. 2025 Jun;79(6):327-335.

doi: 10.1111/pcn.13810. Epub 2025 Mar 13.

Neuropsychiatric symptoms cluster and fluctuate over time in behavioral variant frontotemporal dementia

Christopher B Morrow¹, Vidyulata Kamath¹, Bradford C Dickerson², Mark Eldaief², Neguine Rezaii², Bonnie Wong², Scott McGinnis², Ryan Darby³, Adam M Staffaroni⁴, Maria I Lapid⁵, Belen Pascual⁶, Julio C Rojas⁴, Joseph C Masdeu⁶, Kyrana Tsapkini⁷, Edward D Huey⁸, Daniel W Fisher⁹, Alexander Pantelyat⁷, Akshata Balaji¹, Eric Sah^{1

10}, Irene Litvan¹¹, Katya Rascovsky¹², Nupur Ghoshal¹³, Kimiko Domoto-Reilly⁹, John Kornak¹⁴, Chiadi U Onyike¹; ALLFTD Consortium

Collaborators, Affiliations

Collaborators

ALLFTD Consortium:
Muhammad Abdullah, Liana Apostolova, Brian Appleby, Sami Barmada, Ece Bayram, Bradley Boeve, Hugo Botha, Adam L Boxer, Andrea Bozoki, Danielle Brushaber, David Clark, Ciaran M Considine, R Ryan Darby, Gregory S Day, Bradford Dickerson, Dennis Dickson, Kimiko Domoto-Reilly, Emily Dwosh, Kelley Faber, Anne Fagan, Julie A Fields, Jamie C Fong, Tatiana Foroud, Leah K Forsberg, Douglas R Galasko, Ralitza Gavrilova, Tania Gendron, Daniel Geschwind, Nupur Ghoshal, Jill Goldman, Jonathan Graff-Radford, Neill Graff-Radford, Ian M Grant, Murray Grossman, Chadwick M Hales, Matthew Hall, Hilary W Heuer, Lawrence S Honig, Hsiung Ging-Yuek Robin, Eric Huang, Edward D Huey, David Irwin, Noah Johnson, David T Jones, Kejal Kantarci, David Knopman, Tyler Kolander, John Kornak, Walter Kremers, Justin Kwan, Argentina Lario Lago, Maria Lapid, Shannon B Lavigne, Suzee Lee, Gabriel C Léger, Irene Litvan, Peter Ljubenkov, Diane Lucente, Ian R Mackenzie, Joseph C Masdeu, Lauren Massimo, Scott McGinnis, Corey T McMillan, Mario F Mendez, Carly Mester, Toji Miyagawa, Joie Molden, Chiadi Onyike, Alexander Pantelyat, Belen Pascual, Henry Paulson, Leonard Petrucelli, Peter Pressman, Rosa Rademakers, Vijay Ramanan, Eliana Marisa Ramos, Katherine P Rankin, Meghana Rao, Katya Rascovsky, Kristoffer W Rhoads, Aaron Ritter, Erik D Roberson, Emily Rogalski, Julio C Rojas, Howard J Rosen, Rodolfo Savica, William Seeley, Allison Snyder, Adam M Staffaroni, Anna Campbell Sullivan, Jeremy Syrjanen, M Carmela Tartaglia, Jack Taylor, Philip W Tipton, Marijne Vandebergh, Sandra Weintraub, Dylan Wint, Bonnie Wong, Jennifer Yokoyama

Affiliations

¹ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
² Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Charlestown, Massachusetts, USA.
³ Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁴ Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
⁵ Department of Psychiatry and Neurology, Mayo Clinic, Rochester, Minnesota, USA.
⁶ Department of Neurology, Houston Methodist Research Institute, Houston, Texas, USA.
⁷ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁸ Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, Rhode Island, USA.
⁹ Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA.
¹⁰ Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
¹¹ Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.
¹² Department of Neurology and Penn Frontotemporal Degeneration Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
¹³ Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
¹⁴ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.

PMID: 40079430
PMCID: PMC12133425 (available on 2026-06-01)
DOI: 10.1111/pcn.13810

Neuropsychiatric symptoms cluster and fluctuate over time in behavioral variant frontotemporal dementia

Christopher B Morrow et al. Psychiatry Clin Neurosci. 2025 Jun.

. 2025 Jun;79(6):327-335.

doi: 10.1111/pcn.13810. Epub 2025 Mar 13.

Authors

Collaborators

ALLFTD Consortium:
Muhammad Abdullah, Liana Apostolova, Brian Appleby, Sami Barmada, Ece Bayram, Bradley Boeve, Hugo Botha, Adam L Boxer, Andrea Bozoki, Danielle Brushaber, David Clark, Ciaran M Considine, R Ryan Darby, Gregory S Day, Bradford Dickerson, Dennis Dickson, Kimiko Domoto-Reilly, Emily Dwosh, Kelley Faber, Anne Fagan, Julie A Fields, Jamie C Fong, Tatiana Foroud, Leah K Forsberg, Douglas R Galasko, Ralitza Gavrilova, Tania Gendron, Daniel Geschwind, Nupur Ghoshal, Jill Goldman, Jonathan Graff-Radford, Neill Graff-Radford, Ian M Grant, Murray Grossman, Chadwick M Hales, Matthew Hall, Hilary W Heuer, Lawrence S Honig, Hsiung Ging-Yuek Robin, Eric Huang, Edward D Huey, David Irwin, Noah Johnson, David T Jones, Kejal Kantarci, David Knopman, Tyler Kolander, John Kornak, Walter Kremers, Justin Kwan, Argentina Lario Lago, Maria Lapid, Shannon B Lavigne, Suzee Lee, Gabriel C Léger, Irene Litvan, Peter Ljubenkov, Diane Lucente, Ian R Mackenzie, Joseph C Masdeu, Lauren Massimo, Scott McGinnis, Corey T McMillan, Mario F Mendez, Carly Mester, Toji Miyagawa, Joie Molden, Chiadi Onyike, Alexander Pantelyat, Belen Pascual, Henry Paulson, Leonard Petrucelli, Peter Pressman, Rosa Rademakers, Vijay Ramanan, Eliana Marisa Ramos, Katherine P Rankin, Meghana Rao, Katya Rascovsky, Kristoffer W Rhoads, Aaron Ritter, Erik D Roberson, Emily Rogalski, Julio C Rojas, Howard J Rosen, Rodolfo Savica, William Seeley, Allison Snyder, Adam M Staffaroni, Anna Campbell Sullivan, Jeremy Syrjanen, M Carmela Tartaglia, Jack Taylor, Philip W Tipton, Marijne Vandebergh, Sandra Weintraub, Dylan Wint, Bonnie Wong, Jennifer Yokoyama

Affiliations

¹ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
² Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Charlestown, Massachusetts, USA.
³ Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁴ Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
⁵ Department of Psychiatry and Neurology, Mayo Clinic, Rochester, Minnesota, USA.
⁶ Department of Neurology, Houston Methodist Research Institute, Houston, Texas, USA.
⁷ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁸ Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, Rhode Island, USA.
⁹ Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA.
¹⁰ Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
¹¹ Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.
¹² Department of Neurology and Penn Frontotemporal Degeneration Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
¹³ Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
¹⁴ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.

PMID: 40079430
PMCID: PMC12133425 (available on 2026-06-01)
DOI: 10.1111/pcn.13810

Abstract

Aim: Cognitive and behavioral phenomena define behavioral variant frontotemporal dementia (bvFTD), but neuropsychiatric symptoms (NPS) outside the core criteria are common throughout the illness. Identifying how NPS cluster in bvFTD may guide development of future therapies.

Methods: Participants (n = 354) with sporadic and genetic bvFTD were enrolled in the ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration Consortium. Dementia stage was defined as early (CDR® plus NACC FTLD ≤1) or advanced (CDR® plus NACC FTLD ≥1). Baseline and annual follow-up visit data were analyzed to compare NPS across stages of bvFTD. Psychiatric states were captured using the Neuropsychiatric Inventory-Questionnaire and Clinician Judgment of Symptoms. Polychoric cluster analysis was used to describe NPS clusters.

Results: NPS were highly prevalent (≥90%) in early and late bvFTD. Four NPS clusters were identified based on magnitude of factor loadings: affective, disinhibited, compulsive, and psychosis. Neuropsychiatric symptoms fluctuated across visits. In the affective cluster, depression showed the least visit-to-visit stability. In the disinhibited cluster, elation showed the least stability. Symptoms in the psychosis and compulsive clusters (hallucinations, delusions, obsessions/compulsions, and hyperorality) were largely stable, persisting from visit-to-visit in more than 50% of cases. Symptoms in the affective and disinhibited cluster were associated with the highest caregiver burden, while symptoms in the obsessive cluster were associated with the most functional impairment.

Conclusion: NPS in bvFTD are frequent and cluster into four discrete groups. The fluctuating nature of some NPS in bvFTD suggests that they may not be reliable markers of disease progression or stage.

Keywords: FTLD; behavioral symptoms; behavioral variant frontotemporal dementia; frontotemporal lobar degeneration; neuropsychiatry.

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Update of

Neuropsychiatric Symptoms Cluster and Fluctuate Over Time in Behavioral Variant Frontotemporal Dementia.
Morrow CB, Kamath V, Dickerson BC, Eldaief M, Rezaii N, Wong B, McGinnis S, Darby R, Staffaroni AM, Lapid MI, Pascual B, Rojas JC, Masdeu JC, Tsapkini K, Huey ED, Fisher DW, Pantelyat A, Balaji A, Sah E, Litvan I, Rascovsky K, Ghoshal N, Domoto-Reilly K, Kornak J, Onyike CU. Morrow CB, et al. medRxiv [Preprint]. 2024 Sep 28:2024.09.26.24314180. doi: 10.1101/2024.09.26.24314180. medRxiv. 2024. Update in: Psychiatry Clin Neurosci. 2025 Jun;79(6):327-335. doi: 10.1111/pcn.13810. PMID: 39398998 Free PMC article. Updated. Preprint.

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Neuropsychiatric symptoms cluster and fluctuate over time in behavioral variant frontotemporal dementia

Collaborators

Affiliations

Neuropsychiatric symptoms cluster and fluctuate over time in behavioral variant frontotemporal dementia

Authors

Collaborators

Affiliations

Abstract

Update of

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical