bluuebunny/crossref_metadata_2025_split huggingface dataset:
The potential protective benefit of personality on subjective cognitive decline related worry: Results from the Canadian Longitudinal Study on Aging (CLSA)
Authors: Hopper Shawna , Hammond Nicole G , Taler Vanessa , Stinchcombe Arne 
Published: December 2022

AbstractBackgroundSubjective cognitive decline (SCD), a self‐reported decline in cognition, may be a risk factor for Alzheimer’s disease. Recently, SCD‐related worry has been implicated in predicting the progression from SCD to further cognitive decline. Certain personality traits have been linked to cognitive health (i.e., conscientiousness, emotional‐stability, and openness to experience), but little is known about the association between personality traits and worry related to perceived cognitive decline.MethodAnalyzing data from the Canadian Longitudinal Study on Aging (CLSA), a large national study of participants aged 45‐85 at baseline, we sought to identify prospective psychosocial correlates of SCD‐related worry. At baseline, known correlates of cognition (e.g., depression) were measured, as well as the primary predictor of interest, personality traits, which were measured using the Ten‐Item Personality Inventory (TIPI). SCD and SCD‐related worry were measured three years later. Participants who positively endorsed SCD at follow‐up were asked a single‐item assessing their worry about their self‐reported memory decline. Response options ranged from disagree to agree. Multiple imputation using chained equations (MICE) was conducted to account for missing data. An ordinal logistic regression model was used to estimate the odds of reporting greater SCD‐related worry (n = 27,745).ResultMany psychosocial measures were associated with greater SCD‐related worry, for example, being a woman (OR = 1.35, CI: 1.25‐1.45), being younger (OR = 0.99, CI: 0.97‐0.99), and elevated depression symptoms (OR = 1.44, CI: 1.32‐1.58). With respect to personality traits, higher levels of certain traits were associated with reduced odds of SCD‐related worry: extraversion (OR = 0.96, CI: 0.95‐0.98), conscientiousness (OR = 0.95, CI: 0.92‐0.97), and emotional stability (OR = 0.86, CI: 0.84‐0.88). Openness to experience (OR = 1.01, CI: 0.99‐1.03), and agreeableness (OR = 1.00, CI: 0.97‐1.03), were not associated with SCD‐related worry.ConclusionHigher levels of extraversion, conscientiousness, and emotional stability were associated with higher worry regarding perceived decline in cognitive functioning. This information may help identify individuals at a greater risk of future cognitive impairment and dementia.
Short antibiotic treatment followed by regular administration of acid suppressant (proton pump inhibitor) reduce AB42 load in the brain and in the gut.
Authors: Chevalier Claire , Marizzoni Moira , Tournier Benjamin , Paquis Arthur , Gueorguiev Boris R , Millet Philippe , Frisoni Giovanni B 
Published: December 2022

AbstractBackgroundFecal microbiota transplantation (FMT) from healthy mice, microbiota depletion with antibiotic treatment (ABT) or with germ free mice have been associated with a reduction of cerebral amyloid load in Alzheimer’s disease (AD) mice models, indicating that the gut microbiota can modulate amyloid load in the brain. Interestingly, amyloid can also deposit in the gut, particularly within proximity to vasculature, nerves, and nerve plexuses. Additionally, acid suppressant drug such as proton pump inhibitors (PPI) have been shown to modify the gut microbial population. Here we postulate that ABT+PPI could modulate the gut microbiota and amyloid load in the gut and in the brain.MethodSixty female, two‐year old 3xTg mice (APPSWE, PS1M146V and TauP301L) were divided in 2 groups and received: (1) 2‐weeks of ABT to deplete the microbiota followed by recurrent PPI administration simultaneously with (FMT) once a week for 2 months or (2) FMT only at same frequency. The FMTs consisted in i) water, ii) litter mate mice and, iii) bacteria isolated from 1 young and 1 cognitively unimpaired elderly donor to test different microbiota.ResultAfter 60 days of treatment, Ab42 and Ab40 were measured by ELISA in the hippocampus and the colon. We observed that ABT‐PPI treatment reduced the soluble and insoluble form of Ab42 in the hippocampus (ANOVA p<0.05) and, interestingly, also in the colon (ANOVA p<0.05), independently of the microbiota transplanted. This was specific to the Ab42 isoform as no differences was observed in the levels of AB40.ConclusionThe results suggest that ABT‐PPI can reduced Ab42 in the brain as well as in the gut in an AD mice model, independently of the microbiota transplanted. The link between the amyloid in the gut and in the brain remain a black box. More research is needed to rule out that the Ab detection in the gut is not due to randomly deposited circulating amyloid from blood. Also, the short ABT intervention and the 2 months delay before sample collection suggests that the driver of the effect observed is the PPI. This will be confirmed by testing the administration of PPI only.
Assessment of decisional capacity for Alzheimer’s disease PET disclosure among cognitively symptomatic individuals
Authors: Rahman‐Filipiak Annalise , Feldman Sara J , Lesniak Mary , Milliken Marie , Roberts J. Scott , Hampstead Benjamin M. 
Published: December 2022

AbstractBackgroundOlder adults are highly interested in learning their Alzheimer’s disease (AD) positron emission tomography (PET) amyloid‐beta (Aβ) and tau results. However, knowledge about the meaning, uses, and risks of learning personal biomarker results is variable. Tools are needed to assess decisional capacity prior to biomarker disclosure, particularly for individuals with cognitive impairment.Methods30 participants (46.7% female; 93.3% white, age = 71.9±7.14 years) diagnosed with either mild cognitive impairment (MCI; 60.0%) or dementia‐Alzheimer’s type (DAT; 40.0%) completed Aβ and tau PET, an interactive education session and results disclosure decision‐making assessment. When available, cognitively unimpaired care partners (n = 27) attended these sessions and their ability to demonstrate decisional capacity for participant biomarker disclosure was assessed. Decisional elements evaluated included understanding of the meaning of biomarker results, appreciation of risks and benefits of engaging in disclosure, communication of a choice to learn the participant’s biomarker results, and demonstration of a rationale for engaging (or not) in disclosure. Chi‐squared tests were used to assess whether successful demonstration of each element differed by diagnosis.ResultMore participants with MCI (77.8%) than participants with DAT (25.0%) demonstrated disclosure decisional capacity (χ2 = 8.17, p = .008). Across the full sample, participants had the most difficulty understanding the difference between AD and DAT (34.6% incorrect), the meaning of elevated amyloid (19.0% incorrect) or tau (10.0% incorrect), and biomarker disclosure risks (19.0% incorrect). Compared to participants with DAT, those with MCI were more likely to demonstrate understanding of biomarker results (33.3% DAT v. 77.8% MCI; χ2 = 5.93, p = .024) and appreciation of personal benefits and risks of biomarker disclosure (33.3% DAT v. 83.3% MCI; χ2 = 7.75, p = .009). There were no differences in demonstration of rationale or communication of choice by diagnosis. All care partners demonstrated adequate decisional capacity for disclosure of the participant’s PET results.ConclusionAppreciation and understanding, two elements rarely evaluated in clinical or research settings, are more challenging than rationale or choice for cognitively impaired participants to demonstrate. Prior to disclosure, education should emphasize the possible meaning, usefulness, and risks of PET amyloid and tau information. Family or care partner disclosure decision‐making assessment should be a standard part of disclosure protocols.
Cardiovascular health and resilience to cognitive decline and impairment among diverse Hispanics/Latinos: Results from the Study of Latinos‐ Investigation of Neurocognitive Aging (SOL‐INCA)
Authors: Tarraf Wassim , Stickel Ariana M , Wu Benson , Brewer James B. , Gallo Linda C , Talavera Gregory A , Isasi Carmen R , Kaplan Robert , Lipton Richard B. , Daviglus Martha L , Zeng Donglin , Pike James R. , Schneiderman Neil , Rundek Tatjana , Sofer Tamar , Fornage Myriam , DeCarli Charles S. , Fletcher Evan , Branch Craig , Zhou Xiaohong , Gonzalez Hector Leonardo 
Published: December 2022

AbstractBackgroundCardiovascular disease contributes to cognitive impairment and dementia, particularly among populations facing health disparities. However, the long‐term effects of cardiovascular health on later cognitive health have not been examined among Hispanics/Latinos. Therefore, we examined relationships between cardiovascular health with change in cognition and mild cognitive impairment (MCI) among diverse Hispanics/Latinos.MethodHispanics/Latinos (n = 6,223, ages 50‐86 years) were enrolled in the Study of Latinos ‐ Investigation of Neurocognitive Aging (SOL‐INCA), an ancillary study of the Hispanic Community Health Study/SOL (HCHS/SOL). Cardiovascular health was the primary exposure, measured using the American Heart Association’s Life’s Simple 7s (LS7). Outcomes of interest included 7‐year performance in cognition, change in cognition, and MCI prevalence. Cognitive outcomes included measures of learning and memory, verbal fluency, executive functioning and processing speed, and a global composite (average of the z‐scores on each test). Survey linear regressions were used to separately model the associations between LS7 with outcomes of interest, controlling for age, age2, education, language preference, Hispanic/Latino background, and income.ResultsBetter cardiovascular health (higher LS7 Score) was associated with higher global cognitive performance (βGlobal = 0.028 [SE = 0.005], p<0.001). These associations were evident in learning (βB‐SEVLT‐Sum = 0.024 [SE = 0.007], p<0.01), memory (β = 0.024B‐SEVLT‐Recall [SE = 0.008], p<0.01), verbal fluency (β = 0.039WF [SE = 0.008], p<0.001), executive functioning and processing speed (βDSS = 0.027 [SE = 0.007], p<0.001 and βTrails A = ‐0.022 [SE = 0.007], p<0.01). We also observed significant associations between better cardiovascular health and improved global cognitive change (β = 0.023 [SE = 0.008], p<0.01), evident also for learning (βB‐SEVLT‐Sum = 0.017 [SE = 0.008], p<0.05), executive functioning and processing speed (βDSS = 0.034 [SE = 0.008], p<0.001). Lastly, better cardiovascular health decreased the odds ratios for prevalent MCI (ORMCI = 0.90 [0.842, 0.959], p<0.01).ConclusionCardiovascular health was protective of 7‐year cognitive aging and associated with reduced MCI prevalence. Our findings suggest that cardiovascular health may improve resilience to cognitive decline and impairment amongst diverse Hispanics/Latinos, which could prove instrumental in public health efforts for reducing dementia disparities facing Hispanics/Latinos.
Quantifying longitudinal cognitive resilience to Alzheimer’s disease and other neuropathologies
Authors: Wagner Maude , Wilson Robert S. , Leurgans Sue E. , Boyle Patricia A , Bennett David A , Grodstein Francine , Capuano Ana W. 
Published: December 2022

AbstractBackgroundCognitive resilience (CR) has been defined as the continuum of better (or worse) than expected cognition, given the degree of neuropathology. To quantify this concept, existing approaches focus on either cognitive level at a single timepoint (Figure 1A) or slopes of cognitive decline (Figure 1B).MethodIn a prospective study of 1,215 participants, we created a continuous measure of CR defined as the mean of differences between estimated person‐specific and marginal cognitive levels over time, after accounting for neuropathologies (Figure 1C).ResultNeuroticism and depressive symptoms were associated with all CR measures (P‐values<.012); as expected, cognitive activity and education were only associated with the cognitive‐level approaches (P‐values<.0002). However, compared with the existing CR measures focusing on a single measure or slopes of cognition, our new measure yielded stronger relations with risk factors.ConclusionDefining CR based on the longitudinal differences between person‐specific and marginal cognitive levels is a novel and complementary way to quantify CR.
Improved biomarker associations using neuropsychological criteria versus ADNI criteria for diagnosis of MCI in Vietnam‐era veterans with head injury histories
Authors: Ly Monica T. , Bondi Mark W. , Edmonds Emily C. , Delano‐Wood Lisa 
Published: December 2022

AbstractBackgroundCompared to conventional Petersen/Winblad criteria for mild cognitive impairment (MCI), our prior work has shown that neuropsychological or “actuarial” criteria more accurately predicts progression to dementia, and is more strongly associated with Alzheimer’s disease (AD) biomarkers and imaging profiles. However, research to date has been conducted in relatively healthy samples with few comorbidities. Given that history of traumatic brain injury (TBI) and post‐traumatic stress disorder (PTSD) is common in older veteran populations, and both conditions are well‐documented risk factors for AD, we compared Jak/Bondi neuropsychological and ADNI MCI criteria to examine cross‐sectional cognitive and biomarker profiles in a well‐characterized sample of Vietnam‐era veterans with history of TBI and PTSD.Method186 veterans (mean age = 70.11) from the DoD‐ADNI study with history of TBI were evaluated for MCI using (1) ADNI criteria: subjective memory concern, objective memory impairment using WMS‐R Logical Memory, and Clinical Dementia Rating Global = 0.5; and (2) neuropsychological criteria: >1 standard deviation (SD) below age‐appropriate norms on two tests within any cognitive domain, or >1 SD below age‐appropriate norms on one test across all domains. Accounting for age and education, linear regression evaluated relationships between MCI diagnosis and AD biomarkers (Aβ42, total tau [t‐tau], and phosphorylated tau [p‐tau]). Logistic regression evaluated whether PTSD symptoms (CAPS total score) predicted MCI.ResultRoughly 17% of the sample met neuropsychological criteria for MCI, while 13% met ADNI criteria. Agreement between criteria was poor (κ = .17). APOE4 carrier status did not predict diagnosis by either criteria. MCI diagnosis using neuropsychological criteria was associated with higher t‐tau (p = .049) and p‐tau (p = .04), but not Aβ42 (p = .15), while ADNI diagnosis was not associated with any biomarkers (p>.05). PTSD symptoms predicted MCI diagnosis using ADNI (p = .005) but not neuropsychological criteria (p = .19).ConclusionFindings showed that MCI diagnosis using sensitive neuropsychological methods is more strongly associated with AD biomarkers than conventional diagnostic methods. Additionally, ADNI criteria may be capturing false‐positive diagnoses secondary to PTSD. MCI diagnostics benefit from the incorporation of comprehensive neuropsychological methods, particularly in complex populations with medical and psychiatric comorbidities.
The Impact Treatment Imbalance and Patient Enrichment has on Study Sample Size in Early/Mild Alzheimer’s Disease
Authors: Buitendyk Melanie , Rosen Allan , Barnum CJ , Tesi RJ 
Published: December 2022

AbstractBackgroundDisease modification trials in Alzheimer’s Disease (AD) are typically conducted in Early AD patients, combination of patients with mild cognitive impairment (MCI) and mild AD (mAD), despite vastly different progression rates between these two AD groups. A large sample size (SS) is required to show efficacy due to low MCI APRs. Furthermore, treatment group imbalances in patients likely to progress (PLP) may lead to underpowered studies. We quantified the impact on SS of: (1) potential treatment group imbalances in PLPs and (2) PLP enrichment strategies.MethodRoughly 10% of patients diagnosed with MCI progress to dementia within 1 year (Mitchell, 2009). Patients with mAD progress at an APR of 25% (Davis, 2018). To assess the impact on SS, we considered a 1:1 randomized study, stratified by equally sized AD strata (MCI, mAD) with 90% power and 1‐sided 0.025 level Cochran Mantel Haenszel (CMH) test to detect lower APRs in the experimental arm compared to placebo for an odds ratio (OR) = 0.5. To assess the impact of treatment group imbalances in PLPs, we computed SS for various departures from a balanced study. SS calculations were performed after enriching the APR in the MCI or both AD strata.ResultSS increases as more PLPs are assigned to the experimental arm than the control arm. For example, SS is 852 when PLPs are balanced 50%:50% between arms and 932 with a 55%:45% imbalance. When the MCI population is enriched to a 20% APR, SS is 672 for a balanced study and 732 with a 55%:45% imbalance. The following figure displays the impact of a PLP enrichment strategy on SS by increasing APRs by 5% in each AD strata, assuming no treatment group imbalances in PLPs.ConclusionPrediction (Davis, 2018) and machine learning (James, 2021) models have been developed to classify PLPs. Using such tools to stratify patients by PLP status at randomization minimizes the risk of having an underpowered study. The same tools can be used to enrich both the MCI and mild AD populations with PLPs to reduce SS requirements.
Combinatorial therapeutic effect of Environmental Enrichment and a Poly‐herbal formulation against amyloid‐beta induced Alzheimer’s disease in rodents
Authors: Rajendran Kayalvizhi , Krishnan Uma Maheswari , Chellappan David raj , Babu Aadhithyan 
Published: December 2022

AbstractBackgroundAlzheimer’s disease (AD), a common form of dementia currently has no single disease‐modifying drug to halt disease progression. Environmental enrichment (EE) has emerged as an effective therapeutic strategy against various brain disorders. Our previous studies have revealed that the phytoformulation BN was effective in improving cognition and working memory in rodent models induced with cholinergic deficits. BN also inhibited tau hyperphosphorylation, increased dendritic arborization, and modulated AKT and MAPK pathways. In the present study, we propose to evaluate the combinatorial effect of BN and EE against AD.MethodA rodent model of AD was created in Wistar rats through bilateral intra‐hippocampal injection of 100 µg/µL amyloid beta(1‐42). After ten days, the animals were randomly divided in to five groups (GII to GVI) and compared with normal animals (GI). The treatment regimen was commenced with GII acting as disease control, GIII receiving BN (844 mg/kg b.w), GIV receiving combined treatment of EE and BN, GV received only EE and GVI receiving the standard drug donepezil (4 mg/kg b.w.) for a period of 28 days. The cognition and spatial learning were assessed using behavioral studies. Gene and protein expression of key molecular targets were performed to gain insights into the molecular mechanism involved in the combination therapy. Amyloid plaque load was detected using thioflavin S, and dendritic morphology was studied using Golgi‐Cox staining. For EE, cages measuring 60×60×60 cm containing a running wheel, play tubes, ladder, balls, toys, and nesting material that are rearranged weekly, were used to study behavioral changes associated with cognitive stimulation.ResultWe found improved exploratory behaviour of the animals in EE when compared to their counterparts in normal cages. Other behavioral patterns like chewing, physical activity, sorting are significantly higher in animals subjected to the combination of EE and therapy when compared to animals treated in the conventional environment. The cognition and behavioral studies coupled with the histopathological results, gene and protein expression studies will help in establishing the molecular mechanism of the combination.ConclusionThe results from this study open up new therapeutic directions involving environmental factors and multi‐targeted therapeutic agents against AD.
Cerebrovascular disease and dementia: exploring causal pathways
Authors: Sargurupremraj Muralidharan , Soumare Aicha , Bis Joshua C , Adams Hieab H.H. , Dufouil Carole , Milani Lili , Gudnason Vilmundur , van Duijn Cornelia M , Winsvold Bendik , Launer Lenore J. , Seshadri Sudha , Debette Stéphanie 
Published: December 2022

AbstractBackgroundCerebrovascular disease is increasingly recognized as playing a major role in the pathophysiology of dementia. We aimed to (i) explore the relation of genetically determined white matter hyperintensity burden (WMH) – a common MRI‐marker of covert cerebral small vessel disease (cSVD) – with risk of dementia and Alzheimer disease (AD); (ii) compare it with the relation of dementia/AD and genetically determined blood pressure (BP) and stroke, respectively a major risk factor and complication of WMH.MethodUsing a suite of two‐sample Mendelian randomization (MR) approaches we examined the association of genetic instruments for WMH, BP and stroke with AD, leveraging summary statistics of genome‐wide association studies. In addition to differentiating the causal effects of the exposure from shared effects of genetic instruments and outcome, we used multivariable approaches to estimate direct effects after accounting for potential confounders. Next, we used Cox proportional hazard and multi‐state models in 8 CHARGE cohorts to test the association of genetically determined WMH, BP and stroke with incident dementia (N = 10,034 cases) in a longitudinal setting and examined the relation of polygenic scores (PGS) for WMH, BP, and stroke with incident dementia (subtypes).ResultUsing two‐sample MR approaches we show strong evidence for a causal association of WMH with AD, with a marked increase (27.8%) in the direct effect of WMH on AD after accounting for confounding effects in a multivariable scheme. In population‐based longitudinal cohorts genetically determined WMH also showed nominal association with incident all dementia [HR: 1.01(1.00‐1.01)] and a WMH PGS was associated with increased risk of all dementia and AD [HR: 1.12(1.02‐1.23)], even after adjusting for interim stroke. In contrast, genetically determined stroke and BP showed (a trend to) an inverse association with AD using two‐sample MR, which was partly reversed (for BP) in a longitudinal setting.ConclusionOur results support a causal association of increasing WMH volume with dementia/AD risk, with indications that this may be specific to cSVD rather than reflecting the impact of related vascular phenotypes on dementia/AD, highlighting cSVD as an important target for prevention.