frontotemporal dementia


Summary: The most common clinical form of FRONTOTEMPORAL LOBAR DEGENERATION, this dementia presents with personality and behavioral changes often associated with disinhibition, apathy, and lack of insight.

Top Publications

  1. Lam B, Halliday G, Irish M, Hodges J, Piguet O. Longitudinal white matter changes in frontotemporal dementia subtypes. Hum Brain Mapp. 2014;35:3547-57 pubmed
    b>Frontotemporal dementia is a degenerative brain condition characterized by focal atrophy affecting the frontal and temporal lobes predominantly...
  2. Ronchi D, Riboldi G, Del Bo R, Ticozzi N, Scarlato M, Galimberti D, et al. CHCHD10 mutations in Italian patients with sporadic amyotrophic lateral sclerosis. Brain. 2015;138:e372 pubmed publisher
  3. Klein Z, Takahashi H, Ma M, Stagi M, Zhou M, Lam T, et al. Loss of TMEM106B Ameliorates Lysosomal and Frontotemporal Dementia-Related Phenotypes in Progranulin-Deficient Mice. Neuron. 2017;95:281-296.e6 pubmed publisher
    ..Thus, Grn and Tmem106b genes have opposite effects on lysosomal enzyme levels, and their interaction determines the extent of neurodegeneration. ..
  4. Olney N, Alquezar C, Ramos E, Nana A, Fong J, Karydas A, et al. Linking tuberous sclerosis complex, excessive mTOR signaling, and age-related neurodegeneration: a new association between TSC1 mutation and frontotemporal dementia. Acta Neuropathol. 2017;134:813-816 pubmed publisher
  5. Warren J, Rohrer J, Rossor M. Clinical review. Frontotemporal dementia. BMJ. 2013;347:f4827 pubmed publisher
  6. Cipolotti L, Healy C, Spanò B, Lecce F, Biondo F, Robinson G, et al. Strategy and suppression impairments after right lateral prefrontal and orbito-frontal lesions. Brain. 2016;139:e10 pubmed publisher
  7. Kurzwelly D, Krüger S, Biskup S, Heneka M. A distinct clinical phenotype in a German kindred with motor neuron disease carrying a CHCHD10 mutation. Brain. 2015;138:e376 pubmed publisher
  8. Vogel A, Poole M, Pemberton H, Caverlé M, Boonstra F, Low E, et al. Motor speech signature of behavioral variant frontotemporal dementia: Refining the phenotype. Neurology. 2017;89:837-844 pubmed publisher
    To provide a comprehensive description of motor speech function in behavioral variant frontotemporal dementia (bvFTD). Forty-eight individuals (24 bvFTD and 24 age- and sex-matched healthy controls) provided speech samples...
  9. Li T, Xie Y, Bowe B, Xian H, Al Aly Z. Serum phosphorus levels and risk of incident dementia. PLoS ONE. 2017;12:e0171377 pubmed publisher
    ..The identification of serum phosphorous as a risk factor for incident dementia has public health relevance and might inform the design and implementation of risk reduction strategies. ..

More Information


  1. Neary D, Snowden J. Frontal lobe dementia, motor neuron disease, and clinical and neuropathological criteria. J Neurol Neurosurg Psychiatry. 2013;84:713-4 pubmed publisher
  2. Ahmed R, Iodice V, Daveson N, Kiernan M, Piguet O, Hodges J. Autonomic dysregulation in frontotemporal dementia. J Neurol Neurosurg Psychiatry. 2015;86:1048-9 pubmed publisher
  3. Stopford C, Thompson J, Richardson A, Neary D, Snowden J. Working memory in Alzheimer's disease and frontotemporal dementia. Behav Neurol. 2010;23:177-9 pubmed publisher
  4. van Blitterswijk M, Rademakers R. Neurodegenerative disease: C9orf72 repeats compromise nucleocytoplasmic transport. Nat Rev Neurol. 2015;11:670-2 pubmed publisher
  5. O Connor C, Landin Romero R, Clemson L, Kaizik C, Daveson N, Hodges J, et al. Behavioral-variant frontotemporal dementia: Distinct phenotypes with unique functional profiles. Neurology. 2017;89:570-577 pubmed publisher
    To identify distinct behavioral phenotypes of behavioral-variant frontotemporal dementia (bvFTD) and to elucidate differences in functional, neuroimaging, and progression to residential care placement...
  6. Eisen A, Braak H, Del Tredici K, Lemon R, Ludolph A, Kiernan M. Cortical influences drive amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2017;88:917-924 pubmed publisher
    ..Further, such a concept could explain the recognised widespread imaging abnormalities of the ALS neocortex and the accepted relationship between ALS and frontotemporal dementia.
  7. Fletcher P, Clark C, Warren J. Music, reward and frontotemporal dementia. Brain. 2014;137:e300 pubmed publisher
  8. Donadio V, Incensi A, Rizzo G, Capellari S, Pantieri R, Stanzani Maserati M, et al. A new potential biomarker for dementia with Lewy bodies: Skin nerve ?-synuclein deposits. Neurology. 2017;89:318-326 pubmed publisher
    ..23 patients with nonsynucleinopathy dementia (NSD; 13 with young-onset Alzheimer disease dementia, 6 frontotemporal dementia, and 4 vascular dementia), and 25 healthy controls...
  9. Monahan Z, Ryan V, Janke A, Burke K, Rhoads S, Zerze G, et al. Phosphorylation of the FUS low-complexity domain disrupts phase separation, aggregation, and toxicity. EMBO J. 2017;36:2951-2967 pubmed publisher
    Neuronal inclusions of aggregated RNA-binding protein fused in sarcoma (FUS) are hallmarks of ALS and frontotemporal dementia subtypes...
  10. Bertoux M, Volle E, de Souza L, Funkiewiez A, Dubois B, Habert M. Neural correlates of the mini-SEA (Social cognition and Emotional Assessment) in behavioral variant frontotemporal dementia. Brain Imaging Behav. 2014;8:1-6 pubmed
    Although Frontotemporal Dementia (FTD) is the second most common form of dementia after Alzheimer’s disease, its diagnosis remains particularly challenging today...
  11. Gao F, Almeida S, López González R. Dysregulated molecular pathways in amyotrophic lateral sclerosis-frontotemporal dementia spectrum disorder. EMBO J. 2017;36:2931-2950 pubmed publisher
    b>Frontotemporal dementia (FTD), the second most common form of dementia in people under 65 years of age, is characterized by progressive atrophy of the frontal and/or temporal lobes...
  12. Floeter M, Traynor B, Farren J, Braun L, Tierney M, Wiggs E, et al. Disease progression in C9orf72 mutation carriers. Neurology. 2017;89:234-241 pubmed publisher
    ..Participants were classified as asymptomatic, amyotrophic lateral sclerosis (ALS), ALS-familial frontotemporal dementia (FTD), or behavioral-variant FTD by clinical diagnostic criteria...
  13. Hardy C, Agustus J, Marshall C, Clark C, Russell L, Brotherhood E, et al. Functional neuroanatomy of speech signal decoding in primary progressive aphasias. Neurobiol Aging. 2017;56:190-201 pubmed publisher
  14. Halliday M, Radford H, Zents K, Molloy C, Moreno J, Verity N, et al. Repurposed drugs targeting eIF2α-P-mediated translational repression prevent neurodegeneration in mice. Brain. 2017;140:1768-1783 pubmed publisher
    ..In tauopathy-frontotemporal dementia mice, both drugs were neuroprotective, rescued memory deficits and reduced hippocampal atrophy...
  15. Pochet R, Nicaise C, Mitrecic D. Translation of the focus toward excellence in translational science: comment on "TDP-43 Repression of Nonconserved Cryptic Exons is Compromised in ALS-FTD". Croat Med J. 2015;56:493-5 pubmed
  16. Hogan A, Don E, Rayner S, Lee A, Laird A, Watchon M, et al. Expression of ALS/FTD-linked mutant CCNF in zebrafish leads to increased cell death in the spinal cord and an aberrant motor phenotype. Hum Mol Genet. 2017;26:2616-2626 pubmed publisher
    ..Additionally, this study presents a valuable new tool for use in ongoing studies investigating the pathobiology of ALS-linked CCNF mutations. ..
  17. Johnson J, Glynn S, Gibbs J, Nalls M, Sabatelli M, Restagno G, et al. Mutations in the CHCHD10 gene are a common cause of familial amyotrophic lateral sclerosis. Brain. 2014;137:e311 pubmed publisher
  18. Kumfor F, Irish M, Hodges J, Piguet O. Discrete Neural Correlates for the Recognition of Negative Emotions: Insights from Frontotemporal Dementia. PLoS ONE. 2013;8:e67457 pubmed publisher
    Patients with frontotemporal dementia have pervasive changes in emotion recognition and social cognition, yet the neural changes underlying these emotion processing deficits remain unclear...
  19. Ucedo D, Santos K, Santana A. Language in Frontotemporal Dementia: an analysis in light of Enunciative-Discursive Neurolinguistics. Codas. 2017;29:e20160154 pubmed publisher
    ..aim of this case study was to perform a cross-sectional analysis of spontaneous speech of a patient with Frontotemporal Dementia (FTD)...
  20. Hodges J. Familial frontotemporal dementia and amyotrophic lateral sclerosis associated with the C9ORF72 hexanucleotide repeat. Brain. 2012;135:652-5 pubmed publisher
  21. Esteras N, Rohrer J, Hardy J, Wray S, Abramov A. Mitochondrial hyperpolarization in iPSC-derived neurons from patients of FTDP-17 with 10+16 MAPT mutation leads to oxidative stress and neurodegeneration. Redox Biol. 2017;12:410-422 pubmed publisher
    ..The 10+16 intronic mutation in MAPT gene, encoding tau, causes frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), by altering the splicing of the gene and inducing an ..
  22. Holm I, Isaacs A, Mackenzie I. Absence of FUS-immunoreactive pathology in frontotemporal dementia linked to chromosome 3 (FTD-3) caused by mutation in the CHMP2B gene. Acta Neuropathol. 2009;118:719-20 pubmed publisher
  23. Harper L, Bouwman F, Burton E, Barkhof F, Scheltens P, O Brien J, et al. Patterns of atrophy in pathologically confirmed dementias: a voxelwise analysis. J Neurol Neurosurg Psychiatry. 2017;88:908-916 pubmed publisher
    ..The results of this study are available for further examination via NeuroVault ( ..
  24. Filippi M, Basaia S, Canu E, Imperiale F, Meani A, Caso F, et al. Brain network connectivity differs in early-onset neurodegenerative dementia. Neurology. 2017;89:1764-1772 pubmed publisher
    ..functional brain network architecture in early-onset Alzheimer disease (EOAD) and behavioral variant frontotemporal dementia (bvFTD)...
  25. Moreno F, Indakoetxea B, Barandiaran M, Caballero M, Gorostidi A, Calafell F, et al. The unexpected co-occurrence of GRN and MAPT p.A152T in Basque families: Clinical and pathological characteristics. PLoS ONE. 2017;12:e0178093 pubmed publisher
    ..A152T MAPT variant has been identified in 18 Basque families affected by frontotemporal dementia (FTD). We aimed to investigate the influence of the p...
  26. Moens T, Partridge L, Isaacs A. Genetic models of C9orf72: what is toxic?. Curr Opin Genet Dev. 2017;44:92-101 pubmed publisher
    ..expansion in the gene C9orf72 is the most common genetic cause of both amyotrophic lateral sclerosis and frontotemporal dementia. Pathogenesis may occur either due to loss of function of the C9orf72 gene, or a toxic gain of function, ..
  27. Cui B, Cui L, Liu M, Ma J, Fang J. Amyotrophic lateral sclerosis with frontotemporal dementia presented with prominent psychosis. Chin Med J (Engl). 2014;127:3996-8 pubmed
  28. Müller K, Andersen P, Hübers A, Marroquin N, Volk A, Danzer K, et al. Two novel mutations in conserved codons indicate that CHCHD10 is a gene associated with motor neuron disease. Brain. 2014;137:e309 pubmed publisher
  29. Saxon J, Thompson J, Jones M, Harris J, Richardson A, Langheinrich T, et al. Examining the language and behavioural profile in FTD and ALS-FTD. J Neurol Neurosurg Psychiatry. 2017;88:675-680 pubmed publisher
    A proportion of patients with behavioural variant frontotemporal dementia (bvFTD) develop amyotrophic lateral sclerosis (ALS)...
  30. Piguet O, Kumfor F, Hodges J. Diagnosing, monitoring and managing behavioural variant frontotemporal dementia. Med J Aust. 2017;207:303-308 pubmed
    Behavioural variant frontotemporal dementia is characterised by insidious changes in personality and interpersonal conduct that reflect progressive disintegration of the neural circuits involved in social cognition, emotion regulation, ..
  31. Mackenzie I, Nicholson A, Sarkar M, Messing J, Purice M, Pottier C, et al. TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics. Neuron. 2017;95:808-816.e9 pubmed publisher
    Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features...
  32. Lansdall C, Coyle Gilchrist I, Jones P, Vázquez Rodríguez P, Wilcox A, Wehmann E, et al. Apathy and impulsivity in frontotemporal lobar degeneration syndromes. Brain. 2017;140:1792-1807 pubmed publisher
    ..We proposed an alternative, dimensional approach that spans behavioural and language variants of frontotemporal dementia, progressive supranuclear palsy and corticobasal syndrome...
  33. Lall D, Baloh R. Microglia and C9orf72 in neuroinflammation and ALS and frontotemporal dementia. J Clin Invest. 2017;127:3250-3258 pubmed publisher
    ..that is characterized by loss of motor neurons and shows clinical, pathological, and genetic overlap with frontotemporal dementia (FTD)...
  34. Palluzzi F, Ferrari R, Graziano F, Novelli V, Rossi G, Galimberti D, et al. A novel network analysis approach reveals DNA damage, oxidative stress and calcium/cAMP homeostasis-associated biomarkers in frontotemporal dementia. PLoS ONE. 2017;12:e0185797 pubmed publisher
    b>Frontotemporal Dementia (FTD) is the form of neurodegenerative dementia with the highest prevalence after Alzheimer's disease, equally distributed in men and women...
  35. Rademakers R. C9orf72 repeat expansions in patients with ALS and FTD. Lancet Neurol. 2012;11:297-8 pubmed publisher
  36. Lehmer C, Oeckl P, Weishaupt J, Volk A, Diehl Schmid J, Schroeter M, et al. Poly-GP in cerebrospinal fluid links C9orf72-associated dipeptide repeat expression to the asymptomatic phase of ALS/FTD. EMBO Mol Med. 2017;9:859-868 pubmed publisher
    The C9orf72 GGGGCC repeat expansion is a major cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD)...
  37. Joshi A, Mendez M, Kaiser N, Jimenez E, Mather M, Shapira J. Skin conductance levels may reflect emotional blunting in behavioral variant frontotemporal dementia. J Neuropsychiatry Clin Neurosci. 2014;26:227-32 pubmed publisher
    Emotional blunting is a core diagnostic feature of behavioral variant frontotemporal dementia (bvFTD)...
  38. Ju J, Weihl C. p97/VCP at the intersection of the autophagy and the ubiquitin proteasome system. Autophagy. 2010;6:283-5 pubmed
  39. Day G, Farb N, Tang Wai D, Masellis M, Black S, Freedman M, et al. Salience network resting-state activity: prediction of frontotemporal dementia progression. JAMA Neurol. 2013;70:1249-53 pubmed
    ..baseline resting-state measures within the salience network and changes in behavior among patients with frontotemporal dementia. Baseline resting-state functional magnetic resonance imaging data and longitudinal clinical measures ..
  40. Andersen P. ALS and FTD: two sides of the same coin?. Lancet Neurol. 2013;12:937-8 pubmed publisher
  41. Laforce R. Behavioral and language variants of frontotemporal dementia: a review of key symptoms. Clin Neurol Neurosurg. 2013;115:2405-10 pubmed publisher
    ..This paper summarizes the key symptoms of the behavioral and language variants of frontotemporal dementia. The behavioral variant of frontotemporal dementia (bvFTD) is characterized by severe changes in behavior ..
  42. Russo A, Scardigli R, La Regina F, Murray M, Romano N, Dickson D, et al. Increased cytoplasmic TDP-43 reduces global protein synthesis by interacting with RACK1 on polyribosomes. Hum Mol Genet. 2017;26:1407-1418 pubmed publisher
  43. Moujalled D, Grubman A, Acevedo K, Yang S, Ke Y, Moujalled D, et al. TDP-43 mutations causing amyotrophic lateral sclerosis are associated with altered expression of RNA-binding protein hnRNP K and affect the Nrf2 antioxidant pathway. Hum Mol Genet. 2017;26:1732-1746 pubmed publisher
    ..Our findings indicate that further exploration of the interplay between hnRNP K (or other hnRNPs) and Nrf2-mediated antioxidant signaling is warranted and may be an important driver for motor neuron degeneration in ALS. ..
  44. Kawamura M. [The Role of Brodmann Area 12: Taste, Social Cognition, and Mental Time]. Brain Nerve. 2017;69:375-381 pubmed publisher
    ..Our recent study also demonstrated that this area may serve as time order judgement or mental time travel. ..
  45. Kleinberger G, Brendel M, Mracskó É, Wefers B, Groeneweg L, Xiang X, et al. The FTD-like syndrome causing TREM2 T66M mutation impairs microglia function, brain perfusion, and glucose metabolism. EMBO J. 2017;36:1837-1853 pubmed publisher
    ..2 (TREM2) increase the risk for several neurodegenerative diseases including Alzheimer's disease and frontotemporal dementia (FTD). Homozygous TREM2 missense mutations, such as p...
  46. Premi E, Grassi M, van Swieten J, Galimberti D, Graff C, Masellis M, et al. Cognitive reserve and TMEM106B genotype modulate brain damage in presymptomatic frontotemporal dementia: a GENFI study. Brain. 2017;140:1784-1791 pubmed publisher
    b>Frontotemporal dementia is a heterogeneous neurodegenerative disorder with around a third of cases having autosomal dominant inheritance...
  47. Kim H, Jeon B, Yun J, Seong M, Park S, Lee J. Screening for MAPT and PGRN mutations in Korean patients with PSP/CBS/FTD. Parkinsonism Relat Disord. 2010;16:305-6 pubmed publisher
  48. Papma J, Jiskoot L, Panman J, Dopper E, den Heijer T, Donker Kaat L, et al. Cognition and gray and white matter characteristics of presymptomatic C9orf72 repeat expansion. Neurology. 2017;89:1256-1264 pubmed publisher
    ..tests, T1-weighted MRI, and diffusion tensor imaging within our cohort study of autosomal dominant frontotemporal dementia (FTD)...
  49. Harrison A, Shorter J. RNA-binding proteins with prion-like domains in health and disease. Biochem J. 2017;474:1417-1438 pubmed publisher
    ..genetics to the etiology of several neurodegenerative diseases, including amyotrophic lateral sclerosis, frontotemporal dementia, and multisystem proteinopathy...
  50. Mishra A, Ferrari R, Heutink P, Hardy J, Pijnenburg Y, Posthuma D. Gene-based association studies report genetic links for clinical subtypes of frontotemporal dementia. Brain. 2017;140:1437-1446 pubmed publisher
    Genome-wide association studies in frontotemporal dementia showed limited success in identifying associated loci...
  51. Paul J, West J, Gitler A. Cell Biology. Clogging information flow in ALS. Science. 2014;345:1118-9 pubmed publisher
  52. Zhang M, Xi Z, Zinman L, Bruni A, Maletta R, Curcio S, et al. Mutation analysis of CHCHD10 in different neurodegenerative diseases. Brain. 2015;138:e380 pubmed publisher
  53. Gelpi E, Van der Zee J, Turon Estrada A, Van Broeckhoven C, Sanchez Valle R. TARDBP mutation p.Ile383Val associated with semantic dementia and complex proteinopathy. Neuropathol Appl Neurobiol. 2014;40:225-30 pubmed publisher
  54. Seo J, Kritskiy O, Watson L, Barker S, Dey D, Raja W, et al. Inhibition of p25/Cdk5 Attenuates Tauopathy in Mouse and iPSC Models of Frontotemporal Dementia. J Neurosci. 2017;37:9917-9924 pubmed publisher
    ..To further validate the role of p25/Cdk5 in tauopathy, we used frontotemporal dementia patient-derived induced pluripotent stem cells (iPSCs) carrying the Tau P301L mutation and generated ..
  55. Curtis A, Masellis M, Hsiung G, Moineddin R, Zhang K, Au B, et al. Sex differences in the prevalence of genetic mutations in FTD and ALS: A meta-analysis. Neurology. 2017;89:1633-1642 pubmed publisher
    ..the prevalence of mutations in the 3 most common genes that cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)-chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN), or microtubule-..
  56. Schroeter M, Bzdok D, Eickhoff S, Neumann J. Frontomedian cortex is central for moral deficits in behavioural variant frontotemporal dementia. J Neurol Neurosurg Psychiatry. 2015;86:700-1 pubmed publisher
  57. Itoh N, Nagai T, Watanabe T, Taki K, Nabeshima T, Kaibuchi K, et al. Valosin-containing protein (VCP) is a novel IQ motif-containing GTPase activating protein 1 (IQGAP1)-interacting protein. Biochem Biophys Res Commun. 2017;493:1384-1389 pubmed publisher
    ..VCP) which is a causative gene in patients with inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD). The physiological interaction of IQGAP1 with VCP was confirmed by an immunoprecipitation assay...
  58. Deming Y, Cruchaga C. TMEM106B: a strong FTLD disease modifier. Acta Neuropathol. 2014;127:419-22 pubmed publisher
  59. De Conti L, Borroni B, Baralle M. New routes in frontotemporal dementia drug discovery. Expert Opin Drug Discov. 2017;12:659-671 pubmed publisher
    Research into the pathogenic mechanisms behind frontotemporal dementia (FTD) has yielded several new targets for therapeutic intervention; such targets include specific new pathways uncovered by mutations as well as targets involving the ..
  60. She A, Kurtser I, Reis S, Hennig K, Lai J, Lang A, et al. Selectivity and Kinetic Requirements of HDAC Inhibitors as Progranulin Enhancers for Treating Frontotemporal Dementia. Cell Chem Biol. 2017;24:892-906.e5 pubmed publisher
    b>Frontotemporal dementia (FTD) arises from neurodegeneration in the frontal, insular, and anterior temporal lobes...
  61. Kim B, Irwin D, Song D, Daniel E, Leveque J, Raquib A, et al. Optical coherence tomography identifies outer retina thinning in frontotemporal degeneration. Neurology. 2017;89:1604-1611 pubmed publisher
    ..7 vs 97.4 μm, p = 0.01) and EZ (14.4 vs 15.1 μm, p = 0.01) than controls. FTD is associated with outer retina thinning, and this thinning correlates with disease severity. ..
  62. Poetter C, Stewart J. Treatment of indiscriminate, inappropriate sexual behavior in frontotemporal dementia with carbamazepine. J Clin Psychopharmacol. 2012;32:137-8 pubmed publisher
  63. Gramaglia C, Cantello R, Terazzi E, Carecchio M, D Alfonso S, Chieppa N, et al. Early onset frontotemporal dementia with psychiatric presentation due to the C9ORF72 hexanucleotide repeat expansion: a case report. BMC Neurol. 2014;14:228 pubmed publisher
    b>Frontotemporal dementia (FTD) may present with psychiatric symptoms, usually together with neurological ones and in cases with a family history of dementia...