Journal of Alzheimer’s Disease
Top medRxiv preprints most likely to be published in this journal, ranked by match strength.
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IntroductionThis study investigates the effects of vortioxetine on cognitive performance in patients with mild cognitive impairment (MCI) in a randomized controlled trial (RCT). MCI is characterized by memory impairment and deficits in other cognitive domains and has been found to progress into Alzheimers dementia (AD) in some cases. In a recent open-label, single-arm study, vortioxetine, an antidepressant, was associated with improved cognitive function in patients with MCI, however, no placebo...
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BackgroundAlzheimers disease (AD) is a major public health issue with rising prevalence due to global aging. In France, official estimates report a societal cost of {euro}2.3 billion, however likely underestimating the true economic burden. MethodsA comprehensive economic model was developed to estimate the ADs societal cost in France. The model incorporated diagnosis timings (early, average, late), disease stages (MCI, mild, severe AD), direct and indirect costs, and different payors. Results...
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INTRODUCTIONThe association of blood-based biomarkers of neuropathology with cognition, dementia, and mortality and how these association potentially differ by race/ethnicity, has not been examined in large, diverse, nationally-representative samples of adults. METHODSThe sample included Health and Retirement Study (HRS) respondents over age 50 with blood-based neuropathology biomarker, demographic, and cognitive data (n=4,214). A{beta}-40, A{beta}-42, neurofilament light chain (NfL), and glial...
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ImportanceTraumatic brain injury (TBI) is a risk factor for dementia and is known to impact levels of several Alzheimers disease (AD) blood biomarkers. Plasma pTau217/ A{beta}42 ratio has been reported to be 90% accurate for detection of brain amyloid in civilian cohorts. ObjectiveTo evaluate the accuracy of emerging AD blood biomarkers in Veterans with and without TBI history. DesignWe assessed the performance of the FDA-approved plasma pTau217/A{beta}42 ratio and plasma levels of pTau217 and...
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INTRODUCTIONBilingualism is among several lifestyle factors associated with protection against cognitive decline, yet the biological mechanisms through which it exerts these effects remain poorly understood. METHODSWe compared neuropsychological functioning and biofluid markers of brain health between active (n = 280) and passive (n = 287) Spanish-Catalan bilinguals with biomarker-confirmed Alzheimers disease (AD). RESULTSActive bilinguals outperformed passive bilinguals on tests assessing att...
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ObjectiveTo evaluate long-term antemortem exposure to four pollutants in relation to Alzheimers disease (AD), cerebrovascular, and other dementia-related neuropathologies, measured at autopsy. DesignRetrospective cohort study. SettingIndividual participant data from four Rush Alzheimers Disease Center (RADC) longitudinal cohort studies: Memory and Aging Project, Minority Aging Research Study, Rush Clinical Core, and Latino Core. The cohorts enrolled participants residing in Chicago, Illinois (...
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BackgroundThe relationship between hip osteoarthritis (hip OA) and Alzheimers disease (AD) presents a critical paradox within the emerging "bone-brain axis": widespread phenotypic comorbidity sharply contradicts evolutionary theories of biological antagonism. This study integrates longitudinal and multi-omic analyses to determine whether this clinical overlap masks an underlying genetic neuroprotection. MethodsWe analyzed longitudinal phenotypic data from 261,767 UK Biobank participants using C...
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aStructured abstractO_ST_ABSBACKGROUNDC_ST_ABSOver the past couple of decades, the role of infections, as well as the involvement of the immune system, have been highlighted in the development of dementia. METHODData from the Wisconsin Registry for Alzheimers Prevention cohort were utilized for the analysis. A history of medical conditions was searched across the cohort, and known infections and autoimmune conditions were recorded for each participant. These conditions were then compared with t...
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BackgroundEmerging evidence suggests that microbiota play a role in Alzheimers disease (AD) pathology and cognitive performance. Interventions targeting the oral-brain axis may offer neuroprotective benefits, particularly during the early stages of cognitive impairment. This randomized controlled trial (RCT) investigated whether a multistrain probiotic supplement could modulate AD-related plasma biomarkers and cognitive function in older adults with early cognitive impairment. MethodsParticipan...
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INTRODUCTIONPeople with mild cognitive impairment (MCI) are candidates for early intervention, but not all progress to Alzheimers disease (AD) dementia. Identifying a subgroup at highest risk may improve treatment targeting. METHODSWe analyzed data from participants with MCI enrolled in the Alzheimers Disease Neuroimaging Initiative (ADNI). Cognitive domains included memory, executive functioning, language, and visuospatial abilities. We evaluated baseline performance and 6-month change scores,...
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IntroductionAlzheimers disease (AD) disproportionately affects women, with accumulating evidence suggestion a contributary role of hormones in this disparity. Given the known influence of hormones on brain health and cognition, characterizing specific profiles in dementia is crucial. In addition, sex-stratified hormonal alterations in AD and other dementias remain poorly understood. MethodsWe quantified nine steroid hormones: 11-deoxycortisol, 17-hydroxyprogesterone, aldosterone, cortisol, dihy...
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BackgroundCognitively unimpaired (CU) adults vary substantially in their risk of developing mild cognitive impairment (MCI), yet most subtyping approaches focus on downstream neurobiological or cognitive markers rather than upstream, modifiable risk factors. We aimed to identify clinically meaningful subgroups of CU adults defined by integrated comorbid, behavioral, and social risk profiles, and to evaluate heterogeneity in both incident MCI risk and cardiometabolic treatment effects. MethodsWe...
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IntroductionThe eligibility of anti-amyloid disease-modifying therapies (DMTs) and their integration into clinical practice in some institutions requires a specific range of Mini-Mental State Examination (MMSE) scores. Reliance on this pencil-and-paper psychometric instrument imposes operational burdens and risks perpetuating health disparities due to the tests known educational and cultural biases. This study evaluates the efficacy of the Digital Clock and Recall (DCR) - a rapid, FDA-listed dig...
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Background and ObjectivesProgression from mild cognitive impairment (MCI) to Alzheimers Disease and Related Dementias (AD/ADRD) varies widely across individuals, yet the mechanisms underlying this heterogeneity remain unclear. Identifying clinical and social determinants influencing this transition could enable earlier intervention. While cardiovascular and social risk factors are established contributors to dementia incidence, their role in progression from MCI to dementia may differ. Few studi...
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AbstractO_ST_ABSBackgroundC_ST_ABSAlzheimers disease is associated with impairments in decision making that undermine autonomy, health behaviors, and quality of life. Effort-based decision making, the process of weighing reward value against effort costs, is particularly disrupted in aging and Alzheimers disease. However, aging is also characterized by a shift toward socioemotional and prosocial goals, which may preserve motivation and effortful behavior. Understanding prosocial effort-based dec...
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Recent mechanistic evidence identifies lithium deficiency as a driver of Alzheimers disease and related dementias (ADRD) pathogenesis. To evaluate this hypothesis in a population-based setting, we emulated a target trial comparing ADRD progression after initiation of lithium versus antiepileptic mood stabilizers among adults [≥]55 years with bipolar disorder and mild neurocognitive disorder, using US Medicare claims with replication in two commercial databases. Lithium initiation was associa...
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Aging is the strongest known risk factor for Alzheimers disease (AD), and elevated plasma amyloid-{beta} (A{beta}) levels in healthy adults are associated with increased AD risk. Aging is also associated with autonomic imbalance, characterized by increased sympathetic and decreased parasympathetic activity. In our previous randomized clinical trial, we found that four weeks of daily slow-paced breathing designed to enhance parasympathetic activity reduced plasma A{beta}42 and A{beta}40 levels in...
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IntroductionThis clinical trial investigates the efficacy and safety of a personalized 15-day accelerated intermittent theta-burst stimulation (aiTBS) protocol, targeted at either the default mode network (DMN) or the fronto-parietal network (FPN), in individuals with mild Alzheimers disease (AD). Methods45 patients with mild AD were randomized 1:1:1 to receive 15 consecutive days of high-dose aiTBS (7200 pulses/day) targeting the DMN or FPN, or sham. The primary outcome was the change in ADAS-...
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ObjectivesTo develop a simple risk prediction model for cognitive decline in a Chinese older adult cohort, and to evaluate its performance and transportability through temporal validation and external validation in a Japanese older adult cohort. MethodsThe prediction model was developed using a derivation cohort of 5,985 cognitively normal older adults from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2015). A comparison of seven machine learning algorithms was conducted, an...
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Early-onset Alzheimers disease (EOAD) and Late-onset AD (LOAD) differ in clinical presentations and rates of progression. We aimed to compare baseline and longitudinal tau PET burden, and their relationship with clinical variables in amyloid-PET positive, cognitively impaired participants from the Longitudinal Early-Onset Alzheimers Disease Study (EOAD; n=390) and Alzheimers Disease Neuroimaging Initiative (LOAD; n=211). Patients with EOAD showed higher baseline tau PET retention, broader neuroa...