bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurobehavioral, and Cytoarchitecture Evaluation of the Therapeutic Potential of n‐butanol fraction of Phoenix dactylifera L. on lead acetate triggered neurodegenerative changes in Wistar rats
Authors: Lazarus Stephen S , Musa Sunday Abraham , Agbon Abel Noserenme , Sunday B Oladele 
Published: January 2025

AbstractBackgroundLead, a pervasive and toxic environmental pollutant, of particular concern is its impact as a trigger for neurodegenerative diseases. Phoenix dactylifera (date palm), has garnered attention due to its pharmacological properties: antioxidant and anti‐inflammatory, attributed to its rich flavonoid content. This assessed the therapeutic potentials of n‐butanol fraction of P. dactylifera (BFPD) on the behavioral and histomorphology of hippocampus lead acetate (PbA)‐induced neurotoxicity in Wistar rats.MethodForty‐two rats were categorized into seven groups (n = 7). Two experimental phases were employed: Toxicity‐phase, and Treatment‐phase. Toxicity‐phase: all rats received PbA (120 mg/kg), for 14 days, except group one (control); Treatment‐phase: group II (sacrificed), group III (Natural recovery), while groups (IV‐VII) received (500 mg/kg, 750 mg/kg and 1000 mg/kg) n‐BFPD and (100 mg/kg) vitamin C (as reference antioxidant). Treatment was via oral route, which lasted for 28 days. Therapeutic properties of n‐BFPD were assessed using Neurobehavioral assessment: Morris water maze performance and Novel object recognition test for (spatial memory, learning, and cognition); Oxidative stress biomarkers were assay using Malondialdehyde [MDA], and Superoxide dismutase [SOD], and microscopic hippocampus examination (CA1 and CA3) using histological and histochemical staining techniques and quantification of Nissl substance stain intensity using a computer running image analysis software (imageJ).ResultPbA‐treated group revealed neurodegenerative changes as remarkable (p<0.05) memory, learning and cognition impairment, elevation MDA levels and decrease in antioxidant enzymes (SOD), and cytoarchitectural distortions evidenced by necrotic nuclei, vacuolation and pyknosis, compared to the control. However, treatment with n‐BFPD revealed cognitive improvement in memory and learning; decreased MDA levels and increased SOD activities. Mild distortion‐to‐relatively normal neuronal cytoarchitecture relative to the control was also observed with n‐BFPD treatment.Conclusionn‐BFPD possesses potential therapeutic properties against PbA‐induced neurobehavioural and cognitive deficit and pathological changes which are indicator of neurodegenerative diseases.Keyword: cytoarchitecture, cognition, neurodegeneration
Pathological Associations with Rate of Progression of Frontotemporal Dementia
Authors: Magee Rogan , Ohm Daniel T , Rhodes Emma , Massimo Lauren , Wolk David A , Lee Eddie B , McMillan Corey T , Irwin David J 
Published: January 2025

AbstractBackgroundThere is considerable variability in the rate of clinical progression among individuals with frontotemporal dementia (FTD) and prognostic markers are lacking. Moreover, due to the rarity of postmortem data, the relationship between rate of progression and postmortem tau and TDP‐43 proteinopathy is understudied.MethodTo explore the pathologic underpinnings of differences in clinical progression of FTD, we used clinical data collected by the Penn Center for Neurodegenerative Disease Research from 130 patients with autopsy‐confirmed frontotemporal lobar degeneration (FTLD‐tau = 62, FTLD‐TDP = 68) across six domains (age at onset, survival in years, first Clinical Dementia Rating [CDR] scale score, first Mini‐Mental State Examination [MMSE] score, annual change in CDR, annual change in MMSE). We used principal components analysis to scale and collapse these data into two dimensions, and k means to automatically select three clusters based on silhouette width. We used automated digital pathology to measure mean percent area occupied (AO%) by TDP‐43 pathologic inclusions in up to 17 distinct autopsied brain regions.ResultPCA (Fig 1A) Cluster 3 progressed relatively fastest and was enriched for FTLD‐TDP cases and GRN mutation carriers (Table 1). Among FTLD‐TDP cases, TDP type E was enriched in cluster 3 (3 of 4) and type C was enriched in cluster 1 (13 of 16). Among FTLD‐tau cases, progressive supranuclear palsy was overrepresented in cluster 1 (19 of 20). Principal component 1 (PC1) negatively correlated with independent measures of functional outcomes extracted from the clinical record, including the time to develop incontinence and complete dependence in activities of daily living (Figure 1B, C). PC1 correlated with the average pathologic TDP‐43 AO% in FTLD‐TDP cases (Figure 2).ConclusionTaken together, these results suggest that increased rate of clinical progression may relate to increased burden of TDP‐43 observed postmortem. The heterogeneity in the prognosis of FTLD may be driven by biological factors, such as disease activity. Further, FTLD‐TDP (especially FTLD‐GRN) may associate with faster progression. Biomarkers of FTLD‐TDP and/or improved access to mutation testing may improve prognostication in the care of FTD.
Classification of Microglia in Human Alzheimer’s Disease Postmortem Cases
Authors: Stephen Terri‐Leigh , Nguyen Kenneth , Hawes Debra , Breningstall Bayla M , Bienkowski Michael S 
Published: January 2025

AbstractBackgroundMicroglia undergo varying regional dependent functional changes, which can exacerbate cognitive decline in Alzheimer’s disease, but the full clinical relevance remains unclear. Ramified microglia survey the micro‐environment and inert/amoeboid microglia engulf debris. A third morphological type; rod microglia, have been observed in a number of pathological conditions, but are relatively understudied. It has been suggested that they form after acute neurological insult and understanding their anatomical distribution across brains with Alzheimer’s disease may provide useful information regarding disease progression.MethodUniversity of Southern California Alzheimer’s Disease Research Center (USC ADRC) post‐mortem hippocampal and prefrontal cortical sections were immunostained with 4G8 for amyloid, AT8 for neurofibrillary tau tangles and Iba1 for microglia and imaged using an Olympus VS120 slide scanning microscope. 20 Alzheimer’s disease cases and 10 control cases were selected to best represent population demographics (balanced for sex and ApoE genotype). We utilized Ilastik machine learning toolkit to classify amyloid pathology (dense, diffuse, and amyloid precursor protein), neurofibrillary tangles, neuritic plaques and microglia (rod, inert and ramified) within stained tissue section images. These classifications were then overlaid within manually segmented region maps (aligned with the Allen Human Brain Atlas) using the Quantitative Imaging Toolkit (QIT).ResultOur findings revealed elevated rod and inert microglial staining in Alzheimer’s disease cases compared to controls alongside an increase in pathology burden across disease stage. Ramified microglia were reduced in Alzheimer’s disease cases compared to controls. Iba1 was correlated with amyloid pathology, specifically in the dentate gyrus (DG) of the hippocampus. Rod microglia were significantly more elongated with more processes in Alzheimer’s disease cases compared to controls. In general ramified had more processes, inert tended to be smaller with rod falling in between.ConclusionRegional variations in microglia morphology and function in Alzheimer’s disease could reflect differences in Alzheimer’s disease cell type susceptibility and have implications for understanding the disease progression.
Validating a measure of diminished motivation across the lifespan: Preliminary findings.
Authors: Scott Bonnie M , Rana Amtul‐Noor , Hilsabeck Robin C. 
Published: January 2025

AbstractBackgroundMotivational disturbances are a major harbinger for dementia, being associated with a two‐ to seven‐fold higher conversion rate from mild cognitive impairment. However, there are currently no objective assessment methods for identifying motivational disturbances in older adults (OA). Here, we present preliminary findings from a larger study which aims to validate an objective behavioral measure of effort in OAs by investigating the effects of age, risk, and reward (gain vs. risk trials), and effort type (physical vs. cognitive) on motivated decision‐making.MethodTwo modified versions of the Effort Expenditure for Rewards Task (EEfRT) were developed, including one requiring physical effort (i.e., finger tapping: P‐EEfRT) and one requiring cognitive effort (i.e., working memory: C‐EEfRT). Both tasks included an equal number of gain and loss trials in which participants could choose to expend greater effort to either win or avoid losing points on each trial. Five younger (YA: ages 19‐22) and six older (OA: ages 67‐78) adults completed these tasks along with a cognitive screener and self‐report symptom inventories.ResultYAs and OAs did not differ in cognitive status nor accuracy scores on the experimental tasks. A significant main effect and interaction of risk/reward magnitude and outcome valence (gain/loss) was found for the frequency of hard task selections on both the P‐EEfRT and C‐EEfRT, suggesting that the decision to exert greater physical and cognitive effort was significantly influenced by the combination of these task parameters in both age groups. A significant age group X outcome valence effect was also observed for both tasks, with YAs exhibiting considerably greater effort expenditure on trials with the possibility of gaining vs. losing points while OAs exhibited a similar pattern of performance for medium to large outcomes on the P‐EEfRT but failed to modulate their responses across task conditions on the C‐EEfRT. Finally, greater self‐reported symptoms of fatigue, apathy, and anhedonia were associated with lower cognitive and physical effort expenditure in the OA group and with slower decision‐making reaction times in the YA group.ConclusionFindings suggest that the influence of risk and reward on cognitive and physical effort‐based decision‐making varies across the lifespan.
Vascular health influences the correspondence between self‐report of physical activity and activity measures obtained with a smartwatch
Authors: Chaturvedi Riya , Holmqvist Sophia L. , Kaplan Marina , Simone Stephanie M. , Tassoni Molly B. , Mckniff Moira , Giovanetti Tania 
Published: January 2025

AbstractBackgroundGreater physical activity (PA) is associated with better cognitive and vascular health, but accurate assessment of PA is challenging. Self‐report questionnaires of PA may be compared against objective measures from smartwatch sensors; the correspondence between measures may be influenced by a variety of factors such as cognition or age. The focus of this study was to identify baseline participant characteristics (vascular risk, cognition) that influence the association between self‐reported PA and PA measured with a Garmin Vivosmart 4 smartwatch in a racially diverse sample of older adults.Method32 older adults (M age = 68.53); 32% Black/African American) with healthy cognition (n = 26) or mild cognitive impairment (n = 6) completed the International Physical Activity Questionnaire (IPAQ) to assess PA (moderate and vigorous intensity, walking; metabolic equivalent [MET] minutes) and the Framingham Stroke Risk Profile (FSRP) to assess vascular risk. A cognitive composite was evaluated as an average of t scores from several neuropsychological tests. PA was also measured over a 30‐day period in which participants wore a Garmin Vivosmart 4 smartwatch for 23 hours/day that captured duration of moderate and vigorous intensity PA and daily steps. Smartwatch measures were averaged across the 30‐day monitoring period. Discrepancy scores between the three Garmin PA metrics and three corresponding self‐reported PA measures were computed as the difference between sample‐based z‐scores. Relations between discrepancy scores and demographics/clinical characteristics were analyzed using Spearman correlations or independent samples t‐tests.ResultGreater overreporting of self‐reported walking PA was significantly related to lower education (ρ = ‐.440, p = .012) and greater vascular risk (ρ = .433, p = .013). There were no significant relations between overreporting of moderate/vigorous intensity PA and participant characteristics. There were no significant relations between cognition or sex and overreporting of PA.ConclusionVascular health was associated with overreporting of PA on self‐report measures relative to objective measures obtained with a smartwatch, but vascular health influenced only one of three measures (i.e., step count). Cognitive abilities and sex were not associated with discrepancies between subjective and objective measures of PA. Further work is needed to determine whether vascular heath biases either self‐report or sensor measures of daily steps in older adults.
Cognitive Flexibility in Bilinguals and Multilinguals and Its Implications for Dementia
Authors: Akkunje Preetie Shetty , Ramesh Keerthana , Archa Sasi Kumar , Hegde Prasanna Suresh , Thaut Michael H. 
Published: January 2025

AbstractBackgroundVerbal fluency (VF) is crucial for language processing and cognitive flexibility, involving selective attention, inhibition, set shifting, response generation, and self‐monitoring. VF assessment includes two distinct tasks, i.e., phonemic and semantic VF. It assesses long‐term verbal semantic memory, phonological awareness, lexical–semantic access, and executive function. Semantic VF is mainly based on generating semantic associations, whereas phonemic VF is based majorly on executive functions instead of lexicon–semantic networks. Even though the VF involves several neural substrates majorly is coordinated by superior frontal lobe and temporal lobe for phonemic and semantic VF, respectively. This study aims to assess VF in linguistically diverse young adults of bilingual and multilingual individuals and its contributing insights into language‐cognition interplay.MethodA prospective cross‐sectional research study recruited 120 participants, divided into two groups: bilinguals (proficient in at least two languages;n = 60) and multilinguals (proficient in at least three languages;n = 60), identified through the Language Experience and Proficiency Questionnaire. Inclusion criteria encompassed participants aged 20‐50, of both genders, with standard education up to graduation. Participants with neurological or psychiatric language disorders and those scoring ≤25 on the Montreal Cognitive Assessment were excluded from the study. Research‐specific assessments, including Spontaneous speech of Western Aphasia Battery, Addenbrooke’s Cognitive Examination‐III for cognitive functions and VF tests (phonemic & semantic VF, phonemic & semantic switching tasks, alternating language task, controlled semantic association task), were conducted in L1, L2 for bilinguals and L1, L2, and L3 for multilinguals. Statistical evaluation was done using SPSS‐version‐29.0.10, utilizing descriptive statistics, Likelihood ratio, Chi‐square, and Independent sample t’‐tests.ResultsParticipants recruited showed no significant difference between groups for age, gender and education highlighting linguistic‐diversity of participants which is essential for comprehending potential variations in research findings and their general applicability. The results revealed that bilinguals outperformed multilinguals in semantic VF tasks while multilinguals outperformed bilinguals in phonemic verbal VF tasks.ConclusionThe adaptability in switching between semantic fields and linguistic‐dimensions of temporal lobe, particularly evident in bilinguals, underscores the cognitive advantages of bilingualism. These findings are crucial for formulating targeted interventions tailored to the unique needs of linguistically‐diverse dementia patients, to strengthen neural‐networks which can account for the principles of neuroplasticity.
Remote digital memory assessment in middle‐aged and older adults: Feasibility, reliability, and construct validity
Authors: Clark Lindsay R. , Basche Kristin E , Peterson Amanda , Rosario Hannah , Johnson Sterling C. , Düzel Emrah , Berron David 
Published: January 2025

AbstractBackgroundFrequent and remote cognitive assessment may improve sensitivity to subtle cognitive decline associated with preclinical Alzheimer’s disease (AD). Our objective was to evaluate the feasibility, reliability, and construct validity of repeated remote memory assessment in late middle‐aged and older adults.MethodParticipants were recruited from longitudinal aging cohorts to complete medial temporal lobe‐based memory paradigms (Object‐In‐Room Recall [ORR], Mnemonic Discrimination for Objects and Scenes [MDT‐OS], Complex Scene Recognition [CSR]) using the neotiv application on a smartphone or tablet at repeated intervals over one year. Participants were randomized to a task schedule (biweekly or bimonthly burst) for a total of 24 ten‐minute remote sessions. Feasibility metrics included participation, retention, compliance, and acceptability. Intraclass correlation coefficients (ICC) assessed test‐retest reliability over an 8‐week period. Analysis of covariance (ANCOVA) models including covariates of demographics, device type, and task schedule were used to evaluate relationships between neotiv baseline performance and traditional memory scores (Rey Auditory Verbal Learning Test [RAVLT]; Preclinical Alzheimer’s Cognitive Composite [PACC]).ResultOf 280 potentially eligible adults, n = 180 consented (64% participation rate). Of 180 consented, n = 133 completed at least one session and n = 119 completed or nearly completed all sessions (retention rate = 66% for all consented and 89% for all completed 1+ session). Delayed retrieval sessions were completed within expected timeframes in 72% of sessions. Greater than 90% of respondents felt the application was easy to use, instructions were understood, and the frequency and length of remote sessions were appropriate. 60% enjoyed completing the tasks (34% felt neutral) and 40% preferred mobile tests to traditional cognitive testing (42% felt neutral). Test‐retest reliability was moderate (ICC = 0.54‐0.70). RAVLT and PACC were significantly associated with MDT‐OS, CSR, and ORR performance (p’s <.001).ConclusionChallenges to participation occurred primarily during enrollment; future studies may allocate additional support facilitating registration and initial task completion within the application. Acceptability of the mobile tasks was high. The mobile memory paradigms exhibited moderate test‐retest reliability and were significantly related to gold‐standard cognitive tests. Overall, findings support preliminary feasibility, reliability, and validity of the neotiv tasks in assessing memory function in cognitively healthy adults enriched for AD risk.
Attention‐deficit/hyperactivity disorder impacts the development of neuropsychiatric symptoms in Alzheimer’s disease
Authors: Leffa Douglas Teixeira , Bellaver Bruna , Povala Guilherme , Ferreira Pamela C. L. , Ferrari‐Souza João Pedro , Lussier Firoza Z , Soares Carolina , Zalzale Hussein , Bauer‐Negrini Guilherme , Abbas Sarah , Karikari Thomas K , Rohde Luis Augusto , Molina Brooke , Pascoal Tharick Ali 
Published: January 2025

AbstractBackgroundRecent studies have shown that patients with attention‐deficit/hyperactivity disorder (ADHD) are more likely to be diagnosed with mild cognitive impairment (MCI) and Alzheimer’s Disease (AD). Increased genetic risk for ADHD, measured with ADHD polygenic risk scores (ADHD‐PRS), was associated with a more severe AD presentation, including worse cognitive function and higher tau pathology. Neuropsychiatric symptoms (NPSs) are common in AD and are hypothesized to occur with disease progression. It is unclear whether ADHD predispose individuals to the development of NPSs.MethodWe used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to investigate the associations between ADHD‐PRS and the development of NPSs in cognitively impaired (CI, including MCI and AD) subjects who had brain amyloidosis at baseline. NPSs were assessed with the NPI or NPI‐Q and divided into four syndromes: hyperactive (agitation, disinhibition, irritability, and aberrant motor behavior), psychosis (delusions, hallucinations, and night‐time behavior disturbances), apathy (apathy and appetite and eating abnormalities), and affective (depression and anxiety). Additionally, we tested the specificity of our findings by analyzing the association between the genetic risk for depression, bipolar disorder (BD), schizophrenia, and autism spectrum disorder (ASD) with the development of NPSs. Data were represented with Kaplan‐Meier survival curves, and analyses were performed with Cox proportional hazards regression models controlled by age, sex, and ancestry.ResultWe evaluated data from 852 participants (636 MCI [74.1%], 350 women [40.8%], mean [SD] age of 73.4 [7.3] years). ADHD‐PRS was associated with a higher risk of developing hyperactive (HR 1.41; 95% CI 1.04‐1.89) and apathy (HR 1.34; 95% CI 1.01‐1.77) symptoms, but not psychosis (HR 1.04; 95% CI 0.78‐1.41) or affective (HR 0.97; 95% CI 0.72‐1.32) symptoms. There was no association between the genetic risk for depression, BP, schizophrenia, or ASD with any neuropsychiatric syndrome.ConclusionFindings indicate that a higher genetic risk for ADHD may be a risk factor for the development of hyperactive and apathy symptoms in CI individuals. These effects were specific for ADHD and were not observed for other prevalent psychiatric disorders. Clinically, our results contribute to the literature that highlights the need for tailored assessments for CI individuals with ADHD histories.