White Matter Changes Associated with Resting Sympathetic Tone in Frontotemporal Dementia vs. Alzheimer's Disease.

Mario F Mendez,Madelaine Daianu,Elvira Jimenez,Paul Thompson,Simantini J Karve

doi:10.1371/journal.pone.0142445

Mario F Mendez, Madelaine Daianu + Show 3 more

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https://doi.org/10.1371/journal.pone.0142445

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Abstract

BackgroundResting sympathetic tone, a measure of physiological arousal, is decreased in patients with apathy and inertia, such as those with behavioral variant frontotemporal dementia (bvFTD) and other frontally-predominant disorders.ObjectiveTo identify the neuroanatomical correlates of skin conductance levels (SCLs), an index of resting sympathetic tone and apathy, among patients with bvFTD, where SCLs is decreased, compared to those with Alzheimer’s disease (AD), where it is not.MethodsThis study analyzed bvFTD (n = 14) patients and a comparison group with early-onset AD (n = 19). We compared their resting SCLs with gray matter and white matter regions of interest and white matter measures of fiber integrity on magnetic resonance imaging and diffusion tensor imaging.ResultsAs expected, bvFTD patients, compared to AD patients, had lower SCLs, which correlated with an apathy measure, and more gray matter loss and abnormalities of fiber integrity (fractional anisotropy and mean diffusivity) in frontal-anterior temporal regions. After controlling for group membership, the SCLs were significantly correlated with white matter volumes in the cingulum and inferior parietal region in the right hemisphere.ConclusionAmong dementia patients, SCLs, and resting sympathetic tone, may correlate with quantity of white matter, rather than with gray matter or with white matter fiber integrity. Loss of white matter volumes, especially involving a right frontoparietal network, may reflect chronic loss of cortical axons that mediate frontal control of resting sympathetic tone, changes that could contribute to the apathy and inertia of bvFTD and related disorders.

Highlights

Apathy, inertia, and emotional blunting are core symptoms of behavioral variant frontotemporal dementia, a neurodegenerative disease which manifests behavioral disinhibition, hyperorality, lack of empathy, compulsive behaviors, and a dysexecutive neuropsychological profile [1]
BvFTD patients, compared to Alzheimer’s disease (AD) patients, had lower skin conductance levels (SCLs), which correlated with an apathy measure, and more gray matter loss and abnormalities of fiber integrity in frontal-anterior temporal regions
Loss of white matter volumes, especially involving a right frontoparietal network, may reflect chronic loss of cortical axons that mediate frontal control of resting sympathetic tone, changes that could contribute to the apathy and inertia of behavioral variant frontotemporal dementia (bvFTD) and related disorders

Summary

Introduction

Inertia, and emotional blunting are core symptoms of behavioral variant frontotemporal dementia (bvFTD), a neurodegenerative disease which manifests behavioral disinhibition, hyperorality, lack of empathy, compulsive behaviors, and a dysexecutive neuropsychological profile [1]. Apathy, which is a disturbance of motivation involving loss of goal-oriented behavior, interest, and emotional expression [4,5], is associated with decreased physiological arousal and sympathetic tone [6,7,8,9]. BvFTD is an excellent model for studying the neuroanatomical basis of resting sympathetic tone because of neuropathology in frontal regions involved in sympathetic control and because of the presence of decreased skin conductance levels (SCLs)[10,11,12]. Skin conductance, which solely depends on sympathetic innervation of the sweat glands, is a readily measurable index of resting sympathetic and physiological arousal [6,13]. A measure of physiological arousal, is decreased in patients with apathy and inertia, such as those with behavioral variant frontotemporal dementia (bvFTD) and other frontally-predominant disorders

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