EC Neurology

Review Article Volume 17 Issue 5 - 2025

The Essentials in Behavioral Variant Frontotemporal Dementia

Sacristán HE1,2*, Falco Muñiz S2, Belzuz RL2, Liotta CA3 and Mauriño A4

1Neurology Department, Dr. Anselmo Marini Municipal Rehabilitation Institute, Vicente López, Assistant Professor of Neurology, School of Medicine, UBA and Full Professor of Neurology, School of Health Sciences, University of Morón, Buenos Aires, Argentina 2Hospital Teaching Unit, Prof. Bernardo Houssay Hospital, School of Medicine, UBA, Buenos Aires, Argentina 3MD, Shoals Primary Care, Sheffield, Alabama, American Board of Family Medicine Certified, USA 4MD, Department of Therapeutic Trials, Institute of Cognitive Neurology, INECO, Buenos Aires, Argentina

*Corresponding Author: Sacristán HE, Neurology Department, Dr. Anselmo Marini Municipal Rehabilitation Institute, Vicente López, Assistant Professor of Neurology, School of Medicine, UBA and Full Professor of Neurology, School of Health Sciences, University of Morón, Buenos Aires, Argentina.
Received: April 07, 2025; Published: April 23, 2025



Behavioral variant frontotemporal dementia (bvFTD) is an important dementia syndrome in clinical practice. In this paper, we describe the clinical, anatomical, genetic, pathological and neuroradiological features of this entity. We discuss diagnostic strategies and how to approach the management of the different symptoms. bvFTD is a clinical syndrome, not a disease, and there are controversies regarding the definitive diagnosis. This syndrome must be distinguished from psychiatric diseases and other neurodegenerative syndromes that present a predominant behavioral component. Accurate knowledge of the underlying proteinopathy remains a challenge, however, the ability to differentiate bvFTD from atypical forms of Alzheimer's disease (AD) has improved. In the management of this condition, consideration should be given to: 1-preventing caregiver distress, 2-defining behavioral strategies, 3-symptom-based psychopharmacology, and 4-genetic counseling. Understanding the genetic basis of individuals with familial fronto-temporal dementia (fFTD) allows for an early and accurate diagnosis. Clinical trials designed to delay the onset of symptoms or slow their progression are currently underway, but several questions remain. No treatments have been found that significantly improve symptoms or modify the biological course of bvFTD. A better understanding of the pathophysiology will allow for the development of new and effective therapies. The clinical characteristics and the different pharmacological and non-pharmacological treatment options are discussed.

 Keywords: Fronto-Temporal Dementia; Neurodegeneration; Diagnosis; Treatment

  1. Bang J., et al. “Frontotemporal dementia”. Lancet10004 (2015): 1672-1682.
  2. Calandri I and Magrath Guimet N. “Demencia fronto temporal. 50 preguntas en Neuropsiquiatria clinica”. Bagnati P, Sarasola D, Allegri R y Kremer J. Capítulo 3.1rd edition (2018): 103-125.
  3. Turcano P., et al. “Incidence of frontotemporal disorders in Olmsted County: a population-based study”. Alzheimer's and Dementia 3 (2020): 482-490.
  4. Onyike CU and Diehl-Schmid J. “The epidemiology of frontotemporal dementia”. International Review of Psychiatry 2 (2013): 130-137.
  5. Hendriks S., et al. “Global prevalence of young-onset dementia: a systematic review and meta-analysis”. JAMA Neurology9 (2021): 1080-1090.
  6. Nilsson C., et al. “Age-related incidence and family history in frontotemporal dementia: data from the Swedish Dementia Registry”. PLoS One4 (2014): e0094901.
  7. Heuer HW., et al. “Comparison of sporadic and familial behavioral variant frontotemporal dementia (FTD) in a North American cohort”. Alzheimer's and Dementia 1 (2020): 60-70.
  8. Jeroen Bruinsma., et al. “'They simply do not understand': a focus group study exploring the lived experiences of family caregivers of people with frontotemporal dementia”. Aging and Mental Health 2 (2022): 277-285.
  9. Sara Tookey., et al. “Exploring experiences and needs of spousal carers of people with behavioural variant frontotemporal dementia (bvFTD) including those with familial FTD (fFTD): a qualitative study”. BMC Geriatrics1 (2022): 185.
  10. Ying Li Tan., et al. “Psychological and social impacts of frontotemporal dementia on caregivers and family members - A systematic review”. General Hospital Psychiatry 86 (2024): 33-49.
  11. S Robinson-Whelen., et al. “Long-term caregiving: what happens when it ends?”. Journal of Abnormal Psychology 4 (2001): 573-584.
  12. Richard Schulz., et al. “End-of-life care and the effects of bereavement on family caregivers of persons with dementia”. New England Journal of Medicine 20 (2003): 1936-1942.
  13. Betty R Ferrell., et al. “National Consensus Project Clinical Practice Guidelines for Quality Palliative Care Guidelines, 4th Edition”. Journal of Palliative Medicine 12 (2018): 1684-1689.
  14. Rosen HJ., et al. “Tracking disease progression in familial and sporadic fronto-temporal lobar degeneration: recent findings from ARTFL and LEFFTDS”. Alzheimer's and Dementia 1 (2020): 71-78.
  15. Hutton M., et al. “Association of missense and 5’-splice-site mutations in tau with the inherited dementia FTDP-17”. Nature 6686 (1998): 702-705.
  16. Baker M., et al. “Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome17”. Nature7105 (2006): 916-919.
  17. De Jesus-Hernandez M., et al. “Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS”. Neuron2 (2011): 245-256.
  18. Renton AE and Majounie E Waite. “A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD”. Neuron 2 (2011): 257-268.
  19. Moore KM., et al. “Age at symptom onset and death and disease duration in genetic frontotemporal dementia: an international retrospective cohort study”. Lancet Neurology2 (2020): 145-156.
  20. Ramos EM., et al. “Age Genetic screening of a large series of North American sporadic and familial frontotemporal dementia cases”. Alzheimer's and Dementia 1 (2020): 118-130.
  21. Neary D., et al. “Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria”. Neurology6 (1998): 1546-1554.
  22. Rascovsky K., et al. “Sensitivity of revised diagnostic criteria for the behavioral variant of frontotemporal dementia”. Brain 9 (2011): 2456-2477.
  23. Elahi FM and Miller BL. “A clinipathological approach to the diagnosis of dementia”. Nature Reviews Neurology8 (2017): 457-476.
  24. Rabinovici GD and Miller BL. “Frontotemporal lobar degeneration”. CNS Drugs5 (2010): 375-398.
  25. Riedl L., et al. neuropsychiatric disease and treatment 2014. 10, 297.
  26. Besser LM and Galvin JE. “Diagnostic experience reported by caregivers of patients with frontotemporal degeneration”. Neurology Clinical Practice 4 (2020): 298-306.
  27. Knopman D., et al. “Essentials of the proper diagnoses of mild cognitive impairment, dementia, and major subtypes of dementia”. Mayo Clinic Proceedings 10 (2003): 1290-1308.
  28. Choudhury P., et al. “Pick’s disease: clinicopathologic characterization of 21 cases”. Journal of Neurology 9 (2020): 2697-2704.
  29. Johnen A and Bertoux M. “Psychological and cognitive markers of behavioral variant frontotemporal dementia-a clinical neuropsychologist's view on diagnostic criteria and beyond”. Frontiers in Neurology 10 (2019): 594.
  30. Piguet O., et al. “Behavioural-variant frontotemporal dementia: diagnosis, clinical staging, and management”. The Lancet Neurology2 (2011): 162-172.
  31. Boeve B and Graff-Radford N. “Cognitive and behavioral features of c9FTD/ALS”. Alzheimer's Research and Therapy 4 (2012): 29.
  32. Snowden JS., et al. “Distinct clinical and pathological characteristics of frontotemporal dementia associated with C9ORF72 mutations”. Brain3 (2012): 693-708.
  33. West T., et al. “A blood based diagnostic test incorporating plasma Aβ42/40 ratio, ApoE proteotype, and age accurately identifies brain amyloid status: findings from a multi cohort validity analysis”. Molecular Neurodegeneration 1 (2021): 30.
  34. Thijssen EH., et al. “Diagnostic value of plasma phosphorylated tau181 in Alzheimer’s disease and frontotemporal lobar degeneration”. Nature Medicine 3 (2020): 387-397.
  35. Thijssen EH., et al. “Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer’s disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study”. Lancet Neurology9 (2021): 739-752.
  36. Eratne D., et al. “A pilot study of the utility of cerebrospinal fluid neurofilament light chain in differentiating neurodegenerative from psychiatric disorders: a “C-reactive protein” for psychiatrists and neurologists?” Australian and New Zealand Journal of Psychiatry 1 (2020): 57-67.
  37. Katisko K., et al. “Serum neurofilament light chain is a discriminative biomarker between frontotemporal lobar degeneration and primary psychiatric disorders”. Journal of Neurology1 (2020): 162-167.
  38. Palmqvist S., et al. “Discriminative accuracy of plasma phosphor tau 217 for Alzheimer disease vs other neurodegenerative disorders”. Journal of the American Medical Association8 (2020): 772-781.
  39. Staffaroni AM., et al. “Assessment of executive function declines in presymptomatic and mildly symptomatic familial frontotemporal dementia: NIH-EXAMINER as a potential clinical trial endpoint”. Alzheimer's and Dementia 1 (2020): 11-21.
  40. Kumfor F., et al. “Assessing the “social brain” in dementia: applying TASIT-S”. Cortex 93 (2017): 166-177.
  41. Rankin KP. “Measuring behavior and social cognition in FTLD”. Advances in Experimental Medicine and Biology 1281 (2021): 51-65.
  42. Boeve B., et al. “Advances and controversies in frontotemporal dementia: characterization, diagnosis, biomarkers, and therapeutic considerations”. Lancet Neurology3 (2022): 258-272.
  43. Wicklund MR., et al. “Frontotemporal brain sagging syndrome: an SIH-like presentation mimicking FTD”. Neurology16 (2011): 1377-1382.
  44. Levy JP., et al. “18f-Mk-6240 tau-pet in genetic frontotemporal dementia”. Brain: A Journal of Neurology5 (2022): 1763-1772.
  45. Blazhenets G., et al. “18f]pi-2620 binding patterns in patients with suspected Alzheimer disease and frontotemporal lobar degeneration”. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine 12 (2023): 1980-1989.
  46. Tagai K., et al. “High-contrast in vivo imaging of tau pathologies in alzheimer's and non-alzheimer's disease tauopathies”. Neuron1 (2021): 42-58.e8.
  47. Tagai K., et al. “An optimized reference tissue method for quantification of tau protein depositions in diverse neurodegenerative disorders by PET with F-Pm-Pbb3 (F-Apn-1607)”. NeuroImage 264 (2022): 119763.
  48. Younes K and Miller BL. “Frontotemporal dementia: neuropathology, genetics, neuroimaging, and treatments”. The Psychiatric Clinics of North America2 (2020): 331-344.
  49. Ljubenkov PA and Boxer AL. “FTLD treatment: current practice and future possibilities”. Advances in Experimental Medicine and Biology 1281 (2021): 297-310.
  50. Neumann M and Mackenzie IRA. “Review: neuropathology of non-tau frontotemporal lobar degeneration”. Neuropathology and Applied Neurobiology 1 (2019): 19-40.
  51. Chen Q and Kantarci K. “Imaging biomarkers for neurodegeneration in presymptomatic familial frontotemporal lobar degeneration”. Frontiers in Neurology 11 (2020): 80.
  52. Premi E., et al. “Early neurotransmitters changes in prodromal frontotemporal dementia: A GENFI study”. Neurobiology of Disease 179 (2023): 106068.
  53. Murley AG and Rowe JB. “Neurotransmitter deficits from frontotemporal lobar degeneration”. Brain: A Journal of Neurology5 (2018): 1263-1285.
  54. Gregory C., et al. “Theory of mind in patients with frontal variant frontotemporal dementia and Alzheimer’s disease: theoretical and practical implications”. Brain4 (2002): 752-764.
  55. Wylie MA., et al. “Management of frontotemporal dementia in mental health and multidisciplinary settings”. International Review of Psychiatry 2 (2013): 230-236.
  56. Herrmann N., et al. “Serotoninergic function and treatment of behavioral and psychological symptoms of fronto temporal dementia”. The American Journal of Geriatric Psychiatry9 (2012): 789-797.
  57. Mendez MF., et al. “Stereotypical movements and fronto-temporal dementia”. Movement Disorders6 (2005): 742-745.
  58. Moretti R., et al. “Fronto temporal dementia: paroxetine as a possible treatment of behavior symptoms”. European Neurology1 (2003): 13-19.
  59. Deakin JB., et al. “Paroxetine does not improve symptoms and impairs cognition in fronto temporal dementia: a double blind randomized controlled trial”. Psychopharmacology4 (2004): 400-408.
  60. Lebert F., et al. “Fronto temporal dementia: a randomized, controlled trial with trazodone”. Dementia and Geriatric Cognitive Disorders4 (2004): 355-359.
  61. Burke A., et al. “The clinical problem of neuropsychiatric signs and symptoms in dementia”. Continuum2 (2013): 382-396.
  62. Lee D and MD Mary Slomkowski. “Brexpiprazole for the treatment of agitation in Alzheimer Dementia. A Randomized Clinical Trial Pharm D”. JAMA Neurology 12 (2023): 1307-1316.
  63. Stahl SM. “Mechanism of action of pimavanserin in Parkinson’s disease psychosis: Targeting serotonin 5HT2A and 5HT2C receptors”. CNS Spectrums 4 (2016b): 271-527.
  64. Young JJ., et al. “Fronto temporal dementia: Latest evidence and clinical implications”. Therapeutic Advances in Psychopharmacology1 (2018): 33-48.
  65. Buccellato FR., et al. “Frontotemporal dementia: From genetics to therapeutic approaches”. Expert Opinion on Investigational Drugs6 (2024): 561-573.
  66. Panza F., et al. “Development of disease-modifying drugs for frontotemporal dementia spectrum disorders”. Nature Reviews. Neurology4 (2020): 213-228.
  67. Logroscino G., et al. “Promising therapies for the treatment of frontotemporal dementia clinical phenotypes: from symptomatic to disease-modifying drugs”. Expert Opinion on Pharmacotherapy9 (2019): 1091-1107.
  68. Desmarais P., et al. “Therapeutic trial design for frontotemporal dementia and related disorders”. Journal of Neurology, Neurosurgery, and Psychiatry4 (2019): 412-423.
  69. Benussi A and Borroni B. “Advances in the treatment and management of frontotemporal dementia”. Expert Review of Neurotherapeutics7 (2023): 621-639.
  70. Allen W. “Medical ethics issues in dementia and end of life”. Current Psychiatry Reports6 (2020): 31.
  71. Diehl-Schmid J., et al. “Behavioral variant frontotemporal dementia: advanced disease stages and death. A step to palliative care”. International Journal of Geriatric Psychiatry8 (2017): 876-881.

Sacristán HE., et al. “The Essentials in Behavioral Variant Frontotemporal Dementia”. EC Neurology  17.5 (2025): 01-19.

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