84| Behavioral Variant Frontotemporal Dementia – A Conversation With Dr. Bruce Miller

We discuss behavioral variant frontotemporal dementia (bvFTD) with Bruce Miller, MD, a behavioral neurologist at UCSF.  We first talk about overlap and differences between the various FTD spectrum conditions and related diseases.  Next, we cover the neuropathology, genetics, neuroimaging, phenocopy syndrome, classic clinical and behavioral syndrome, cognitive profile, treatment options, and patient/caregiver resources.

A pdf of the transcript for this episode is available here.

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About Bruce

Bruce L. Miller, MD, is a behavioral neurologist who studies the underlying mechanisms of neurocognitive disorders and is a world-renowned expert in the diagnosis and management of dementia.  He holds the A.W. and Mary Margaret Clausen Distinguished Professorship in Neurology at the University of California, San Francisco, directs the UCSF Memory and Aging Center, and is a director of the Global Brain Health Institute. He is the principal investigator of the NIH-sponsored Alzheimer’s Disease Research Center and program project grant on frontotemporal dementia. In addition, he helps lead the Tau Consortium and the Bluefield Foundation, precision medicine collaborations, focused on developing treatments for tauopathies and progranulin-mediated forms of frontotemporal dementia.

Dr. Miller has been featured in Fortune Magazine, the New York Times, 60 Minutes, the Charlie Rose Show and the PBS Newshour. He has authored more than 800 publications and written several books: The Human Frontal Lobes, The Behavioral Neurology of Dementia and Frontotemporal Dementia. He has received many awards including the Potamkin Award from the American Academy of Neurology, the Elliot Royer Award from the San Francisco Neurological community, the UCSF Academic Senate Distinction in Mentoring Award, and the Robert A. Fishman Award and Lecture. In 2016, Dr. Miller was elected to the National Academy of Medicine.

Selected Resources

The Association for Frontotemporal Degeneration

UCSF FTD Information Page

UCSF bvFTD Information Page

Selected References

Bang, J., Spina, S., & Miller, B. L. (2015). Frontotemporal dementia. The Lancet, 386(10004), 1672-1682. https://doi.org/10.1016/s0140-6736(15)00461-4

Deleon, J., & Miller, B. L. (2018). Frontotemporal dementia. Handbook of Clinical Neurology, 148, 409-430. https://doi.org/10.1016/B978-0-444-64076-5.00027-2

Ducharme, S., Price, B. H., Larvie, M., Dougherty, D. D., & Dickerson, B. C. (2015, Sep 1). Clinical Approach to the Differential Diagnosis Between Behavioral Variant Frontotemporal Dementia and Primary Psychiatric Disorders. American Journal of Psychiatry, 172(9), 827-837. https://doi.org/10.1176/appi.ajp.2015.14101248

Ferrari, R., Hernandez, D. G., Nalls, M. A., Rohrer, J. D., Ramasamy, A., Kwok, J. B. J., Dobson-Stone, C., Brooks, W. S., Schofield, P. R., Halliday, G. M., Hodges, J. R., Piguet, O., Bartley, L., Thompson, E., Haan, E., Hernández, I., Ruiz, A., Boada, M., Borroni, B., Padovani, A., Cruchaga, … Momeni, P. (2014). Frontotemporal dementia and its subtypes: a genome-wide association study. The Lancet Neurology, 13(7), 686-699. https://doi.org/10.1016/s1474-4422(14)70065-1

Ferrari, R., Hernandez, D. G., Nalls, M. A., Rohrer, J. D., Ramasamy, A., Kwok, J. B. J., Dobson-Stone, C., Brooks, W. S., Schofield, P. R., Halliday, G. M., Hodges, J. R., Piguet, O., Bartley, L., Thompson, E., Haan, E., Hernández, I., Ruiz, A., Boada, M., Borroni, B., Padovani, A., … Momeni, P. (2014). Frontotemporal dementia and its subtypes: a genome-wide association study. The Lancet Neurology, 13(7), 686-699. https://doi.org/10.1016/s1474-4422(14)70065-1

Ferrari, R., Kapogiannis, D., Huey, E. D., & Momeni, P. (2011, May). FTD and ALS: a tale of two diseases. Current Alzheimer Research, 8(3), 273-294. https://doi.org/10.2174/156720511795563700

Ghetti, B., Buratti, E., Boeve, B., Rademakers, R. (Eds.) (2021) Frontotemporal Dementias: Emerging Milestones of the 21st Century, Springer

Gitlin, L. N., Winter, L., Vause Earland, T., Adel Herge, E., Chernett, N. L., Piersol, C. V., & Burke, J. P. (2009, Jun). The Tailored Activity Program to reduce behavioral symptoms in individuals with dementia: feasibility, acceptability, and replication potential. Gerontologist, 49(3), 428-439. https://doi.org/10.1093/geront/gnp087

Heuer, H. W., Wang, P., Rascovsky, K., Wolf, A., Appleby, B., Bove, J., Bordelon, Y., Brannelly, P., Brushaber, D. E., Caso, C., Coppola, G., Dickerson, B., Dickinson, S., Domoto-Reilly, K., Faber, K., Ferrall, J., Fields, J., Fishman, A., Fong, J., … Consortia, L. (2020, Jan). Comparison of sporadic and familial behavioral variant frontotemporal dementia (FTD) in a North American cohort. Alzheimers & Dementia, 16(1), 60-70. https://doi.org/10.1002/alz.12046

Hua, A. Y., Chen, K. H., Brown, C. L., Lwi, S. J., Casey, J. J., Rosen, H. J., Miller, B. L., & Levenson, R. W. (2019, Dec 30). Physiological, behavioral and subjective sadness reactivity in frontotemporal dementia subtypes. Social Cognitive and Affective Neuroscience, 14(12), 1453-1465. https://doi.org/10.1093/scan/nsaa007

Illán-Gala, I., Casaletto, K. B., Borrego-Écija, S., Arenaza-Urquijo, E. M., Wolf, A., Cobigo, Y., Goh, S. Y. M., Staffaroni, A. M., Alcolea, D., Fortea, J., Blesa, R., Clarimon, J., Iulita, M. F., Brugulat-Serrat, A., Lladó, A., Grinberg, L. T., Possin, K., Rankin, K. P., Kramer, … Rosen, H. J. (2021). Sex differences in the behavioral variant of frontotemporal dementia: A new window to executive and behavioral reserve. Alzheimer’s & Dementia, 17(8), 1329-1341. https://doi.org/https://doi.org/10.1002/alz.12299

Karageorgiou, E., & Miller, B. L. (2014, Apr). Frontotemporal lobar degeneration: a clinical approach. Seminars in Neurology, 34(2), 189-201. https://doi.org/10.1055/s-0034-1381735

Krueger, C. E., Dean, D. L., Rosen, H. J., Halabi, C., Weiner, M., Miller, B. L., & Kramer, J. H. (2010, Jan-Mar). Longitudinal rates of lobar atrophy in frontotemporal dementia, semantic dementia, and Alzheimer’s disease. Alzheimer Disease and Associated Disorders, 24(1), 43-48. https://doi.org/10.1097/WAD.0b013e3181a6f101

Lanata, S. C., & Miller, B. L. (2016, May). The behavioural variant frontotemporal dementia (bvFTD) syndrome in psychiatry. Journal of Neurology, Neurosurgery, and Psychiatry, 87(5), 501-511. https://doi.org/10.1136/jnnp-2015-310697

Liljegren, M., Naasan, G., Temlett, J., Perry, D. C., Rankin, K. P., Merrilees, J., Grinberg, L. T., Seeley, W. W., Englund, E., & Miller, B. L. (2015, Mar). Criminal behavior in frontotemporal dementia and Alzheimer disease. JAMA Neurology, 72(3), 295-300. https://doi.org/10.1001/jamaneurol.2014.3781

Liu, A. J., Staffaroni, A. M., Rojas-Martinez, J. C., Olney, N. T., Alquezar-Burillo, C., Ljubenkov, P. A., La Joie, R., Fong, J. C., Taylor, J., Karydas, A., Ramos, E. M., Coppola, G., Boxer, A. L., Rabinovici, G. D., Miller, B. L., & Kao, A. W. (2020). Association of Cognitive and Behavioral Features Between Adults With Tuberous Sclerosis and Frontotemporal Dementia. JAMA Neurology, 77(3), 358-366. https://doi.org/10.1001/jamaneurol.2019.4284

Ljubenkov, P. A., Staffaroni, A. M., Rojas, J. C., Allen, I. E., Wang, P., Heuer, H., Karydas, A., Kornak, J., Cobigo, Y., Seeley, W. W., Grinberg, L. T., Spina, S., Fagan, A. M., Jerome, G., Knopman, D., Boeve, B. F., Dickerson, B. C., Kramer, J., Miller, … Rosen, H. J. (2018, Oct). Cerebrospinal fluid biomarkers predict frontotemporal dementia trajectory. Annals of Clinical and Translational Neurology, 5(10), 1250-1263. https://doi.org/10.1002/acn3.643

Merrilees, J., Klapper, J., Murphy, J., Lomen-Hoerth, C., & Miller, B. L. (2010, May 3). Cognitive and behavioral challenges in caring for patients with frontotemporal dementia and amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis, 11(3), 298-302. https://doi.org/10.3109/17482961003605788.

O’Connor, C. M., Clemson, L., Brodaty, H., Jeon, Y. H., Mioshi, E., & Gitlin, L. N. (2014, May). Use of the Tailored Activities Program to reduce neuropsychiatric behaviors in dementia: an Australian protocol for a randomized trial to evaluate its effectiveness. International Psychogeriatrics, 26(5), 857-869. https://doi.org/10.1017/S1041610214000040

O’Connor, C. M., Clemson, L., Brodaty, H., Low, L. F., Jeon, Y. H., Gitlin, L. N., Piguet, O., & Mioshi, E. (2019, Feb). The tailored activity program (TAP) to address behavioral disturbances in frontotemporal dementia: a feasibility and pilot study. Disability and rehabilitation, 41(3), 299-310. https://doi.org/10.1080/09638288.2017.1387614

Olney, N. T., Spina, S., & Miller, B. L. (2017, May). Frontotemporal Dementia. Neurologic Clinics, 35(2), 339-374. https://doi.org/10.1016/j.ncl.2017.01.008

Perry, D. C., Brown, J. A., Possin, K. L., Datta, S., Trujillo, A., Radke, A., Karydas, A., Kornak, J., Sias, A. C., Rabinovici, G. D., Gorno-Tempini, M. L., Boxer, A. L., De May, M., Rankin, K. P., Sturm, V. E., Lee, S. E., Matthews, B. R., Kao, A. W., Vossel, … Seeley, W. W. (2017, Dec 1). Clinicopathological correlations in behavioural variant frontotemporal dementia. Brain, 140(12), 3329-3345. https://doi.org/10.1093/brain/awx254

Perry, D. C., Sturm, V. E., Seeley, W. W., Miller, B. L., Kramer, J. H., & Rosen, H. J. (2014, Jun). Anatomical correlates of reward-seeking behaviours in behavioural variant frontotemporal dementia. Brain, 137(Pt 6), 1621-1626. https://doi.org/10.1093/brain/awu075

Possin, K., Laluz, V., Alcantar, O., Miller, B., & Kramer, J. (2010, 10/01). Distinct Neuroanatomical Substrates and Cognitive Mechanisms of Figure Copy Performance in Alzheimer’s Disease and Behavioral Variant Frontotemporal Dementia. Neuropsychologia, 49, 43-48. https://doi.org/10.1016/j.neuropsychologia.2010.10.026

Pressman, P. S., & Miller, B. L. (2014, Apr 1). Diagnosis and management of behavioral variant frontotemporal dementia. Biological Psychiatry, 75(7), 574-581. https://doi.org/10.1016/j.biopsych.2013.11.006

Ramanan, S., Bertoux, M., Flanagan, E., Irish, M., Piguet, O., Hodges, J. R., & Hornberger, M. (2017, Jan). Longitudinal Executive Function and Episodic Memory Profiles in Behavioral-Variant Frontotemporal Dementia and Alzheimer’s Disease. Journal of the International Neuropsychological Society, 23(1), 34-43. https://doi.org/10.1017/S1355617716000837

Ranasinghe, K. G., Rankin, K. P., Lobach, I. V., Kramer, J. H., Sturm, V. E., Bettcher, B. M., Possin, K., Christine You, S., Lamarre, A. K., Shany-Ur, T., Stephens, M. L., Perry, D. C., Lee, S. E., Miller, Z. A., Gorno-Tempini, M. L., Rosen, H. J., Boxer, A., Seeley, W. W., Rabinovici, G. D., … Miller, B. L. (2016, Feb 16). Cognition and neuropsychiatry in behavioral variant frontotemporal dementia by disease stage. Neurology, 86(7), 600-610. https://doi.org/10.1212/WNL.0000000000002373

Ranasinghe, K. G., Rankin, K. P., Pressman, P. S., Perry, D. C., Lobach, I. V., Seeley, W. W., Coppola, G., Karydas, A. M., Grinberg, L. T., Shany-Ur, T., Lee, S. E., Rabinovici, G. D., Rosen, H. J., Gorno-Tempini, M. L., Boxer, A. L., Miller, Z. A., Chiong, W., DeMay, M., Kramer, J. H., Possin, … & Miller, B. L. (2016, Sep 1). Distinct Subtypes of Behavioral Variant Frontotemporal Dementia Based on Patterns of Network Degeneration. JAMA Neurology, 73(9), 1078-1088. https://doi.org/10.1001/jamaneurol.2016.2016

Rascovsky, K., Hodges, J. R., Knopman, D., Mendez, M. F., Kramer, J. H., Neuhaus, J., van Swieten, J. C., Seelaar, H., Dopper, E. G., Onyike, C. U., Hillis, A. E., Josephs, K. A., Boeve, B. F., Kertesz, A., Seeley, W. W., Rankin, K. P., Johnson, J. K., Gorno-Tempini, M. L., Rosen, H., Prioleau-Latham, C. E., … Miller, B. L. (2011, Sep). Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain, 134(Pt 9), 2456-2477. https://doi.org/10.1093/brain/awr179

Rohrer, J. D. (2012, Mar). Structural brain imaging in frontotemporal dementia. Biochim Biophys Acta, 1822(3), 325-332. https://doi.org/10.1016/j.bbadis.2011.07.014

Rohrer, J. D., Geser, F., Zhou, J., Gennatas, E. D., Sidhu, M., Trojanowski, J. Q., Dearmond, S. J., Miller, B. L., & Seeley, W. W. (2010, Dec 14). TDP-43 subtypes are associated with distinct atrophy patterns in frontotemporal dementia. Neurology, 75(24), 2204-2211. https://doi.org/10.1212/WNL.0b013e318202038c

Seo, S. W., Thibodeau, M. P., Perry, D. C., Hua, A., Sidhu, M., Sible, I., Vargas, J. N. S., Gaus, S. E., Rabinovici, G. D., Rankin, K. D., Boxer, A. L., Kramer, J. H., Rosen, H. J., Gorno-Tempini, M. L., Grinberg, L. T., Huang, E. J., DeArmond, S. J., Trojanowski, J. Q., Miller, B. L., & Seeley, W. W. (2018, Mar 20). Early vs late age at onset frontotemporal dementia and frontotemporal lobar degeneration. Neurology, 90(12), e1047-e1056. https://doi.org/10.1212/WNL.0000000000005163

Staffaroni, A. M., Bajorek, L., Casaletto, K. B., Cobigo, Y., Goh, S. M., Wolf, A., Heuer, H. W., Elahi, F. M., Ljubenkov, P. A., Dever, R., Kornak, J., Appleby, B., Bove, J., Bordelon, Y., Brannelly, P., Brushaber, D., Caso, C., Coppola, G., Dheel, C., … Rosen, H. J. (2020, Jan). Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia: NIH-EXAMINER as a potential clinical trial endpoint. Alzheimers & Dementia: the journal of the Alzheimer’s Association, 16(1), 11-21. https://doi.org/10.1016/j.jalz.2019.01.012

Staffaroni, A. M., Ljubenkov, P. A., Kornak, J., Cobigo, Y., Datta, S., Marx, G., Walters, S. M., Chiang, K., Olney, N., Elahi, F. M., Knopman, D. S., Dickerson, B. C., Boeve, B. F., Gorno-Tempini, M. L., Spina, S., Grinberg, L. T., Seeley, W. W., Miller, B. L., Kramer, J. H., … Rosen, H. J. (2019). Longitudinal multimodal imaging and clinical endpoints for frontotemporal dementia clinical trials. Brain, 142(2), 443-459. https://doi.org/10.1093/brain/awy319

Takeda, A., Sturm, V. E., Rankin, K. P., Ketelle, R., Miller, B. L., & Perry, D. C. (2019, Jul-Sep). Relationship Turmoil and Emotional Empathy in Frontotemporal Dementia. Alzheimer Disease & Associated Disorders, 33(3), 260-265. https://doi.org/10.1097/WAD.0000000000000317

Valente, E. S., Caramelli, P., Gambogi, L. B., Mariano, L. I., Guimaraes, H. C., Teixeira, A. L., & de Souza, L. C. (2019, Apr 1). Phenocopy syndrome of behavioral variant frontotemporal dementia: a systematic review. Alzheimers Research and Therapy, 11(1), 30. https://doi.org/10.1186/s13195-019-0483-2

Younes, K., & Miller, B. L. (2020, 2020/06/01/). Frontotemporal Dementia: Neuropathology, Genetics, Neuroimaging, and Treatments. Psychiatric Clinics of North America, 43(2), 331-344. https://doi.org/https://doi.org/10.1016/j.psc.2020.02.006

Younes, K., & Miller, B. L. (2020, 2020/06/01/). Neuropsychiatric Aspects of Frontotemporal Dementia. Psychiatric Clinics of North America, 43(2), 345-360. https://doi.org/https://doi.org/10.1016/j.psc.2020.02.005