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

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The field of Alzheimer's disease and related dementias (ADRD) urgently requires inclusive research to ensure the priorities and outcomes of research apply to those most impacted. We postulate public and participant involvement (PPI) as a pathway to achieving the best science, both in research that informs health and social policy as well as in therapeutic studies to treat and prevent ADRD. This position

INTRODUCTIONWe investigated the effects of multiple cerebrovascular disease (CeVD) neuroimaging markers on brain functional connectivity (FC), and how such CeVD‐related FC changes interact with plasma phosphorylated tau (p‐tau)181 (an Alzheimer's disease [AD] marker) to influence downstream neurodegeneration and cognitive changes.METHODSMultivariate associations among four CeVD markers and whole‐brain

Frontotemporal dementia (FTD) is one of the leading causes of young-onset dementia before age 65, typically manifesting as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). Although FTD affects all populations across the globe, knowledge regarding the pathophysiology and genetics derives primarily from studies conducted in North America and Western

Pathological and neuroimaging alterations in the cerebellum of Alzheimer's disease (AD) patients have been documented. However, the role of cerebellum-derived radiomic and structural connectome modeling in the prediction of AD progression remains unclear.

White matter hyperintensities (WMH) and infarcts found on magnetic resonance imaging (MR infarcts) are common biomarkers of cerebrovascular disease. In this review, we summarize the methods, publications, and conclusions stemming from the Alzheimer's Disease Neuroimaging Initiative (ADNI) related to these measures. We combine analysis of WMH and MR infarct data from across the three main ADNI cohorts

Vascular cognitive impairment (VCI) is highly heterogeneous, with unclear pathogenesis. Individuals with vascular risk factors (VRF), cerebral small vessel disease (CSVD), and stroke are all at risk of developing VCI. To address the growing challenges posed by VCI, the “Vascular, Imaging and Cognition Association of China” (VICA) was established.

We aimed to investigate which factors affect plasma biomarker levels via amyloid beta (Aβ)-independent or Aβ-dependent effects and improve the predictive performance of these biomarkers for Aβ positivity on positron emission tomography (PET).

Development of Alzheimer's disease (AD) pathology in Down's syndrome (DS) occurs within a compressed timeline compared to sporadic or other genetic forms of AD.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) Administrative Core oversees and coordinates all ADNI activities, to ensure the success and maximize the impact of ADNI in advancing Alzheimer's disease (AD) research and clinical trials. It manages finances and develops policies for data sharing, publications using ADNI data, and access to ADNI biospecimens. The Core develops and executes pilot

INTRODUCTIONIn a nested case–control study, we examined how cerebral perfusion relates to cognitive status and amyloid in the oldest‐old (i.e., 90 years of age and older).METHODSStudy participants included 113 dementia‐free older adults (76 cognitively normal [CN]; 37 cognitively impaired, no dementia [CIND]) from the 90+ Study (mean age = 92.9, SD = 2.4). We quantified regional perfusion from arterial

INTRODUCTIONAlzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within non‐Hispanic White (NHW) populations. Here we provide an extensive survey of the proteomic landscape of AD across diverse racial/ethnic groups.METHODSTwo cortical regions, from multiple centers, were harmonized by uniform neuropathological diagnosis. Among

Decades of research have provided evidence that Alzheimer's disease (AD) is caused in part by cerebral accumulation of amyloid beta‐protein (Aβ). In 2023, the US Food and Drug Administration gave full regulatory approval to a disease‐modifying Aβ antibody for early AD. Secondary prevention trials with Aβ antibodies are underway. We summarize peer‐reviewed evidence for targeting Aβ and argue that regulators

INTRODUCTIONInterventions to treat speech‐language difficulties in primary progressive aphasia (PPA) often use word accuracy as a highly comparable outcome. However, there are more constructs of importance to people with PPA that have received less attention.METHODSFollowing Core Outcome Set Standards for Development Recommendations (COSSTAD), this study comprised: Stage 1 – systematic review to identify

INTRODUCTIONThe pathogenesis of two major pathogenic characters—amyloid beta (Aβ) accumulation and hyperphosphorylated tau protein—in the brains of patients with Alzheimer's disease (AD) remains unclear.METHODSWestern blot and immunofluorescence staining were performed to detect the proteins in the brains of Thorase conditional knockout/transgenic mice and their littermates. A co‐immunoprecipitation

Blood‐based biomarkers continue to be explored for disease detection, monitoring of progression, and therapeutic outcomes as the diagnostic determination of Alzheimer's Disease in Down Syndrome (DS‐AD) remains challenging in clinical settings. This perspective highlights the current status of this effort. Overall, amyloid (A), tau (T), and neurodegeneration (AT[N]) blood‐based biomarkers have been

Dementia is a major health issue in Latin America and the Caribbean (LAC), with a prevalence of 9.5% and an incidence of 26.0 per 1000 among people over 60 years. With cases expected to triple by 2050, there is an urgent need for more extensive local research in this field.1 Despite advancements in neuroimaging and protein biomarkers, significant gaps remain in understanding how biological mechanisms

We investigate sex-specific topological structures associated with typical Alzheimer's disease (AD) dementia using a novel state-of-the-art latent space estimation technique.

The Health Equity Scholars Program (HESP) addresses the critical need for a diverse, culturally competent workforce to study and treat older adults from underrepresented populations (URPs) with Alzheimer's disease and related dementias (AD/ADRD). The HESP offers tailored mentored training in AD/ADRD research concepts, aiming to develop successful independent researchers. It recruits Scholars from underrepresented

Limited research has explored the effect of cardiovascular risk and amyloid interplay on cognitive decline in East Asians.

Dementia prevention in Africa is critically underexplored, despite the continent's high prevalence of modifiable risk factors. With a predominantly young and middle-aged population, Africa presents a prime opportunity to implement evidence-based strategies that could significantly reduce future dementia cases and mitigate its economic impact. The multinational Africa-FINGERS program offers an innovative

Factors responsible for the deposition of pathological tau in the brain are incompletely understood. This study links macroscale tau deposition in the human brain to cerebrospinal fluid (CSF) flow dynamics using resting-state functional magnetic resonance imaging (rsfMRI).

INTRODUCTIONDespite the recognized importance of including ethnic diversity in Alzheimer's disease (AD) research, substantial knowledge gaps remain, particularly in Asian populations.METHODSRNA sequencing was performed on blood samples from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) to perform differential gene expression (DGE), gene co‐expression

INTRODUCTIONSemorinemab, an anti‐tau monoclonal antibody, was assessed in two Phase II trials for Alzheimer's disease (AD). Plasma and cerebrospinal fluid (CSF) biomarkers provided insights into the drug's potential mechanism of action.METHODSQualified assays were used to measure biomarkers of tau, amyloidosis, glial activity, neuroinflammation, synaptic function, and neurodegeneration from participant

INTRODUCTIONAlzheimer's disease (AD) is the most common form of dementia in the elderly. Given that AD neuropathology begins decades before symptoms, there is a dire need for effective screening tools for early detection of AD to facilitate early intervention.METHODSHere, we used tree‐based and deep learning methods to train polyomic prediction models for AD affection status and age at onset, employing

“Everyday technologies” have long been suggested as digital tools to improve life for and enhance care of persons with Alzheimer's disease and related dementias (ADRD). Within this realm, there is a need to balance potential drawbacks of technologies with their ability to positively impact patient and care partner centered outcomes. To facilitate this goal, we endeavored to provide a common language

INTRODUCTIONWe investigated hippocampal synaptic density using synaptic vesicle 2A positron emission tomography (PET), and its association with amyloid beta (Aβ) and cognitive performance in healthy apolipoprotein E (APOE) ε4 carriers.METHODSSynaptic density was assessed in 46 individuals (APOE ε4/ε4 n = 14; APOE ε3/ε4 n = 16; APOE ε3/ε3 n = 16) with [11C]UCB‐J‐PET standardized uptake value ratios

Not all individuals who experience mild cognitive impairment (MCI) transition through progressive stages of cognitive decline at the same rate, if at all. Previous observational studies have identified the retrosplenial cortex (RSC) as an early site of hypometabolism in MCI which seems to be predictive of later transition to Alzheimer's disease (AD).

The Everyday Cognition scale (ECog-39) scores are associated with future cognitive decline. We investigated whether the 12-item ECog (ECog-12), which is being collected in Alzheimer's Disease Neuroimaging Initiative (ADNI)4, can predict progression.

INTRODUCTIONWhile the influence of cross‐sectional β‐amyloid (Aβ) on longitudinal changes in cognition is well established, longitudinal change‐on‐change between Aβ and cognition is less explored.METHODSA series of bivariate latent change score models (LCSM) examined the relationship between changes in 11C‐Pittsburgh Compound‐B (PiB) positron emission tomography (PET) and the Preclinical Alzheimer's

The revised criteria for diagnosis and staging of Alzheimer's disease (AD)1 update the 2018 Research Framework and reaffirm the concept of AD as a primary biological entity. These new criteria focus on biomarkers that represent distinct pathological processes, measurable in living individuals using neuroimaging and biofluid assays to track disease course. Specifically, the framework proposes three

We were particularly interested in the 2024 Revised Criteria for Diagnosis and Staging of Alzheimer's Disease (AD) from the Alzheimer's Association (AA) workgroup. These criteria seek to update the biological definition of AD, originally introduced in 2011, to inform both research and clinical care.1 The proposal of a formal transition from a clinico-biological to a purely biological disease definition

INTRODUCTIONPeople living with dementia are less likely to be admitted to high‐rated nursing homes than people without dementia, despite their increased care needs. We investigated the effect of admission to nursing homes with higher staffing ratings on adverse outcomes for individuals with and without dementia post‐hospitalization.METHODSAmong Traditional Medicare beneficiaries discharged to nursing

The genetic pathways that influence longitudinal heterogeneous changes in Alzheimer's disease (AD) may provide insight into disease mechanisms and potential therapeutic targets.

The Alzheimer's Disease Neuroimaging Initiative-4 (ADNI-4) Engagement Core was launched to advance Alzheimer's disease (AD) and AD-related dementia (ADRD) health equity research in underrepresented populations (URPs). We describe our evidence-based, scalable culturally informed, community-engaged research (CI-CER) model and demonstrate its preliminary success in increasing URP enrollment.

BACKGROUNDSynaptic and extrasynaptic distribution of N‐methyl‐D‐aspartate receptors (NMDARs) has not been addressed in the brain from Alzheimer´s disease (AD) subjects, despite their contribution to neurodegeneration.METHODSWe have developed a protocol to isolate synaptic and extrasynaptic membranes from controls and AD frontal cortex. We characterized the distribution of the NMDAR subunits GluN2B

October 23, 2024: This article published in Early View in error. The article is under embargo and will republish shortly.

INTRODUCTIONEmerging preclinical evidence suggests that semaglutide, a glucagon‐like peptide receptor agonist (GLP‐1RA) for type 2 diabetes mellitus (T2DM) and obesity, protects against neurodegeneration and neuroinflammation. However, real‐world evidence for its ability to protect against Alzheimer's disease (AD) is lacking.METHODSWe conducted emulation target trials based on a nationwide database

Identifying low-cost, minimally-invasive screening instruments for Alzheimer's disease (AD) trial enrichment will improve the efficiency of AD trials.

Metabolic dysregulation is a hallmark of neurodegenerative diseases, including Alzheimer's disease (AD) and progressive supranuclear palsy (PSP). Although metabolic dysregulation is a common link between these two tauopathies, a comprehensive brain metabolic comparison of the diseases has not yet been performed.

INTRODUCTIONAssessing treatments for Alzheimer's disease (AD) relies on reliable tools for measuring AD progression. In this analysis, we evaluate the sensitivity of clinical progression measures in AD within randomized controlled trials (RCTs) with confirmed positive amyloid (Aβ+) status prior to trial enrollment.METHODSExcluding trials targeting non‐cognitive symptoms, we conducted meta‐analyses

INTRODUCTIONPeople with dementia may benefit from psychological therapies for depression or anxiety, but evidence of their effectiveness in atypical dementia is limited.METHODSUsing electronic health‐care records of > 2 million people who attended psychological therapy services in England between 2012 and 2019, we examined pre–post therapy symptom changes and compared therapy outcomes among 523 people