Jacob Vogel

McGill University | McGill · Montreal Neurological Institute

Numerous brain disorders demonstrate structural brain abnormalities, which are thought to arise from molecular perturbations or connectome miswiring. The unique and shared contributions of these molecular and connectomic vulnerabilities to brain disorders remain unknown, and has yet to be studied in a single multi-disorder framework. Using MRI morp...

Importance: National Institute on Aging-Alzheimer's Association (NIA-AA) workgroups have proposed biological research criteria intended to identify individuals with preclinical Alzheimer disease (AD). Objective: To assess the clinical value of these biological criteria to identify older individuals without cognitive impairment who are at near-te...

Background Cognitive reserve and resilience are terms used to explain interindividual variability in maintenance of cognitive health in response to adverse factors, such as brain pathology in the context of aging or neurodegenerative disorders. There is substantial interest in identifying tractable substrates of resilience to potentially leverage t...

The Brain Imaging Data Structure (BIDS) is a specification accompanied by a software ecosystem that was designed to create reproducible and automated workflows for processing neuroimaging data. BIDS Apps flexibly build workflows based on the metadata detected in a dataset. However, even BIDS valid metadata can include incorrect values or omissions...

BACKGROUND The spatial layout of large-scale functional brain networks differs between individuals and is particularly variable in association cortex implicated in a broad range of psychiatric disorders. However, it remains unknown whether this variation in functional topography is related to major dimensions of psychopathology in youth. METHODS T...

The distribution of Alzheimer’s disease (AD) tau pathology varies systematically and causes a diverse array of syndromes. This forum article provides a brief overview of key controversies in untangling the complexity of AD subtypes, explores potential causes of AD variability in the population, and discusses clinical relevance and future directions...

Numerous brain disorders demonstrate structural brain abnormalities, which are thought to arise from molecular perturbations or connectome miswiring. The unique and shared contributions of these molecular and connectomic vulnerabilities to brain disorders remain unknown, and has yet to be studied in a single multi-disorder framework. Using MRI morp...

Numerous brain disorders demonstrate structural brain abnormalities, which are thought to arise from molecular perturbations or connectome miswiring. The unique and shared contributions of these molecular and connectomic vulnerabilities to brain disorders remain unknown, and has yet to be studied in a single multi-disorder framework. Using MRI morp...

Importance There is currently no consensus as to which biomarkers best predict longitudinal tau accumulation at different clinical stages of Alzheimer disease (AD). Objective To describe longitudinal [¹⁸F]RO948 tau positron emission tomography (PET) findings across the clinical continuum of AD and determine which biomarker combinations showed the...

Objective: We investigated the mediation effects of subcortical volume change in the relationship of amyloid beta (Aβ) and lacune with cognitive function in patients with mild cognitive impairment (MCI). Methods: We prospectively recruited 101 patients with MCI who were followed up with neuropsychological tests, MRI, or Pittsburgh compound B (PiB)...

A large body of evidence has shown decreased cerebral blood flow (CBF) in Alzheimer’s disease (AD). However, the link between CBF and the primary AD pathologies as well as synaptic integrity remains unclear. Baseline CBF was measured using arterial spin labeling (ASL) in a 3T MRI scanner in 137 cognitively unimpaired individuals with and without am...

In Alzheimer’s disease, postmortem studies have shown that the first cortical site where neurofibrillary tangles appear is the transentorhinal region, a subregion within the medial temporal lobe that largely overlaps with area 35, and the entorhinal cortex. Here we used tau‐PET imaging to investigate the sequence of tau pathology progression within...

Regulation of gene expression drives protein interactions that govern synaptic wiring and neuronal activity. The resulting coordinated activity among neuronal populations supports complex psychological processes, yet how gene expression shapes cognition and emotion remains unknown. Here, we directly bridge the microscale and macroscale by mapping g...

The spatial layout of large-scale functional brain networks differs between individuals and is particularly variable in association cortex that has been implicated in a broad range of psychiatric disorders. However, it remains unknown whether this variation in functional topography is related to major dimensions of psychopathology in youth. Capital...

Subtype and Stage Inference (SuStaIn) is an unsupervised learning algorithm that uniquely enables the identification of subgroups of individuals with distinct pseudo-temporal disease progression patterns from cross-sectional datasets. SuStaIn has been used to identify data-driven subgroups and perform patient stratification in neurodegenerative dis...

Although several studies have shown decreased cerebral blood flow (CBF) in Alzheimer's disease (AD), the role of hypoperfusion in the disease pathogenesis remains unclear. Combining arterial spin labeling MRI, positron emission tomography, and biomarkers of cerebrospinal fluid, we investigated the associations between CBF and the key mechanisms in...

Amyloid-beta (Aβ) deposition is one of the hallmark pathologies in both sporadic Alzheimer's disease (sAD) and autosomal dominant Alzheimer's disease (ADAD), the latter of which is caused by mutations in genes involved in Aβ processing. Despite Aβ deposition being a centerpiece to both sAD and ADAD, some differences between these AD subtypes have b...

Over the past 25 years, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, there are no reference standards against which to anchor measures of individual differences in brain morphology, in contrast to growth charts for traits such as height and weight. Here, we built an interactive online...

Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we ident...

In Alzheimer's disease, postmortem studies have shown that the first cortical site where neurofibrillary tangles appear is the transentorhinal region, a subregion within the medial temporal lobe that largely overlaps with area 35, and the entorhinal cortex. Here we used tau-PET imaging to investigate the sequence of tau pathology progression within...

Resting-state functional connectivity is suggested to be cross-sectionally associated with both vascular burden and Alzheimer's disease (AD) pathology. However, evidence is lacking regarding longitudinal changes in functional connectivity. This study includes 247 cognitively unimpaired individuals with a family history of sporadic AD (185 women/ 62...

Studies in cells, animals and humans have each provided evidence that, in an Alzheimer’s disease (AD) context, tau may be spreading through the brain transneuronally. This information may be useful for modeling the spread of tau in humans. However, such models are confounded by the substantial heterogeneity in spreading patterns observed in AD. In...

The Braak staging scheme describes a stereotypical spread of tau pathology in Alzheimer’s disease (AD). However, apparent subtypes described at autopsy and clinical variants of AD both suggest variability in the pattern of tau spreading across the population. To address this discrepancy, we applied a validated spatiotemporal clustering algorithm to...

Alzheimer's disease (AD) is characterized by the progressive spread of tau pathology throughout the cerebral cortex. The pattern of spread is thought to be fairly consistent across individuals, though more recent work has demonstrated substantial variability in the AD population that is often associated with distinct clinical phenotypes. Still, a s...

Objective To determine whether atrophy relates to phenotypical variants of posterior cortical atrophy (PCA) recently proposed in clinical criteria; dorsal, ventral, dominant-parietal and caudal, we assessed associations between latent atrophy factors and cognition. Methods We employed a data-driven Bayesian modelling framework based on latent Diri...

Tau is a hallmark pathology of Alzheimer’s disease, and animal models have suggested that tau spreads from cell to cell through neuronal connections, facilitated by β-amyloid (Aβ). We test this hypothesis in humans using an epidemic spreading model (ESM) to simulate tau spread, and compare these simulations to observed patterns measured using tau-P...

The impact of multisite acquisition on rsfMRI connectivity has recently gained attention. We provide consistency values (Pearson's correlation) between resting-state fMRI (rsfMRI) connectivity maps of an adult volunteer (Csub) scanned 25 times over 3.5 years at 13 sites using the Canadian Dementia Imaging Protocol (CDIP, www.cdip-pcid.ca). This dat...

Introduction Cross-sectional studies suggest that cardiovascular risk factors and Alzheimer’s disease (AD) biomarkers are associated with abnormal brain resting-state functional connectivity in aging and AD; however, evidence is missing regarding longitudinal changes in functional connectivity. In this study, we investigate whether cholesterol leve...

The functional organization of the hippocampus is distributed as a gradient along its longitudinal axis that explains its differential interaction with diverse brain systems. We show that the location of human tissue samples extracted along the longitudinal axis of the adult human hippocampus can be predicted within 2mm using the expression pattern...

We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of...

Age being the main risk factor for Alzheimer's disease, it is particularly challenging to disentangle structural changes related to normal brain ageing from those specific to Alzheimer's disease. Most studies aiming to make this distinction focused on older adults only and on a priori anatomical regions. Drawing on a large, multi-cohort dataset ran...

Studies using resting-state functional magnetic resonance imaging (rsfMRI) are increasingly collecting data at multiple sites in order to speed up recruitment or increase sample size. The main objective of this study was to assess the long-term consistency of rsfMRI connectivity maps derived at multiple sites and vendors using the Canadian Dementia...

Posterior cortical atrophy is a clinical-radiological syndrome characterized by visual processing deficits and atrophy in posterior parts of the brain, most often caused by Alzheimers disease pathology. Recent consensus criteria describe four distinct phenotypical variants of posterior cortical atrophy defined by clinical and radiological features;...

It remains unclear which grey matter (GM) changes are associated with Alzheimer's disease (AD), and how these changes might differ from normal brain aging. Using independent component analysis of GM maps on a large, multi-cohort dataset, we derived morphometric networks and investigated GM volume in such networks in young, old adulthood, and AD. GM...

The functional organization of the hippocampus is distributed as a gradient along its longitudinal axis that explains its differential interaction with diverse brain systems. We show that the location of human tissue samples extracted along the longitudinal axis of the hippocampus can be predicted within 2mm using the expression pattern of less tha...

Background Although amnestic mild cognitive impairment (aMCI) is generally considered to be a prodromal stage of Alzheimer’s disease, patients with aMCI show heterogeneous patterns of progression. Moreover, there are few studies investigating data-driven cognitive trajectory in aMCI. We therefore classified patients with aMCI based on their cogniti...

Studies using resting-state functional magnetic resonance imaging (rsfMRI) are increasingly collecting data at multiple sites in order to speed up recruitment or increase sample size. Multisite studies potentially introduce systematic biases in connectivity measures across sites, which may negatively impact the detection of clinical effects. Long-t...

Background: Brain reserve is a concept introduced to explain why Alzheimer's disease (AD) patients with a greater brain volume prior to onset of pathology generally have better clinical outcomes. In this review, we provide a historical background of the emergence of brain reserve and discuss several aspects that need further clarification, includi...

Alzheimer's disease is preceded by a lengthy 'preclinical' stage spanning many years, during which subtle brain changes occur in the absence of overt cognitive symptoms. Predicting when the onset of disease symptoms will occur is an unsolved challenge in individuals with sporadic Alzheimer's disease. In individuals with autosomal dominant genetic A...

We aimed to compare the longitudinal outcome of amnestic mild cognitive impairment (aMCI) patients with significant Pittsburgh Compound B uptake [PiB(+) aMCI] and those without [PiB(-) aMCI]. Cerebral β-amyloid was measured in 47 patients with aMCI using PiB-positron emission tomography (PET) (31 PiB(+) aMCI and 16 PiB(-) aMCI). Clinical (N = 47) a...

Previous positron emission tomography (PET) studies have quantified filamentous tau pathology using regions-of-interest (ROIs) based on observations of the topographical distribution of neurofibrillary tangles in post-mortem tissue. However, such approaches may not take full advantage of information contained in neuroimaging data. The present study...

Importance Alzheimer disease (AD) develops during several decades. Presymptomatic individuals might be the best candidates for clinical trials, but their identification is challenging because they have no symptoms. Objective To assess whether a sporadic parental estimated years to symptom onset calculation could be used to identify information abo...

Objective: To assess in a longitudinal study whether subjective cognitive decline (SCD) and brain β-amyloid (Aβ) contribute unique information to cognitive decline. Methods: One hundred thirty-six healthy elderly from the Berkeley Aging Cohort Study were followed up for a mean of 4 years. SCD and affective measures were generated from the Geriat...

Highlights Reliable functional brain network subtypes accompany cognitive impairment in AD Symptom-related subtypes exist in the default-mode, limbic and salience networks A limbic subtype is associated with a familial risk of AD in healthy older adults Limbic subtypes also associate with beta amyloid deposition and ApoE4 In Brief We found reliabl...

Significance statement: Few studies have combined measurement of brain dopamine with examination of the neural basis of cognition in youth and aging to delineate the underlying mechanisms of these associations. Combining in vivo PET imaging of dopamine synthesis capacity, fMRI, and a sensitive measure of cognitive flexibility, we reveal three core...

View largeDownload slide See Sarazin et al . (doi: 10.1093/brain/aww041 ) for a scientific commentary on this article. The PET tracer [ ¹⁸ F]-AV-1451 allows visualization of tau pathology in living subjects. Ossenkoppele et al. employ the tracer in patients with distinct Alzheimer's disease variants to investigate correlates of tau deposition. Pat...

Tau pathology is a hallmark of Alzheimer’s disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent ¹⁸F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention i...

Single lifestyle factors affect brain biomarkers and cognition. Here we addressed the covariance of various lifestyle elements and investigated their impact on positron emission tomography (PET)-based β-amyloid (Aβ), hippocampal volume and cognitive function in aged controls. Lower Aβ burden was associated with a lifestyle comprising high cognitive...

A 'frontal variant of Alzheimer's disease' has been described in patients with predominant behavioural or dysexecutive deficits caused by Alzheimer's disease pathology. The description of this rare Alzheimer's disease phenotype has been limited to case reports and small series, and many clinical, neuroimaging and neuropathological characteristics a...