bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebrovascular disease is associated with memory function in the Health and Aging in Africa Longitudinal Study of an INDEPTH community in rural South Africa
Authors: Cotton‐Samuel Dejania , Farrell Meagan T. , Wagner Ryan G. , Bassil Darina T. , Mahlalehla Nomsa , Igwe Kay C. , Ohene‐Kwofie Daniel , Manly Jennifer J. , Mngomezulu Victor , Tollman Stephen , Berkman Lisa F. , Brickman Adam M. 
Published: December 2023

AbstractBackgroundHealth and Aging in Africa Longitudinal Study of an INDEPTH community in South Africa (HAALSI) is a sister study to the US‐based Health and Retirement Study. The purpose of HAALSI is to characterize the social, economic, biological, physical, and mental health factors in a population‐representative cohort of older adults in a rural community in Agincourt, South Africa. Beginning in 2020, as part of an Alzheimer’s disease and related disorders (ADRD) substudy, we conducted neuropsychological evaluations and structural magnetic resonance imaging (MRI) in a subset of HAALSI participants. Here, we report preliminary observations on the relationship of white matter hyperintensity (WMH) volume, a marker of small vessel cerebrovascular disease, and hippocampal volume, a marker of neurodegeneration, on memory function in a group of substudy participants.MethodNinety‐nine HAALSI ADRD participants with available MRI scans and neuropsychological outcomes at time of analysis (mean ± SD; age = 70.3 ± 10.9, 87% with no formal education or some primary education) were included in these analyses. Participants received research‐grade, harmonized 1.5T MRI scanning at a private hospital and were evaluated with a battery of neuropsychological tests. Using in‐house developed software and FreeSurfer, respectively, we derived total WMH volume and total hippocampal volume. We examined the association of these variables with memory function, operationalized as the delayed recall score of the Logical Memory Test, adapted for context.ResultAdjusting for education level, increased WMH volume was associated with poorer performance on the Logical Memory Test (standardized β = ‐0.21, p<0.05) but hippocampal volume was not (standardized β = 0.09, p = 0.41). Associations of these MRI markers with memory function did not interact with education level.ConclusionIn these preliminary analyses of older adults in a rural South African community, markers of small vessel cerebrovascular disease but not neurodegeneration are associated with poorer cognitive outcomes. Future work will examine the pathways that give rise to cognitive impairment and dementia in this rural South African population and track cognitive trajectories over time.
A logarithm derived from Mokken scaling analysis of the Addenbrooke’s Cognitive Examination–Revised discriminates with high accuracy Alzheimer’s disease from behavioral variant frontotemporal dementia
Authors: Amaral‐Carvalho Viviane , Lima‐Silva Thais Bento , Mariano Luciano Inácio , de Souza Leonardo Cruz , Guimarães Henrique Cerqueira , Bahia Valeria S , Nitrini Ricardo , Barbosa Maira Tonidandel , Yassuda Monica Sanches , Caramelli Paulo 
Published: December 2023

AbstractBackgroundThe ACE‐R is an accurate and brief cognitive battery for the detection of mild dementia, especially for the discrimination between Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD). The aim of this study was to develop a logarithm based on discriminative items of the ACE‐R for AD combined with relevant demographic characteristics that may help to differentiate AD from bvFTD.MethodThe ACE‐R was administered to 102 patients with mild dementia due to probable AD and 37 patients with mild bvFTD from two Brazilian research centers. All individuals were submitted to the Mattis Dementia Rating Scale (DRS) and the ACE‐R. The performance of the patients was compared and analyzed. Mokken scaling analysis was applied to identify the latent trait on the AD Group, and later, multivariate logistic regression and ROC curve analysis were carried out to assess the ACE‐R’s ability to discriminate AD and bvFTD.ResultMean ± SD total scores in the ACE‐R were 70.2 ± 10.8 in AD and 72.2 in bvFTD. AD Mokken ACE‐R (MokACE‐R‐AD) comprises 12 items measuring the same latent concept. In our sample, logistic regression with cross‐validation pointed that MokACE‐R‐AD, Age, Male sex, and items Orientation to time and location and the item of Memory (name and address recall) share importance as independent variables (p<0.05) to differentiate AD from bvFTD. The proposed logarithm reached an area under the ROC curve of 0.922, with 88% sensitivity, 88% specificity, 71% PPV and 96% NPV.ConclusionThe new logarithm using the ACE‐R items achieved high diagnostic accuracy in identifying mild AD versus bvFTD. Furthermore, the final ROC curves showed the superiority of the model proposed in relation to the analysis of the subscales individually or the VLOM ratio, as the literature previously reported. Further analysis in larger samples, with biomarkers or pathological confirmation, are necessary to confirm these findings.
Cerebellar‐cortical functional connectivity is associated with Alzheimer’s disease pathology and cerebellar atrophy
Authors: Kim Soyun , Adams Jenna N. , Stith Lea , Taylor Lisa M. , Harris Alyssa L. , McMillan Liv , Yassa Michael A. ,   The Alzheimer’s Disease Neuroimaging Initiative
Published: December 2023

AbstractBackgroundBrain atrophy has been associated with Alzheimer’s disease (AD) pathology. Previous research also suggests that functional connectivity (FC) among distributed neural networks is disrupted in preclinical AD. The cerebellum has been thought to play a crucial role in motor control, yet recent evidence points to its additional role in non‐motor domains as well as cognitive decline in AD. Cerebellar volume has been shown to decline along the course of AD progression. Moreover, neuroimaging studies have delineated intrinsic cerebellar‐cortical functional networks that presumably support cognitive functions. Despite the accumulating findings on neurodegeneration or FC, how cerebellar FC and atrophy relate to AD pathology in the early stage has not been extensively investigated.MethodData from 83 cognitively normal older adults (mean 71.0 yrs, 66% females) in the Alzheimer’s Disease Neuroimaging Initiative were analyzed. Volumetric data were obtained from FreeSurfer 6.0 segmentation. Resting state fMRI scans were preprocessed using the CONN Toolbox. Aβ and tau standardized uptake value ratio (SUVR) data were obtained from [18F]‐Florbetapir or [18F]‐Florbetaben (Aβ) and [18F]‐Flortaucipir (tau) PET scans. For Aβ, SUVR values were transformed to the Centiloid scale, and a global summary measure was used. For tau, SUVR values in the temporal meta regions of interest were used. Seed‐based functional connectivity metrics were computed using the 7 cerebellar parcellations (Buckner et al., 2011) that are functionally coupled to different cortical networks (Yeo et al., 2011).ResultCerebellar volume showed no significant relationship with amyloid or tau SUVR. By contrast, hippocampal atrophy was positively associated with amyloid or tau SUVR and showed trending significance (ps < 0.1). Increased Aβ burden was associated with increased cerebellar‐cortical FC in the attention, frontoparietal, and default mode networks. Increased tau load was associated with increased cerebellar‐cortical FC in the visual, somatomotor, and attention networks. Cerebellar volume was associated with cerebellar‐cortical FC in the visual, somatomotor, attention networks, but not with the limbic, frontoparietal, or default mode networks.ConclusionOur findings suggest that functional cerebellar‐cortical connectivity varies with amyloid and tau pathology in different networks, and such functional changes may precede cerebellar atrophy in preclinical AD.
Relationship for co‐trajectories of cognitive decline and late‐life depression with postmortem neuropathology
Authors: Yang Mu , Tio Earvin S. , Schneider Julie A , Bennett David A. A , Felsky Daniel 
Published: December 2023

AbstractBackgroundThe etiopathological relationship between late‐life cognitive decline and symptoms of depression remains unclear. Existing longitudinal studies have mostly grouped participants into distinct groups based on clinical diagnoses, and very few have analyzed postmortem neuropathology. Here we identified trajectories of both cognition and depressive symptoms in an elderly cohort over up to 27 years using growth mixture modeling (GMM), identifying co‐trajectory subgroups, and characterizing them with respect to postmortem neuropathologies.MethodWe analyzed 3,010 participants enrolled without dementia (mean age = 78) from the Religious Orders Study and Rush Memory and Aging Project (ROS/MAP). All included participants were evaluated for at least three annual visits for both depressive symptoms (using a modified Center for Epidemiologic Studies Depression Scale) and 19 cognitive tasks (yielding a global cognitive function summary score). A subset of 1,732 participants had complete postmortem neuropathological assessment data available. Latent trajectory subgroups were identified independently for global cognition and depressive symptoms using GMM with non‐linear time effects. Interaction effects of cognitive and depressive trajectory subgroups on neuropathologies were assessed using linear models.ResultThree trajectory subgroups (Figure 1) were identified for both cognitive decline (minimal (n = 1,232), slow (n = 1,325) and fast (n = 302)) and depressive symptoms (sustained low (n = 1,815), moderately increasing (n = 762) and consistently elevated (n = 433)). These subgroups showed significant overlap (chi‐square p = 0.0001), and their intersections defined nine co‐trajectories. A significant interaction effect (p = 0.0062) was identified between cognitive decline and depressive symptom trajectory subgroups for brain‐wide levels of paired helical filament tau; among only individuals experiencing fast cognitive decline, sustained lower depressive symptoms were associated with higher levels of tau (Figure 2).ConclusionLongitudinal cognitive decline and depressive symptom trajectories in late‐life are not independent. Intriguingly, we observed the highest tau burden in those individuals with both sustained low depressive symptoms and fast rates of cognitive decline. Given that use of antidepressants may lower tau levels (Dafsari & Jessen, 2020), future models of neuropathology in trajectory‐based analyses will incorporate patterns of medication status.
Associations between physical activity and sedentary behaviour patterns and cognition: A cross‐sectional analysis of the Canadian Longitudinal Study on Aging
Authors: Balbim Guilherme Moraes , Falck Ryan S , Liu‐Ambrose Teresa 
Published: December 2023

AbstractBackgroundEngaging in regular physical activity (PA) and limited sedentary behaviour (SB) are critical for healthy cognitive aging. However, it is unclear what combination of PA and SB patterns (e.g., high PA and low SB, high PA and high SB, etc.) is most beneficial for cognition. We thus examined how different combinations of PA and SB were associated with cognitive performance in community‐dwelling middle‐aged and older adults.MethodA cross‐sectional analysis using baseline data from the Comprehensive cohort of the Canadian Longitudinal Study on Aging (CLSA; 2010‐2015) among participants with complete PA and SB data (n = 23,125; age range 45‐86 years). PA and SB were indexed using the Physical Activity Scale for the Elderly (PASE) and cognition using a three‐factor structural equation model (i.e., memory, executive function, and verbal fluency). Participants' PA and SB levels were classified as 1) low PA and high SB; 2) low PA and low SB; 3) high PA and high SB; and 4) high PA and low SB. Linear regressions assessed associations between PA and SB combinations and cognition, adjusted for age, sex, activities of daily living, income level, educational attainment, and depression. Contrasts with Bonferroni correction tested associations of combinations of PA and SB with cognition.ResultHigh PA was associated with better cognition whether combined with low or high SB. A high PA and low SB combination was associated with better executive function (Estimated mean difference = ‐0.24, 95%CI ‐0.39 to ‐0.10, p<0.001) and verbal fluency (Estimated mean difference = ‐0.29, 95%CI ‐0.42 to ‐0.16, p<0.001) vs. low PA and low SB. A combination of high PA and high SB was associated with better executive function (Estimated mean difference = 0.17, 95%CI 0.01 to 0.33, p = 0.034) and verbal fluency (Estimated mean difference = 0.20, 95%CI 0.05 to 0.34, p = 0.002) vs. high PA and low SB. Surprisingly, low PA and high SB was associated with better executive function vs. low PA and low SB (Estimated mean difference = 0.26, 95%CI 0.11 to 0.41, p<0.001) (Table 1 and Figure 1).ConclusionHigh PA, irrespective of SB, is associated with better cognition. Low PA levels may be more detrimental to cognition than high SB levels.
Elevated Tau burden in Amygdala and Hippocampus amongst older participants with psychosis
Authors: Johnson Aubrey S. , Ziaggi Galen , Smith Anna C. , Guzmán Diana S. , Okafor Amarachukwu , Huey Edward D. , Kreisl William Charles , Talmasov Daniel , Lao Patrick J. 
Published: December 2023

AbstractBackgroundPsychosis is a debilitating cluster of symptoms occurring in some Alzheimer’s Disease (AD) patients, and is defined by the presence of delusions and/or hallucinations. Previous studies suggest that psychosis in AD patients is associated with increased tau burden and accelerated cognitive decline. We sought to assess differences in tau burden between cognitively impaired patients with psychosis(+P) and those without psychosis(‐P).MethodTwenty‐six ADNI participants with psychosis (+P; 11.5% CDR0, 42.3% CDR0.5, 30.7% CDR1, 11.5% CDR2, 4% CDR3, 77±7yr old, 50% women, 16±3yr education, 92% White) and 26 without psychosis were matched by CDR, age, sex, education, and race (‐P; 11.5% CDR0, 42.3% CDR0.5, 30.7% CDR1, 11.5% CDR2, 4% CDR3, 77±6yr old, 54% women, 15±3yr education, 92% White). The +P group was defined based on any endorsement of hallucinations or delusions on Neuropsychiatric Inventory. Flortaucipir PET data were processed according to ADNI methods. Difference in tau burden was assessed using a paired t‐test on the ROI and voxel‐level between +P and ‐P groups in Braak regions as well as the amygdala, hippocampus, and frontal, temporal, and parietal lobes A follow‐up voxelwise t‐test was performed within the +P group between those with and without concurrent symptoms at the time of their scan. Analyses were corrected for amyloid‐level and voxel‐wise analyses were evaluated at p<0.001 without multiple comparisons correction.ResultDescriptively, participant‐level scans demonstrated a variety of tau patterns, often with right laterality. Tau was elevated for +P participants compared to ‐P in the amygdala (0.6 [0.25, 0.96]; p = 0.003) and the hippocampus (0.3 [0.04, 0.55]; p = 0.03), while marginally elevated in the frontal cortex (0.09 [‐0.002, 0.189]; p = 0.06) [Figure1]. Voxel‐wise, elevated tau was localized to the amygdala, hippocampus, thalamus, and right frontal lobe [Figure2]. Additionally, with concurrent delusion symptomatology, elevated tau was localized to Braak III/IV regions [Figure3].ConclusionTau burden in the amygdala may be a potential biomarker of psychosis across the AD continuum. Right‐sided laterality is consistent with psychosis‐related structural changes and psychosis‐related tau binding needs to be assessed further. Given that early psychosis in AD is associated with faster cognitive decline, these results could inform the development of prognostic biomarkers.
Sex and genotype dependent differences in amyloid beta levels and lipid metabolism in type 2 diabetic APPxhQC transgenic mice
Authors: Babalola Joshua Adekunle , Lang Magdalena , George Meekha , Stracke Anika , Loeffler Tina , Schilcher Irene , Flunkert Stefanie , Neddens Joerg , Prokesch Manuela , Leitinger Gerd , Lass Achim , Hoefler Gerald , Hutter‐Paier Birgit 
Published: December 2023

AbstractBackgroundAccumulation of amyloid beta (Aβ) and tau proteins have for decades been thought to be central in the pathogenesis of Alzheimer’s disease (AD). More recently, a plethora of evidence emerged that links metabolic dysfunctions such as obesity, type 2 diabetes (T2D), and dyslipidemia with the pathophysiology of AD. In this study, we investigated the effects of streptozocin and high fat diet (HFD) induced T2D on lipid and amyloid beta metabolism in APPxhQC transgenic mice and their wild‐type littermates.MethodAPPxhQC mice were generated by crossbreeding APPSL with hQC mice. As controls wild‐type littermates were used. APPSL mice express human APP751 with the Swedish and the London mutation on a C57Bl/6RccHsd background. hQC mice express human glutaminyl cyclase (QC) enzyme on B6CBAF1/J background. Plasma lipids (triglycerides and cholesterol) and liver function enzymes (aspartate aminotransferase and alanine transaminase, ALT and ALT, respectively) were determined by ELISA. Brain concentrations of soluble and insoluble Aβ 1‐38, 1‐40 and 1‐42 peptides were determined using an immunosorbent assay (Mesoscale discovery immunosorbent assay) while pGlu Aβ1‐42 was measured by ELISA. Hepatic mRNA expression levels of genes involved in cholesterol efflux and lipid metabolism were determined by quantitative real time polymerase chain reaction (qRT‐PCR).ResultT2D induced increased concentrations of plasma cholesterol as well as AST and ALT levels. The magnitudes, however, were dependent on sex and genotype and were statistically significant in female wild‐type mice, while a similar pattern was observed in APPxhQC transgenes. These increased plasma concentrations were accompanied by a down‐regulation of hepatic gene expression levels of LRP1, ABCA1, PPARα, PBC1β, and NEP that were statistically significant in female wild‐type mice, while a similarly pattern was observed in APPxhQC transgenic mice. More interestingly, T2D provoked a progressive shift of brain Aβ 1‐38 and 1‐40 from soluble to insoluble forms in male APPxhQC mice and a significant increase of pyroglutamate modified Aβ 1‐42 in female mice.ConclusionT2D in APPxhQC mice provokes a shift from soluble to large insoluble polymers of Aβ in the brain, corroborates the deteriorating role of T2D in the progression of AD
The TIE‐93 : a cross‐cultural facial emotion recognition assessment adapted for multicultural Alzheimer’s dementia patients
Authors: Bourdage Renelle , Franzen Sanne , Papma Janne M. , Palisson Juliette , Joy Charlotte , Garcin Béatrice , Narme Pauline 
Published: December 2023

AbstractBackgroundFacial emotion recognition testing in patients with Alzheimer’s disease (AD) dementia has been recently identified as essential for early detection and differential diagnostics (García‐Casal et al., 2019; Strijkert et al., 2022). However, experts in neuropsychology identified that emotion recognition remains one of the most difficult domains to assess in culturally diverse populations due to a lack of culturally adapted tools (Franzen et al., 2021). To address this resource gap, this study validated a cross‐cultural test for emotion recognition; the TIE‐93.MethodFifty‐six patients with AD and 240 healthy controls (aged 60 years and older), from French and multicultural backgrounds, were included in the study. The TIE‐93 is composed of eight panels with six photos of actors displaying six different emotions (happiness, anger, disgust, fear, sadness and neutral). The participant is given a scenario with an emotion cue and are asked to identify which of the six emotions displayed matches the scenario.ResultIn healthy controls, analyses showed a negative correlation between performance and age (r = ‐.15, p<.05), and a positive correlation with education level (r = .4, p<.001). Given the difference in education level between French and multicultural participants, comparisons were made within cultures. Multicultural AD patients (n = 23) were compared to multicultural controls (n = 148) using an ANCOVA with education as a covariate. A significant effect was found for diagnosis (F(1, 168) = 6.6; p<0.01), with lower scores in AD patients compared to controls, as well as a significant emotion x diagnosis interaction (F(1, 168) = 5; p<0.05). The intergroup effect was significant only for disgust (p<0.001), fear (p<0.05) and anger (p<0.01). French AD patients (n = 33) were compared to French controls (n = 93) using an ANOVA, as education did not differ between groups. Results showed a significant effect for diagnosis (F(1, 123) = 10.3; p<0.005) with a non‐significant emotion x diagnosis interaction (F(1, 123) = 3.1; p = 0.08). However, the diagnosis effect was significant for all emotions except happiness: disgust (p<0.05), sadness (p<0.01), neutral (p<0.05), fear (p = 0.005), anger (p<0.05).ConclusionThe TIE‐93 seems valid for assessing facial emotion recognition in multicultural populations, demonstrating a decline in facial emotion recognition in patients with AD as compared to healthy controls.
Feasibility, satisfaction, and test‐retest reliability of repeated remote memory assessments with older adults
Authors: Basche Kristin E , Berron David , Peterson Amanda , Allison Samantha , Johnson Sterling C , Düzel Emrah , Clark Lindsay R. 
Published: December 2023

AbstractBackgroundFrequent, remote cognitive assessments may improve sensitivity to subtle cognitive decline associated with preclinical Alzheimer’s disease (AD). To gain insight on how use of this technology can be optimized, the objective of this study is to determine if feasibility, satisfaction, or test‐retest reliability (TRR) vary depending on task frequency schedules or demographic characteristics.MethodParticipants were recruited from a longitudinal aging cohort to complete three memory tasks via smartphone or tablet using the neotiv application: Object‐In‐Room Recall (ORR), Mnemonic Discrimination for Objects and Scenes (MDT‐OS), and Complex Scene Recognition (CSR). Participants were randomly assigned to complete 24 remote sessions over one year either: (1) every other week or (2) for multiple days within one week every other month. Each session lasted approximately 10 minutes, including one memory task followed by a delayed retrieval session 90 minutes later. Chi‐square tests were used to assess differences in feasibility, acceptability for participants who completed at least 3 sessions, and satisfaction based on task schedule, gender, age, or education. ICC was used to determine TRR of visit 2 to 3 (“V2‐V3”) and an average of visits 1+2 and 3+4 (“V1+2‐V3+4”).Result115 participants (mean age = 68.4, 66% women) enrolled; 49 completed all remote sessions to date (Table 1). Willingness to enroll differed by education (X2 = 4.2, p = .04), such that participants with at least a bachelor’s degree were more likely to enroll. Withdrawal from the study occurred more often for those scheduled to the every other week condition (X2 = 6.2, p = .01) than the every other month condition. Measures of acceptability and satisfaction did not differ by task schedule or demographics. TRR from V2‐V3 and V1+2‐V3+4 were adequate, (CSR: ICC = 0.56 and 0.64, ORR: ICC = 0.58 and 0.66, MDT‐OS: ICC = 0.38 and 0.52).ConclusionParticipants with a bachelor’s degree or higher were more likely to enroll. Reported satisfaction was similar for both task frequency schedules; however, drop‐outs occurred more frequently in those assigned to complete tasks every other week, which could suggest that it is a less optimal task schedule. TRR was moderate for all three tasks. Altogether, results suggest that repeated mobile cognitive testing can be utilized to track cognitive performance remotely.