Neuropathological substrate of self-conscious emotion deficits in neurodegenerative dementia (P6.199)

OBJECTIVE: To assess the neuropathological substrate of self-conscious emotion deficits in neurodegenerative dementia. BACKGROUND: Impaired physiological and behavioral self-conscious emotional reactivity has been correlated with pregenual anterior cingulate cortex (pACC) atrophy in patients with frontotemporal dementia (FTD) and other neurodegenerative disorders. Alzheimer’s disease (AD), in contrast, shows evidence to increased social sensitivity. DESIGN: We sought to determine the brain structures in which neuropathology predicted physiological responses to a test of self-conscious emotional reactivity in FTD and AD. METHODS: We identified patients with an autopsy diagnosis of Pick’s disease (PiD) or AD who underwent self-conscious emotional reactivity assessment during life using a well-validated karaoke singing task. Skin conductance level (SCL), a marker of sympathetic nervous system reactivity, was measured at baseline and while the participants watched the video clip of their karaoke performance. Correlations were assessed between physiological measures and (a) neurodegeneration composite scores (neuronal loss, gliosis, and microvacuolation changes) and (b) disease protein deposition burden (tau, beta amyloid). We focused on the pACC and periaqueductal grey (PAG), regions involved in autonomic response generation. RESULTS: Four subjects had a clinical diagnosis of behavioral variant FTD and a pathological diagnosis of PiD, and 6 had a clinical and pathological diagnosis of AD. A mixed model analysis of variance was used. Across all subjects, lower SCL were associated with more severe neurodegeneration in the pACC (p=0.003) and with the severity of neuronal tau burden in the PAG (p Disclosure: Dr. Spina has nothing to disclose. Dr. Sturm has nothing to disclose. Dr. Lwi has nothing to disclose. Dr. Verstaen has nothing to disclose. Dr. Otero has nothing to disclose. Dr. Grinberg has nothing to disclose. Dr. Levenson has nothing to disclose. Dr. Miller has received personal compensation in an editorial capacity for Cambridge University Press, Guilford Publications, Inc., and Neurocase. Dr. Seeley has nothing to disclose.