bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammatory changes underlying sepsis‐induced cognitive deficits in the Tau P301S mouse model of Alzheimer’s disease
Authors: Smith Camryn , Tienda Adriana , Harrison Fiona E. 
Published: January 2025

AbstractBackgroundThe prevalence of sepsis and delirium in the elderly is a risk factor for subsequent diagnosis of Alzheimer’s disease and related dementias (ADRD). Post‐sepsis impairments include changes in memory, attention, emotional function, and neuromuscular strength. Studies have shown a link between the prolonged activation of microglia after infection. However, the exact mechanisms remain unclear. Challenges in modeling delirium in animal models include use of young animals, short trial endpoints, and sickness behaviors that can confound behavioral assessments. We sought to address these challenges using animals with additional ADRD‐related neuropathology. We hypothesized that age and ADRD neuropathology will be associated with greater and prolonged microglial dysfunction, and poorer behavioral outcomes after sepsis.MethodMale and female Tau P301S mice were used for this study at 5 months of age. These mice exhibit tau tangles, microgliosis and cell loss by 8 months of age. Mice of each genotype received either a polymicrobial cecal slurry injection to cause sepsis, or a vehicle control injection. Health scores of the mice were collected across the sickness timeline. Four days after infection, following recovery, behavior paradigms were conducted including y‐maze, fear conditioning, activity, rotarod, and nest‐building. The mice were then euthanized, and brains and plasma were collected to measure the progression of Alzheimer’s pathology and inflammatory response post‐infection.ResultMale mice of both genotypes were more sensitive to the cecal slurry treatments than females as indicated by sickness scores and time to recover. In male mice, P301S mice were more sensitive to the chronic effects of sepsis with greater changes in locomotor activity and tests of learning and memory.ConclusionThe data supports the link between poorer outcomes following sepsis in the presence of existing Alzheimer’s pathology and highlight a difference in the response to a systemic inflammatory challenge between male and female mice. These mice were tested prior to major development of ADRD‐related pathology to understand how additional inflammatory challenges may drive progression of ADRD pathology and behavioral changes. Future studies will confirm the range of neuropathological and neuroinflammatory changes in these mice.
A health intervention improves cognition in older adults at risk for Alzheimer’s Disease
Authors: Gray Michelle , Urbina Ray G , Jones Megan , Campitelli Anthony , Gills Joshua L , Paulson Sally , Glenn Jordan M. 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) is the 7th leading cause of death and 6th most burdensome disease among US older adults. With pharmacological treatments for AD being predominantly ill‐effective, alternative, non‐pharmacological prevention and treatment strategies warrant exploration. Personal health coaching provides individualized strategies designed to improve physical, social, and emotional health leading to positive behavior changes that may improve cognitive ability. The purpose of the present investigation was to examine the effects of a health intervention on cognitive outcomes.MethodAdults (n = 184), 60+ years, completed a 24‐month health intervention. All participants had their APOE4 status determined at baseline. Each participant completed either a monthly health coaching (HC) session or received bi‐weekly health education information email (HE). RBANS and ECOG‐12 were completed at baseline and 24 months. A repeated measures ANOVA was completed to determine changes in health intervention groups and APOE4 carrier groups over time.ResultRBANS was significantly improved after HE for most tested RBANS cognitive paradigms (Language, Immediate and Delayed Memory, and Attention) among APOE4 non‐carriers. The HC intervention significantly improved Immediate Memory, and Attention among APOE4 non‐carriers. Among APOE4 carriers, HE improved Delayed Memory and the HC intervention improved Immediate Memory. ECOG‐12 values were significantly improved for both intervention groups, but only for APOE4 non‐carriers.ConclusionBoth HC and HE produced significant improvements in many cognitive paradigms among APOE4 non‐carriers, though subjective cognitive decline was only improved in APOE4 non‐carriers. More information is needed to dissect the impetus for the changes in cognition.
Visual Cognitive Assessment Test (VCAT): A language‐neutral test to detect mild cognitive impairment and dementia in multinational cohorts
Authors: Ng Kok Pin , Ong Gwen Cui Fann , Saffari Seyed Ehsan , Bernardes Marina Musse , de Carvalho Antonella Brun , Schilling Lucas Porcello , Ranganathan Anandhi , Raghu Rema , Rosa‐Neto Pedro , Gauthier Serge , Liu Yidan , Li Xiaofeng , Baek Min Jae , Kim SangYun , Kandiah Nagaendran 
Published: January 2025

AbstractBackgroundCognitive assessments are essential for the diagnosis of mild cognitive impairment (MCI) and dementia. However, existing tests are mostly developed in English‐speaking cohorts. Hence, their application in multilingual populations will need translation which may affect their test psychometrics. VCAT is a language‐neutral visual‐based assessment that is developed to address this issue. While VCAT was validated in Southeast Asian countries, its performance in diverse language cohorts remains unclear. Here, we aim to compare the utility of VCAT with established screening tests, Montreal Cognitive Assessment (MoCA) and Mini‐Mental State Examination (MMSE), in distinguishing MCI and dementia from cognitively normal (CN) individuals in a multinational study.MethodsThis study supported by the Alzheimer’s Association has recruited 670 participants (294 CN, 244 MCI, 132 Dementia) from Brazil, Canada, China, India, Korea and Singapore and recruitment is ongoing. We standardized the administration of MMSE, MoCA and VCAT across all study sites. Participants answered a questionnaire on their demographics and underwent cognitive assessments (MMSE, MoCA and VCAT) on the same day. The performance of VCAT in distinguishing MCI and dementia from CN were assessed within each sites using the area under the curve (AUC) analysis.ResultsThe demographics, diagnosis and cognitive scores of the participants from each site were summarized in Table 1. The AUCs of VCAT in detecting MCI+Dementia vs CN were 0.979 for Brazil, 0.708 for Canada, 0.929 for China, 0.956 for Korea, 0.808 for India and 0.731 for Singapore. In comparison, the AUCs of MoCA in detecting MCI+Dementia vs CN were 0.771 for Brazil, 0.751 for Canada, 0.899 for China, 0.964 for Korea, 0.806 for India and 0.682 for Singapore, while the AUCs for MMSE in detecting MCI+Dementia vs CN were 0.896 for Brazil, 0.721 for Canada, 0.891 for China, 0.895 for Korea, 0.712 for India and 0.640 for Singapore.ConclusionVCAT showed satisfactory discriminative validity in differentiating MCI+Dementia from CN participants within multinational, multilingual cohorts. VCAT was also comparable to the MoCA and MMSE. Further analysis in a larger cohort within our study will be performed to validate the utility of VCAT globally.
Informant characteristics are associated with the Clinical Dementia Rating Sum of Boxes scores in the Alzheimer’s Disease patients participating in the National Alzheimer’s Coordinating Center Uniform Data Set
Authors: Vargas‐González Juan‐Camilo , Santuccione Antonella , Castro Laura , Ferretti Maria Teresa , Tartaglia Maria Carmela 
Published: January 2025

AbstractBackgroundThe Clinical Dementia Rating Sum of Boxes (CDR‐SB) is a widely used measurement score to stage dementia severity; it has become one of the most common outcome measurements in Alzheimer’s Disease (AD) research. The CDR‐SB requires an informant to provide information to stage a patient’s dementia severity. The effect of the informant’s characteristics including sex and relationship with patients on the CDR‐SB is unknown. We aimed to evaluate the effect of the informant’s sex and relationship to the patient on the CDR‐SB scores in patients with Alzheimer’s Disease with mild cognitive impairment or dementia included in the National Alzheimer’s Coordinating Center Uniform Data Set (NACC‐UDS).MethodWe included all participants from the NACC‐UDS that had AD as the principal diagnosis, with information about the Mini‐Mental State Examination or Montreal Cognitive Assessment scores, and informant sex and relationship to patient; we also analyzed the possible interaction between these characteristics, and the outcome was the CDR‐SB. We performed a conditional growth model using multilevel linear regression analysis.ResultWe included data from 20636 participants, totalling 47727 visits with a median of 2 (1‐4) visits. Patients' age at the initial visit was 74.0±9.4 years and 54.1% were females. Informant characteristics were mean 66.2±13.2 years of age, 69.1% were females, and the relationship to patients was 60.5% spouse or partner, 26.7% children and 12.8% other relation. The CDR‐SB scores were 0.20 (CI 95%: 0.11 to 0.29) higher when the informant was female. When comparing to informant’s relationship with the baseline being spouse or partner, the CDR‐SB was 0.39 (CI 95%: 0.25 to 0.53) higher when the informant was the child of the patient and 0.18 (CI 95%: ‐0.35 to ‐0.01) lower if other relationship. The only significant interaction was between informant relationships other than spouse or child and female patients where the scores were 0.24 (CI95%: 0.03 to 0.46) higher.ConclusionWe found that the CDR‐SB scores are significantly modified according to informant characteristics in the NACC‐UDS patients with AD diagnosis. These results are clinically relevant because informant characteristics should not affect AD patient staging, and future research should evaluate how to manage these confounding variables.
Affective symptoms and quality of life in persons experiencing subjective cognitive decline: A cross‐sectional analysis
Authors: Watry Rebecca Ann‐Maria , Hadidi Niloufar , Kreitzer Mary Jo , Bhimani Rozina , Yu Fang , Salisbury Dereck L. 
Published: January 2025

AbstractBackgroundSubjective Cognitive Decline (SCD) is a prevalent condition impacting 11.7% of older adults, which increases the risk for mild cognitive impairment and dementia. The transition to SCD and dementia is often accompanied by an increase in affective symptoms (i.e., anxiety and depression) and decreased quality of life (QoL). Affective symptoms in SCD increase the risk of Alzheimer’s disease (AD) compared to SCD alone. SCD plus (SCD+) is a condition that is known to increase the likelihood of preclinical AD, including amyloid‐beta and pathologic tau deposition. The relationships among SCD symptoms, affective symptoms, and QoL have been observed; however, they remain poorly understood. We aimed to explore the associations between SCD, affective symptoms, and QoL and identify any differences within the SCD+ subset of individuals.MethodsCommunity‐recruited individuals with SCD (n = 38) were divided into two groups SCD+ (those with >3 SCD+ features [Table 1]) and non‐SCD+. We used correlational analysis to determine relationships among SCD symptoms, affective symptoms, QoL overall, and four QoL domains.ResultsThe mean age of participants was 74.6 (7.5) years of age (Table 2). Demographic variables were not significantly different between groups. In the entire sample, significant correlations were found between anxiety and depressive symptoms (r = 0.44, p = <0.01); anxiety symptoms with overall (r = ‐0.38., p = 0.02), physical (r = ‐0.39, p = 0.02), and psychological QoL (r = ‐0.57, p <0.01); and depressive symptoms with overall (r = ‐0.49, p = <0.01), physical (r = ‐0.49, p = <0.01), psychological (r = ‐0.53, p = <0.01), and social (r = ‐0.35, p = 0.03) QoL (Table 3). Some of these correlations remained significant in the SCD+ group.ConclusionA significantly positive correlation exists between anxiety and depressive symptoms in SCD. Multiple negative correlations exist between affective symptoms and QoL in SCD. Some of these remain significant in those with SCD+. This research provides preliminary information on the relationships between SCD symptoms, affective symptoms, and QoL. Further research with a larger sample is necessary to better understand the interactions between SCD and SCD+ with affective symptoms and QoL.
Characterizing accelerated long‐term forgetting in preclinical Alzheimer’s disease using the Boston Remote Assessment for NeuroCognitive Health (BRANCH)
Authors: Molinare Cassidy , Soberanes Daniel , Dubbelman Mark A. , Hsieh Stephanie , Johnson Keith A , Sperling Reisa A , Rentz Dorene M , Marshall Gad A , Amariglio Rebecca E , Papp Kathryn V , Jutten Roos J 
Published: January 2025

AbstractBackgroundAccelerated long‐term forgetting (LTF) is characterized by unimpaired retention of information after short‐term delays (e.g., 20‐30 minutes) with increased forgetting at longer intervals (e.g., weeks to months). Previous studies have suggested that assessing LTF may provide a useful marker of preclinical Alzheimer’s disease (AD). However, assessing LTF over longer intervals is challenging using standardized in‐clinic paper‐pencil cognitive tests. Here, we leverage remote, digital cognitive testing to investigate LTF at different timepoints and its association with AD biomarkers in cognitively unimpaired (CU) older adults.MethodN = 61 CU older adults (age = 76.5±8.5, 67.2% female, 18% Aβ+) with amyloid (PiB) and tau (FTP) PET completed the Boston Remote Assessment for NeuroCognitive Health (BRANCH) at‐home on a personal device for seven consecutive days, including a Face‐Name Matching Task with identical stimuli each day. Learning across seven days was quantified using a previously validated multi‐day learning curve (MDLC) metric. Participants were asked to recall previously learned face‐name pairs after 1‐week (Median = 8(IQR = 7‐35) days) and after 6 months (Median = 6.67(IQR = 6.35,7.85) months). LTF was computed by dividing the percentage of correctly recalled face‐name pairs by a participant’s maximum performance during the 7‐day learning phase. We used linear regression models to examine the associations between LTF and initial MDLCs, global amyloid burden, entorhinal cortex (EC) and inferior‐temporal (IT) tau deposition, correcting for age, sex, and education when needed (covariates with a p‐value > 0.1 were excluded).ResultBetter initial MDLCs were associated with less accelerated LTF after 1 week (β = 0.55,95%CI[0.00‐1.09],p = 0.048), but not after 6 months (β = 0.34,95%CI[‐0.35–1.02],p = 0.329). There were no associations between LTF and global amyloid burden. However, higher EC tau was associated with accelerated 1‐week LTF (β = ‐0.18,95%CI[‐0.31—0.05],p = 0.009) but not with extended LTF(β = ‐0.14,95%CI[‐0.35–0.07],p = 0.172). In contrast, higher IT tau was associated with accelerated LTF after 6 months (β = ‐0.38,95%CI[‐0.75—0.01],p = 0.045), but not after 1 week (β = ‐0.15,95%CI[‐0.43–0.13],p = 0.280) (Figures 1‐2).ConclusionWe showed that 1‐week LTF is associated with initial learning and EC tau, and LTF at an extended interval of 6 months was associated with IT tau. This suggests that accelerated LTF may be an early cognitive sign in preclinical AD, but that assessing LTF over different time intervals may reveal unique information.
The role of negative affect, depression, and perceived disease susceptibility in self‐reported dementia worry
Authors: Gehling Jacklyn , Jacova Claudia , Robertson Frank , Dhaliwal Ravneet K. 
Published: January 2025

AbstractBackgroundWorry about developing Alzheimer’s disease and related dementias (ADRD), otherwise known as dementia worry, is a construct of significant interest in ADRD‐related health behaviors. In the present analysis, we aimed to understand dementia worry in the framework of the Health Belief Model by investigating the contribution of perceived risk/susceptibility and psychological factors including depression and negative affect.MethodAn English‐speaking community sample free of neurocognitive diagnoses (n = 279) who were aged 60‐96 (M = 73.8), 52% women, and had a mean education of 14.9 years (range = 10‐20) completed a Qualtrics online survey probing their perceptions of ADRD. Participants rated their worry about developing ADRD on a 5‐point scale (1 = not at all worried to 5 = very worried) and indicated which of 10 evidence‐based risk factors they believed contributed. Endorsed risk factors were summed for analysis. Participants also completed the Patient Health Questionnaire (PHQ‐2) and the Positive and Negative Affect Schedule (PANAS). A three‐step hierarchical regression analysis with age and education entered in step 1, ADRD Risk Sum entered in step 2, and PHQ‐2 and PANAS‐Negative Affect scores entered in step 3 was conducted predicting ADRD Worry. We first tested depression and negative affect in separate models in step 3 and found that each contributed. We then combined them into a single model to better understand the contribution of each.ResultParticipants had a mean score of .51 on the PHQ‐2 (SD = 1.07), a mean score of 7.11 on PANAS‐Negative Affect (SD = 3.26), endorsed on average 2.77 ADRD risk factors (SD = 1.83), and ranked their worry at 2.05 on average (SD = .93). In the final model, age and education did not predict ADRD Worry, whereas ADRD Risk Sum did (R‐squared change = .03, B = .09, p<.05), and negative affect and depression scores contributed further (R‐squared change = .04), but only PHQ‐2 scores were predictive (B = .16, p<.05). The contribution of ADRD Risk Sum remained significant after entry of the affective variables in step 3.ConclusionWe found that in a community sample of adults aged 60 and above, higher levels of dementia worry were associated with higher perceived disease susceptibility and poorer emotional status indexed by negative affect and, more importantly, depression.
Examination of intrapersonal and affective characteristics associated with everyday function among older adults with subjective cognitive decline
Authors: Farias Sarah Tomaszewski 
Published: January 2025

AbstractBackgroundThe purpose of this study was to evaluate a variety of intrapersonal factors that may also be associated with everyday functional outcomes in older adults with subjective cognitive decline (SCD).Participants and MethodsParticipants included 127 older adults with SCD (age M = 73.1, SD = 4.9; education M = 15.4, SD = 2.2; 80% female, 89% White) who were enrolled in an NIH funded randomized controlled trial teaching memory support strategies and healthy lifestyles (R01AG066748). This study utilized baseline data from the trial, prior to the start of the intervention. Everyday function was measured across a variety of instrumental activities of daily living (IADLs). Key independent variables of interest included self‐rated positive and negative affect, life satisfaction, resiliency, life purpose, health literacy, and perceived competence. Linear regression was used to assess associations between key independent variables and each outcome. Model building began with simple models including one key independent variable in addition to demographics (age, education, gender). A final model was then built including all variables that met a trend level association in those models (p<.15). Correlations between variables were assessed for collinearity. All analyses were conducted in R and a p‐value less than 0.05 was considered statistically significant.ResultsWhen examining predictors of IADLs, positive affect (.001), negative affect (p = .05), resiliency (p = .1) and life purpose (p = .03) were all identified in individual models as having a potential association with IADLs after controlling for demographics. When all four variables were included in a final model, along with demographics, positive affect (p = .03) remained significantly associated with IADLs. Specifically, higher positive affect was associated with greater independence in IADLs.ConclusionsIn this study we show that positive affect is an important predictor of better self‐reported IADL functioning in a group of older adults at risk for cognitive and functional decline. Positive affect has previously been associated with a host of health outcomes, but to our knowledge this is the first finding showing it may bolster everyday functioning and reduce disability. Findings may have important implications for interventions that focus on improved well‐being as a way to bolster everyday functioning among older adults with SCD.
Association of Majority versus Minority First Language Multilingualism and Socioeconomic Status on Cognition among Older Indian Adults
Authors: Strangmann Iris M. , Avila Justina F , Petrosyan Sarah , Meijer Erik , Nichols Emma , Narayanan Shrikanth , Aksman Leon M. , Lee Jinkook , Rentería Miguel Arce 
Published: January 2025

AbstractBackgroundSome research suggests that multilingualism confers a cognitive advantage, but this association may be confounded by linguistic and socioeconomic factors. Multilinguals can differ on their first language such that it could be a societal majority‐ or minority‐language, resulting in distinct reasons for‐ and experiences with‐ becoming/being multilingual, along with different socioeconomic opportunities. We evaluated the association of multilingualism (Monolingual, Multilingual‐Majority, Multilingual‐Minority) and socioeconomic status (SES) on cognition among older adults.MethodThe analytic sample included 3,918 older adults (65% Monolingual, 23% Multilingual‐Majority, and 12% Multilingual‐Minority) from the Longitudinal Aging Study in India – Diagnostic Assessment of Dementia (LASI‐DAD). Participants reported their first and (any) additional language(s), and completed a cognitive battery assessing executive function, language, memory, and visuospatial domains. Majority language within residential state was determined per the Indian Census. SES was defined by years of education, caste, consumption, and parental education. SES scores were derived through factor analysis and grouped into tertiles (High‐, Medium‐, Low‐SES). The associations of multilingualism and SES were evaluated using Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA), adjusting for age, sex/gender, and rurality.ResultMultilingual‐majority status was associated with better cognitive performance across all domains compared to monolinguals, while multilingual‐minority status performed better on all domains except memory (Table 1). Relative to high‐SES, lower‐ and medium‐SES were associated with worse performance across all domains. Results suggest an interaction between language group and SES (Figure 1). While high‐SES monolinguals performed worse than their multilingual counterparts in all domains ‐ except for memory when compared to high‐SES multilingual‐minority participants ‐ they outperformed low‐ and medium‐SES multilinguals. Although high‐SES multilinguals outperformed low‐/medium‐SES multilinguals in all domains, there were no differences between majority/minority‐multilinguals of equal SES.ConclusionBoth multilingualism, regardless of majority‐minority first language, and socioeconomic status were associated with cognitive benefits. While a multilingual cognitive advantage was more apparent among those with high SES, this advantage did not surpass the independent benefit of high SES, since monolinguals with high‐SES outperformed multilingual older adults with low‐ and medium‐SES. These results suggest that the potential benefits of multilingualism on cognition differs across life‐course socioeconomic determinants of health.