Mahsa Dadar

McGill University | McGill

Lecanemab and donanemab are monoclonal antibody therapies that remove amyloid-beta from the brain. They are the first therapies that alter a fundamental mechanism, amyloid-beta deposition, in Alzheimer disease (AD). To inform Canadian decisions on approval and use of these drugs, the Canadian Consortium on Neurodegeneration in Aging commissioned Wo...

Purpose Immunohistochemical (IHC) and histochemical (HC) staining techniques are widely used on human brains that are post-fixed in formalin and stored in brain banks worldwide for varying durations, from months to decades. Understanding the effects of prolonged post-fixation, postmortem interval (PMI), and age on these staining procedures is impor...

Background and objectives White matter hyperintensities (WMHs) are radiological abnormalities indicative of cerebrovascular dysfunction associated with increased risk for cognitive decline and increase in prevalence in older age. However, there are known sex-differences as older females harbour higher WMH burden than males. Some have hypothesized t...

Recent human magnetic resonance imaging (MRI) studies continually push the boundaries of spatial resolution as a means to enhance levels of neuroanatomical detail and increase the accuracy and sensitivity of derived brain morphometry measures. However, acquisitions required to achieve these resolutions have a higher noise floor, potentially impacti...

Objective Accurate personalized survival prediction in amyotrophic lateral sclerosis is essential for effective patient care planning. This study investigates whether gray and white matter changes measured by magnetic resonance imaging can improve individual survival predictions. Methods We analyzed data from 178 amyotrophic lateral sclerosis pati...

Obesity and its metabolic complications are associated with lower grey matter and white matter densities, whereas weight loss after bariatric surgery leads to an increase in both measures. These increases in grey and white matter density are significantly associated with post-operative weight loss and improvement of the metabolic/inflammatory profi...

Magnetic resonance imaging (MRI) is a valuable non-invasive tool that has been widely used for in vivo investigations of brain morphometry and microstructural characteristics. Post-mortem MRIs can provide complementary anatomical and microstructural information to in vivo imaging and ex vivo neuropathological assessments without compromising the sa...

MRI-detected white matter hyperintensities (WMH) are often recognized as markers of cerebrovascular abnormalities and an index of vascular brain injury. The literature establishes a strong link between WMH burden and cognitive decline, and suggests that the anatomical distribution of WMH mediates cognitive dysfunction. Pathological remodeling of ma...

Background: Parkinson's disease (PD) varies widely across individuals in clinical manifestations and course of progression. Identification and characterization of distinct biological subtypes could help explain this heterogeneity, identify the underlying pathophysiology, and predict disease progression across the subgroups of PD. Objective: We aime...

Objectives Hypertension or high blood pressure (BP) is one of the 12 modifiable risk factors that contribute to 40% of dementia cases that could be delayed or prevented. Although hypertension is associated with cognitive decline and structural brain changes, less is known about the long-term association between variable BP and cognitive/brain chang...

Background: The ability to predict Alzheimers disease (AD) before diagnosis is a topic of intense research. Early diagnosis would aid in improving treatment and intervention options, however, there are no current methods that can accurately predict AD years in advance. This study examines a novel machine learning approach that integrates the combin...

Introduction White matter hyperintensities (WMHs) and cerebral microbleeds are widespread among aging population and linked with cognitive deficits in mild cognitive impairment (MCI), vascular MCI (V-MCI), and Alzheimer's disease without (AD) or with a vascular component (V-AD). In this study, we aimed to investigate the association between brain a...

It is imperative to study sex differences in brain morphology and function. However, there are major observable and unobservable confounding factors that can contribute to the estimated differences. Males have larger head sizes than females. Head size differences not only act as a confounding factor in studying sex differences in the brain, but als...

Introduction: Cognitively healthy older adults may experience self-perceived memory and cognitive deficits, known as subjective cognitive decline (SCD), increasing their risk for dementia-related brain and cognitive changes. This study investigated if questions from the Cognitive Change Index (CCI) and Everyday Cognition Scale (ECog) show similar a...

Immunohistochemical (IHC) and histochemical (HC) staining is widely used for human brains postfixed in formalin for years and decades. Understanding the effect of prolonged post-fixation, postmortem interval (PMI) and age on these staining procedures is important for interpreting their outcomes, thus improving diagnosis and research of brain disord...

Background Irregular word reading has been used to estimate premorbid intelligence in Alzheimer’s disease (AD) dementia. However, reading models highlight the core influence of semantic abilities on irregular word reading, which shows early decline in AD. The primary objective of this study is to ascertain whether irregular word reading serves as a...

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that predominantly targets the motor system. Spread of pathology is thought to be driven by both local vulnerability and network architecture. Namely, molecular and cellular features may confer vulnerability to specific neuronal populations, while synaptic contacts may a...

Background Brain banks provide small tissue samples to researchers, while gross anatomy laboratories could provide larger samples, including complete brains to neuroscientists. However, they are preserved with solutions appropriate for gross-dissection, different from the classic neutral-buffered formalin (NBF) used in brain banks. Our previous wor...

INTRODUCTION We assessed whether macro‐ and/or micro‐structural white matter properties are associated with cognitive resilience to Alzheimer's disease pathology years prior to clinical onset. METHODS We examined whether global efficiency, an indicator of communication efficiency in brain networks, and diffusion measurements within the limbic netw...

For over a century, brain research narrative has mainly centered on neuron cells. Accordingly, most neurodegenerative studies focus on neuronal dysfunction and their selective vulnerability, while we lack comprehensive analyses of other major cell types’ contribution. By unifying spatial gene expression, structural MRI, and cell deconvolution, here...

INTRODUCTION While studies report that sleep disturbance can have negative effects on brain vasculature, its impact on cerebrovascular diseases such as white matter hyperintensities (WMHs) in beta‐amyloid‐positive older adults remains unexplored. METHODS Sleep disturbance, WMH burden, and cognition in normal controls (NCs), and individuals with mi...

Importance: Vascular and structural brain changes are increasingly recognized for their role in cognitive decline and progression of neurodegenerative conditions including Alzheimer's disease (AD). Despite advances in imaging technologies, the exact contribution of these brain changes to disease processes remains a subject of ongoing research. Obje...

Magnetic resonance imaging (MRI) is a valuable non-invasive tool that has been widely used for in vivo investigations of brain morphometry and microstructural characteristics. Postmortem MRIs can provide complementary anatomical and microstructural information to in vivo imaging and ex vivo neuropathological assessments without compromising the sam...

The volume of the lateral ventricles is a reliable and sensitive indicator of brain atrophy and disease progression in behavioural variant frontotemporal dementia. In this study, we validate our previously developed automated tool using ventricular features (known as VentRa) for the classification of behavioural variant frontotemporal dementia vers...

For over a century, brain research narrative has mainly centered on neuron cells. Accordingly, most whole-brain neurodegenerative studies focus on neuronal dysfunction and their selective vulnerability, while we lack comprehensive analyses of other major cell-types’ contribution. By unifying spatial gene expression, structural MRI, and cell deconvo...

Background Brain banks provide small tissue samples to researchers, while gross anatomy laboratories could provide larger samples, including complete brains to neuroscientists. However, they are preserved with solutions appropriate for gross-dissection, different from the classic neutral-buffered formalin (NBF) used in brain banks. Our previous wor...

Apolipoprotein (APOE) ɛ4 positivity and subjective cognitive decline (SCD) both increase risk of Alzheimer’s disease (AD) development. However, few studies have examined the relationship between SCD and APOE status, especially using longitudinal data. The current study examined whether APOE is associated with the rate of cognitive change in SCD and...

Background: High blood pressure (BP) is one of the twelve modifiable risk factors that contribute to 40% of dementia cases that could be delayed or prevented. Although high BP is associated with cognitive decline and structural brain changes, less is known about the long-term association between variable BP and cognitive/brain changes. This study w...

Brain Age Gap (BAG) is defined as the difference between the brain's predicted age and the chronological age of an individual. Magnetic resonance imaging (MRI)-based BAG can quantify acceleration of brain aging, and is used to infer brain health as aging and disease interact. Motion in the scanner is a common occurrence that can affect the acquired...

Background The apolipoprotein (APOE) e4 allele is a known risk factor for Alzheimer’s disease (AD), while the e2 allele is thought to be protective. As few studies have examined the relationship between brain pathologies, atrophy, and white matter hyperintensities (WMHs) and APOE status in those with the e2e4 genotype, we do so here. Methods We an...

Background Recent studies have shown sleep disturbances occur in people with Alzheimer’s disease (AD), with sleep being impacted before the onset of clinical symptoms. White matter hyperintensities (WMHs) are cerebrovascular disease‐related pathological changes that develop with increased age and are also associated with AD. While studies have show...

Background One of the earliest pathological events in the course of AD is thought to be the degeneration of cholinergic neurons in the basal forebrain (Grothe et al. 2012). The largest cluster of cholinergic cells within the basal forebrain are found in the Nucleus basalis of Meynert (NbM) (Hampel et al. 2020). Studies show that loss of cholinergic...

Background Hippocampal volume (HCvol) is an important biomarker in the study of neurodegeneration (1‐3). A drawback of HCvol as a clinical biomarker is its high variability across the population (4). While the common approach to account for this variability is to normalize for head‐size variability using the intracranial volume (ICV) (5), other app...

Background MRI‐detected white matter hyperintensities (WMHs), a marker of cerebrovascular‐pathology, are common in Alzheimer’s disease (AD) and related dementias (ADRDs). In stroke, WMH‐volume was found to correlate most with stroke risk‐factors in the anterior cerebral arterial‐territory. Since the relationship between WMHs and arterial‐territorie...

Background Hippocampal volume (HCvol) is an important biomarker in the study of neurodegeneration (1‐3). Given its high variability (4) HCvol is commonly normalized using the intracranial volume (HCvol/ICV) (5). The Hippocampal‐to‐ventricle ratio (HVR) considers instead the nearby expanding ventricular space and has shown stronger negative associat...

Background We aimed to investigate the association between cortical brain age and white matter hyperintensities (WMH) in diverse forms of clinically‐defined vascular conditions. Our hypothesis was that a higher WMH burden would be associated with higher cortical brain age in all clinical subtypes. Method We used standardized MRI data obtained from...

Background We aimed to investigate the association between cortical brain age and white matter hyperintensities (WMH) in diverse forms of clinically‐defined vascular conditions. Our hypothesis was that a higher WMH burden would be associated with higher cortical brain age in all clinical subtypes. Method We used standardized MRI data obtained from...

The apolipoprotein (APOE) ɛ4 allele is a risk factor for Alzheimer's disease (AD), while the ɛ2 allele is thought to be protective against AD. Few studies have examined the relationship between brain pathologies, atrophy, and white matter hyperintensities (WMHs) and APOE status in those with the ɛ2ɛ4 genotype and results are inconsistent for those...

Background Within the spectrum of Lewy body disorders (LBD), both Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are characterized by gait and balance disturbances, which become more prominent under dual-task (DT) conditions. The brain substrates underlying DT gait variations, however, remain poorly understood in LBD. Objective To in...

White matter hyperintensities (WMHs) are radiological abnormalities reflecting cerebrovascular dysfunction detectable using magnetic resonance imaging (MRI). WMHs are often present in individuals at the later stages of the lifespan and in prodromal stages in the Alzheimer’s Disease spectrum. Tissue alterations underlying WMHs may include demyelinat...

INTRODUCTION: White matter hyperintensities (WMHs) and cerebral microbleeds are widespread among aging population and linked with cognitive deficits in mild cognitive impairment (MCI), vascular MCI (V-MCI), and Alzheimers disease without (AD) or with a vascular component (V-AD). In this study, we aimed to investigate the association between brain a...

Background Irregular word reading has been used to estimate premorbid intelligence in Alzheimer’s disease (AD) dementia. However, reading models highlight the core influence of semantic abilities on irregular word reading, which shows early decline in AD. The general aim of this study is to determine whether irregular word reading is a valid estima...

BACKGROUND White matter hyperintensities (WMHs) are associated with cognitive decline and progression to mild cognitive impairment (MCI) and dementia. It remains unclear if sex differences influence WMH progression or the relationship between WMH and cognition. METHODS Linear mixed models examined the relationship between risk factors, WMHs, and c...

For over a century, brain research narrative has mainly centered on neuron cells. Accordingly, most whole-brain neurodegenerative studies focus on neuronal dysfunction and their selective vulnerability, while we lack comprehensive analyses of other major cell-types’ contribution. By unifying spatial gene expression, structural MRI, and cell deconvo...

For over a century, brain research narrative has mainly centered on neuron cells. Accordingly, most whole-brain neurodegenerative studies focus on neuronal dysfunction and their selective vulnerability, while we lack comprehensive analyses of other major cell-types’ contribution. By unifying spatial gene expression, structural MRI, and cell deconvo...

The discovery that metabolic alterations often coexist with neurodegenerative conditions has sparked interest in the examination of gastrointestinal factors as potential modulators of brain health. Here, we examined the role of adipokines (leptin, adiponectin, resistin, and IL6) and insulin on different markers of brain atrophy in participants on t...

Introduction Brain Age Gap (BAG) is defined as the difference between the brain’s predicted age and the chronological age of an individual. Magnetic resonance imaging (MRI)-based BAG can quantify acceleration of brain aging, and is used to measure brain health as aging and disease interact. Motion in the scanner is a common occurrence that can affe...

The Nucleus Basalis of Meynert (NbM) is the main source of cholinergic projection to the entorhinal cortex (EC) and hippocampus (HC), where acetylcholine plays a key role in their function. Both cholinergic cells of NbM and their receptive targets in the EC and HC show sensitivity to neurofibrillary degeneration during the early stages of Alzheimer...

Background and Objectives White matter hyperintensities are pathological brain changes that are associated with increased age and cognitive decline. However, the association of white matter hyperintensity burden with amyloid positivity and conversion to dementia in people with mild cognitive impairment (MCI) is unclear. The aim of the current study...

Much research has focused on neurodegeneration in aging and Alzheimer's disease (AD). We developed Scoring by Nonlocal Image Patch Estimator (SNIPE), a non-local patch-based measure of anatomical similarity and hippocampal segmentation to measure hippocampal change. While SNIPE shows enhanced predictive power over hippocampal volume, it is unknown...

Background Nucleus basalis of Meynert (NbM) is the main source of cholinergic projection to the cerebral cortex, including entorhinal cortex (EC). Both cholinergic cells of NbM and their receptive targets in EC show degeneration during early stages of Alzheimer’s disease (AD). While precise delineation of NbM region on T1w scans is difficult due to...

Background People with subjective cognitive decline (SCD+) are thought to be at greater risk of Alzheimer’s disease (AD). The Nucleus basalis of Meynert (NbM) has been shown to change early in AD (Fernández‐Cabello et al., 2020), and it is the main source of cholinergic projection to entorhinal cortex (EC) (Mesulam et al., 2013). We thus investigat...

For over a century, brain research narrative has mainly centered on neuron cells. Accordingly, most whole-brain neurodegenerative studies focus on neuronal dysfunction and their selective vulnerability, while we lack comprehensive analyses of other major cell-types’ contribution. By unifying spatial gene expression, structural MRI, and cell deconvo...

INTRODUCTION: Apolipoprotein (APOE)e4 and subjective cognitive decline (SCD) increase risk of Alzheimer's disease. However, few studies have examined the relationship between SCD and APOE, especially using longitudinal data. The current study examined whether APOE is associated with the rate of cognitive change in SCD. METHODS: Linear mixed effects...

BACKGROUND: The apolipoprotein (APOE) e4 allele is a known risk factor for Alzheimer's disease (AD), while the e2 allele is thought to be protective against AD. Few studies have examined the relationship between brain pathologies, atrophy, and white matter hyperintensities (WMHs) and APOE status in those with the e2e4 genotype and results are incon...

Background While studies report that sleep disturbance can have negative effects on brain vasculature, its impact on cerebrovascular disease such as white matter hyperintensities (WMHs) in beta-amyloid positive older adults remains unexplored. Methods Linear regressions, mixed effects models, and mediation analysis examined the cross-sectional and...

Background: Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are part of a spectrum of Lewy body disorders, who exhibit a range of cognitive and gait impairments. Cognitive-motor interactions can be examined by performing a cognitive task while walking and quantified by a dual task cost (DTC). White matter hyperintensities (WMH) on mag...

Background: Slowed rates of cognitive decline have been reported in individuals with higher cognitive reserve (CR), but interindividual discrepancies remain unexplained. Few studies have reported a birth cohort effect, favoring later-born individuals, but these studies remain scarce. Objective: We aimed to predict cognitive decline in older adul...

Hippocampal changes are associated with increased age and cognitive decline due to mild cognitive impairment (MCI) and Alzheimer's disease (AD). These associations are often observed only in the later stages of decline. This study examined if hippocampal grading, a method measuring local morphological similarity of the hippocampus to cognitively no...

Background Obesity and its metabolic complications are associated with lower gray matter (GM) and white matter (WM) density, whereas weight loss after bariatric surgery leads to an increase in both measures. These increases of GM and WM density are significantly associated with post-operative weight loss and improvement of the metabolic/inflammator...

Importance: White matter hyperintensity (WMH) accumulation is associated with increased cognitive decline and progression to mild cognitive impairment (MCI) and dementia. The prevalence and outcomes of MCI and dementia differ between males and females. However, it is currently unclear as to whether sex differences influence WMH progression and the...

Background The identification of biomarkers for early detection of Alzheimer’s disease (AD) is critical to the development of therapies and interventions targeted at symptom management and tracking the pathophysiology of disease. The endorsement of subjective cognitive decline (SCD) has emerged as a potential indicator of early change in cognitive...

Background Increased age and cognitive decline are both associated with changes in the hippocampus. These associations are often measured using hippocampal volume measurements and changes in episodic memory. Some studies have also observed a relationship between hippocampal volume and global cognition. However, these studies often only find associa...

Background To develop new Alzheimer’s disease (AD) treatments, diagnostic tools must be applied before too much irreversible neurodegeneration occurs. One of the key features used to identify AD neurodegeneration is hippocampal (HC) volume. However, prediction accuracy using HC volume is not high enough to be implemented in clinical and research se...

Background Cerebral small vessel disease (CSVD), often measured using white matter hyperintensities (WMHs) is a pathological change to the brain that increases ones’ risk for both age‐related cognitive decline and dementia. Several studies have noted that there is greater risk of CSVD in African Americans than in Caucasians. However, limited resear...

Quality control (QC) is an important part of all scientific analysis, including neuroscience. With manual curation considered the gold standard, there remains a lack of available tools that make manual neuroimaging QC accessible, fast, and easy. In this article we present Qrater, a containerized web-based python application that enables viewing and...

Background Quality control (QC) is particularly important in vulnerable populations like patients with dementia where movement artifacts as well as registration failures may be more prevalent. From our need to review the quality of tens of thousands of raw MR images and reviewing the steps of our pre‐ and post‐processing pipelines, we developed Qra...

Background Previous research suggests that white matter hyperintensities, amyloid, and tau contribute to cognitive decline. It remains unknown as to how these factors relate to one another and how they jointly contribute to cognitive decline in normal aging. The goal of this study was to examine the association between these pathologies and their r...

Background White matter hyperintensities (WMHs) are pathological changes that develop with increased age and are associated with cognitive decline. Most research on WMHs has neglected to examine regional differences and instead focuses on using a whole‐brain approach. This study examined regional WMH differences and their association with different...

Increased age and cognitive impairment is associated with an increase in cerebrovascular pathology often measured as white matter hyperintensities (WMHs) on MRI. Whether WMH burden differs between cognitively unimpaired older adults with subjective cognitive decline (SCD +) and without subjective cognitive decline (SCD −) remains conflicting, and c...