Cerebrovascular reactivity impairment in genetic frontotemporal dementia

Abstract

INTRODUCTION: Cerebrovascular reactivity (CVR) is an indicator of cerebrovascular health and its signature in hereditary frontotemporal dementia (FTD) remains unknown. We investigated CVR in genetic FTD and its relationship to cognition. METHODS: CVR differences were assessed between 284 pre-symptomatic and 124 symptomatic mutation carriers, and 265 non-carriers, using resting-state fluctuation amplitudes (RSFA) on component-based and voxel-level RSFA maps. Associations and interactions between RSFA, age, genetic status, and cognition were examined using generalised linear models. RESULTS: Compared to non-carriers, mutation carriers exhibited greater RSFA reductions, predominantly in frontal cortex. These reductions increased with age. The RSFA in these regions correlated with cognitive function in symptomatic and, to a lesser extent, pre-symptomatic individuals, independent of disease stage. DISCUSSION: CVR impairment in genetic FTD predominantly affects frontal cortical areas, and its preservation may yield cognitive benefits for at-risk individuals. Cerebrovascular health may be a potential target for biomarker identification and disease-modifying efforts.