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Hyperorality in Frontotemporal Dementia: How Psychiatric and Neural Correlates Change Across the Disease Course

Morrow, C.; Onyike, C.; Pantelyat, A.; Smith, G.; Leoutsakos, J.-M.; Faria, A.; Graff-Radford, N.; Darby, R.; Ghoshal, N.; Staffaroni, A.; Rascovsky, K.; Miyagawa, T.; Balaji, A.; Tsapkini, K.; Lapid, M.; Mendez, M.; Litvan, I.; Pascual, B.; Rojas-Rodriguez, J.; Wszolek, Z.; Domoto-Reilly, K.; Kornak, J.; Kamath, V.; ALLFTD Consortium,

2024-02-20 psychiatry and clinical psychology
10.1101/2024.02.19.24302699 medRxiv
Show abstract

ObjectivesHyperorality is one of the core features of behavioral variant frontotemporal dementia (bvFTD), however, the cognitive, psychiatric, and neuroanatomic correlates of hyperorality across disease stages remain unclear. This study works to fill this knowledge gap by exploring these associations in the early and advanced stages of bvFTD. MethodsParticipants with sporadic and genetic bvFTD were enrolled in the ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration consortium (ALLFTD). The primary analyses used baseline data to compare cognitive and psychiatric symptoms in those with and without hyperorality stratified by disease severity. Linear multivariable regressions adjusting for age and total intracranial volume were used to examine baseline associations between regional gray matter volumes and hyperorality status. Five anatomic regions of interest were pre-selected for analysis based on previously identified neuroanatomic correlates of hyperorality in bvFTD. ResultsHyperorality was present in 50% of early-stage bvFTD participants (n = 136) and was associated with higher rates of ritualistic/compulsive behavior. Hyperorality was present in 63% of advanced-stage participants (n = 208) and was associated higher rates of apathy, and ritualistic/compulsive behavior. Regional gray matter volumes were similar in those with and without hyperorality in early-stage participants. In the advanced-stage participants, hyperorality was associated with lower gray matter volumes in the right dorsal and ventral striatum. ConclusionsHyperorality emerges early in bvFTD and is accompanied by deficits in social cognition and complex-ritualistic behavior prior to clinically significant gray matter volume loss. These findings suggest that early identification and treatment of hyperorality could improve neuropsychiatric trajectories in bvFTD.

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