Tau-network mapping of domain-specific cognitive impairment in Alzheimer's disease.

Fibrillar tau gradually progresses in the brain during the course of Alzheimer's disease (AD). However, the contribution of tau accumulation in a given brain region to decline in different cognitive domains and thus phenotypic heterogeneity in AD remains unclear. Here, we leveraged the functional connectome to link the locality of tau accumulation to domain-specific cognitive impairment.

ApoE4 and Connectivity-Mediated Spreading of Tau Pathology at Lower Amyloid Levels.

Importance: For the Alzheimer disease (AD) therapies to effectively attenuate clinical progression, it may be critical to intervene before the onset of amyloid-associated tau spreading, which drives neurodegeneration and cognitive decline. Time points at which amyloid-associated tau spreading accelerates may depend on individual risk factors, such as apolipoprotein E ε4 (ApoE4) carriership, which is linked to faster disease progression; however, the association of ApoE4 with amyloid-related tau spreading is unclear.

Objective: To assess if ApoE4 carriers show accelerated amyloid-related tau spreading and propose amyloid positron emission tomography (PET) thresholds at which tau spreading accelerates in ApoE4 carriers vs noncarriers.

Combined Connectomics, MAPT Gene Expression, and Amyloid Deposition to Explain Regional Tau Deposition in Alzheimer Disease.

Objective: We aimed to test whether region-specific factors, including spatial expression patterns of the tau-encoding gene MAPT and regional levels of amyloid positron emission tomography (PET), enhance connectivity-based modeling of the spatial variability in tau-PET deposition in the Alzheimer disease (AD) spectrum.

Methods: We included 685 participants (395 amyloid-positive participants within AD spectrum and 290 amyloid-negative controls) with tau-PET and amyloid-PET from 3 studies (Alzheimer's Disease Neuroimaging Initiative, F-AV-1451-A05, and BioFINDER-1). Resting-state functional magnetic resonance imaging was obtained in healthy controls (n = 1,000) from the Human Connectome Project, and MAPT gene expression from the Allen Human Brain Atlas.

Combining tau-PET and fMRI meta-analyses for patient-centered prediction of cognitive decline in Alzheimer's disease.

Background: Tau-PET is a prognostic marker for cognitive decline in Alzheimer's disease, and the heterogeneity of tau-PET patterns matches cognitive symptom heterogeneity. Thus, tau-PET may allow precision-medicine prediction of individual tau-related cognitive trajectories, which can be important for determining patient-specific cognitive endpoints in clinical trials. Here, we aimed to examine whether tau-PET in cognitive-domain-specific brain regions, identified via fMRI meta-analyses, allows the prediction of domain-specific cognitive decline.

Magnetic resonance imaging measures of brain volumes across the EXPEDITION trials in mild and moderate Alzheimer's disease dementia.

Introduction: Solanezumab is a monoclonal antibody that preferentially binds soluble amyloid beta and promotes its clearance from the brain. The aim of this post hoc analysis was to assess the effect of low-dose solanezumab (400 mg) on global brain volume measures in patients with mild or moderate Alzheimer's disease (AD) dementia quantified using volumetric magnetic resonance imaging (vMRI) data from the EXPEDITION clinical trial program.

Methods: Patients with mild or moderate AD (EXPEDITION and EXPEDITION2) and mild AD (EXPEDITION3), were treated with either placebo or solanezumab (400 mg) every 4 weeks (Q4W) for 76 weeks.

Predicting the Emergence of Major Neurocognitive Disorder Within Three Months After a Stroke.

Neurocognitive disorder (NCD) is common after stroke, with major NCD appearing in about 10% of survivors of a first-ever stroke. We aimed to classify clinical- and imaging factors related to rapid development of major NCD 3 months after a stroke, so as to examine the optimal composition of factors for predicting rapid development of the disorder. We hypothesized that the prediction would mainly be driven by neurodegenerative as opposed to vascular brain changes.

Lanabecestat: Neuroimaging results in early symptomatic Alzheimer's disease.

Introduction: Lanabecestat, a beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) inhibitor, was investigated as a potential Alzheimer's disease (AD)-modifying treatment. As previously reported, amyloid beta (Aβ) neuritic plaque burden reduction did not result in clinical benefit. Lanabecestat's effects on neuroimaging biomarkers and correlations between neuroimaging biomarkers and efficacy measures are reported.

GEFF: Graph embedding for functional fingerprinting.

It has been well established that Functional Connectomes (FCs), as estimated from functional MRI (fMRI) data, have an individual fingerprint that can be used to identify an individual from a population (subject-identification). Although identification rate is high when using resting-state FCs, other tasks show moderate to low values. Furthermore, identification rate is task-dependent, and is low when distinct cognitive states, as captured by different fMRI tasks, are compared.