bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing effects of demographic variables on current and novel neuropsychological measures in older adults with and without Alzheimer’s disease
Authors: Reed Alexandra M. , Duff Kevin , Schaefer Sydney Y 
Published: January 2025

AbstractBackgroundNeuropsychological assessments are often affected by demographic factors, such as age, education, and sex. These demographic variables frequently lead to differences in test scores between minorities and non‐minorities, lowering diagnostic accuracy of Alzheimer’s disease (AD) among minoritized groups. A new test (quick Behavioral Exam to Advance Neuropsychological Screening, or qBEANS) has been developed to assess early signs of AD. The current study compared the influence of demographic variables on qBEANS and other neuropsychological tests that are commonly used in the assessment of AD.MethodIn this study, 165 participants (68 cognitively unimpaired; 52 amnestic Mild Cognitive Impairment; 45 mild AD) completed the Symbol Digit Modalities Test (SDMT), Hopkins Verbal Learning Test‐Revised (HVLTR); Brief Visuospatial Memory Test‐Revised (BVMTR); and Trails Making Test (TMT) A and B. Participants also completed the qBEANS, which involves spooning two raw kidney beans at once with the nondominant hand to one of three target cups in a simple sequence, with higher scores being worse performance. Effects of age, education, and sex on raw test scores were analyzed using multivariable linear regression, with p‐values adjusted for multiple comparisons. Fisher transformations were used to examine if current tests were more affected by demographic variables than qBEANS.ResultParticipants' are was 65‐91 years (mean = 74.1) and education was 12‐20 years (mean = 16), with 56.3% female. Significant age effects were observed for all tests except qBEANS (p = .10) and TMT‐A (p = .73), with older ages being associated with worse scores. Similarly, there were significant education effects for all tests except qBEANS (p = .41), TMT‐A (p = .73), and TMT‐B (p = .31), with fewer years of education being associated with worse scores. Only the HVLTR (total and delayed recall) showed a significant sex effect, with females performing better than males. The overall influence of age, education, and sex on qBEANS scores was significantly smaller than the SDMT, HVLTR, and BVMTR (no different with TMT‐A or TMT‐B).ConclusionUnlike most neuropsychological tests, qBEANS may be appropriate for screening diverse populations without controlling for demographic variables. Future research should consider populations with lower educational attainment, as well as race, ethnicity, and native language on qBEANS relative to other neuropsychological measures.
A Challenging Case of Lewy Body Disease in a Symptomatic Patient Negative for Phosphorylated Alpha‐Synuclein: Implications for Lewy Body Spectrum Disorders
Authors: Alhneif Mohammad , Cherukuwada Lakshmi , Keating Mallory , Corbett William Cole , Gonzalez Angelique D. , Ogunbona Oluwaseun , Bieniek Kevin F. , Seshadri Sudha , Etemadmoghadam Shahroo , Flanagan Margaret E 
Published: January 2025

AbstractBackgroundLewy bodies (LBs), characterized by intraneuronal inclusions of misfolded alpha‐synuclein (α‐syn) protein, are the pathological hallmark of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Because this protein is phosphorylated at serine‐129 in 90% of LBs, its phosphorylation is considered a crucial pathogenic event in LB formation and disease development. Here, we present a unique brain autopsy case of a DLB patient with widespread LBs that were negative for phosphorylated‐α‐syn, challenging traditional diagnostic criteria.MethodAn 86‐year‐old male with a history of agent orange exposure presented with cognitive decline, REM sleep behavior disorder, tremors, and visual hallucinations. Clinical workup was inconclusive, suggesting atypical Parkinsonism or possible DLB. Postmortem neuropathological examination of H&E slides revealed numerous LB‐appearing inclusions in the midbrain. To confirm their identity, immunohistochemical staining for pSYN64, an antibody against phosphorylated‐α‐syn, was performed which showed negative staining (with an appropriately positive control slide which verified that the stain worked). Further immunohistochemistry with antibodies against P62, LB509, and anti‐nitro‐α/β‐synuclein as well as pSYN64 in other brain regions was performed. P62 is regarded as a surrogate marker of α‐Syn inclusions and LB509 is known to stain total α‐syn. Anti‐nitro‐α/β‐synuclein detects nitrated synuclein.ResultThe LB‐like inclusions in all brain regions including the midbrain showed positive staining for P62 and LB509, confirming their α‐synuclein content, but pSYN64 was consistently negative. Anti‐nitro‐α/β‐Synuclein showed scattered staining. The LB disease in this case was neocortical stage, which explains the patient’s cognitive impairment. Additionally, brainstem involvement justifies his parkinsonism during life.ConclusionThis case challenges the long‐held notion that phosphorylated‐α‐syn is an essential component of LBs especially needed to cause clinical symptoms. The absence of phosphorylated‐α‐syn LBs in a symptomatic patient suggests that additional proteins, or alternative mechanisms of abnormal protein accumulation may be involved in disease pathogenesis. This report highlights the complexity of LB pathology and emphasizes the need for continued research to unravel the diverse protein aggregates and mechanisms underlying LB formation and neurodegeneration. By expanding our understanding of LB spectrum disorders, we can enhance diagnostic procedures and facilitate the development of targeted therapies for patients with these diverse and debilitating conditions.
Preliminary Findings from EMPOWER: Evaluating Memory as Part of Women’s Routine Care
Authors: Joyce Jillian L. , Cosentino Stephanie , Rizer Sandra , Dargie Samantha A. , Chapman Silvia , Mora Laura , Libon David J. , Tom Sarah E. , Marder Karen , Rosser Mary 
Published: January 2025

AbstractBackgroundDespite evidence that Alzheimer’s disease (AD) related pathological changes occur earlier in women than men, women are diagnosed later. To address this care disparity, the Evaluating Memory as Part of Women’s Routine Care (EMPOWER) program was established to integrate cognitive screening into routine gynecological well‐woman visits. Recent work has demonstrated the feasibility of conducting subjective cognitive screening at the well‐woman visit. The extent to which such subjective screening maps onto objective cognitive screening is critical. Here we outline preliminary results from the EMPOWER program, where both a subjective memory screener and a novel digital cognitive assessment were used to screen cognition.MethodWomen 50 and older appearing for routine gynecological well‐woman visits at the Columbia University Integrated Women’s Health Center were eligible to participate in this study. Participants completed a subjective cognitive survey, the Screener for Cognitive Problems in Everyday Life (SCOPE), as well as a digital cognitive task, the Linus Health Core Cognitive Evaluation (CCE). The SCOPE scores range from 0‐5, and endorsement of any item is considered a positive screen. The CCE comprises a digitized version of the Mini‐Cog (three‐word recall and clock‐drawing). CCE performance ranges from 0‐5 points, with 4‐5 as Normal, 2‐3 as Borderline, and 0‐1 as Impaired.ResultOf 130 eligible women, 71 (55%) were recruited. Table 1 provides descriptive demographic and cognitive data. Total number of items endorsed on the SCOPE was associated with total CCE performance (Table 2). Additionally, women that screened SCOPE positive were more likely to perform in the borderline/impaired category of the CCE (Table 3).ConclusionIntegrating cognitive screening into the routine gynecological well‐woman exam can identify midlife and older women experiencing cognitive difficulties, a critical step in addressing the care disparity. The current study demonstrates the validity of a subjective cognitive screener for detecting early cognitive dysfunction. A limitation of the study is the lack of ethnic and racial diversity, especially groups that are at increased risk for AD. Ongoing work is expanding EMPOWER to clinics that serve a more sociodemographically diverse patient population. Future work should include longitudinal monitoring to assess both subjective and objective cognitive changes over time.
Exploring the Intersection Between Seizures, Traumatic Brain Injury, and the Risk of Incident Cognitive Impairment in Cognitively Normal Older Adults
Authors: Babulal Ganesh M. , Trani Jean‐Francois , Zhu Yiqi 
Published: January 2025

AbstractBackgroundSeizures, traumatic brain injury (TBI), and dementia increase in prevalence with age. However, the role of seizure and TBI on cognitive impairment risk (CI) is unclear. This study investigated how a diagnosis of seizures and TBI was associated with the progression to CI and assessed the role of medications.MethodWe analyzed data from the National Alzheimer’s Coordinating Center (NACC) (June 2020 data‐freeze). Inclusion criteria required participants 1) aged 65 years or older at their first visit, 2) cognitively normal at baseline (Clinical Dementia Rating [CDR] score of 0), and 3) complete information on race, age, gender, and education. 8,139 participants were included and followed until dropout or the first instance of CI progressing CDR 0 to 0.5. Seizure and TBI were determined by the clinician’s judgment based on medical history and the participant’s annual visits. Medication categories were derived by NACC using Ultum/Lexi‐Comp© therapeutic drug categories. Age, sex, race/ethnicity, and education were included as control variables. Cox proportional hazards model examined the associations between the diagnosis of seizure, TBI, or both and the progression of cognitive impairment measured by CDR. To account for selection bias, we applied propensity score weighting (PSW) with the inverse probability treatment weighting (IPSW) technique.ResultUnadjusted survival models found a diagnosis of seizures significantly increased the hazard ratio (HR) of CI progression by 58% (p < 0.05), while the diagnosis of TBI increased the HR by 28% (p < 0.05). After applying IPSW to reduce the selection biases, the diagnosis of seizures increased the HR for CI by 39% (p < 0.05), TBI increased it by 25% (p < 0.001), and having both seizure and TBI diagnoses increased the risk of CI by 56% (p < 0.05). The use of antipsychotic, anxiolytic, sedative, or hypnotic agents and angiotensin‐converting enzyme (ACE) inhibitors was found to reduce the risk of CI significantly.ConclusionThe presence of seizure or TBI was significantly associated with the increased risks of CI. Antipsychotic, anxiolytic, sedative, or hypnotic agents and angiotensin‐converting enzyme (ACE) inhibitors were associated with a reduced risk, emphasizing the importance of early treatment.
Impact of smell dysfunction of Covid‐19 in older adults on cognition and quality of life
Authors: Velayudhan Latha , Mitchell James , Pickering Ellie , Palmer Abbie , Richards Megan , Khan Zunera , Corbett Anne , Ballard Clive G , Aarsland Dag 
Published: January 2025

AbstractBackgroundSmell dysfunction has been one of coronavirus disease 2019 (Covid‐19) symptoms. Identification of those with these symptoms are important as olfactory impairment in general has been studied to have increased mortality, poor quality of life, increased incidence of depression and risk for dementia. Smell dysfunction related to Covid‐19 in older adults and its impact is lesser studied. We evaluated impact of covid‐19 infection and smell dysfunction on cognition and quality of life in older adults above 50 years of age.MethodsA longitudinal online survey, Smell and Taste Function in Older Adults in the Covid‐19 Pandemic (STAP) was added as a sub‐study to the ongoing remote wider study‐ Platform for Research Online to investigate Genetics and Cognition in Ageing (www.protect.org.uk). A separate ethics approval was sought for STAP (Reference LRS‐19/20‐18549). Interested participants of PROTECT study within the UK completed online questionnaire following consent, on a quarterly basis for a year. Information on Covid‐19 symptoms, testing, diagnosis, re‐infections, vaccinations and management was collected as part of the questionnaire in addition to socio‐demographic details, medical and lifestyle history and quality of life.ResultsOf the 3725 participants who took part in the baseline survey since June 2021, 1017 participants completed the follow up survey with the addendum questionnaire on re‐infections, vaccination history and other symptoms including self‐reported cognitive problems. The mean age was 66.65 years (7.87) and 80.5% were women. Of the 437 of the participants who reported having had Covid‐19 infection, 116 participants (26.5%) had partial or total smell loss. Olfactory impairment caused by Covid‐19 was associated with poorer quality of life especially social activities, diet and mood. People with Covid‐19 related smell impairment had significantly higher mental fatigue, attention and concentration problems, difficulties with memory, planning and organising, word and name finding difficulties and making decisions.ConclusionsOlder adults with smell dysfunction related to Covid‐19 infection had poorer quality of life and cognitive abilities affected. Further research is needed not only to understand the longitudinal course of smell impairment related to Covid‐19 and cognition, but also important to devise interventions to support these individuals to improve their well‐being.
Uncovering Molecular Features that Contribute to Tau Spread and Aggregation
Authors: Rauch Jennifer 
Published: January 2025

AbstractBackgroundTauopathies are a class of neurodegenerative diseases marked by tau protein spread and aggregation. Recently, our group described the cellular receptor Low‐density lipoprotein Receptor‐related Protein 1 (LRP1) as a regulator of tau spread. Knockdown of LRP1 halts tau spread in human induced pluripotent stem cell‐derived neurons and the mouse brain, indicating potential therapeutic implications. However, a comprehensive understanding of the tau‐LRP1 molecular complex remains elusive.MethodOur research focuses on elucidating the tau‐LRP1 structural interface and investigating how tau aggregate structure influences LRP1 processing. We are using covalent‐labeling mass spectrometry to map the tau‐LRP1 interface in vitro and in cells. We are isolating brain‐derived tau oligomers from various tauopathies and measuring their dependence on LRP1 using cell culture models of tau propagation.ResultOur results have identified residues critical for the interaction between tau and LRP1. Further, we have determined that brain‐derived tau oligomers utilize LRP1 for their endocytosis and that this is potentially dependent on structural elements of tau oligomers.ConclusionOur work provides insights into the structural aspects underlying tau‐LRP1 interactions and lays the groundwork for the design of potential disease therapeutics.
Comparison of skin carotenoid content and dietary intake between cognitively normal older adults and older adults with Alzheimer’s Disease: an updated matched‐pair analysis
Authors: Keller Jessica E , Sullivan Debra K , Taylor Matthew K , Burns Jeffrey M , Swerdlow Russell H 
Published: January 2025

AbstractBackgroundAlzheimer’s Disease (AD) is a systemic metabolic disease with a variable number and type of clinical symptoms mostly impacting the brain. Skin carotenoid content (SCC) is an objective measure of carotenoid‐containing fruit and vegetable intake that has been validated in diverse populations. Our previous findings suggest SCC scores differ between older adults with and without AD regardless of dietary intake of carotenoids. Therefore, our objective was to investigate this correlation across a larger sample of matched pairs.MethodBaseline data from two dietary interventions (NCT03860792, NCT03841539) were analyzed. Pairs are exact matches for sex, race/ethnicity, and education and are matched within three years of age and 5 kg/m2 body mass index. Each pair (n = 26 pairs) includes one cognitively normal (MMSE > 25), community dwelling older adult (‘CN’) and one community dwelling older adult with AD (‘AD’). Baseline self‐reported dietary intake data (3‐day food records) were collected, reviewed, and entered into the Nutrition Data System for Research (NDSR 2019) database by a Registered Dietitian. SCC scores were collected through pressure‐mediated reflection spectroscopy via VeggieMeter® (Longevity Link Corporation, Holladay, UT). Paired samples t‐tests were used to compare differences in SCC scores and dietary intake (IBM SPSS, version 29). Significance was set at p = 0.05.ResultSCC scores were different between matched pairs (SCC scores: AD 194.62, CN 281.50, p = 0.002). There was no difference in dietary intake between AD and CN pairs for daily energy (1768 vs 1824kcal/day; p = 0.75), fat (75.6 vs 78.7g/day; p = 0.71), carbohydrate (196.7 vs 190.0g/day; p = 0.73), or protein (74.3 vs 76.3g/day; p = 0.77), respectively. Both groups had similar food group intake (p‐value range 0.18‐0.84), including all fruit and vegetable groups except CN had higher intake of non‐citrus fruit (p = 0.03; +0.59 servings/day). Individual carotenoid intake was not different between groups (total vitamin A, p = 0.31; beta‐carotene, p = 0.31; alpha‐carotene, p = 0.41; beta‐cryptoxanthin, p = 0.54; lutein+zeaxanthin, p = 0.32; lycopene, p = 0.42).ConclusionThis updated analysis suggests that individuals with AD have lower skin carotenoid content compared to matched cognitively unimpaired individuals. These differences are not explained by differences in diet suggesting that AD may be associated with disease‐associated biochemical features that are metabolism‐related and not limited to the brain.
Lifetime stressor exposure and cognition in community‐dwelling older Latino adults from the Boston Latino Aging Study
Authors: Martinez Jairo E. , Badillo‐Cabrera Alex L , Félix Nikole A Bonillas , Martinez Lusiana , Munera Diana , Vila‐Castelar Clara , Giudicessi Averi , Schwab Nadine A , Gomez Liliana A Ramirez , Gatchel Jennifer R. , Saldana Daniel G , Catalan Marta Gonzalez , Slavich George M , Tompson Martha , Cronin‐Golomb Alice , Quiroz Yakeel T. 
Published: January 2025

AbstractBackgroundStressors occurring over the lifespan (i.e., lifetime stressor exposure) are hypothesized to contribute to greater risk of cognitive decline and dementia. There is a higher prevalence of Alzheimer’s disease and related disorders in Latinos compared to non‐Latino Whites. Relative to non‐Latino Whites, Latinos report higher levels of stress, but few studies have examined lifetime stressor exposure in Latinos. To address this gap, we used the Stress and Adversity Inventory for Adults (Adult‐STRAIN) translated into Spanish to examine lifetime stressor exposure and its relation to cognition in community‐dwelling older Latino adults.Method110 participants from the Boston Latino Aging Study (BLAST) were included (mean age = 68.7 [SD = 8.4] years, mean 10.5 [SD = 5.3] years of education, 85 females, 28 with mild cognitive impairment). The Adult STRAIN was used to assess lifetime stressor exposure and severity. The Preclinical Alzheimer’s Cognitive Composite‐5 (PACC5), adapted for Spanish speakers, was used to assess cognitive performance (z‐scores) across five measures (Mini‐Mental State Examination [MMSE]; Wechsler Adult Intelligence Scale‐4th edition Coding; Free and Cued Selective Reminding Test; NEUROPSI Atención y Memoria: Logical Memory; and Category Fluency [Animals]). Linear regressions examined associations between lifetime stressor exposure, stressor severity, age, sex, education, and cognition.ResultOn average, participants reported 27.7 (SD = 13.8, range = 5‐85; possible range = 0‐166) total lifetime stressors with a total severity score of 65.0 (SD = 35.7, range = 4‐162; possible range = 0‐265) or the equivalent of an average severity rating between “moderately” and “quite” stressful for each stressor. Older age was associated with fewer total lifetime stressors (β = ‐.39, p = .01) and lower total stressor severity (β = ‐1.34, p = .008). There were no associations between education or sex and total lifetime stressor exposure or total stressor severity (ps>.09). Neither PACC5 nor MMSE performance alone was associated with total lifetime stressor exposure or total stressor severity after adjusting for age (ps>.52).ConclusionOlder Latino adults reported moderately severe stressors across their lifetime. With age, older Latinos reported fewer lifetime stressors and lower stressor severity, perhaps due to cohort effects or positivity bias. Future studies with larger samples are needed to elucidate the impact of lifetime stressors on older Latinos. The Adult‐STRAIN may be a useful tool in characterizing this relation.
Validation Study of A Novel VR‐Based Cognitive Assessment Tool: Influences of Demographic Characteristics
Authors: Yerlikaya Deniz , Arsoy Erdil , Sükuti Murat , Baytimur Meliha Beste , Özbilgen Eda , Şenyer Seray , Baytimur Emre , Sarıdede Dilek Betül , Bayatlı Simay , Duru Adil Deniz 
Published: January 2025

AbstractBackgroundEmerging technologies paves the way for the development of novel cognitive assessment approaches. Virtual reality (VR) has high ecological validity, increases participant engagement, and allows the assessment of functions that are challenging to evaluate with traditional methods. The present study aimed to validate a novel cognitive assessment tool and investigate the effects of demographical variables.MethodA total of 575 healthy individuals aged between 18‐66 years were included in the study. A subgroup of the participants (n = 326) attended the verbal and visual versions of the computerized N‐back task. All participants underwent the modified version of NORA VRx™ ‐ Core experience. Seven metrics were calculated from working memory, attention, and information processing tasks during the experience. The relative contributions of the age, education and gender variables on the VR‐based metrics were assessed with multiple linear regression analysis. The concurrent validity was investigated by the correlation between VR‐based scores and N‐back scores using the Pearson Correlation.ResultsAge, gender, and education were significant predictors of the working memory scores, whereas only age and education were the significant predictors for the information processing scores. All the calculated cognitive scores worsened with the increasing age and lower education levels. Male had better scores in working memory and attention measures than female. The correct answer number at the verbal and visual N‐back tasks showed moderate correlations with the VR‐based scores. The working memory scores showed the strongest correlations with the 2‐ and 3‐back conditions (p<0.001 for all).ConclusionThe present study introduces a novel and valid cognitive assessment tool. The sample was stratified according to age and education and norm values were prepared accordingly. In the future studies, it is important to determine the characteristics of the population aged 50 years and older and to examine the discriminatory power of the novel tool among various patient groups.