Skip to main content Accessibility help
Hostname: page-component-888d5979f-g6cgc Total loading time: 1.24 Render date: 2021-10-28T06:09:47.198Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": true, "newCiteModal": false, "newCitedByModal": true, "newEcommerce": true, "newUsageEvents": true }

Book contents

Chapter 9 - Frontotemporal dementia

Published online by Cambridge University Press:  01 December 2016

Bruce L. Miller
University of California, San Francisco
Bradley F. Boeve
Mayo Clinic, Minnesota
Get access


Image of the first page of this content. For PDF version, please use the ‘Save PDF’ preceeding this image.'
Publisher: Cambridge University Press
Print publication year: 2016

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


Knopman, DS, Roberts, RO. Estimating the number of persons with frontotemporal lobar degeneration in the US population. J Mol Neurosci 2011; 45(3): 330–5.CrossRefGoogle ScholarPubMed
Knopman, DS, Petersen, RC, Edland, SD, et al. The incidence of frontotemporal lobar degeneration in Rochester, Minnesota, 1990 through 1994. Neurology 2004; 62(3): 506–8.CrossRefGoogle ScholarPubMed
Neary, D, Snowden, JS, Northen, B, et al. Dementia of frontal lobe type. J Neurol Neurosurg Psychiatry 1988; 51(3): 353–61.CrossRefGoogle ScholarPubMed
Brun, A. Frontal lobe degeneration of non-Alzheimer type. I. Neuropathol Arch Gerontol Geriatr 1987; 6(3): 193208.CrossRefGoogle ScholarPubMed
Goldman, JS, Farmer, J, Wood, EM, et al. Comparison of family histories in FTLD subtypes and related tauopathies. Neurology 2005; 65(11): 1817–9.CrossRefGoogle Scholar
Pick, A. Uber die Beziehungen der senilen Hirnatrophie zur Aphasie. Prager Med Wochensch 1892; 17: 165–7.Google Scholar
Alzheimer, A. Uber eigenartige Krankheitsfalle des spateren Alters. Z Ges Neurol Psychiatr 1911; 4: 356–85.CrossRefGoogle Scholar
Neary, D, Snowden, JS, Bowen, DM, et al. Neuropsychological syndromes in presenile dementia due to cerebral atrophy. J Neurol Neurosurg Psychiatry 1986; 49(2): 163–74.Google ScholarPubMed
Gustafson, L. Frontal lobe degeneration of non-Alzheimer type. II. Clinical picture and differential diagnosis. Arch Gerontol Geriatr 1987; 6(3): 209–23.CrossRefGoogle ScholarPubMed
Mann, DMA, South, PW, Snowden, JS, et al. Dementia of frontal lobe type: neuropathology and immunohistochemistry. J Neurol Neurosurg Psychiatry 1993; 56: 605–14.CrossRefGoogle ScholarPubMed
Knopman, DS, Mastri, AR, Frey, WHD, et al. Dementia lacking distinctive histologic features: a common non-Alzheimer degenerative dementia. Neurology 1990; 40(2): 251–6.CrossRefGoogle ScholarPubMed
Jagust, WJ, Reed, BR, Seab, JP, et al. Clinical–physiologic correlates of Alzheimer’s disease and frontal lobe dementia. Am J Physiol Imaging 1989; 4: 8996.Google ScholarPubMed
Miller, BL, Cummings, JL, Villanueva-Meyer, J, et al. Frontal lobe degeneration: clinical, neuropsychological, and SPECT characteristics. Neurology 1991; 41(9): 1374–82.CrossRefGoogle ScholarPubMed
Varma, AR, Snowden, JS, Lloyd, JJ, et al. Evaluation of the NINCDS–ADRDA criteria in the differentiation of Alzheimer’s disease and frontotemporal dementia. J Neurol Neurosurg Psychiatry 1999; 66(2): 184–8.CrossRefGoogle ScholarPubMed
de Leon, MJ, Convit, A, DeSanti, S, et al. Contribution of structural neuroimaging to the early diagnosis of Alzheimer’s disease. Int Psychogeriatr 1997; 9(Suppl 1): 183–90; discussion 247–52.CrossRefGoogle ScholarPubMed
Thompson, PM, Hayashi, KM, de Zubicaray, G, et al. Dynamics of gray matter loss in Alzheimer’s disease. J Neurosci 2003; 23(3): 9941005.Google Scholar
Kitagaki, H, Mori, E, Yamaji, S, et al. Frontotemporal dementia and Alzheimer disease: evaluation of cortical atrophy with automated hemispheric surface display generated with MR images. Radiology 1998; 208(2): 431–9.CrossRefGoogle ScholarPubMed
Read, SL, Miller, BL, Mena, I, et al. SPECT in dementia: clinical and pathological correlation. J Am Geriatr Soc 1995; 43(11): 1243–7.CrossRefGoogle ScholarPubMed
Miller, BL. Clinical advances in degenerative dementias. [See comments.] Br J Psychiatry 1997; 171(18): 13.CrossRefGoogle ScholarPubMed
Neary, D, Snowden, JS, Gustafson, L, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998; 51(6): 1546–54.CrossRefGoogle ScholarPubMed
Rascovsky, K, Hodges, JR, Knopman, D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 2011; 134(Pt 9): 2456–77.CrossRefGoogle ScholarPubMed
Gorno-Tempini, ML, Hillis, AE, Weintraub, S, et al. Classification of primary progressive aphasia and its variants. Neurology 2011; 76(11): 1006–14.CrossRefGoogle ScholarPubMed
Roberson, ED, Hesse, JH, Rose, KD, et al. Frontotemporal dementia progresses to death faster than Alzheimer disease. Neurology 2005; 65(5): 719–25.CrossRefGoogle ScholarPubMed
Johnson, JK, Diehl, J, Mendez, MF, et al. Frontotemporal lobar degeneration: demographic characteristics of 353 patients. Arch Neurol 2005; 62(6): 925–30.CrossRefGoogle ScholarPubMed
Lomen-Hoerth, C, Anderson, T, Miller, B. The overlap of amyotrophic lateral sclerosis and frontotemporal dementia. Neurology 2002; 59(7): 1077–9.CrossRefGoogle ScholarPubMed
Murphy, JM, Henry, RG, Langmore, S, et al. Continuum of frontal lobe impairment in amyotrophic lateral sclerosis. Arch Neurol 2007; 64(4): 530–4.Google ScholarPubMed
Seeley, WW, Bauer, AM, Miller, BL, et al. The natural history of temporal variant frontotemporal dementia. Neurology 2005; 64(8): 1384–90.CrossRefGoogle ScholarPubMed
Josephs, KA, Petersen, RC, Knopman, DS, et al. Clinicopathologic analysis of frontotemporal and corticobasal degenerations and PSP. Neurology 2006; 66(1): 41–8.CrossRefGoogle ScholarPubMed
Mathuranath, PS, Xuereb, JH, Bak, T, et al. Corticobasal ganglionic degeneration and/or frontotemporal dementia? A report of two overlap cases and review of literature. J Neurol Neurosurg Psychiatry 2000; 68(3): 304–12.CrossRefGoogle ScholarPubMed
Kertesz, A, Munoz, DG. Diagnostic controversies: is CBD part of the “Pick complex.” Adv Neurol 2000; 82: 223–31.Google ScholarPubMed
Mann, DM, South, PW. The topographic distribution of brain atrophy in frontal lobe dementia. Acta Neuropathol 1993; 85(3): 334–40.CrossRefGoogle ScholarPubMed
Seeley, WW, Carlin, DA, Allman, JM, et al. Early frontotemporal dementia targets neurons unique to apes and humans. Ann Neurol, 2006; 60(6): 660–7.CrossRefGoogle ScholarPubMed
Krill, JJ, Halliday, GM. Pathological staging of frontotemporal lobar degeneration. J Mol Neurosci 2011; 45(3): 379–83.Google Scholar
Mandelkow, EM, Mandelkow, E. Biochemistry and cell biology of tau protein in neurofibrillary degeneration. Cold Spring Harb Perspect Med 2012; 2(7): a006247.CrossRefGoogle ScholarPubMed
Kovacs, GG, Rozemuller, AJ, van Swieten, JC, et al. Neuropathology of the hippocampus in FTLD-tau with Pick bodies: a study of the BrainNet Europe Consortium. Neuropathol Appl Neurobiol 2013; 39(2): 166–78.CrossRefGoogle ScholarPubMed
Brun, A. Frontal lobe degeneration of non-Alzheimer type. I. Neuropathology. Arch Gerontol Geriatr 1987; 6(3): 193208.CrossRefGoogle ScholarPubMed
Boxer, AL, Geschwind, MD, Belfor, N, et al. Patterns of brain atrophy that differentiate corticobasal degeneration syndrome from progressive supranuclear palsy. Arch Neurol 2006; 63(1): 81–6.CrossRefGoogle ScholarPubMed
Fujino, Y, Wang, DS, Thomas, N, et al. Increased frequency of argyrophilic grain disease in Alzheimer disease with 4R tau-specific immunohistochemistry. J Neuropathol Exp Neurol 2005; 64(3): 209–14.CrossRefGoogle ScholarPubMed
Soma, K, Fu, YJ, Wakabayashi, K, et al. Co-occurrence of argyrophilic grain disease in sporadic amyotrophic lateral sclerosis. Neuropathol Appl Neurobiol 2012; 38(1): 5460.CrossRefGoogle ScholarPubMed
Neumann, M, Sampathu, DM, Kwong, LK, et al. Ubiquinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006; 314: 130–3.CrossRefGoogle Scholar
Mackenzie, IR, Neumann, M, Baborie, A, et al. A harmonized classification system for FTLD-TDP pathology. Acta Neuropathol 2011; 122(1): 111–13.CrossRefGoogle ScholarPubMed
Miller, ZA, Rankin, KP, Graff-Radford, NR, et al. TDP-43 frontotemporal lobar degeneration and autoimmune disease. J Neurol Neurosurg Psychiatry 2013; 84(9): 956–62.CrossRefGoogle ScholarPubMed
Koppers, M, van Blitterswijk, MM, Vlam, L, et al. VCP mutations in familial and sporadic ALS. Neurobiol Aging 2012; 33: 837.e7–13.CrossRefGoogle Scholar
Neumann, M, Rademakers, R, Roeber, S, et al. A new subtype of frontotemporal lobar degeneration with FUS pathology. Brain 2009; 132(Pt 11): 2922–31.CrossRefGoogle ScholarPubMed
Urwin, H, Josephs, KA, Rohrer, JD, et al. FUS pathology defines the majority of tau- and TDP-43-negative frontotemporal lobar degeneration. Acta Neuropathol 2010; 120: 3341.CrossRefGoogle ScholarPubMed
Chow, TW, Miller, BL, Hayashi, VN, et al. Inheritance of frontotemporal dementia. Arch Neurol 1999; 56(7): 817–22.CrossRefGoogle ScholarPubMed
van Swieten, JC, Stevens, M, Rosso, SM, et al. Phenotypic variation in hereditary frontotemporal dementia with tau mutations. Ann Neurol, 1999; 46(4): 617–26.3.0.CO;2-I>CrossRefGoogle ScholarPubMed
Wilhelmsen, KC, Lynch, T, Pavlou, E, et al. Localization of disinhibition–dementia–parkinsonism–amyotrophy complex to 17q21–22. Am J Hum Genetics 1994; 55: 1159–65.Google Scholar
Seelaar, H, Rohrer, JD, Pijnenburg, YA, et al. Clinical, genetic and pathological heterogeneity of frontotemporal dementia: a review. J Neurol Neurosurg Psychiatry 2011; 82: 476–86.CrossRefGoogle ScholarPubMed
Rohrer, JD, Warren, JD. Phenotypic signatures of genetic frontotemporal dementia. Curr Opin Neurol 2011; 24(6): 542–9.CrossRefGoogle ScholarPubMed
Hong, M, Zhukareva, V, Vogelsberg-Ragaglia, V, et al. Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17. Science 1998; 282(5395): 1914–17.CrossRefGoogle ScholarPubMed
Baker, M, Mackenzie, IR, Pickering-Brown, SM, et al. Mutations in progranulin casue tau-negative frontotemporal dementia linked to chromosome 17. Nature 2006; 442: 916–19.CrossRefGoogle Scholar
Cruts, M, Gijselinck, I, van der Zee, J, et al. Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 2006; 442(7105): 920–4.CrossRefGoogle ScholarPubMed
Coppola, G, Karydas, A, Rademakers, R, et al. Gene expression study on peripheral blood identifies progranulin mutations. Ann Neurol 2008; 64: 92–6.CrossRefGoogle ScholarPubMed
Finch, N, Baker, M, Crook, R, et al. Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members. Brain 2009; 132(Pt3): 583–91.CrossRefGoogle ScholarPubMed
Finch, N, Carrasquillo, MM, Baker, M, et al. TMEM106B regulates progranulin levels and the penetrance of FTLD in GRN mutation carriers. Neurology 2011; 76: 467–74.CrossRefGoogle ScholarPubMed
Hsiung, GYR, Fok, A, Feldman, HH, et al. rs5848 polymorphism and serum progranulin level. J Neurol Sci 2011; 300(1–2): 2832.CrossRefGoogle ScholarPubMed
Rademakers, R, Baker, M, Gass, J, et al. Phenotypic variability associated with progranulin haploinsufficiency in patients with the common 1477C➔T (Arg493X) mutation: an international initiative. Lancet Neurol 2007; 6 : 857–68.CrossRefGoogle ScholarPubMed
Cenik, B, Sephton, CF, Cenik, BK, et al. Progranulin: a proteolytically processed protein at the crossroads of inflammation and neurodegeneration. J Biol Chem 2012; 287(39): 32298–306.CrossRefGoogle ScholarPubMed
Kao, AW, Eisenhut, RJ, Martens, LH, et al. A neurodegenerative disease mutation that accelerates the clearance of apoptotic cells. Proc Natl Acad Sci USA 2011; 108(11): 4441–6.CrossRefGoogle ScholarPubMed
Ryan, CL, Baranowski, DC, Chitramuthu, BP, et al. Progranulin is expressed within motor neurons and promotes neuronal cell survival. BMC Neurosci 2009; 10 : 130.CrossRefGoogle ScholarPubMed
Lomen-Hoerth, C, Murphey, J, Langmore, S, et al. Are amyotrophic lateral sclerosis patients cognitively normal? Neurology 2003; 60(7): 1094–7.CrossRefGoogle ScholarPubMed
Lomen-Hoerth, C, Anderson, T, Miller, B. The overlap of amyotrophic lateral sclerosis and frontotemporal dementia. Neurology 2002; 59(7): 1077–9.CrossRefGoogle ScholarPubMed
Hosler, BA, Siddique, T, Sapp, PC, et al. Linkage of familial amyotrophic lateral sclerosis with frontotemporal dementia to chromosome 9q21-q22. JAMA 2000; 284: 1664–9.CrossRefGoogle ScholarPubMed
DeJesus-Hernandez, M, Mackenzie, IR, Boeve, BF, et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 2011; 72: 245–56.CrossRefGoogle ScholarPubMed
Renton, AE, Majounie, E, Waite, A, et al. A hexanucleotide repeat expansion in C9ORF72 is the casue of chromosome 9p21-linked ALS-FTD. Neuron 2011; 72: 257–68.CrossRefGoogle Scholar
Sha, S, Takada, LT, Rankin, KP, et al. Frontotemporal dementia due to C9ORF72 mutations: clinical and imaging features. Neurology 2012; 79: 1002–11.CrossRefGoogle ScholarPubMed
Takada, LT, Pimentel, MLV, DeJesus-Hernandez, M, et al. Frontotemporal dementia in a Brazilian kindred with the C9ORF72 mutation. Arch Neurol 2012; 69(9): 1149–53.CrossRefGoogle Scholar
Ash, PE, Bieniek, KF, Gendron, TF, et al. Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALS. Neuron 2013; 77(4): 639–46.CrossRefGoogle Scholar
Gallagher, MD, Suh, E, Grossman, M, et al. TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9ORF72 hexanucleotide repeat expansions. Acta Neuropathol 2014; 127(3): 407–18.CrossRefGoogle ScholarPubMed
van Blitterswijk, M, Mullen, B, Nicholson, AM, et al. TMEM106B protects C9ORF72 expansion carriers against frontotemporal dementia. Acta Neuropathol 2014; 127(3): 397406.CrossRefGoogle ScholarPubMed
Hoffman, JM, Welsh-Bohmer, KA, Hanson, M, et al. FDG PET imaging in patients with pathologically verified dementia. J Nucl Med 2000; 41(11): 1920–8.Google ScholarPubMed
Rosen, HJ, Gorno-Tempini, ML, Goldman, WP, et al. Patterns of brain atrophy in frontotemporal dementia and semantic dementia. Neurology 2002; 58(2): 198208.CrossRefGoogle Scholar
Chan, D, Fox, NC, Jenkins, R, et al. Rates of global and regional cerebral atrophy in AD and frontotemporal dementia. Neurology 2001; 57(10): 1756–63.CrossRefGoogle ScholarPubMed
Rabinovici, GD, Furst, AJ, O’Neil, JP, et al. 11C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. Neurology 2007; 68(15): 1205–12.CrossRefGoogle ScholarPubMed
Edwards-Lee, T, Miller, BL, Benson, DF, et al. The temporal variant of frontotemporal dementia. Brain 1997; 120(Pt 6): 1027–40.CrossRefGoogle ScholarPubMed
Galton, CJ, Patterson, K, Graham, K, et al. Differing patterns of temporal atrophy in Alzheimer’s disease and semantic dementia. Neurology 2001; 57(2): 216–25.CrossRefGoogle Scholar
Chan, D, Fox, NC, Scahill, RI, et al. Patterns of temporal lobe atrophy in semantic dementia and Alzheimer’s disease. Ann Neurol 2001; 49(4): 433–42.CrossRefGoogle ScholarPubMed
Mummery, CJ, Patterson, K, Wise, RJ, et al. Disrupted temporal lobe connections in semantic dementia. Brain 1999; 122(Pt 1): 6173.CrossRefGoogle ScholarPubMed
Hodges, JR, Patterson, K. Nonfluent progressive aphasia and semantic dementia: a comparative neuropsychological study. J Int Neuropsychol Soc 1996; 2(6): 511–24.CrossRefGoogle ScholarPubMed
Rosen, HJ, Kramer, JH, Gorno-Tempini, ML, et al. Patterns of cerebral atrophy in primary progressive aphasia. Am J Geriatr Psychiatry 2002; 10(1): 8997.CrossRefGoogle ScholarPubMed
Moretti, R, Torre, P, Antonello, RM, et al. Rivastigmine in frontotemporal dementia: an open-label study. Drugs Aging 2004; 21: 93107.CrossRefGoogle Scholar
Kertesz, A, Morlog, D, Light, M, et al. Galantamine in frontotemporal dementia and primary progressive aphasia. Dement Geriatr Cogn Disord 2008; 25: 178–85.CrossRefGoogle ScholarPubMed
Mendez, MF, Shapira, JS, McMurtray, A, et al. Preliminary findings: behavioral worsening on donepezil in patients with frontotemporal dementia. Am J Geriatr Psychiatr 2007; 15: 84–7.CrossRefGoogle ScholarPubMed
Boxer, AL, Knopman, DS, Kaufer, DI, et al. Memantine in patients with frontotemporal lobar degeneration: a multicenter, randomized, double-blind, placebo-controlled trial. Lancet Neurol 2013; 12: 149–56.CrossRefGoogle Scholar
Hermann, N, Black, SE, Chow, T, et al. Serotonergic function and treatment of behavioral and psychological symptoms of frontotemporal dementia. Am J Geriatr Psychiatr 2012; 20: 789–97.CrossRefGoogle Scholar
Swartz, JR, Miller, BL, Lesser, IM, et al. Frontotemporal dementia: treatment response to serotonin selective reuptake inhibitors. J Clin Psychiatry 1997; 58: 212–16.CrossRefGoogle Scholar
Lebert, F, Stekke, W, Hasenbroekx, C, et al. Frontotemporal dementia: a randomized, controlled trial with trazodone. Dement Geriatr Cogn Disord 2004; 17: 355–9.CrossRefGoogle ScholarPubMed
Curtis, RC, Resch, DS. Case of Pick’s central lobar atrophy with apparent stabilization of cognitive decline after treatment with risperidone. J Clin Psychopharmacol 2000; 20: 384–5.CrossRefGoogle ScholarPubMed
Fellgiebel, A, Muller, MJ, Hiemke, C, et al. Clinical improvement in a case of frontotemporal dementia under aripiprazole treatment corresponds to partial recovery of disturbed frontal glucose metabolism. World J Biol Psychiatry 2007; 8: 123–6.CrossRefGoogle Scholar
Moretti, R, Torre, P, Antonello, RM, et al. Olanzapine as a treatment of neuropsychiatric disorders of Alzheimer’s disease and other dementias: a 24-month follow-up of 68 patients. Am J Alzheimers Dis Other Demen 2003; 18: 205–14.CrossRefGoogle ScholarPubMed
Chow, TW, Mendez, MF. Goals in symptomatic pharmacologic management of frontotemporal lobar degeneration. Am J Alzheimers Dis Other Demen 2002; 17: 267–72.CrossRefGoogle ScholarPubMed
Huey, ED, Garcia, C, Wassermann, EM, et al. Stimulant treatment of frontotemporal dementia in 8 patients. J Clin Psychiatry 2008; 69: 1981–2.CrossRefGoogle ScholarPubMed

Send book to Kindle

To send this book to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats

Send book to Dropbox

To send content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about sending content to Dropbox.

Available formats

Send book to Google Drive

To send content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about sending content to Google Drive.

Available formats