escape XCL MAO‐B has also been reported to be γ‐secretase associated protein and regulate neuronal amyloid β‐peptide levels. Thus, increased MAO‐B activity may be one of the reasons why AD is more common in women.ConclusionBoth CSF levels of HVA and 5HIAA were significantly higher in women in AD, presumably due to increased MAO activity.
Discrimination early Alzheimer’s disease from mild cognitive impairment by using Easy Z‐score Imaging System for ECD SPECT
Authors: Pai Ya‐Tang , Pai Ming‐Chyi 
Published: December 2023

AbstractBackgroundProdromal AD progresses to dementia at a higher annual rate. Since cholinesterase inhibitor benefits early AD patients, discrimination between MCI due to AD and non‐MCI due to AD remains important.MethodWe conducted a retrospective study of MCI cases at National Cheng Kung University Hospital (NCKUH) from 2017 to 2019. Those who showed hypometabolism at posterior cingulate cortex, precuneus, or posterior parietal cortex on brain ECD SPECT and EZIS severity greater than 1.19 were categorized as MCI due to AD; in contrast, patients with EZIS severity lesser than 1.19 were categorized as non‐MCI due to AD. Clinical outcomes included deterioration of CASI, MMSE, SB scores and conversion from MCI to dementia.ResultThere was positive correlation between EZIS severity and deterioration of CASI, MMSE, SB according to multiple regression results, indicating EZIS severity could predict cognitive progression in three years follow‐up. There was no difference in dementia conversion rate between two groups either by chi‐square method or Kaplan‐Meier method, and EZIS severity was not a significant variable in binary logistic regression analysis for conversion. However, there was a trend toward greater dementia conversion rate in the EZIS‐favored MCI due to AD group, and in the second half period of follow‐up as seen on Kaplan‐Meier curves.ConclusionDuring three years of follow‐up, MCI patients with greater EZIS severity were significantly associated with worse cognitive assessment scores, and there was a trend toward greater dementia conversion rate based on cutoff value 1.19 of EZIS severity.
The relationship between physical activity and cognitive functioning in older adults: a cross‐sectional study from the ELSI‐Brazil data
Authors: Rabelo Wendell Lima , da Mata Fabiana A F , Barbosa Matheus Ghossain , Bertola Laiss , Lima‐Costa Maria Fernanda , Ferri Cleusa P 
Published: December 2023

AbstractBackgroundPopulation aging is rapidly taking place in low‐ and middle‐income countries (LMIC) and is contributing to an increased prevalence of chronic conditions, such as dementia. Physical activity (PA) is a well‐known protective factor for cardiovascular conditions and is related to biological processes linked to cognition. Most studies linking PA with cognition come from high income countries. This study explores the relationship between PA and cognitive function in a representative sample of Brazilians aged 50 and above.MethodThis is a secondary analysis of the Brazilian Longitudinal Study of Ageing (ELSI‐Brazil) baseline data. We stratified the level of PA as low, moderate, or high according to the metabolic equivalent of task (MET) spent on different PA over a week. We also considered the level of PA recommended by the World Health Organization (WHO). The domains considered for cognitive function were memory (short‐term memory, episodic and total), and verbal fluency. Logistic regression models were conducted to estimate the relationship between PA and each of the cognitive domains.Result7,994 individuals with complete data were considered for the final sample. They were primarily female (52%), with a mean age of 62.9 years (SD = 9.7), did not live alone (91.5%), and had 5.6 years of schooling (SD = 4.4). Higher levels of PA were related to better cognitive performance in respect of short‐term memory (β = 0.17, CI 95% 0.08‐0.25), total memory (β = 0.14, CI 95% 0.05‐0.22) and global cognition (β = 0.10, CI 95% 0.03‐0.16). The results were in the same direction for the WHO PA recommendations variable.ConclusionThis study shows that different levels of PA, measured in different ways, may have benefits on cognition for older people. These findings can be used to support public health interventions promoting the practice of PA. Longitudinal studies are needed to further clarify this relationship.
Insomnia and Neurocognitive Functioning in Cognitively Healthy Older Adults
Authors: Dixon Bradley J. , Halter Colt M , Woodard John L. 
Published: December 2023

AbstractBackgroundInsomnia is the most common sleep disorder in older adults, affecting the ability to fall and stay asleep for approximately 15‐35% of aging adults (Buysse et al., 2011). Additionally, sleep fragmentation and disordered sleep are well‐established symptoms of Alzheimer’s disease (AD). Patients and their caregivers frequently find these sleep changes distressing; however, the relationship between insomnia and preclinical Alzheimer’s disease remains unclear. The purpose of the present study is to compare performance on neurocognitive measures between cognitively healthy older adults with and without clinician‐determined insomnia to assess whether insomnia acutely impacts cognitive functioning.MethodData were obtained from the National Alzheimer’s Coordinating Center (NACC) database. As part of ongoing data collection, NACC participants completed surveys and underwent a neuropsychological evaluation. Participants who were cognitively healthy at baseline, reported insomnia status, and were at least 65 years of age were included (N = 3,733). Clinicians determined the presence of insomnia (present/absent). A series of Welch’s t‐tests were used to compare insomnia status groups on demographic factors (age, educational attainment, and sex) as well as neurocognitive measures typically related to Alzheimer’s disease (animal and vegetable fluency, letter fluency, Trail‐Making Test, Benson Complex Figure delayed recall, Montreal Cognitive Assessment delayed recall).ResultPreliminary analyses of sample characteristics found evidence that individuals with insomnia were older than those without insomnia (t(784.11) = 2.046, p = 0.041). As expected, clinician‐determined insomnia was more common in men than women (χ2
(1) = 29.638, p < .001). Group comparisons indicated no cross‐sectional relationship between insomnia status and neurocognitive measures (all p >.05, all d ≤ .06).ConclusionDisordered sleep is often seen in Alzheimer’s disease, yet the nature and timing of this relationship are unclear. We found no association between insomnia status and neurocognitive performance in a large, cross‐sectional sample of healthy older adults. It is possible that sleep disturbance is not a preclinical symptom of AD but instead may emerge closer to or following AD diagnosis. Alternatively, the nature of the disordered sleep may not be related to insomnia per se but could reflect difficulty sleeping during the night and remaining awake during the day.
RIP Kinase 1 (RIPK1) modulates disease associated microglial response during demyelination
Authors: Goodwani Sunil , Lightfoot Yaima Luzardo , Ford Bianca Gabrielle , Calderon Olivia , McReynolds Morgan , Allton Kendra , Ma Jiacheng , Botte Alexandra , Trinh Ronnie The Pong , Pearson Troy , Ding Grant S. , Acton Paul , Lewis Richard T , Ray William J 
Published: December 2023

AbstractBackgroundRIP Kinase 1 (RIPK1) is known to regulate necroptotic cell death in response to pro‐inflammatory signaling in cells where apoptotic signaling has been compromised. Aberrant RIPK1 activation has been implicated in several neurodegenerative disorders such as Alzheimer’s disease, Multiple Sclerosis, and Amyotrophic Lateral Sclerosis.MethodTo investigate the role of RIPK1 in regulating the microglial response to demyelination, we administered a highly selective CNS penetrant RIPK1 inhibitor to C57Bl6 mice fed with cuprizone. We studied the microglial response using RNA Sequencing, single‐cell RNA Sequencing, lipidomics, and proteomics.ResultTranscriptomic analysis of isolated microglia and brain cytokine levels revealed that rapid demyelination induced by Cuprizone diet led to a strong disease‐associated microglia (DAM) response. Of the 1957 transcripts regulated in isolated microglia (padj<0.05) by the demyelination, RIPK1 inhibition significantly attenuated the microglial transcriptomic response of 497 transcripts (padj<0.1). Single‐cell RNA Sequencing analysis revealed that RIPK1 inhibition modified demyelination‐associated microglial sub‐clusters. Furthermore, soluble TREM2, a marker of microglia activation, was reduced, as were several cytokines in the brain. Open field analysis of these mice showed that RIPK1 inhibition rescued Cuprizone‐induced motor impairment. Proteomics and lipidomics analyses demonstrated RIPK1‐dependent changes in brain lipid metabolism.ConclusionRIPK1 signaling promotes an inflammatory response that involves modulation of key regulatory pathways associated with demyelinating disorders.