Feindel Brain and Mind Series: Vascular Risks, Cortical Atrophy & Dementia

Vascular Risk Factors, Cortical Atrophy, and Dementia: Genes, Cells, and Molecules

Abstract: Zdenka Pausova will present research investigating the role of vascular risk factors in the etiology of cortical atrophy, Alzheimer’s disease, and related dementia. Her work combines genetics and in silico transcriptomics with brain magnetic resonance imaging (MRI) in large-scale, population-based cohorts. This clinical research is complemented by studies in mice, which employ parallel brain MRI, serial two-photon tomography, and single-cell transcriptomics to provide cellular- and process-level insights.

Bio: For the past 25 years, Zdenka Pausova’s laboratory has studied the causes and consequences of obesity throughout the lifespan, with recent work focusing on obesity as a negative vascular risk factor for brain health. With a background in medicine, endocrinology, and genetics, she integrates knowledge from these fields with the latest technological advances. Her team combines multi-omics—genetics, epigenetics, transcriptomics, and metabolomics—with detailed phenotyping, including brain and body magnetic resonance imaging, in large-scale, population-based cohorts. Parallel studies in mouse models complement this research, enabling exploration of causality and insights into cellular and molecular mechanisms.

Dr. Pausova has published over 230 papers in peer-reviewed journals and holds an H-index of 77. She co-directs the Saguenay Youth Study (SYS), a longitudinal study of 2,000 adolescents and their parents investigating cardiometabolic and brain health. She contributes her expertise and SYS data to numerous international collaborative consortia, including NeuroCHARGE and ENIGMA. Within these collaborations, she has recently led two major projects: (i) metabolomic profiling of cerebral small vessel disease in over 9,000 participants (Circulation, 2022, PMID: 35050683), and (ii) genetic studies of the relationships between cerebral small vessel disease, cortical atrophy, and dementia in more than 50,000 participants, complemented by replication in 500,000 individuals (Nature Communications, 2024, PMID: 39496600). She has also leveraged other large-scale datasets, including the UK Biobank, where her team demonstrated that cortical tissue loss in type 2 diabetes begins early—during the prediabetic stage—and may involve dysregulated excitatory neuron signalling (Diabetes Care, 2023, PMID: 37824790).

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