The brain correlates of behavioral disturbances in frontotemporal dementia

Abstract

AbstractBackgroundVarious studies have researched singular or clusters of behaviors in frontotemporal dementia (FTD) correlating them with regional brain atrophy in structural MRI data, or hypometabolism in FDG‐PET images, but a multimodal approach is lacking. We identify the brain correlates of modes of variation (i.e., factors) explaining the variability of behavioral and psychological symptoms (BPSD) in frontotemporal dementia (FTD) using multimodal imaging.MethodImaging and behavioral data from 93 FTD patients acquired at NIH were analyzed. They underwent extended neuropsychological assessment including several scales measuring BPSD (UCLA NPI, FrSBe, and Neurobehavioral rating scale), T1‐weighted MRI, and FDG‐PET imaging. Factor analysis was used on the behavioral data to identify modes of variation of BPSD potentially pointing to few common neurobiological substrates across the FTD sample. The identified modes were then related to intersubject brain variability using a newly developed fusion method run on maps of gray matter volume and FDG metabolism obtained.ResultA factor related to decreased emotional/cognitive interaction (loading scores of apathy, executive dysfunction, withdrawal) correlated with volume and function of the right anterior cingulate and orbito‐frontal cortex. A factor expressing variability on mutacism versus disinhibition/euphoria continuum was associated with dysfunction of the right superior primary motor cortex. A factor related to the presence of hallucinations/delusions/suspiciousness was associated with dysfunction of the right anterior insula.ConclusionBPSD variability in patients with FTD can be explained by 3 major modes of variations, each associated with intersubject brain structure/function variability of the right frontal lobe.