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AD/PD 2023 | Brain atrophy in iRBD is driven by mitochondrial function-associated genes

Shady Rahayel, PhD, Montreal Neurological Institute and Hospital (McGill University), Montreal, Canada, discusses his recent investigation into the genetic underpinnings of brain atrophy changes in isolated REM sleep behavior disorder (iRBD). This study was conducted in 171 patients with videopolysomnography-confirmed iRBD, who had clinical data and MRI imaging data available. Consistent with previous findings, it was shown that patients with iRBD had cortical thinning, in comparison to a control group of 238. Additionally, the more a brain region was thinned, the higher the expression of genes involved in mitochondrial functioning. However, it is unclear whether differing mitochondrial function is a starting point for increased atrophy or if there are other mechanisms influencing mitochondrial function that induce atrophy. It was also noted that the amount of structural change seen was correlated with that of neighboring regions, supporting the notion that RBD is constrained by the connectome architecture. When compared with patients with Alzheimer’s disease (AD), the gene enrichment and connectivity patterns were distinct from those with iRBD, suggesting that cortical thinning related to mitochondrial dysfunction may specific to synucleinopathies such as Parkinson’s disease and dementia with Lewy bodies. This interview took place at the AD/PD™ 2023 congress in Gothenburg, Sweden.

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