Journal of Alzheimer's Disease

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

IntroductionPhosphorylated tau-217 (p-tau 217) is widely used as a plasma-based biomarker for Alzheimers Disease (AD) detection, demonstrating superior accuracy for detecting brain amyloid pathology. However, 30-50% of patients fall within an intermediate diagnostic "gray zone" where biomarker results are indeterminate, often decreasing physician confidence and requiring subsequent diagnostic workup. To address this, we developed a two-stage machine learning algorithm GRAD: Gatekeeper & Reflex ...

Biomarkers from diverse methodological domains are increasingly important in the detection, diagnosis and tracking of neurological diseases and brain health, yet they are often evaluated in isolation. Statistical integration approaches, such as factor analysis, provide a means to combine complementary biomarkers and capture higher-order domains of brain health. Exploratory factor analysis has previously been employed to identify latent brain health constructs using multimodal MRI, fluid biomarke...

INTRODUCTIONDementia reflects vascular and neurodegenerative processes in late life, yet studies often examine risks and outcomes individually. This study tested whether the cumulative burden of risks relates to structural brain pathology and cognition, and whether brain markers mediate these associations. METHODSCross-sectional data were drawn from 38,414 older adults in the National Alzheimers Coordinating Center database. A composite score summed ten binary risk factors: hypertension, diabet...

White matter microstructural abnormalities are increasingly found to be associated with cognitive impairment in Alzheimers Disease (AD). Here, we investigated the relationship between visual short-term memory (VSTM) performance, measured using a digital cognitive task, and integrity of brain white matter tracts. 52 AD and 60 age-matched healthy controls were recruited from the Oxford Cognitive Disorders Clinic. An established digital VSTM test - the Oxford Memory Task (OMT) - was used to measur...

Lifestyle and environmental factors such as diet, physical activity, residential greenspace exposure, alcohol consumption, and sleep are increasingly promoted as modifiable targets for maintaining cognitive health and mitigating age-related decline. Yet, it remains unclear how well they predict cognitive functioning and, importantly, to what extent their associations with cognition are reflected in brain and bodily health. Here, we applied machine learning to multimodal data from over 10,000 UK ...

INTRODUCTIONThe pathophysiology and risk factors for Alzheimers disease (AD) and dementia are insufficiently known. We studied the connections between gut microbiome, overall dementia and AD in a prospective, population-based cohort. METHODSWe followed a population based random sample of 4,055 individuals (FINRISK 2022) for 16 years, with 330 cases of incident dementia and 280 AD cases. Gut microbiome community diversity and composition were assessed against future dementia and AD risk. Competi...

Age and coronary artery disease (CAD) are known risk factors for cognitive decline and dementia, in which cerebral blood flow (CBF) has as a key role. Cardiorespiratory fitness (CRF) has shown consistent links with brain health and dementia, though its association with CBF and whether it differs depending on age or disease status remains limited. The main aim of this study was to examine the association of CRF, assessed through the six-minute walk test (6MWT) and peak oxygen uptake (VO2peak), wi...

Plasma p-tau217 closely tracks amyloid-{beta} (A{beta}) pathology, yet its ability to predict long-term clinical progression in cognitively unimpaired (CU) adults remains uncertain. We analyzed harmonized data from 2,705 CU participants (Agemean=69.8{+/-}7years; Female=63%) across six longitudinal cohorts with up to 13.5 years of follow-up. Cox models evaluated associations between p-tau217 and progression to a clinical diagnosis of cognitive impairment, while natural cubic spline models assesse...