Dementia risk estimation in persons at risk and the predictive turn in Alzheimer's disease-The PreTAD project: Study protocol with an ethical, clinical, linguistic, and legal approach.

Background: Despite progress in the field of Alzheimer's disease (AD) dementia risk estimation, little is known about its impact at the individual and societal levels.

Objective: Introducing the explorative tri-national PreTAD project (The Predictive Turn in Alzheimer's Disease: Ethical, Clinical, Linguistic and Legal Aspects), which aims to (1) learn about attitudes, needs, and perspectives on AD dementia risk estimation of the general population and cognitively unimpaired individuals with and without contact to memory clinics, (2) identify anticipated impacts of AD dementia risk estimation and (3) discuss the implications of the paradigm shift in medicine at individual and societal levels from an ethical, linguistic and legal perspective.

Methods: Different approaches are used: (1) an assessment of a population without experience with dementia, (2) an assessment in memory clinics, and (3) an online survey of the general population.

Frequency and Clinical Outcomes Associated With Tau Positron Emission Tomography Positivity.

Importance: Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD).

Objective: To provide estimates of the frequency of tau PET positivity and its associated risk of clinical outcomes.

Design, Setting, And Participants: Longitudinal study using data pooled from 21 cohorts, comprising a convenience sample of 6514 participants from 13 countries, collected between January 2013 and June 2024.

Targeting brain health in subjective cognitive decline: insights from a multidomain randomized controlled trial.

Background: Multidomain lifestyle interventions are a promising approach to prevent cognitive decline, but their effects in subjective cognitive decline (SCD) remain controversial. We investigated the effects of lifestyle interventions on cognition and brain integrity in these at-risk individuals.

Methods: One-hundred twenty-eight older adults with SCD were randomly assigned to either Active Control Intervention (ACI), i.

Validating the Amyloid Cascade Through the Revised Criteria of Alzheimer's Association Workgroup 2024 for Alzheimer Disease.

Background And Objectives: The amyloid cascade hypothesis posits that Alzheimer disease (AD) progresses from amyloid deposition to tau deposition, neurodegeneration, and eventually cognitive impairment and is the foundation of the revised criteria of Alzheimer's Association Workgroup 2024 (AA-2024). To account for copathologies and cognitive resilience that affect the penetrance of the AD cascade, AA-2024 introduced a 2-dimensional biological-clinical staging framework. We aimed to estimate the proportion of persons along the AD continuum whose biological and clinical trajectories align with the amyloid cascade.

Microstructural assessment of the locus coeruleus-entorhinal cortex pathway and association with ATN markers in cognitive impairment.

Introduction: Whether Alzheimer's disease pathology involves white matter pathways connecting the locus coeruleus (LC) to the entorhinal cortex (EC) is unclear. In this cross-sectional observational study, we investigated the microstructural integrity of the LC-EC pathway in relation to amyloid, tau, and neurodegeneration (ATN) biomarkers along the cognitive spectrum from normal cognition to dementia.

Methods: One hundred twenty-four participants underwent clinical assessment, diffusion-weighted imaging, structural magnetic resonance imaging (N), amyloid (A), and tau (T) positron emission tomography.

Resilience in Alzheimer's disease: Impact of operationalization and methodological choices.

Introduction: Resilience, the ability to maintain cognition or brain integrity despite Alzheimer's disease (AD) pathology, is often quantified using the residual approach. However, the variability in methodology and correction methods for this approach raises concerns about the interpretability of findings across studies.

Methods: We assessed brain resilience (BR) and cognitive resilience (CR) in a memory clinic population using the residual approach.

Brain health services for the secondary prevention of cognitive impairment and dementia: Opportunities, challenges, and the business case for existing and future facilities.

A European Task Force has recently developed and published the concept and protocols for the setup of the innovative health offer of Brain Health Services for the secondary prevention of dementia and cognitive impairment (dBHS). dBHS are outpatient health care facilities where adult persons can find an assessment of their risk of developing cognitive impairment and dementia, have their risk level and contributing factors communicated using appropriate language supported by adequate communication tools, can decide to participate to programs for personalized risk reduction if at higher risk, and benefit from cognitive enhancement interventions. This health offer is distinct from that of currently active memory clinics.

Unraveling the link between frailty and Alzheimer's disease biomarkers in patients with mild cognitive impairment.

Alzheimer's disease (AD) can be identified through biomarkers of amyloid (A) and tau (T) pathology. Frailty, a measure of biological aging, could impact the association between AD neuropathology and its clinical manifestation. We aimed to investigate the relationship between frailty and AD biomarkers among people with mild cognitive impairment (MCI) attending a university memory clinic.

Three-Objects-Three-Places Episodic Memory Test to Screen Mild Cognitive Impairment and Mild Dementia: Validation in a Memory Clinic Population.

Background: The Three-Objects-Three-Places (3O3P) test is a 5-min screen for episodic memory impairment due to Alzheimer's disease, known for its briefness and easy administration, culture- and language-free nature, and the absence of specific equipment. However, no studies have validated its potential in memory clinic cohorts. The aim of this study was to test its convergent, discriminant, and known-group validities and to define thresholds for its clinical use.

Early-phase F-Flortaucipir tau-PET as a proxy of brain metabolism in Alzheimer's disease: a comparison with F-FDG-PET and early-phase amyloid-PET.

Purpose: As dual-phase amyloid-PET can evaluate amyloid (A) and neurodegeneration (N) with a single tracer injection, dual-phase tau-PET might be able to provide both tau (T) and N. Our study aims to assess the association of early-phase tau-PET scans and F-fluorodeoxyglucose (FDG) PET and their comparability in discriminating Alzheimer's disease (AD) patients and differentiating neurodegenerative patterns.

Methods: 58 subjects evaluated at the Geneva Memory Center underwent dual-phase F-Flortaucipir-PET with early-phase acquisition (eTAU) and F-FDG-PET within 1 year.

Fingerprints of brain disease: connectome identifiability in Alzheimer's disease.

Functional connectivity patterns in the human brain, like the friction ridges of a fingerprint, can uniquely identify individuals. Does this "brain fingerprint" remain distinct even during Alzheimer's disease (AD)? Using fMRI data from healthy and pathologically ageing subjects, we find that individual functional connectivity profiles remain unique and highly heterogeneous during mild cognitive impairment and AD. However, the patterns that make individuals identifiable change with disease progression, revealing a reconfiguration of the brain fingerprint.

Subjective cognitive decline: Memory complaints, cognitive awareness, and metacognition.

Cognitive complaints are common in elderly subjects and are a frequent reason for referral to memory clinics. If the complaints are not associated with objective cognitive impairment, the condition is labelled subjective cognitive decline (SCD). SCD is often considered as a stage antedating objective impairment, and an at-risk condition for subsequent dementia.

Association of glial fibrillary acid protein, Alzheimer's disease pathology and cognitive decline.

Increasing evidence shows that neuroinflammation is a possible modulator of tau spread effects on cognitive impairment in Alzheimer's disease. In this context, plasma levels of the glial fibrillary acidic protein (GFAP) have been suggested to have a robust association with Alzheimer's disease pathophysiology. This study aims to assess the correlation between plasma GFAP and Alzheimer's disease pathology, and their synergistic effect on cognitive performance and decline.

Comparison of plasma and neuroimaging biomarkers to predict cognitive decline in non-demented memory clinic patients.

Background: Plasma biomarkers of Alzheimer's disease (AD) pathology, neurodegeneration, and neuroinflammation are ideally suited for secondary prevention programs in self-sufficient persons at-risk of dementia. Plasma biomarkers have been shown to be highly correlated with traditional imaging biomarkers. However, their comparative predictive value versus traditional AD biomarkers is still unclear in cognitively unimpaired (CU) subjects and with mild cognitive impairment (MCI).

Alterations in gamma frequency oscillations correlate with cortical tau deposition in Alzheimer's disease.

We assessed the relationship of gamma oscillations with tau deposition in Alzheimer's disease (AD) and other cognitive diseases, as both are altered during the disease course and relate to neurodegeneration. We retrospectively analyzed data from 7 AD, tau positive patients and 9 tau negative patients, who underwent cerebral amyloid PET and tau PET, and EEG within 12 months. Relative gamma power was higher in tau positive (AD) patients than in tau negative patients (p < .

Insights into single-timepoint ASL hemodynamics: what visual assessment and spatial coefficient of variation can tell.

Purpose: Arterial spin labeling (ASL) represents a noninvasive perfusion biomarker, and, in the study of nonvascular disease, the use of the single-timepoint ASL technique is recommended. However, the obtained cerebral blood flow (CBF) maps may be highly influenced by delayed arterial transit time (ATT). Our aim was to assess the complexity of hemodynamic information of single-timepoint CBF maps using a new visual scale and comparing it with an ATT proxy, the "coefficient of spatial variation" (sCoV).

Head-to-head study of diagnostic accuracy of plasma and cerebrospinal fluid p-tau217 versus p-tau181 and p-tau231 in a memory clinic cohort.

Background And Objective: Phosphorylated tau (p-tau) 217 has recently received attention because it seems more reliable than other p-tau variants for identifying Alzheimer's disease (AD) pathology. Thus, we aimed to compare the diagnostic accuracy of plasma and CSF p-tau217 with p-tau181 and p-tau231 in a memory clinic cohort.

Methods: The study included 114 participants (CU = 33; MCI = 67; Dementia = 14).

A comparison of visual assessment and semi-quantification for the diagnostic and prognostic use of [F]flortaucipir PET in a memory clinic cohort.

Purpose: [F]Flortaucipir PET is a powerful diagnostic and prognostic tool for Alzheimer's disease (AD). Tau status definition is mainly based in the literature on semi-quantitative measures while in clinical settings visual assessment is usually preferred. We compared visual assessment with established semi-quantitative measures to classify subjects and predict the risk of cognitive decline in a memory clinic population.

ATN profile classification across two independent prospective cohorts.

Background: The ATN model represents a research framework used to describe in subjects the presence or absence of Alzheimer's disease (AD) pathology through biomarkers. The aim of this study was to describe the prevalence of different ATN profiles using quantitative imaging biomarkers in two independent cohorts, and to evaluate the pertinence of ATN biomarkers to identify comparable populations across independent cohorts.

Methods: A total of 172 subjects from the Geneva Memory Clinic and 113 volunteers from a study on healthy aging at the University Hospital of Zurich underwent amyloid (A) and tau (T) PET, as well as T1-weigthed MRI scans using site-specific protocols.

The impact of tau deposition and hypometabolism on cognitive impairment and longitudinal cognitive decline.

Introduction: Tau and neurodegeneration strongly correlate with cognitive impairment, as compared to amyloid. However, their contribution in explaining cognition and predicting cognitive decline in memory clinics remains unclarified.

Methods: We included 94 participants with Mini-Mental State Examination (MMSE), tau positron emission tomography (PET), amyloid PET, fluorodeoxyglucose (FDG) PET, and MRI scans from Geneva Memory Center.

Prognostic value of imaging-based ATN profiles in a memory clinic cohort.

Purpose: The ATN model represents a research framework used to classify subjects based on the presence or absence of Alzheimer's disease (AD) pathology through biomarkers for amyloid (A), tau (T), and neurodegeneration (N). The aim of this study was to assess the relationship between ATN profiles defined through imaging and cognitive decline in a memory clinic cohort.

Methods: One hundred-eight patients from the memory clinic of Geneva University Hospitals underwent complete clinical and neuropsychological evaluation at baseline and 23 ± 5 months after inclusion, magnetic resonance imaging, amyloid and tau PET scans.

Patterns of amyloid accumulation in amyloid-negative cases.

Amyloid staging models showed that regional abnormality occurs before global positivity. Several studies assumed that the trajectory of amyloid spread is homogeneous, but clinical evidence suggests that it is highly heterogeneous. We tested whether different amyloid-β (Aβ) patterns exist by applying clustering on negative scans and investigating their demographics, clinical, cognitive, and biomarkers correlates, and cognitive trajectories.