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@ARTICLE{Marth:284346,
      author       = {Marth, Lena and Martinez-Murcia, Francisco J and
                      Górriz-Sáez, Juan-Manuel and Denecke, Jannis and Ewers,
                      Michael and Prix, Catharina and Stockbauer, Anna Christina
                      and Bernhardt, Alexander Maximilian and Wagemann, Olivia and
                      Wlasich, Elisabeth and Kustermann, Julia and Peters, Oliver
                      and Hellmann-Regen, Julian and Droste Zu Senden, Louise and
                      Priller, Josef and Spruth, Eike Jakob and Spottke, Annika
                      and Asperger, Hannah and Schroeck, Friederike and Gamez,
                      Anna and Schneider, Anja and Fliessbach, Klaus and Dinter,
                      Elisabeth and Linn, Jennifer and Günther, Rene and
                      Wiltfang, Jens and Schott, Björn H and Bähr, Mathias and
                      Zerr, Inga and Flöel, Agnes and Malinowski, Robert and
                      Buerger, Katharina and Janowitz, Daniel and Duzel, Emrah and
                      Glanz, Wenzel and Lüsebrink, Falk and Teipel, Stefan J and
                      Kilimann, Ingo and Prudlo, Johannes and Hermann, Andreas and
                      Synofzik, Matthis and Mengel, David and Beichert, Lukas and
                      Müller, Doreen and Petzold, Gabor C and Yakupov, Renat and
                      Hetzer, Stefan and Dechent, Peter and Scheffler, Klaus and
                      Schönecker, Sonja and Levin, Johannes},
      title        = {{P}atterns and {T}rajectories of {B}ehavioral and
                      {N}europsychiatric {S}ymptoms in {F}rontotemporal {D}ementia
                      and {P}rimary {P}rogressive {A}phasia.},
      journal      = {Neurology},
      volume       = {106},
      number       = {4},
      issn         = {0028-3878},
      address      = {Philadelphia, Pa.},
      publisher    = {Wolters Kluwer},
      reportid     = {DZNE-2026-00117},
      pages        = {e214510},
      year         = {2026},
      abstract     = {Behavioral 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.},
      keywords     = {Humans / Male / Female / Aphasia, Primary Progressive:
                      psychology / Aphasia, Primary Progressive: diagnostic
                      imaging / Aphasia, Primary Progressive: pathology / Aphasia,
                      Primary Progressive: complications / Aphasia, Primary
                      Progressive: physiopathology / Frontotemporal Dementia:
                      psychology / Frontotemporal Dementia: diagnostic imaging /
                      Frontotemporal Dementia: pathology / Frontotemporal
                      Dementia: complications / Frontotemporal Dementia:
                      physiopathology / Aged / Middle Aged / Magnetic Resonance
                      Imaging / Atrophy: pathology / Neuropsychological Tests /
                      Prospective Studies / Brain: pathology / Brain: diagnostic
                      imaging / Disease Progression / Cohort Studies},
      cin          = {Clinical Research (Munich) / AG Levin / AG Simons / AG
                      Peters / AG Endres / AG Priller / AG Spottke / Clinical
                      Research Platform (CRP) / AG Schneider / Patient Studies
                      (Bonn) / AG Falkenburger / AG Wiltfang / AG Fischer /
                      Clinical Dementia Research (Göttingen) / AG Zerr / AG
                      Düzel / AG Teipel / AG Hermann / AG Gasser / AG Petzold},
      ddc          = {610},
      cid          = {I:(DE-2719)1111015 / I:(DE-2719)1111016 /
                      I:(DE-2719)1110008 / I:(DE-2719)5000000 / I:(DE-2719)1811005
                      / I:(DE-2719)5000007 / I:(DE-2719)1011103 /
                      I:(DE-2719)1011401 / I:(DE-2719)1011305 / I:(DE-2719)1011101
                      / I:(DE-2719)1710012 / I:(DE-2719)1410006 /
                      I:(DE-2719)1410002 / I:(DE-2719)1440015 /
                      I:(DE-2719)1440011-1 / I:(DE-2719)5000006 /
                      I:(DE-2719)1510100 / I:(DE-2719)1511100 / I:(DE-2719)1210000
                      / I:(DE-2719)1013020},
      pnm          = {353 - Clinical and Health Care Research (POF4-353) / 351 -
                      Brain Function (POF4-351) / 352 - Disease Mechanisms
                      (POF4-352)},
      pid          = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-351 /
                      G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41592266},
      doi          = {10.1212/WNL.0000000000214510},
      url          = {https://pub.dzne.de/record/284346},
}