Patterns and Trajectories of Behavioral and Neuropsychiatric Symptoms in Frontotemporal Dementia and Primary Progressive Aphasia.
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Marth Lena, Martinez-Murcia Francisco J, Górriz-Sáez Juan-Manuel, Denecke Jannis, Ewers Michael, Prix Catharina, Stockbauer Anna Christina, Bernhardt Alexander Maximilian, Wagemann Olivia, Wlasich Elisabeth, Kustermann Julia, Peters Oliver, Hellmann-Regen Julian, Droste Zu Senden Louise, Priller Josef, Spruth Eike Jakob, Spottke Annika, Asperger Hannah, Schroeck Friederike, Gamez Anna, Schneider Anja, Fliessbach Klaus, Dinter Elisabeth, Linn Jennifer, Günther Rene, Wiltfang Jens, Schott Björn H, Bähr Mathias, Zerr Inga, Flöel Agnes, Malinowski Robert, Buerger Katharina, Janowitz Daniel, Duzel Emrah, Glanz Wenzel, Lüsebrink Falk, Teipel Stefan J, Kilimann Ingo, Prudlo Johannes, Hermann Andreas, Synofzik Matthis, Mengel David, Beichert Lukas, Müller Doreen, Petzold Gabor C, Yakupov Renat, Hetzer Stefan, Dechent Peter, Scheffler Klaus, Schönecker Sonja, Levin Johannes
Аннотация
METHODS: We included participants diagnosed with behavioral variant FTD (bvFTD) or PPA according to Rascovsky and Gorno-Tempini criteria from the German Center for Neurodegenerative Diseases Clinical Registry Study of Neurodegenerative Diseases-FTD prospective multicenter observational cohort study. Symptoms were assessed using the Neuropsychiatric Inventory-Questionnaire. Principal component analysis (PCA) was used to delineate symptom groups. Subsequently, frequency and severity across diagnostic groups were examined. We applied linear mixed-effects models to describe the longitudinal evolution of symptoms. Associations with MRI-assessed atrophy were investigated using linear regression models.
RESULTS: A total of 314 patients (42.4% female, mean age 65.52 [SD 9.0] years) with bvFTD or PPA were included. MRI was available for 134 of 314 individuals. PCA revealed 4 natural symptom groups, labeled active behavioral, passive behavioral, affective, and psychotic phenotypes. Symptom groups were observed at comparable frequencies across diagnostic groups. Time from symptom onset (0.130 [0.044-0.217], p < 0.003), sex (1.376 [0.666-2.087], p < 0.001), and the interaction between the nonfluent variant of PPA and sex (-1.940 [-3.242 to -0.638], p = 0.004) showed a significant effect on the active behavioral phenotype, with symptom severity increasing over time and being most pronounced in men with bvFTD. Patients with bvFTD exhibited more severe passive behavioral symptoms compared with any other diagnostic group. For the affective phenotype, a significant interaction between time and sex (0.063 [0.010-0.117], p = 0.021) indicated a progressive increase in symptom severity in men over time. Furthermore, we found robust neuroanatomical correlations of passive behavioral symptoms with subcortical and bilateral frontal and cingulate cortical atrophy.
DISCUSSION: Our findings demonstrate that behavioral and neuropsychiatric symptoms are prevalent in both bvFTD and PPA. Their severity depends on the disease duration, phenotypic group, and sex. This detailed understanding of symptomatology is crucial for optimizing patient care, diagnostic evaluations, and the design of clinical trials. Limitations comprise the lack of neuropathologic validation and the limited availability of MRI data.