bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Effects of Extracts from Leaves of Horseradish Tree Species (Moringa oleifera and Moringa stenopetala) on Memory Index, Monoamine Oxidase activity and Tyrosine Hydroxylase mRNA Expression in Paraquat‐induced Model of Parkinson s disease in Fruit Flies (Drosophila melanogaster)
Authors: Aro Olayemi Philemon , Adefegha Adeniyi Stephen , Ogunsuyi Opeyemi Babatunde , Oboh Ganiyu 
Published: December 2023

AbstractBackgroundPD is now understood to be a multi‐system brain condition affecting multiple non‐dopaminergic transmitter systems that grow more prominent as the disease develops. Recent epidemiological and experimental studies have connected pesticides, particularly paraquat, to Parkinson’s disease. Even though the horseradish tree (Moringa oleifera) is a very promising ethnobotanical plant with a wealth of medicinal applications, little is known about the bioactive qualities of alkaloid extracts from its leaves.MethodThis study investigated the comparative modulatory effects of alkaloid extracts of Moringa leaves on the survival rate of paraquat‐induced flies, as well as specific biochemical and genetic markers related to Parkinson’s disease in the heads of the fliesResultThe results showed that the alkaloid extract increased fly survivability (p <0.05). M. Stenopetala (50 mg/ml) extract reduced monoamine oxidase and acetylcholinesterase activity more than M. oleifera. Compared to the paraquat‐induced group, M. Stenopetala also increased the amounts of superoxide dismutase, glutathione‐S‐transferase, catalase, and total thiols. Gene expression data show that the induced group had lower levels of catalase and TH mRNA expression compared to the treated groups. It was shown that M. oleifera had a greater ameliorative impact than M. stenopetala on catalase mRNA expression, whereas M. stenopetala had a considerably greater ameliorative effect on TH mRNA expression than M. oleifera.ConclusionIn this research, paraquat‐induced fruit flies were treated with alkaloid extracts from Moringa leaves, and the results showed that the M. Stenopetala variety had a more effective therapeutic effect than M. oleifera.
MAPT subhaplotypes and chronic traumatic encephalopathy
Authors: Han Xudong , Petrosky Jillian , Bald Sarah , Zhang Yichi , Sherva Richard , Chung Jaeyoon , Abdolmohammadi Bobak , Durape Shruti , Martin Brett M , Palmisano Joseph N , Farrell Kurt W. , Farrell John , Cherry Jonathan D , Alvarez Victor E. , Huber Bertrand R. , Alosco Michael L , Tripodis Yorghos , Stern Robert A , Stein Thor D. , Farrer Lindsay A. , Crary John F. , McKee Ann C. , Mez Jesse B. 
Published: December 2023

AbstractBackgroundExposure to repetitive head impacts (RHI) is the main risk‐factor for chronic traumatic encephalopathy (CTE), a neurodegenerative disease characterized by perivascular hyperphosphorylated tau deposition. However, the occurrence and severity of CTE varies widely among those with similar RHI exposure, suggesting other factors, including genetics, may contribute. The MAPT gene, which codes for the tau protein, is implicated in other tauopathies, but has not been investigated in CTE. The 17q21.31 region, containing MAPT, includes a megabase‐long inversion (H1/H2; European ancestry only) and copy‐number variations, including α, β and γ segments, which can be characterized as nine segregating structural subhaplotypes. We investigated associations between these subhaplotypes, CTE, and related clinical and neuropathological outcomes.Method458 male brain donors of European ancestry from the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Brain Bank with known RHI exposure from contact sports and/or military service were evaluated for CTE status, CTE stage (0 = absent; 4 = most severe), semiquantitative tau burden (0 = absent; 3 = most severe) across 11 brain regions and dementia based on informant report. Donors were genotyped on ∼5,000 SNPs across the 17q21.31 region in 2 batches. SHAPEIT and IMPUTE2 were used to phase and impute 12 biallelic surrogate markers and then SHAPEIT was used again to estimate 9 subhaplotypes. We tested the subhaplotype associations with CTE and the above outcomes in regression models adjusted for age at death and 10 principal components of population substructure. Results were meta‐analyzed across batches using the inverse variance method in METAL. Permutation testing was used to account for multiple testing and correlated data.ResultThe imputation quality of the surrogate markers was good (info score:0.516‐0.797). There were no significant associations with CTE status. The H1β1γ1 subhaplotype (frequency = 0.39) was significantly associated with dementia (OR = 1.90; padj = 0.019) and semiquantitative tau burden in the amygdala (OR = 1.53; padj = 0.025), entorhinal cortex (OR = 1.50; padj = 0.047), inferior parietal cortex (OR = 1.51; padj = 0.039), middle frontal cortex (OR = 1.48; padj = 0.045), and superior temporal cortex (OR = 1.67; padj = 0.002). H1β1γ1 was nominally associated with CTE stage (OR = 1.35; p = 0.027).ConclusionThese findings suggest a relationship between MAPT region structural variation and CTE‐related outcomes. Extension in a richly characterized living cohort of elite American football players is ongoing.
Impact of the COVID‐19 pandemic on enrollment at United States Alzheimer’s Disease Research Centers
Authors: Shaaban C. Elizabeth , Lin Hsing‐Hua Sylvia , Ren Dianxu , Lingler Jennifer H 
Published: December 2023

AbstractBackgroundImpacts of the COVID‐19 pandemic have been disproportionate by race/ethnicity and sex. We aimed to characterize the impact of the pandemic on enrollment in US Alzheimer’s Disease Research Centers (ADRCs) overall and by race/ethnicity and sex using National Alzheimer’s Coordinating Center (NACC) data.MethodsWe included data on N = 8875 participants (mean age, 69.4 years; 59% female; 9% Hispanic/Latino; 14% Black/African American) from 29 ADRCs with ≥5 years of data and study visits after 2020 (e.g., baseline visits from January 2017‐December 2021). We used interrupted time series (ITS) analyses to assess the relationship of the pandemic on enrollment and calculated projected date of recovery of pre‐pandemic enrollment overall and by race, ethnicity, and sex.ResultsEnrollment dropped to 0% of pre‐pandemic levels in April 2020; through December 2021, enrollment recovered to only 46% of pre‐pandemic levels. Participants enrolled during the pandemic (vs pre‐pandemic) were less likely to be: women, cognitively normal, and able to live independently. They were slightly younger, slightly more educated, and more likely to: be married, be referred by a doctor, nurse, or other professional, and come in for a clinical or mixed clinical and research study evaluation (p’s<0.05). The two groups did not vary by race, ethnicity, living situation (alone or with others), or co‐participant characteristics. ITS demonstrated that the pandemic caused an immediate 79% drop in enrollment rate, with an estimated post‐pandemic increase in enrollment of 0.92%/month, leading to a projected recovery date of January 2026. Due to parallel pre‐ and post‐pandemic enrollment slopes among Black/African American participants, we could not predict a recovery date for this group. Projected recovery varied by ethnicity with Hispanic participant enrollment recovering earlier than non‐Hispanic participant enrollment (January 2022 vs. April 2027), largely because Hispanic participant enrollment was declining nearly 1.5%/month pre‐pandemic. Recovery date projections also varied by sex, with female participant enrollment recovering sooner than male participant enrollment (June 2025 vs. May 2027).ConclusionsStrategies to speed enrollment recovery should be developed and implemented, with special attention given to Black/African American and Hispanic enrollment. Funders and researchers should be aware of and account for ongoing COVID‐19 impact on ADRD research enrollment.
Mediterranean diet protects against neuroinflammation and degeneration in female nonhuman primates
Authors: Shively Carol A. , Negrey Jacob D. , Frye Brett M. , Johnson Corbin S.C. , Kim Jeongchul , Barcus Richard A. , Lockhart Samuel N. , Whitlow Christopher T. , Chiou Kenneth L. , Snyder‐Mackler Noah , Montine Thomas J. , Craft Suzanne , Register Thomas C. 
Published: December 2023

AbstractBackgroundMediterranean diets may reduce Alzheimer’s disease (AD) risk and preserve cognitive function relative to Western diets in part by protecting against neuroinflammation. In middle‐aged humans that subsequently develop AD, increased cortical thickness precedes atrophy. It is hypothesized that the initial increase in brain volumes may be due to early neuroinflammation that precedes neurodegeneration (Pegueroles et al. Alzheimers Dement 2017). Long term impacts of diet patterns on health are difficult to quantify in human beings. Thus, we addressed this hypothesis in cynomolgus macaques (Macaca fascicularis), a nonhuman primate that undergoes age‐related changes in brain structure and function, and responds to Western diets, like humans.Methods38 middle‐aged (mean = 12 years of age) female macaques were fed a Western or Mediterranean diet for 2.5 years in a randomized nonhuman primate trial. Changes from baseline in volumes of total brain, gray, cortical gray, and white matter, cerebrospinal fluid and (CSF), were determined by structural MRI. We also generated thickness‐based AD temporoparietal meta‐ROIs based on the AD clinical literature as previously described (Frye et al., 2021 Alzheimers Dement. 2021;17:733). Transcriptional profiles in the temporal cortex were determined at the end of the study by RNAseq.ResultsWestern diet led to increases in temporoparietal cortical thicknesses, total brain and gray matter volumes, and diminished cerebrospinal fluid and white matter volumes. Diet significantly altered expression of seven genes (FDR<0.05). The Mediterranean group had lower expression of CDK14, a proinflammatory regulator, and higher expression of BTN2A1, KATNB1, LFNG, MRC2, SLCA32, and TMEM268, many of which have anti‐inflammatory associations. Several differentially expressed genes were correlated with AD‐relevant brain volumes. CDK14 was positively correlated with total brain, total gray, and cortical gray matter volumes and temporoparietal cortical thickness (Figure, Mediterranean = yellow), and negatively correlated with total white matter and CSF volumes. LFNG, MRC2, and SLCA32 were negatively correlated with total brain, total gray, and cortical gray matter volume, as well as temporoparietal cortical thickness, and positively correlated with CSF volume (all p’s<0.05).ConclusionThese results suggest that the Mediterranean diet protects against, whereas the Western diet promotes, AD‐relevant neuroinflammation associated with early increases in gray matter volumes.
Flortaucipir tau PET in former American football players
Authors: Su Yi , Protas Hillary D. , Luo Ji , Chen Kewei , Alosco Michael L , Adler Charles , Balcer Laura , Bernick Charles B. , Au Rhoda , Banks Sarah J , Barr William , Coleman Michael J , Dodick David W. , Katz Douglas I , Marek Kenneth , Mariani Megan , McClean Michael D , McKee Ann C. , Mez Jesse B. , Daneshvar Daniel H , Palmisano Joseph N , Peskind Elaine R , II Robert W Turner , Wethe Jennifer , Rabinovici Gil D. , Johnson Keith A. , Tripodis Yorghos , Cummings Jeffrey L. , Shenton Martha E , Stern Robert A , Reiman Eric M. ,   DIAGNOSE CTE Research Project Investigators
Published: December 2023

AbstractBackgroundChronic traumatic encephalopathy (CTE) is a neurodegenerative disease thought to be caused, in part, by repetitive head impact (RHI) exposure and characterized by phosphorylated tau deposition with varying patterns in the cerebral cortex. Flortaucipir tau PET data from the DIAGNOSE CTE Research Project was examined to investigate tau PET patterns and its relation to RHI exposure in former professional and college American football players.MethodIn this study, 218 DIAGNOSE CTE participants, ages 45‐74, with flortaucipir PET were included; 104 were former National Football League players (PRO), 58 were former college football players (COL), and 56 had no history of contact sports, other exposure to RHI, or traumatic brain injury (UE). Regional flortaucipir uptake was quantified using established procedures for three previously defined statistical regions (superior frontal, left parietal, and medial temporal) and compared across the three groups. Association analyses were also performed to examine the relationship between flortaucipir uptake and exposure to RHI using the cumulative head impact index for linear acceleration g‐force (CHII‐G). The potential clinical utility of flortaucipir PET for CTE was also investigated by examining its ability to differentiate participants meeting criteria for traumatic encephalopathy syndrome (TES) and probable or possible level of certainty for CTE pathology from those who do not meet those criteria.ResultSignificantly higher flortaucipir uptake was observed in former football players than in participants without RHI exposure, controlling for age and race for the superior frontal region (Fig. 1A), left parietal, and medial temporal regions. Association between regional flortaucipir uptake and CHII‐G was only observed in the superior frontal region in former players (PRO+COL) 60 years and older (Fig. 1B) and no association was observed in the full PRO+COL group. Flortaucipir PET was not able to differentiate TES groups in former football players (Fig. 1C).ConclusionElevated flortaucipir uptake was observed in former American football players to a group of unexposed men. The association between flortaucipir uptake and exposure to RHI may require a long latent period to manifest. Further investigation of more sensitive tau PET tracers and quantification techniques is warranted to better characterize CTE related tau pathology.
White matter hyperintensities: A long‐term consequence of repetitive head impacts?
Authors: Alosco Michael L , Ly Monica T. , Tuz‐Zahra Fatima , Tripodis Yorghos , Adler Charles , Balcer Laura , Bernick Charles B. , Peskind Elaine R , Mariani Megan , Au Rhoda , Banks Sarah J , Barr William , Wethe Jennifer , Bondi Mark W. , Delano‐Wood Lisa , Cantu Robert , Coleman Michael J , Dodick David W. , McClean Michael D , Mez Jesse B. , Palmisano Joseph N , Martin Brett M , Lin Alexander P , Koerte Inga , Cummings Jeffrey L. , Reiman Eric M. , Shenton Martha E , Stern Robert A , Bouix Sylvain 
Published: December 2023

AbstractBackgroundRepetitive head impacts (RHI) from American football can lead to tau and non‐tau pathologies that might present as white matter hyperintensities (WMH) on FLAIR MRI. In 2022, we published a study in Alzheimer’s & Dementia that examined WMH and their association with risk factors and clinical function in former elite football players. That study will be presented during this symposium along with new unpublished data that used imaging and fluid biomarkers to examine etiological correlates (tau, amyloid, neurodegeneration, axonal injury, neuroinflammation) of WMH in the same cohort.MethodsThe multi‐site DIAGNOSE CTE Research Project recruited 180 football players and 60 asymptomatic males without RHI (“controls”), all 45‐74 years (Table 1). Participants completed MRI, lumbar puncture, and neuropsychological testing. Lesion Segmentation Toolbox estimated FLAIR WMH, FreeSurfer derived total cortical thickness, and a diffusion pipeline derived average global FA. CSF was analyzed for p‐tau181, Aβ1‐42, NfL, and sTREM2. Tobit regressions compared football players (n = 149) and controls (n = 53) on total and regional log‐WMH and estimated the effects of years of football and age of first exposure (AFE) to football on log‐WMH. Linear regressions evaluated log‐WMH and clinical associations in football players. Structural equation modeling (SEM) examined effects between log‐WMH and cortical thickness, FA, and the CSF biomarkers. Analyses accounted for age, race, revised Framingham Stroke Risk Profile (rFSRP), body mass index, APOE ε4, and evaluation site.ResultsAlosco et al. (2022) found older (i.e., 60+) but not younger football players had greater total, frontal, temporal and parietal log‐WMH compared to controls (FDR‐adjusted p‐values<0.05; Table 2). Among older football players, younger AFE was associated with greater log‐WMH (beta = ‐0.13, 95% CI = ‐0.23,‐0.02). Greater log‐WMH corresponded to worse Trails A‐B (beta = ‐4.32, 95% CI = ‐8.59,‐0.05) and List Learning Long Delay scores (beta = ‐0.56, 95% CI = ‐0.93,‐0.19). Subsequent unpublished SEM analyses in football players (Figure 1) showed the following direct effects on log‐WMH: higher rFSRP, higher CSF p‐tau181, lower FA, and reduced cortical thickness. There were no indirect effects. Compared to controls, SEM associations were stronger in football players exception for cortical thickness.ConclusionsFLAIR WMH might have unique imaging characteristics, risk factors, and pathological underpinnings in people exposed to RHI.
Dysfunctional cerebral glucose transport in Alzheimer’s Disease
Authors: Nowell Joseph , Femminella Grazia Daniela , Ritchie Craig W , Holmes Clive , Walker Zuzana , Ridha Basil H , Lawrence Robert M , McFarlane Brady , Archer Hilary , Coulthard Elizabeth , Underwood Benjamin , Koranteng Paul , Karim Salman , Prasanna Aparna , Junaid Kehinde , McGuinness Bernadette , Nilforooshan Ramin , Thacker Simon , Russell Gregor , Malik Naghma , Mate Vandana , Knight Lucy , Kshemendran Sajeev , Holscher Christian , Harrison John E , Hinz Rainer , Tadros George , Passmore Anthony Peter , Ballard Clive G , Edison Paul 
Published: December 2023

AbstractBackgroundGlucose is the primary energy source required for the homeostatic function of the brain. Glucose transporter 1 (GLUT1) present at the blood‐brain barrier is a key regulator of glucose transport into the brain. Reduced GLUT1 expression is shown to exacerbate Alzheimer’s pathology in rodent models. Here we aimed to establish whether there are regional differences in ineffective glucose transport amongst people living with Alzheimer’s disease.Method125 participants diagnosed with Alzheimer’s dementia, with an [18F]FDG scan with atrial input were enrolled. All participants underwent 3‐tesla magnetic resonance imaging and [18F]FDG scan with continuous and discrete arterial sampling. Spectral analysis was performed to create 1‐minute input‐response function parametric maps. To produce glucose transfer maps we applied the following equation; K1 ⁎ Ca / τ (K1 = 1‐minute IRF map, Ca = Plasma glucose concentration, τ = 1.48 a lumped constant). Glucose transfer maps were then coregistered to the participants’ structural MRI and normalised to MNI space. Regional mean glucose transfer was then calculated for the anterior cingulate cortex, frontal lobe, hippocampus, parahippocampus, occipital lobe, parietal lobe, posterior cingulate cortex, striatum, temporal lobe, and thalamus. A within‐subject ANOVA was then performed to evaluate the regional differences in cerebral glucose transport.ResultThe parahippocampus exhibited the lowest rate of glucose transfer in comparison to all other regions (p < 0.001), followed by the hippocampus. The striatum and occipital lobe demonstrated the regions of the highest mean glucose transportation from blood to the brain. In terms of brain lobes, the temporal lobe showed the lowest rates of glucose transfer, followed by the parietal lobe, then frontal and occipital (p < 0.001).ConclusionWe demonstrate dysfunctional BBB glucose transport in Alzheimer’s disease, with prominent glucose transport abnormalities localised in the parahippocampus. Impaired glucose transport was most apparent within temporal lobe structures. Targeting glucose transfer may be an effective way of treating Alzheimer’s disease.
The relationships between hippocampal cerebrovascular reactivity, hippocampal volume, and episodic memory in healthy ageing
Authors: Wang Congxiyu , Jobbins Lucy , Reid Graham , Hobden Georgina , Mackay Clare , Ebmeier Klaus P , Rieger Sebastian , Patel Raihaan , Kivimäki Mika , Singh‐Manoux Archana , Bulte Daniel , Suri Sana 
Published: December 2023

AbstractBackgroundCerebrovascular biomarkers such as cerebrovascular reactivity (CVR) have previously been associated with episodic memory. However, the relationship between memory and regional CVR within the hippocampus is not well studied. Moreover, whether this association is affected by hippocampal volume remains to be investigated. This study investigated the associations between hippocampal physiology, structure, and memory in ageing.MethodData from 104 participants (Age: Mean = 77±4.9 years) of the ongoing Oxford Heart and Brain Study was analysed for this study. CVR was assessed by a compensatory change in the blood oxygenation level dependent magnetic resonance imaging (MRI) signal in response to a 5% CO2 challenge, hippocampus volume was measured by structural MRI, and episodic memory was assessed with the Hopkins Verbal Learning Test Revised (HVLT‐R).ResultMean hippocampal CVR decreased with age (β = ‐0.004, p = 0.006). Mean hippocampal CVR was positively associated with mean hippocampal volume (β = 0.11, p = 0.010), and this association was driven by the left hippocampus after correcting for age and sex. Higher hippocampal CVR was also associated with better performance on the HVLT (β = 13.8, p = 0.035). This association was fully mediated by hippocampal volume, suggesting a path from cerebrovascular reactivity to episodic memory (Sobel’s z = 2.16, p = 0.030, see Figure 1).ConclusionThis study presents novel findings showing that hippocampal CVR was associated with episodic memory, and this association was mediated by hippocampal volume. This suggests a pathway by which impairments in hippocampal CVR are associated with worse episodic memory via smaller hippocampal volumes.
Cognitive Assessment of Monolingual and Bilingual US Older Latino Populations
Authors: Velez‐Uribe Idaly 
Published: December 2023

AbstractCommonly used neuropsychological tests may not be sensitive to cognitive changes in Native Spanish‐speaking Latinos living in the United States. Cognitive abilities are culturally bound, and therefore cultural and educational factors can influence an individual’s cognitive test performance. Cognitive tests have been most often developed for middle‐class English speakers, and therefore, they may present bias when the same tests are used within the Spanish‐speaking Latino community. Thus, cultural and linguistic factors, as well as other sociodemographic factors, need to be considered to assure validity and fairness in neuropsychological assessments. Culturally appropriate cognitive assessment is a critical issue when working with socio‐economically diverse Latino populations in the US.Many Latino adults in the US are bilingual, with 59% of those speaking English also speaking Spanish. As language experience powerfully shapes the brain and cognitive function, bilingualism may play an important role in decreasing the risk of developing dementia later in life. Studies examining the role of sociocultural factors, including acculturation and quality of education, are needed, as well as research that helps develop more appropriate cognitive tests and normative data for different Latino heritages. In this session, the US Consortium of Aging, Dementia & Latino Studies (CADLAS) Cognition and Assessment Special Interest Group (SIG) will discuss recent developments, current challenges, and opportunities, as well as future research directions in this area. The SIG aims to promote collaborations among investigators from different States in the US to harmonize cognitive measures and assessment across cohorts and advance clinical research with US Latino populations.