Journal of Alzheimer's Disease
Top medRxiv preprints most likely to be published in this journal, ranked by match strength.
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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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IntroductionBoth genetic and modifiable lifestyle factors contribute to dementia risk, yet their separate and joint predictive value for dementia and its intermediate markers (cognitive function and brain structure), is unclear. This study evaluated APOE {varepsilon}4 status, AD polygenic risk (excluding APOE), and the updated LIBRA2 index (14 modifiable factors) in predicting dementia, cognition, and brain imaging biomarkers. MethodsTo examine associations of APOE {varepsilon}4, PRS-APOE, and ...
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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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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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Neurodevelopmental disorders (NDDs) influence lifespan neurocognitive trajectories and can be conceptualized as falling on a continuum. However, transdiagnostic neurodevelopmental investigations in cognitive aging are rare. This preliminary, cross-sectional study aimed at exploring lifespan manifestations of neurodevelopmental vulnerabilities (DVs) in cognitive aging, while adopting a dimensional approach to NDDs. The objectives, covered from childhood to adulthood, were: 1) to describe NDDs-rel...
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The Montreal Cognitive Assessment (MoCA) is widely used to screen for cognitive impairment, yet commonly applied cutoff scores have been found to perform poorly among US Latinos. Prior studies relied on small samples, combining persons with mild cognitive impairment (MCI) and dementia into a single group, or failing to account for multiple intersecting demographic factors. We identified optimal MoCA cutoffs for MCI and dementia among US Latinos while addressing these limitations. We analyzed cro...
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There is a predicted increase in older adults presenting with mild to severe cognitive impairment. Screening tools with high sensitivity are the first frontier in identifying a cognitive pathology; however, to ensure that they are measuring the intended concept or criterion, thorough psychometric procedures should be followed. In this study, convergent criterion validity of Riga Cognitive Screening Task was measured, using cortical thickness of regions of interest as the criterion. 106 older adu...
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INTRODUCTIONChanges in mental health symptoms, and their timing in the preclinical period of dementia, are not well characterised. METHODSWe followed 5,495 Whitehall II participants (median age 68.5; 72.1% male) from their mental health symptoms assessment using the Clinical Interview Schedule-Revised (CIS-R) starting in 2012/13 to dementia diagnosis, death, or 2024. Linear mixed effects regression assessed CIS-R score changes preceding dementia. Flexible parametric models estimated association...
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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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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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Structured AbstractO_ST_ABSBACKGROUNDC_ST_ABSPatient reports are the standard when examining subjective cognitive decline (SCD). Recent research suggests that informant and clinician reports may also be associated with cognition. This study examined differences between patient, informant, and clinician definitions of SCD and their relationship to cognition. METHODSData from 4290 older adults (n=1690 normal controls, NC; n=840 mild cognitive impairment, MCI; n=1760 Alzheimers disease, AD) were e...
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Background and ObjectivesThe aquaporin-4 (AQP4) water channel plays an integral role in clearing brain waste. However, little is known about whether variations in the AQP4 gene contributes to brain health or dementia risk. We aimed to determine whether a functional AQP4 haplotype was associated with cognition, brain volumes, or incident dementia. MethodsThis study included participants from two prospective cohort studies. Firstly, participants from the Original, Offspring, New Offspring Spouse,...
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BackgroundCommunity-based clinical-pathologic studies have been instrumental to examine the association of Alzheimers disease and related disorders (AD/ADRD) with age and dementia in very-old non-Latino Whites. Here, we show the age distribution of four AD and three additional common neuropathologies across the adult lifespan and examine their relation to dementia and cognitive impairment in old and young Brazilian adults. MethodsWe examined 5,376 brains from decedents age 18 years or older (52...
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BackgroundAlzheimers disease (AD) patients are characterized by an early decline of episodic memory due to hippocampal damage. Nonetheless, besides the classical negative symptoms related to episodic memory deficits, i.e. failure to retrieve information, it has been shown that AD patients can also suffer from positives symptoms, i.e. confabulations. Some theoretical accounts have been proposed to explain the cognitive mechanisms underlying confabulation. Yet, even if most of these models have le...
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BackgroundSubjective cognitive decline (SCD) is common in older adults and may precede mild cognitive impairment (MCI). Whether longitudinal changes in self- or study partner (SP)-reported SCD improve early identification of individuals at risk for clinical progression, particularly along the Alzheimers disease (AD) biological continuum, remains unclear. MethodsWe pooled data from two longitudinal observational cohorts (DELCODE and ADNI). Cognitively unimpaired (CU) participants were recruited ...
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ObjectiveTo assess intra-individual cognitive variability (IICV) in relation to Alzheimers Disease (AD) biomarkers. MethodsThe sample included 879 adults from the National Alzheimers Coordinating Center, aged 50 and above with a complete neuropsychological evaluation and AD biomarker data available (64% cognitively intact; 36% cognitively impaired). We conducted a series of moderated regression models where AD biomarkers, neurocognitive status, and their interaction effects predicted IICV. IICV...
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INTRODUCTIONAlzheimers disease (AD) diagnostic guidelines emphasize subjective cognitive decline (SCD) preceding mild cognitive impairment (MCI), implicitly assuming awareness of cognitive decline (ACD) is preserved in preclinical AD. This study aimed to evaluate associations of decreased ACD with multimodal core AD biomarkers in cognitively unimpaired (CU) individuals. METHODSWe analyzed data from CU individuals with baseline CSF biomarkers and 3-year longitudinal neuropsychological assessment...
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ObjectiveDemographic corrections (e.g., sex, education, race, ethnicity) are often applied when assessing cognition in adults; however, these corrections have significant limitations (e.g., using years of education does not capture the quality of, or access to, education). It is therefore critical to develop novel assessment options that are less susceptible to demographic factors. This study compared demographic effects on a verbal memory test and a performance-based test of cognition and daily...
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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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Subtle alterations in awareness may emerge in the preclinical stage of Alzheimers disease (AD), yet their clinical significance and translational relevance remain unclear. This study aimed to evaluate associations of distinct awareness trajectories with clinical and multimodal AD biomarker measurements in cognitively unimpaired (CU) older adults. This prospective study analyzed data from the Anti-Amyloid Treatment in Asymptomatic Alzheimers (A4) and Longitudinal Evaluation of Amyloid Risk and N...