INTRODUCTIONThis study investigated the associations of brain age gap (BAG)—a biological marker of brain resilience—with life exposures, neuroimaging measures, biological processes, and cognitive function.METHODSWe derived BAG by subtracting predicted brain age from chronological age in 739 septuagenarians without dementia or neurological disorders. Robust linear regression models assessed BAG associations

To understand the potential benefits of emerging Alzheimer's disease (AD) therapies within and beyond clinical trial settings, there is a need to advance current outcome measurements into meaningful information relevant to all stakeholders. The relationship between the impact on disease biology and clinically measurable outcomes in cognition, function, and behavior must be considered when defining

INTRODUCTIONCerebrovascular dysfunction occurs in Alzheimer's disease (AD), impairing hemodynamic regulation. Large conductance Ca2+‐activated K+ channels (BKCa) regulate cerebrovascular reactivity and are impaired in AD. BKCa activity depends on intracellular Ca2+ (Ca2+ sparks) and nitro‐oxidative post‐translational modifications. However, whether these mechanisms underlie BKCa impairment in AD remains

INTRODUCTIONWhile there may be microbial contributions to Alzheimer's disease (AD), findings have been inconclusive. We recently reported an AD‐associated CD83(+) microglia subtype associated with increased immunoglobulin G4 (IgG4) in the transverse colon (TC).METHODSWe used immunohistochemistry (IHC), IgG4 repertoire profiling, and brain organoid experiments to explore this association.RESULTSCD83(+)

INTRODUCTIONWe investigated whether early life exposure to state‐level structural sexism influenced late‐life memory trajectories among United Staes (U.S.) ‐born women and men and determined whether associations differed between racialized groups.METHODSParticipants were from the Washington Heights‐Inwood Columbia Aging Project (WHICAP; N = 2314) and Health and Retirement Study (HRS; N = 18,631). State‐level

INTRODUCTIONPlacental growth factor (PlGF) may regulate cerebrovascular permeability. We hypothesized that white matter interstitial fluid accumulation, estimated via magnetic resonance imaging (MRI) free water (FW), would explain the associations between elevated PlGF, white matter hyperintensities (WMH), and cognitive impairment.METHODSMarkVCID consortium participants ≥55 years old with plasma PlGF

The immune system is a key player in the onset and progression of neurodegenerative disorders. While brain resident immune cell‐mediated neuroinflammation and peripheral immune cell (eg, T cell) infiltration into the brain have been shown to significantly contribute to Alzheimer's disease (AD) pathology, the nature and extent of immune responses in the brain in the context of AD and related dementias

INTRODUCTIONStudies using cross‐sectional data or with a short follow‐up period fail to distinguish whether the associations between sleep duration and physical activity with cognitive function result from reverse causation.METHODSThe longitudinal study examined the individual and joint associations, with specific temporality, between sleep duration and physical activity with cognitive function, using

Determining whether disease-modifying treatments (DMTs) in early Alzheimer's disease (AD) provide clinically meaningful benefits to people living with AD is critical and has triggered much debate in the field.1-4 AD is a slowly progressive, ultimately fatal, neurodegenerative disease, characterized by progressive loss in cognitive ability and daily function.5 Current DMTs aim to slow disease progression

INTRODUCTIONProgressive supranuclear palsy (PSP) is a devastating 4R tauopathy affecting motor functions and is often misdiagnosed/underdiagnosed due to a lack of specific biomarkers. Synaptic loss is an eminent feature of tauopathies including PSP. Novel synaptic positron emission tomography tracer UCB‐J holds great potential for early diagnosis; however, there is a substantial knowledge gap in terms

The SORL1 locus exhibits protective effects against Alzheimer's disease (AD) across ancestries, yet systematic studies in diverse populations are sparse.

INTRODUCTIONThis study investigated the impact of trisomy 21 mosaicism (mT21) on Alzheimer's disease (AD) neuropathology in a well‐characterized clinical case described by Ringman et al.METHODSWe describe AD neuropathology in mT21 including amyloid beta, phosphorylated tau, astrogliosis, microgliosis, α‐synuclein, and TAR DNA‐binding protein 43 (TDP‐43) in cerebral cortex, hippocampal subregions, and

INTRODUCTIONRecommendations for advance care planning (ACP) in persons with cognitive impairment are based on expert input without insight from actual ACP conversations.METHODSWe used thematic analysis to analyze transcripts of ACP conversations for 88 older adults with normal cognition (n = 15), mild cognitive impairment (n = 13), and scores consistent with dementia (n = 60).RESULTSPatients with dementia

We investigated the hypothesis that tau burden in the locus coeruleus (LC) correlates with tau accumulation in cortical regions according to the Braak stages and examined whether the relationships differed according to cortical amyloid beta (Aβ) deposition.

The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is evaluating lifestyle interventions in older adults at risk for cognitive decline and dementia. Here we characterize the baseline data set of the POINTER Imaging ancillary study.

Recent research highlights the critical role of inflammation in accelerating amyloid beta and phosphorylated tubulin‐associated protein tau cascade and Alzheimer's disease (AD) progression. Emerging evidence suggests that exercise influences AD by modulating inflammatory responses. We conducted a comprehensive search across multiple online databases. Our approach focused on previous and recent studies

INTRODUCTIONBlood‐based biomarkers (BBMs) can enable early detection of brain amyloid beta (Aβ) pathology in cognitively unimpaired individuals. However, the extent to which common medical conditions affect biomarker performance remains unclear.METHODSParticipants (n = 348) included individuals without cognitive impairment. We studied how brain Aβ associated with BBMs (Aβ42/40, phosphorylated tau [p‐tau]

INTRODUCTIONUsing a single‐nucleus transcriptome derived from the dorsolateral prefrontal cortex of 424 Religious Orders Study and the Rush Memory and Aging Project (ROS/MAP) participants, we investigated the cell type–specific effect of ten vascular endothelial growth factor (VEGF) genes on Alzheimer's disease (AD) endophenotypes.METHODSNegative binomial mixed models were used for differential gene

More than 2 million older Americans from underrepresented racial and ethnic minority groups (URGs) have early‐stage Alzheimer's disease and related dementias (ADRD). There are very few scalable recruitment strategies, particularly for Black older adults, to accelerate participation in ADRD research. The Indiana Alzheimer's Disease Research Center (IADRC) and its Community Advisory Board developed and

INTRODUCTIONChildhood adversity harms neurodevelopment. Literature on late‐life brain health is limited, and findings on late‐life cognition are mixed.METHODSPooling data from Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) and Study of Healthy Aging in African Americans (STAR) cohorts, we assessed the impact of childhood adversity (factor score from seven self‐reported items) on (a) executive

INTRODUCTIONHigh microglial heterogeneities hinder the development of microglia‐targeted treatment for Alzheimer's disease (AD).METHODSWe integrated 0.7 million single‐nuclei RNA‐sequencing transcriptomes from human brains using a variational autoencoder. We predicted AD‐relevant microglial subtype‐specific transition networks for disease‐associated microglia (DAM), tau microglia, and neuroinflammation‐like

INTRODUCTIONThis study presents a novel multi‐view learning approach for machine learning (ML)–based Alzheimer's disease (AD) diagnosis.METHODSA diffusion model is proposed to synthesize the fluorodeoxyglucose positron emission tomography (FDG PET) view from the magnetic resonance imaging T1 weighted imaging (MRI T1WI) view and incorporate two synthesis strategies: one‐way synthesis and two‐way synthesis

INTRODUCTIONWe evaluated whether higher Dietary Inflammatory Index (DII) scores were associated with increased incidence of all‐cause dementia and Alzheimer's disease (AD) dementia over 22.3 years of follow‐up in the community‐based Framingham Heart Study Offspring cohort.METHODSOne thousand four hundred eighty‐seven participants (mean ± standard deviation, age in years 69 ± 6) completed food frequency

BACKGROUNDThe diagnostic and prognostic performance of the novel fluid biomarkers brain‐derived tau (BD‐tau) and phospho‐tau217 (p‐tau217) in Creutzfeldt–Jakob disease (CJD) is not defined.METHODSWe measured cerebrospinal fluid (CSF) and plasma BD‐tau, p‐tau217, p‐tau181, total tau (t‐tau), neurofilament light (NfL), and 14‐3‐3 in 100 CJD patients, 100 with non‐prion rapidly progressive dementia (np‐RPD)

The influence of genetic variation on tau protein aggregation, a key factor in Alzheimer's disease (AD), remains not fully understood. We aimed to identify novel genes associated with brain tau deposition using pathway-based candidate gene association analysis in a Korean cohort.

The revised biomarker framework for diagnosis and staging of Alzheimer's disease (AD) relies on amyloid beta (Aβ) and tau pathologies as core markers, and markers for adjacent pathophysiology, such as neurodegeneration and inflammation. Many of the core fluid biomarkers are phosphorylated tau (p‐tau) fragments, with p‐tau217 showing a prominent association with Aβ and tau. While positron emission tomography

BACKGROUNDWhile cross‐sectional studies suggest a link between arteriosclerosis and cognition, longitudinal research is lacking. We investigated how arteriosclerosis in the heart–brain axis is related to cognitive performance trajectories over time.METHODSWithin the population‐based Rotterdam Study, 2368 participants underwent noncontrast CT to quantify arterial calcification, a hallmark of arteriosclerosis

INTRODUCTIONAlzheimer's disease (AD) typically involves both neurodegenerative and vascular pathologies, each associated with reductions in cerebral blood flow (CBF). However, it remains unclear whether vascular and neural contributions to regional CBF can be differentiated.METHODSUsing 3D background‐suppressed arterial spin labeled perfusion magnetic resonance imaging, we evaluated regional CBF in

We describe the Alzheimer's Disease Neuroimaging Initiative (ADNI) Biomarker Core major activities from October 2004 to March 2024, including biobanking ADNI cerebrospinal fluid (CSF), plasma, and serum biofluid samples, biofluid analyses for Alzheimer's disease (AD) biomarkers in the Biomarker Core and various non-ADNI laboratories, and continuous assessments of pre-analytics.

INTRODUCTIONHeterozygous mutations in the progranulin gene (GRN) leading to decreased progranulin levels are one of the most frequent causes of inherited frontotemporal dementia (FTD). We evaluated progranulin levels in dried blood spots from capillary finger‐stick collection (DBScapillary).METHODSPaired venous Ethylenediaminetetraacetic acid (EDTA) plasma and DBScapillary samples were collected from

INTRODUCTIONThe factors that influence the progression of Alzheimer's disease (AD) after individuals become amyloid‐positive are poorly understood. This study examines how sex influences the longitudinal trajectories of plasma AD and neurodegenerative biomarkers in the years following a person's estimated onset of amyloid‐β.METHODSLinear mixed‐effects modeling investigated overall and sex‐specific

Alterations in locus coeruleus’ (LC) metabolic turnover are associated with Alzheimer's disease (AD)-pathology and cognitive impairment. However, the evolution of these changes across disease stages and their functional relevance remains unknown.

The presence of multiple pathologies is the largest predictor of dementia. A major gap in the field is the in vivo detection of mixed pathologies and their antecedents. The Alzheimer's Disease Research Centers (ADRCs) are uniquely positioned to address this gap. The ADRCs longitudinally follow ≈ 17,000 participants, ranging from cognitively unimpaired to dementia, arising from Alzheimer's disease (AD)

INTRODUCTIONNon‐pharmacological interventions may offer significant benefits to the quality of life for persons with primary progressive aphasia (PPA) and their care partners but have lacked efficacy trials. To help fill the efficacy gap, we provide the feasibility of recruitment, enrollment, randomization, and baseline data for the Communication Bridge‐2 (CB2) randomized controlled trial (RCT).METHODSCB2

INTRODUCTIONAlzheimer's disease (AD) is a highly heritable disease (60%–80%). Amyloid beta (Aβ) 42/40, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) are plasma biomarkers for AD. Clinical biomarker research would be served by an understanding of the sources of variance in these markers.METHODSBlood concentrations of Aβ42/40, NfL, and GFAP of twins and their families (monozygotic

INTRODUCTIONDespite extensive studies on mixed neuropathologies, data from China are limited. This study aims to fill this gap by analyzing brain samples from Chinese brain banks.METHODSA total of 1142 brains from six Chinese brain banks were examined using standardized methods. Independent pathologists conducted evaluations with stringent quality control. Prevalence and correlations of neurological

While the role of apolipoprotein E (APOE) ε4 in Alzheimer's disease (AD) susceptibility has been studied extensively, much less is known about the differences in disease presentation in APOE ε4 carriers versus non-carriers.

This study examines whether phosphorylated plasma Tau217 ratio (pTau217R) can predict tau accumulation in different brain regions, as measured by positron emission tomography (PET) standardized uptake value ratio (SUVR), for staging Alzheimer's disease (AD).

INTRODUCTIONLate‐life air pollution exposure is associated with an increased risk for dementia, with this effect exacerbated among apolipoprotein E‐4 (ApoE‐4) carriers. However, whether midlife occupational exposures likewise influence dementia outcomes, and varies as a function of ApoE‐4 status is unknown.METHODSUsing data from 3814 participants in the Wisconsin Longitudinal Study (WLS), we employed

INTRODUCTIONIdiopathic normal pressure hydrocephalus (iNPH) and cerebral small vessel disease (CVSD) are age‐related diseases, but their prevalence and clinical relationship are unclear.METHODSThis prospective cohort study enrolled 95 patients with probable iNPH in China and evaluated their CSVD burden using magnetic resonance imaging. Linear regression models were used to analyze the association between

INTRODUCTIONIn the research setting, obtaining accurate established biomarker measurements and maximizing use of the precious samples is key. Accurate technologies are available for Alzheimer's disease (AD), but no platform can measure all the established and emerging biomarkers in one run. The NUcleic acid Linked Immuno‐Sandwich Assay (NULISA) is a technology that requires 15 µL of sample to measure

BACKGROUNDPeak‐width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.METHODSWe included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID‐1) Consortium and three replication

Amyloid-PET quantification through the tracer-independent Centiloid (CL) scale has emerged as an essential tool for the accurate measurement of amyloid-β (Aβ) pathology in Alzheimer's disease (AD) patients. The AMYPAD consortium set out to integrate existing literature and recent work from the consortium to provide clinical context-of-use recommendations for the CL scale. Compared to histopathology

Elevated plasma homocysteine (Hcy) is associated with an increased risk of developing neurodegenerative diseases; however, its relationship with the apolipoprotein E (APOE) ε4 allele has not been well characterized.

A key goal of the Alzheimer's Disease NeuroImaging Initiative (ADNI) positron emission tomography (PET) Core is to harmonize quantification of β-amyloid (Aβ) and tau PET image data across multiple scanners and tracers.

INTRODUCTIONNeighborhood environments may promote neurocognitive health in part by providing amenities that encourage physical activity. We examined associations between quantity of walkable facilities, including specifically physical activity facilities (e.g., gyms, recreation centers), with risk of incident dementia.METHODSParticipants included 2923 adults ≥ 65 years old from the Cardiovascular Health

BACKGROUNDAssociations between longitudinal changes of plasma biomarkers and cerebral magnetic resonance (MR)‐derived measurements in Alzheimer's disease (AD) remain unclear.METHODSIn a study population (n = 127) of healthy older adults and patients within the AD continuum, we examined associations between longitudinal plasma amyloid beta 42/40 ratio, tau phosphorylated at threonine 181 (p‐tau181)

INTRODUCTIONMarmosets spontaneously develop pathological hallmarks of Alzheimer's disease (AD) including amyloid beta plaques. However, tau expression in the marmoset brain has been understudied.METHODSIsoforms of tau were examined by western blot, mass spectrometry, immunofluorescence, and immunohistochemical staining.RESULTS3R and 4R tau isoforms are expressed in marmoset brains at both the transcript

INTRODUCTIONIt remains unclear whether the local amyloid‐beta (Aβ) burden in key regions within the default mode network (DMN) affects network and cognitive functions.METHODSParticipants included 1002 individuals from the Chinese Preclinical Alzheimer's Disease Study cohort who underwent 18F‐florbetapir positron emission tomography resting‐state functional magnetic resonance imaging scanning and neuropsychological

New possibilities of biomarker‐based predictive technologies for Alzheimer's disease (AD) have become more reliable as well as more accessible. Standardized clinical recommendations and guidance for counseling and disclosure in this context are not yet well developed. Our scoping review identified publications from database searches in PubMed, PsycINFO, LIVIVO, and Web of Science. Inclusion criteria

INTRODUCTIONThough recognized as a potential cause of autosomal dominant Alzheimer's disease, the pathogenicity of many PSEN2 variants remains uncertain. We compared amyloid beta (Aβ) production across all missense PSEN2 variants in the AlzForum database and, when possible, to corresponding PSEN1 variants.METHODSWe expressed 74 PSEN2 variants, 21 of which had known, homologous PSEN1 pathogenic variants

BACKGROUNDThe history from a relative or caregiver is an important tool for differentiating neurodegenerative disease. We characterized patterns of caregiver questionnaire responses, at diagnosis and follow‐up, on the Cambridge Behavioural Inventory (CBI).METHODSData‐driven multivariate analysis (n = 4952 questionnaires) was undertaken for participants (n = 2481) with Alzheimer's disease (typical/amnestic

INTRODUCTIONPatterns of signal from tau positron emission tomography (tau‐PET) confined to the medial temporal lobe (MTL) or extended into the neocortex may be relevant for Alzheimer's disease (AD) research if they are linked to differential biomarker levels and cognitive decline.METHODSVisual assessment of Tau‐PET [F‐18]florquinitau (FQT) exams from 728 initially non‐demented older adults yielded

BACKGROUNDApproximately 40% of people aged ≥ 65 experience memory loss, particularly in episodic memory. Identifying the genetic basis of episodic memory decline is crucial for uncovering its underlying causes.METHODSWe investigated common and rare genetic variants associated with episodic memory decline in 742 (632 for rare variants) Ashkenazi Jewish individuals (mean age 75) from the LonGenity study

INTRODUCTIONProgression to Alzheimer's disease (AD) dementia from normal cognition (NC) can follow different trajectories, with most progressing through a recognizable mild cognitive impairment stage (NC–MCI–AD), while some individuals transition quickly from NC to AD dementia (NC–AD).METHODSWe compared demographic characteristics, health factors, and cognitive and functional assessments across three

INTRODUCTIONCollaborative dementia care models with care navigation, including the Care Ecosystem, improve outcomes for persons living with dementia (PLWDs) and their caregivers. The effects of continuous care over long periods have not been studied.METHODSIn this randomized clinical trial with 456 PLWD–caregiver dyads with high caregiver burden, we evaluated the cumulative 5‐year treatment effect

INTRODUCTIONOlder adults with mild cognitive impairment (MCI) exhibit deficits in cerebrovascular reactivity (CVR), suggesting CVR is a biomarker for vascular contributions to MCI. This study examined if spontaneous CVR is associated with MCI and memory impairment.METHODSOne hundred sixty‐one older adults free of dementia or major neurological/psychiatric disorders were recruited. Participants underwent

INTRODUCTIONCardiovascular drug use may help prevent dementia; however, current evidence is mixed. Using a case–control design, we investigated the association between duration and combination of multiple cardiovascular drug classes and incident dementia.METHODSFrom the Swedish national registers, we included 88,065 incident dementia cases aged ≥ 70 at diagnosis between 2011 and 2016 and 880,650 age‐

The availability of US Food and Drug Administration (FDA)-approved therapies for early Alzheimer's disease (AD) challenges clinicians and health-care providers with effectively communicating the risks, benefits, burdens, costs and available support associated with these treatments to patients, families, and other health-care providers. The task is essential but complex. The Alzheimer's Association