bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing Race Differences on Performance‐Based Assessment in Older Adults
Authors: Kaplan Marina , Mckniff Moira , Simone Stephanie M. , Callahan Anna , Giovannetti Tania 
Published: January 2025

AbstractBackgroundRace differences on cognitive tests have been widely reported and attributed to psychosocial factors. Cognitive assessment via performance‐based tests of everyday functioning may be less influenced by psychosocial factors, offering ecologically valid and less/unbiased measurement. This study examined differences between Black/African American and White older adults on traditional cognitive tests, self/informant report of everyday function, and a sensitive performance‐based test of everyday function called the Naturalistic Action Task (NAT). We predicted group differences on only traditional cognitive tests.Method100 community dwelling older adults (M age = 73±6.88; 66% Female; 65% White; M education = 16±2.69) from the Philadelphia area completed cognitive tests of episodic memory and executive functioning as well as the NAT, which requires making a breakfast and a lunch using objects on a table. Video recordings of NAT performance were scored for cognitive aspects of performance (accomplishment of task steps, completion time, and errors) as well motor imprecisions/clumsiness (motor errors). Participants and informants also completed questionnaires of the participants’ everyday functioning (Functional Activity Questionnaire, Measurement of Everyday Cognition, The Instrumental Activities of Daily Living – Compensation). Analyses of Covariance adjusting for education were used to evaluate group differences.ResultThe groups differed in education level but not age or sex distribution. As shown in Table 1, after controlling for education, the groups differed on tests of episodic memory and executive function. By contrast, there were no group differences on the NAT cognitive measures, though Black/African American participants made significantly more motor errors. Finally, there were no group differences on any of the self/informant questionnaires.ConclusionConsistent with prior literature, Black/African American older adults and White older adults differed significantly on traditional cognitive tests, even after controlling for education. Group differences were not observed on questionnaires nor on cognitive measures from the performance‐based test of everyday functioning (NAT). However, contrary to prediction Black/African American participants made more motor errors on the performance‐based test (NAT). In sum, performance‐based tests, such as the NAT, should be considered as an alternative to traditional cognitive tests in research and clinical contexts that include racially diverse older adults.
Sex‐specific differences in the association between ApoE genotypes and metabolic syndrome among middle‐aged and older rural Indians
Authors: Azhuvalappil Shilna , Sahadevan Pravin , Sundarakumar Jonas S , Prasad Raghav 
Published: January 2025

AbstractBackgroundMetabolic Syndrome (MetS) is a significant health concern, characterized by a combination of cardio‐ vascular risk factors, influenced by genetic factors including the apolipoprotein E (ApoE). This study examines the sex‐ specific association between ApoE genotypes and MetS in a rural Southern Indian populationMethodThis cross‐ sectional study included 3741 participants aged ≥ 45 years from the rural Srinivaspura Aging, Neuro Senescence and COGnition (SANSCOG) cohort in Karnataka, India. All participants were measured for blood pressure, anthropometric measurements, and fasting concentrations of glucose, triglycerides, cholesterol, high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol. ApoE Genotypes of 1808 males and 1933 females were included in this study. Based on ApoE genotype, participants were categorized into three distinct groups: E2 (ɛ2/ɛ2 or ɛ2/ɛ3 genotype), E3 (ɛ3/ɛ3 genotype) and E4 (ɛ4/ɛ4 or ɛ3/ɛ4 genotype) carriers. Using the data from baseline clinical and biochemical assessments, we defined MetS using two established criteria: National Cholesterol Education Program – Adult Treatment Panel III (NCEP‐ ATP III) and Consensus. Multivariable logistic regression models adjusted for demographic and lifestyle factors, were used to find the sex specific association between ApoE genotypes and MetS also with its individual components.ResultThe study found a significant association between the ApoE E4 allele and MetS in females with an odds ratio (OR) of 1.31 (95% CI: 1.02, 1.69), as per the NCEP ATP III criteria. In contrast, no such association was found in males. We found females with E4 genotype also had a 1.33‐fold increase for hypertriglyceridemia (95% CI: 1.02, 1.73) and a 1.43‐fold increase in the odds of low HDL (95% CI: 1.03, 1.99). Interestingly, E4 female individuals had a 0.72‐ fold decrease in the odds of increased waist circumference (95% CI: 0.53, 0.99). In males, E4 carriers showed a 0.70‐ fold decreased odds of elevated blood pressure (95% CI: 0.54, 0.95). No significant association was found using the Consensus criteria between ApoE genotypes and MetS.ConclusionThis study highlights a significant sex‐ specific association between ApoE E4 allele and MetS and its components, particularly in females, in rural southern India.Keywords: ApoE genotypes, Metabolic syndrome, sex specific
Impact of humanized APOE on brain volumetrics and white matter microstructure within a mouse model for Alzheimer’s Disease
Authors: Bhattrai Avnish , Raikes Adam C. , McLean John W. , Wiegand Jean‐Paul L. , Brinton Roberta Diaz 
Published: January 2025

AbstractBackgroundFrequently utilized Alzheimer’s disease (AD) preclinical models rely on risk factors expressed in familial AD, which accounts for <1% of the clinical AD population. Apolipoprotein (APOE) ε4 is the strongest genetic risk factor for the development of the more prevalent late‐onset Alzheimer’s disease (LOAD). MRI studies demonstrate a link between APOE‐ε4 and reduced gray matter volume as well as lower fractional anisotropy (FA) in AD patients. However, brain volumetric and white matter integrity (WMI) data in preclinical models is lacking. Herein, we report the effect of sex and genotype on local brain volume and WMI in an aged humanized APOE (hAPOE) LOAD mouse model.MethodAged hAPOE ε3/3, ε3/4, and ε4/4 mice (N=43, mean age=24.1 months, Female=20) underwent high‐resolution ex‐vivo structural (T2‐weighted RARE; 75 microns isotropic) and diffusion‐weighted (b = 1000 mm/s2; 200 microns isotropic) MRI imaging. Deformation‐based morphometry was used to identify volumetric differences and WMI was quantified using FA. Mice were classified as ε4 carriers (at least one allele) or non‐carriers (ε3/ε3). Two‐way ANOVAs were used to identify the main effects of ε4 genotype and sex. Results are reported as FDR corrected. p≤0.05 was considered statistically significant.ResulthAPOE‐ε3/ε3 mice had larger olfactory bulbs and parieto‐temporal lobes compared to ε4 carriers and greater mean FA across major white matter tracts. Independent of genotype, females had larger cortical volumes of bilateral temporal and parietal lobes and thalami compared to males. Males had greater volume within the bilateral olfactory bulb, amygdala, hypothalamus, and hippocampi. No sex differences were observed in FA.ConclusionAt 24 months of age (approximately 70 human years), hAPOE ε4 mice exhibited decreased WMI compared to ε3s. Decreased WMI in ε4 carriers is consistent with recent work linking APOE with reduced myelin in the APOE ε4 human brain. Further, sex differences select brain region volumes indicate sex‐specific patterns of aging in this model. Collectively, outcomes of these analyses indicate both sex and APOE genotype differences in both gray matter volumes and in white matter integrity.
Midlife Cardiovascular Risk Factors and Cognitive Decline in a Diverse Cohort of Adults Ages 80 and Older
Authors: George Kristen M. , Gilsanz Paola , Corrada María M. M. , Posis Alexander Ivan B. , Peterson Rachel , Barnes Lisa L. , Kawas Claudia H. , Mungas Dan M. , Decarli Charles , Whitmer Rachel A. 
Published: January 2025

AbstractBackgroundMidlife cardiovascular risk factors (CVRF) are associated with late‐life cognitive impairment, but also mortality. We evaluated their association with cognitive decline in a diverse cohort of older adults who survived to age 80 without diagnosis of dementia.MethodThree harmonized cohorts of long‐term Kaiser Permanente members were pooled and restricted to those aged 80+. We measured CVRF from Multiphasic Health Check‐ups (MHC; 1964‐1985), which assessed hyperlipidemia, hypertension, overweight/obesity, diabetes, and smoking status. Standardized z‐scores for executive function (EF) and verbal episodic memory (VEM) were measured over up to 8 waves (2017‐2023) using the Spanish and English Neuropsychological Assessment Scales. Linear mixed models with random intercepts and slopes associated CVRF, separately, with cognitive decline adjusting for age at MHC, age at cognitive assessment, race (Asian/Black/Latino/white/multiracial), education (≤high school/some college/≤college), assessment mode (in‐person/telephone), and practice effects. Sensitivity analyses evaluated the count of CVD risk factors stratified by smoking status.ResultParticipants (n = 935) averaged 40.6(±7.9) years of age at MHC, 88.0(±4.9) years at baseline cognitive assessment, and 61.4% were women (Table 1). At midlife, 47% had hyperlipidemia, 23% hypertension, 34% overweight/obese, 1% diabetes, and 51% ever smoked. Hyperlipidemia was associated with worse baseline EF (β(95% CI):‐0.24(‐0.36,‐0.12)), smoking was associated with better EF (β:0.13(0.01,0.25)), and hypertension was associated with worse EF (β:‐0.14(‐0.25, 0.002)), though the effect was not statistically significant (Table 2). There were no associations between CVRF and EF decline. Hyperlipidemia was the only CVRF associated with worse baseline VEM (β:‐0.18(‐0.31,‐0.05)), and no CVRF was associated with VEM decline (Table 2). Despite smokers having higher baseline EF compared to nonsmokers, having 3+ CVRF was associated with steeper decline in both groups compared to those with fewer CVRF (Figure 1). Baseline VEM was similar between smokers and non‐smokers, and for both smokers and nonsmokers, the steepest declines in VEM were among those with one CVRF.ConclusionIn this diverse cohort, midlife hyperlipidemia was associated with worse cognition in late life. A positive association between smoking and EF may be indicative of resilience among midlife smokers who have reached age 80+. Regardless of smoking status, multiple CVD risk factors may be detrimental to cognitive function, particularly EF.
APOE4‐related brain vulnerabilities in memory circuitry of midlife women
Authors: Wugalter Katrina A , Thurston Rebecca C , Schroeder Rachel A , Wu Minjie , Aizenstein Howard J , Kamboh M. Ilyas , Derby Carol A. , Maki Pauline M 
Published: January 2025

AbstractBackgroundThe APOE4 genotype appears to confer differential risk of Alzheimer’s disease for women compared to men. As APOE4 effects in midlife women can be subtle (e.g., negligible main effects of APOE4 genotype on cognition and brain outcomes), there is a need for early markers of APOE4‐related brain vulnerabilities to identify those at early risk and guide treatment. We therefore examined whether patterns of brain activity and hippocampal functional connectivity that support verbal memory differ by APOE4 status in midlife women participating in MsBrain, a cohort study of brain health in midlife women.MethodParticipants completed functional magnetic resonance imaging (fMRI) assessments during verbal encoding and recognition tasks. Generalized psychophysiological interaction (gPPI) analyses estimated hippocampal functional connectivity using SPM12 and Conn, with AlphaSim (AFNI) to correct for multiple comparisons. Associations between CVLT indices and brain outcomes (regional activation, left [LHipp] and right hippocampal [RHipp] functional connectivity) were tested via multiple linear regression controlling for age, education, race, and MoCA score. Interactions by APOE4 status (carriers [E3E4 and E4E4] versus non‐carriers [E3E3]) were tested.ResultIn 166 women (mean age=59.31 years, 83.7% white, 32% APOE4 carriers), there was no main effect of APOE4 on verbal memory performance, activation, or hippocampal connectivity. During encoding, APOE4 status moderated the associations between semantic clustering and fMRI measures (e.g., activation of the left superior frontal gyrus and connectivity from LHipp to left middle frontal gyrus and to right parahippocampal gyrus; Figure 1). These associations during encoding were stronger in APOE4 carriers versus noncarriers. During recognition, APOE4 status moderated the associations between: a) total learning and activation of right inferior, middle, and superior frontal gyri; b) clustering and activation of the right superior frontal gyrus; c) total learning and LHipp connectivity to left middle temporal gyrus; and d) clustering and RHipp connectivity to right superior temporal gyrus (Figure 2). For recognition, APOE4 carriers typically showed decreased activation/connectivity, while noncarriers showed neutral or enhanced activation/connectivity.ConclusionThese findings may indicate early compensatory mechanisms in female midlife APOE4 carriers that support verbal memory, serving as potential markers of risk and targets for intervention in midlife APOE4 carriers.
White matter integrity is lower in non‐amnestic than amnestic Alzheimer's disease and differs by clinical syndrome
Authors: Phillips Jeffrey S , Adluru Nagesh , Chung Moo K , Radhakrishnan Hamsi , Olm Christopher A , Cook Philip A. , Gee James C. , Arezoumandan Sanaz , Cousins Katheryn A Q , Wolk David A , McMillan Corey T , Irwin David J 
Published: January 2025

AbstractBackgroundAmnestic mild cognitive impairment and Alzheimer’s disease (aAD) exhibit degeneration of white matter (WM) tracts preceding overt cognitive decline. However, WM changes in non‐amnestic AD (naAD) are understudied. We hypothesized patterns of WM degeneration would differ between aAD and naAD.MethodsWe compared WM degeneration, assessed by 30‐direction diffusion‐weighted imaging (DWI), in 41 individuals with aAD; 67 with naAD diagnoses including logopenic‐variant primary progressive aphasia (lvPPA), posterior cortical atrophy (PCA), behavioral variant AD (bvAD), and corticobasal syndrome (CBS); and 45 with normal cognition (Table 1). We performed deterministic tractography between 148 cortical/subcortical regions; connectivity was quantified by generalized fractional anisotropy (GFA). Tractwise GFA and regional grey matter (GM) volumes were converted to W‐scores adjusting for age and sex. We contrasted GFA between groups using regression models covarying for MMSE score. A mixed effects model was used to assess associations between tractwise GFA and volume of GM endpoints. Additionally, we computed the number of connected components in each person’s brain graph (i.e., number of subgraphs created by progressively stricter thresholds) across 100 GFA values. We contrasted this topological metric between groups and assessed its associations with MMSE and disease duration.ResultsGM volume was lower in naAD and aAD than controls (both p<0.0001) but did not differ between patient groups (p=0.81). aAD and naAD patients had shared WM degeneration in corpus callosum, cingulum, and inferior/superior longitudinal fasciculi; however, WM degeneration was more severe in naAD (Figure 1). In lvPPA, WM degeneration was left‐lateralized; in PCA, GFA was reduced in bilateral parietal, occipital, and temporal areas (Figure 2). Across groups, GM and WM degeneration were significantly associated [F(1,20442)=326.0, p<0.0001]. Topological analysis indicated naAD but not aAD patients had lower global connectivity than controls. A higher component number (indicating reduced connectivity) was associated with longer disease duration and lower MMSE.ConclusionAssociations between GM volume and GFA suggest WM degeneration in naAD is related to AD pathologic change and not an independent process. Greater WM disease in naAD than aAD was not attributable to GM atrophy or symptom severity. Finally, topological metrics may serve as objective markers of global disease progression.
Confounding factors to Alzheimer`s disease plasma biomarkers in patients from a memory‐clinic cohort
Authors: Rodrigues Matheus Scarpatto , Oliveira Markley , Lussier Firoza Z , Ferreira Pamela C.L. , Bauer‐Negrini Guilherme , Povala Guilherme , Felix Cynthia , Abbas Sarah , Zalzale Hussein , Soares Carolina , Saha Pampa , Madeiros Marina Scop , Hong Chang Hyung , Roh Hyun Woong , Karim Helmet T. , de Oliveira Jade , Zimmer Eduardo R. , Karikari Thomas K , Bellaver Bruna , Son Sang Joon , Pascoal Tharick A. 
Published: January 2025

AbstractBackgroundBlood‐based biomarkers for Alzheimer’s disease (AD) are increasingly prevalent and accessible beyond research environments. Consequently, it is crucial to determine whether confounding factors, particularly highly prevalent comorbidities, influence the levels of these blood biomarkers, thereby refining their clinical interpretation. In this study, we examined the impact of comorbidities on plasma AD biomarker levels within a memory‐clinic cohort.MethodWe analyzed 832 individuals (CU: 101, CI: 731) from the BICWALZS cohort with available information of comorbidities and plasma biomarkers measurements. The effect size of each comorbidity to plasma p‐tau217, neurofilament light chain (NfL) protein, glial fibrillary acidic protein (GFAP) and amyloid‐β (Aβ) 42/40 ratio was accessed by the β‐estimate and 95% CI values of linear regression models adjusted by clinical diagnosis, age, and sex. Comparison of biomarkers between comorbidities was carried out by ANOVA.ResultAmong the evaluated comorbidities, plasma creatinine levels, BMI index, sleep disorder, and the presence of kidney disease were the primary comorbidities linked to variations in plasma biomarker concentrations (Figure 1). Analyzing the levels of the biomarkers according to the presence of comorbidities, we observed that individuals with increased plasma creatinine exhibited significantly higher plasma levels of p‐tau217, NfL and GFAP in comparison to the individuals with normal levels of creatinine (p < 0.05, Figure 2A, B, C). The mean of p‐tau217 and NfL, but not of GFAP, was elevated between those with kidney disease (p < 0.05, Figure 2A, B). High plasma NfL levels were observed in individuals with diabetes and hypertension (p < 0.05, Figure 2B). On the other hand, high BMI index was associated with lower plasma p‐tau217, NfL and GFAP compared to individual with normal BMI (Figure 2A,B,C). We also observed that individuals with sleep disorder exhibited decreased plasma p‐tau217 levels (Figure 2A). Plasma Aβ42/40 ratio was not affected by the analyzed comorbidities (Figure 2D).ConclusionOur findings indicate that elevated creatinine levels, a higher BMI index, and the presence of kidney disease are the most significant confounding variables associated with alterations in AD plasma biomarkers. Together, our results shed light on the impact of different comorbidities to the interpretation of biomarker values in real‐world populations.
Sociodemographic and clinical heterogeneity among longitudinal studies in dementia with Lewy bodies
Authors: Kane Joseph PM , Rodriguez‐Porcel Federico , Bayram Ece , Abdelnour Carla , Desmarais Philippe , Echeverri Isabella Delgado , Ikeda Manabu , Gonzalez Maria Camila , Kanemoto Hideki , Poston Kathleen L. , Wyman‐Chick Kathryn A , Ricciardi Mario , Saeed Usman , Samancı Bedia , Satake Yuto , Yu Yueyi , Yu Jin‐Tai , Leverenz James B , Aarsland Dag ,   the ISTAART Lewy body dementias Consortia Working Group
Published: January 2025

AbstractBackgroundInternational collaboration is crucial to the future of research in dementia with Lewy bodies (DLB). Although it is hoped that a single global DLB cohort can be created through combination of data from the many longitudinal studies conducted internationally, a high likelihood of phenotypic heterogeneity may prohibit harmonisation and analysis of datasets. Our primary objective is to determine whether significant heterogeneity is observed in the sociodemographic and clinical characteristics of people with DLB globally.MethodLongitudinal DLB studies and multi‐centre consortia were invited through existing professional networks to contribute limited descriptive clinical and sociodemographic data for their samples using a standardised proforma. One way analysis of variance (ANOVA) with summary statistics as input was used to compare mean scores. χ2 test was used to compare categorical variables.ResultsDescriptive data from 10 projects in seven countries, and one multinational consortium, were shared, comprising a pooled sample of 4157 individuals with DLB. The proportion of males (χ2 = 135, df = 7, p< .01) and the duration of formal education (F(3,6) = 19.41, p<.02) varied significantly between DLB projects. No significant difference in mean age (F(3,7) = 0.87, p = .61) or duration of DLB symptoms at baseline (F(2,6) = 1.46, p = 0.46) was noted, nor was it observed in scores of baseline Mini‐Mental State Examination (MMSE)(F(2,5) = 0.73, p = 0.66), Clinical Dementia Rating (CDR) (F(1,4) = 2.04, p = .48), or Part III of the Unified Parkinson’s Disease Rating Scale (UPDRS) (F(2,6) = 12.9, p = .73).ConclusionDespite a broad range of project methodologies and a diverse group of subjects, little sociodemographic or clinical heterogeneity was observed between longitudinal DLB projects. Interrogation of subject‐level data, rather than descriptive data for each project, and more detailed clinical data on participants would allow further examination of heterogeneity. This could support harmonisation of individual DLB datasets to create a single global DLB cohort.