Cerebrovascular Reactivity at Rest and Its Association With Cognitive Function in People With Genetic Frontotemporal...

Area of Science:

• Neuroscience
• Vascular Biology
• Genetics

Background:

• Cerebrovascular reactivity (CVR) is a key indicator of brain vascular health.
• The CVR signature in familial frontotemporal dementia (FTD) is currently unknown.
• Investigating CVR may reveal novel insights into FTD pathogenesis.

Purpose of the Study:

• To investigate CVR in genetic FTD using resting-state fluctuation amplitudes (RSFAs) derived from fMRI.
• To determine if age moderates differences in RSFA between genetic FTD groups.
• To explore the association between RSFA and cognitive function in individuals at risk for FTD.

Main Methods:

• Utilized data from the prospective Genetic FTD Initiative cohort study.
• Included presymptomatic and symptomatic carriers of C9orf72, GRN, and MAPT mutations, and non-carriers.
• Assessed CVR using component-based and voxel-level RSFA maps, analyzing age-related effects and cognitive associations via generalized linear models.

Main Results:

• Symptomatic carriers showed lower RSFA and a steeper age-related decline in medial frontal and posterior parietal cortex compared to presymptomatic carriers and non-carriers.
• RSFA was inversely correlated with age and positively associated with cognitive function in mutation carriers, irrespective of disease stage.
• These findings highlight specific cortical regions affected by CVR impairment in genetic FTD.

Conclusions:

• CVR impairment in genetic FTD preferentially affects the middle frontal and posterior cortex.
• Preserved CVR may offer cognitive benefits for individuals at risk of FTD.
• Vascular dysfunction in familial FTD presents a potential target for biomarker development and therapeutic strategies.