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000284346 037__ $$aDZNE-2026-00117
000284346 041__ $$aEnglish
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000284346 1001_ $$0P:(DE-2719)9003208$$aMarth, Lena$$b0$$eFirst author$$udzne
000284346 245__ $$aPatterns and Trajectories of Behavioral and Neuropsychiatric Symptoms in Frontotemporal Dementia and Primary Progressive Aphasia.
000284346 260__ $$aPhiladelphia, Pa.$$bWolters Kluwer$$c2026
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000284346 520__ $$aBehavioral and neuropsychiatric symptoms are common in frontotemporal dementia (FTD) and primary progressive aphasia (PPA). However, little is known about their patterns, time course, and association with brain atrophy. We, therefore, aimed to describe behavioral and neuropsychiatric phenotypes in patients with FTD and PPA, leveraging a hypothesis-free/data-driven approach.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.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.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.
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000284346 650_2 $$2MeSH$$aHumans
000284346 650_2 $$2MeSH$$aMale
000284346 650_2 $$2MeSH$$aFemale
000284346 650_2 $$2MeSH$$aAphasia, Primary Progressive: psychology
000284346 650_2 $$2MeSH$$aAphasia, Primary Progressive: diagnostic imaging
000284346 650_2 $$2MeSH$$aAphasia, Primary Progressive: pathology
000284346 650_2 $$2MeSH$$aAphasia, Primary Progressive: complications
000284346 650_2 $$2MeSH$$aAphasia, Primary Progressive: physiopathology
000284346 650_2 $$2MeSH$$aFrontotemporal Dementia: psychology
000284346 650_2 $$2MeSH$$aFrontotemporal Dementia: diagnostic imaging
000284346 650_2 $$2MeSH$$aFrontotemporal Dementia: pathology
000284346 650_2 $$2MeSH$$aFrontotemporal Dementia: complications
000284346 650_2 $$2MeSH$$aFrontotemporal Dementia: physiopathology
000284346 650_2 $$2MeSH$$aAged
000284346 650_2 $$2MeSH$$aMiddle Aged
000284346 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000284346 650_2 $$2MeSH$$aAtrophy: pathology
000284346 650_2 $$2MeSH$$aNeuropsychological Tests
000284346 650_2 $$2MeSH$$aProspective Studies
000284346 650_2 $$2MeSH$$aBrain: pathology
000284346 650_2 $$2MeSH$$aBrain: diagnostic imaging
000284346 650_2 $$2MeSH$$aDisease Progression
000284346 650_2 $$2MeSH$$aCohort Studies
000284346 7001_ $$0P:(DE-2719)9000656$$aMartinez-Murcia, Francisco J$$b1
000284346 7001_ $$00000-0001-7069-1714$$aGórriz-Sáez, Juan-Manuel$$b2
000284346 7001_ $$0P:(DE-2719)2812081$$aDenecke, Jannis$$b3
000284346 7001_ $$0P:(DE-2719)9000543$$aEwers, Michael$$b4
000284346 7001_ $$0P:(DE-2719)9001508$$aPrix, Catharina$$b5$$udzne
000284346 7001_ $$0P:(DE-2719)9002610$$aStockbauer, Anna Christina$$b6$$udzne
000284346 7001_ $$0P:(DE-2719)9002620$$aBernhardt, Alexander Maximilian$$b7
000284346 7001_ $$0P:(DE-2719)9001249$$aWagemann, Olivia$$b8
000284346 7001_ $$00009-0002-2733-7511$$aWlasich, Elisabeth$$b9
000284346 7001_ $$aKustermann, Julia$$b10
000284346 7001_ $$0P:(DE-2719)2811024$$aPeters, Oliver$$b11
000284346 7001_ $$0P:(DE-2719)9003016$$aHellmann-Regen, Julian$$b12$$udzne
000284346 7001_ $$0P:(DE-HGF)0$$aDroste Zu Senden, Louise$$b13
000284346 7001_ $$0P:(DE-2719)2811122$$aPriller, Josef$$b14
000284346 7001_ $$0P:(DE-2719)2812446$$aSpruth, Eike Jakob$$b15
000284346 7001_ $$0P:(DE-2719)2811324$$aSpottke, Annika$$b16
000284346 7001_ $$0P:(DE-2719)9003181$$aAsperger, Hannah$$b17$$udzne
000284346 7001_ $$0P:(DE-2719)9003182$$aSchroeck, Friederike$$b18$$udzne
000284346 7001_ $$0P:(DE-2719)9001536$$aGamez, Anna$$b19$$udzne
000284346 7001_ $$0P:(DE-2719)2812035$$aSchneider, Anja$$b20
000284346 7001_ $$0P:(DE-2719)2811326$$aFliessbach, Klaus$$b21
000284346 7001_ $$0P:(DE-2719)9001016$$aDinter, Elisabeth$$b22$$udzne
000284346 7001_ $$0P:(DE-HGF)0$$aLinn, Jennifer$$b23
000284346 7001_ $$0P:(DE-2719)2811849$$aGünther, Rene$$b24
000284346 7001_ $$0P:(DE-2719)2811317$$aWiltfang, Jens$$b25
000284346 7001_ $$0P:(DE-2719)2814326$$aSchott, Björn H$$b26
000284346 7001_ $$0P:(DE-2719)2811350$$aBähr, Mathias$$b27$$udzne
000284346 7001_ $$0P:(DE-2719)2000058$$aZerr, Inga$$b28
000284346 7001_ $$0P:(DE-2719)2812683$$aFlöel, Agnes$$b29$$udzne
000284346 7001_ $$aMalinowski, Robert$$b30
000284346 7001_ $$0P:(DE-2719)2811351$$aBuerger, Katharina$$b31
000284346 7001_ $$0P:(DE-2719)9002557$$aJanowitz, Daniel$$b32
000284346 7001_ $$0P:(DE-2719)2000005$$aDuzel, Emrah$$b33
000284346 7001_ $$0P:(DE-2719)2811614$$aGlanz, Wenzel$$b34
000284346 7001_ $$0P:(DE-2719)9002520$$aLüsebrink, Falk$$b35$$udzne
000284346 7001_ $$0P:(DE-2719)2000026$$aTeipel, Stefan J$$b36
000284346 7001_ $$0P:(DE-2719)2810394$$aKilimann, Ingo$$b37
000284346 7001_ $$0P:(DE-2719)2380559$$aPrudlo, Johannes$$b38$$udzne
000284346 7001_ $$0P:(DE-2719)2811732$$aHermann, Andreas$$b39
000284346 7001_ $$0P:(DE-2719)2811275$$aSynofzik, Matthis$$b40
000284346 7001_ $$0P:(DE-2719)9000375$$aMengel, David$$b41$$udzne
000284346 7001_ $$00009-0000-9259-9230$$aBeichert, Lukas$$b42
000284346 7001_ $$0P:(DE-2719)2812801$$aMüller, Doreen$$b43$$udzne
000284346 7001_ $$0P:(DE-2719)2810273$$aPetzold, Gabor C$$b44
000284346 7001_ $$0P:(DE-2719)2812398$$aYakupov, Renat$$b45
000284346 7001_ $$aHetzer, Stefan$$b46
000284346 7001_ $$00009-0006-4005-3352$$aDechent, Peter$$b47
000284346 7001_ $$00000-0001-6316-8773$$aScheffler, Klaus$$b48
000284346 7001_ $$00000-0003-4499-7861$$aSchönecker, Sonja$$b49
000284346 7001_ $$0P:(DE-2719)2811659$$aLevin, Johannes$$b50$$eLast author
000284346 773__ $$0PERI:(DE-600)1491874-2$$a10.1212/WNL.0000000000214510$$gVol. 106, no. 4, p. e214510$$n4$$pe214510$$tNeurology$$v106$$x0028-3878$$y2026
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