Chapter 5
Frontotemporal dementia
David C. Perry,
Howard J. Rosen,
David C. Perry
University of California, San Francisco, San Francisco, CA, USA
Search for more papers by this authorHoward J. Rosen
University of California, San Francisco, San Francisco, CA, USA
Search for more papers by this authorDavid C. Perry,
Howard J. Rosen,
David C. Perry
University of California, San Francisco, San Francisco, CA, USA
Search for more papers by this authorHoward J. Rosen
University of California, San Francisco, San Francisco, CA, USA
Search for more papers by this authorBook Editor(s):Michael D. Geschwind MD PhD,
Caroline Racine Belkoura PhD,
Michael D. Geschwind MD PhD
Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA
Search for more papers by this authorCaroline Racine Belkoura PhD
Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA
Search for more papers by this authorSummary
The clinical presentation of frontotemporal dementia (FTD) is varied and includes a behavioral variant with early personality and behavior changes and two primary progressive aphasia syndromes, referred to as the semantic variant and the nonfluent variant. Extrapyramidal syndromes and motor neuron disease are also features of some cases. These core clinical syndromes can be caused by different neuropathologies, and in some cases, there are associated genetic mutations. Treatments are in development to target these molecular pathologies. Currently employed treatments are symptomatic.
References
- Pick A. Uber die Beziehungen der senilen Hirnatrophie zur Aphasie. Prager Medizinische Wochenschrift 1892; 17: 165–167.
- Alzheimer A. Uber eigenartige Krankheitsfalle des sparteren Alters. Psychiatr Nervenkr Z Gesamte Neurol Psychiatr 1911; 4: 356–385.
- Ratnavalli E, Brayne C, Dawson K, Hodges JR. The prevalence of frontotemporal dementia. Neurology 2002 Jun 11; 58(11): 1615–1621.
- Brunnstrom H, Gustafson L, Passant U, Englund E. Prevalence of dementia subtypes: a 30-year retrospective survey of neuropathological reports. Arch Gerontol Geriatr 2009 Jul–Aug; 49(1): 146–149.
- Rosso SM, Donker Kaat L, Baks T, Joosse M, de Koning I, Pijnenburg Y, et al. Frontotemporal dementia in the Netherlands: patient characteristics and prevalence estimates from a population-based study. Brain 2003 Sep; 126(Pt 9): 2016–2022.
- Knopman DS, Petersen RC, Edland SD, Cha RH, Rocca WA. The incidence of frontotemporal lobar degeneration in Rochester, Minnesota, 1990 through 1994. Neurology 2004 Feb 10; 62(3): 506–508.
- Roberson ED, Hesse JH, Rose KD, Slama H, Johnson JK, Yaffe K, et al. Frontotemporal dementia progresses to death faster than Alzheimer disease. Neurology 2005 Sep 13; 65(5): 719–725.
- Johnson JK, Diehl J, Mendez MF, Neuhaus J, Shapira JS, Forman M, et al. Frontotemporal lobar degeneration: demographic characteristics of 353 patients. Arch Neurol 2005 June 1; 62(6): 925–930.
- Woolley JD, Khan BK, Murthy NK, Miller BL, Rankin KP. The diagnostic challenge of psychiatric symptoms in neurodegenerative disease: rates of and risk factors for prior psychiatric diagnosis in patients with early neurodegenerative disease. J Clin Psychiatry 2011 Feb; 72(2): 126–133.
- Neary D, Snowden JS, Northen B, Goulding P. Dementia of frontal lobe type. J Neurol Neurosurg Psychiatry 1988 Mar; 51(3): 353–361.
- Kipps CM, Nestor PJ, Fryer TD, Hodges JR. Behavioral variant frontotemporal dementia: not all it seems? Neurocase 2007 Aug; 13(4): 237–247.
- Fukui T, Kertesz A. Volumetric study of lobar atrophy in Pick complex and Alzheimer's disease. J Neurol Sci 2000 Mar 15; 174(2): 111–121.
- Seeley WW, Crawford R, Rascovsky K, Kramer JH, Weiner M, Miller BL, et al. Frontal paralimbic network atrophy in very mild behavioral variant frontotemporal dementia. Arch Neurol 2008; 65(2): 249.
- Liu W, Miller BL, Kramer JH, Rankin K, Wyss-Coray C, Gearhart R, et al. Behavioral disorders in the frontal and temporal variants of frontotemporal dementia. Neurology 2004 Mar 9; 62(5): 742–748.
- Seeley WW, Carlin DA, Allman JM, Macedo MN, Bush C, Miller BL, et al. Early frontotemporal dementia targets neurons unique to apes and humans. Ann Neurol 2006 Dec; 60(6): 660–667.
- Seeley WW. Selective functional, regional, and neuronal vulnerability in frontotemporal dementia. Curr Opin Neurol 2008 Dec; 21(6): 701–707.
- Lane RD, Reiman EM, Axelrod B, Yun LS, Holmes A, Schwartz GE. Neural correlates of levels of emotional awareness. Evidence of an interaction between emotion and attention in the anterior cingulate cortex. J Cogn Neurosci 1998 Jul; 10(4): 525–535.
- Craig AD. Interoception: the sense of the physiological condition of the body. Curr Opin Neurobiol 2003 Aug; 13(4): 500–505.
- Rosen HJ, Allison SC, Schauer GF, Gorno-Tempini ML, Weiner MW, Miller BL. Neuroanatomical correlates of behavioral disorders in dementia. Brain 2005 Nov; 128(Pt 11): 2612–2625.
- Rankin KP, Gorno-Tempini ML, Allison SC, Stanley CM, Glenn S, Weiner MW, et al. Structural anatomy of empathy in neurodegenerative disease. Brain 2006 Nov; 129(Pt 11): 2945–2956.
- Woolley JD, Gorno-Tempini ML, Seeley WW, Rankin K, Lee SS, Matthews BR, et al. Binge eating is associated with right orbitofrontal-insular-striatal atrophy in frontotemporal dementia. Neurology 2007 Oct 2; 69(14): 1424–1433.
- Whitwell JL, Sampson EL, Loy CT, Warren JE, Rossor MN, Fox NC, et al. VBM signatures of abnormal eating behaviors in frontotemporal lobar degeneration. Neuroimage 2007 Mar; 35(1): 207–213.
- Piguet O, Petersen A, Yin Ka Lam B, Gabery S, Murphy K, Hodges JR, et al. Eating and hypothalamus changes in behavioral-variant frontotemporal dementia. Ann Neurol 2011; 69(2): 312–319.
- Josephs KA, Whitwell JL, Jack CR, Jr. Anatomic correlates of stereotypies in frontotemporal lobar degeneration. Neurobiol Aging 2008 Dec; 29(12): 1859–1863.
- Rosso SM, Roks G, Stevens M, de Koning I, Tanghe HLJ, Kamphorst W, et al. Complex compulsive behavior in the temporal variant of frontotemporal dementia. J Neurol 2001 Nov; 248(11): 965–970.
- Ames D, Cummings JL, Wirshing WC, Quinn B, Mahler M. Repetitive and compulsive behavior in frontal lobe degenerations. J Neuropsychiatry Clin Neurosci 1994 Spring; 6(2): 100–113.
- Ishii K, Sakamoto S, Sasaki M, Kitagaki H, Yamaji S, Hashimoto M, et al. Cerebral glucose metabolism in patients with frontotemporal dementia. J Nucl Med 1998 Nov; 39(11): 1875–1878.
- Foster NL, Heidebrink JL, Clark CM, Jagust WJ, Arnold SE, Barbas NR, et al. FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer's disease. Brain 2007 October 01; 130(10): 2616–2635.
- Gregory CA, Serra-Mestres J, Hodges JR. Early diagnosis of the frontal variant of frontotemporal dementia: how sensitive are standard neuroimaging and neuropsychologic tests? Neuropsychiatry Neuropsychol Behav Neurol 1999 Apr; 12(2): 128–135.
- Krueger CE, Laluz V, Rosen HJ, Neuhaus JM, Miller BL, Kramer JH. Double dissociation in the anatomy of socioemotional disinhibition and executive functioning in dementia. Neuropsychology 2011 Mar; 25(2): 249–259.
- Lough S, Kipps CM, Treise C, Watson P, Blair JR, Hodges JR. Social reasoning, emotion and empathy in frontotemporal dementia. Neuropsychologia 2006; 44(6): 950–958.
- Kosmidis MH, Aretouli E, Bozikas VP, Giannakou M, Ioannidis P. Studying social cognition in patients with schizophrenia and patients with frontotemporal dementia: theory of mind and the perception of sarcasm. Behav Neurol 2008; 19(1–2): 65–69.
- Gregory C, Lough S, Stone V, Erzinclioglu S, Martin L, Baron-Cohen S, et al. Theory of mind in patients with frontal variant frontotemporal dementia and Alzheimer's disease: theoretical and practical implications. Brain 2002 Apr; 125(Pt 4): 752–764.
- Strauss E, Sherman EMS, Spreen O. A compendium of neuropsychological tests: administration, norms, and commentary. 3rd ed. New York: Oxford University Press; 2006.
- Henry JD, Crawford JR. A meta-analytic review of verbal fluency performance following focal cortical lesions. Neuropsychology 2004 Apr; 18(2): 284–295.
- Hornberger M, Piguet O, Graham AJ, Nestor PJ, Hodges JR. How preserved is episodic memory in behavioral variant frontotemporal dementia? Neurology 2010 Feb 9; 74(6): 472–479.
- Pasquier F, Grymonprez L, Lebert F, Van der Linden M. Memory impairment differs in frontotemporal dementia and Alzheimer's disease. Neurocase 2001; 7(2): 161–171.
- Kramer JH, Jurik J, Sha SJ, Rankin KP, Rosen HJ, Johnson JK, et al. Distinctive neuropsychological patterns in frontotemporal dementia, semantic dementia, and Alzheimer disease. Cogn Behav Neurol 2003 Dec; 16(4): 211–218.
- Clinical and neuropathological criteria for frontotemporal dementia. The Lund and Manchester Groups. J Neurol Neurosurg Psychiatry 1994 Apr; 57(4): 416–418.
- Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998 Dec; 51(6): 1546–1554.
- Rascovsky K, Hodges JR, Kipps CM, Johnson JK, Seeley WW, Mendez MF, et al. Diagnostic criteria for the behavioral variant of frontotemporal dementia (bvFTD): current limitations and future directions. Alzheimer Dis Assoc Disord 2007 Oct-Dec; 21(4): S14–8.
- Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, et al. Sensitivity of revised diagnostic criteria for the behavioral variant of frontotemporal dementia. Brain 2011 Aug 2; 134(9): 2456–2477.
- Lamarre AK, Rascovsky K, Bostrom A, Toofanian P, Wilkins S, Sha SJ, et al. Interrater reliability of the new criteria for behavioral variant frontotemporal dementia. Neurology 2013 May 21; 80(21): 1973–1977.
- Mesulam MM. Primary progressive aphasia. Ann Neurol 2001 Apr; 49(4): 425–432.
- Thompson SA, Patterson K, Hodges JR. Left/right asymmetry of atrophy in semantic dementia: behavioral-cognitive implications. Neurology 2003 Nov 11; 61(9): 1196–1203.
- Snowden JS, Thompson JC, Neary D. Knowledge of famous faces and names in semantic dementia. Brain 2004 Apr 1; 127(4): 860–872.
- Seeley WW, Bauer AM, Miller BL, Gorno-Tempini ML, Kramer JH, Weiner M, et al. The natural history of temporal variant frontotemporal dementia. Neurology 2005 Apr 26; 64(8): 1384–1390.
- Rosen HJ, Gorno-Tempini ML, Goldman WP, Perry RJ, Schuff N, Weiner M, et al. Patterns of brain atrophy in frontotemporal dementia and semantic dementia. Neurology 2002 Jan 22; 58(2): 198–208.
- Hodges JR, Patterson K, Ward R, Garrard P, Bak T, Perry R, et al. The differentiation of semantic dementia and frontal lobe dementia (temporal and frontal variants of frontotemporal dementia) from early Alzheimer's disease: a comparative neuropsychological study. Neuropsychology 1999 Jan; 13(1): 31–40.
- Rosen HJ, Allison SC, Ogar JM, Amici S, Rose K, Dronkers N, et al. Behavioral features in semantic dementia vs other forms of progressive aphasias. Neurology 2006 Nov 28; 67(10): 1752–1756.
- Gorno-Tempini ML, Dronkers NF, Rankin KP, Ogar JM, Phengrasamy L, Rosen HJ, et al. Cognition and anatomy in three variants of primary progressive aphasia. Ann Neurol 2004 Mar; 55(3): 335–346.
- Josephs KA, Duffy JR, Strand EA, Whitwell JL, Layton KF, Parisi JE, et al. Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech. Brain 2006 Jun; 129(Pt 6): 1385–1398.
- Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, et al. Classification of primary progressive aphasia and its variants. Neurology 2011 Mar 15; 76(11): 1006–1014.
- Lomen-Hoerth C, Anderson T, Miller B. The overlap of amyotrophic lateral sclerosis and frontotemporal dementia. Neurology 2002 Oct 8; 59(7): 1077–1079.
- Chang JL, Lomen-Hoerth C, Murphy J, Henry RG, Kramer JH, Miller BL, et al. A voxel-based morphometry study of patterns of brain atrophy in ALS and ALS/FTLD. Neurology 2005 Jul 12; 65(1): 75–80.
- Lillo P, Garcin B, Hornberger M, Bak TH, Hodges JR. Neurobehavioral features in frontotemporal dementia with amyotrophic lateral sclerosis. Arch Neurol 2010 Jul; 67(7): 826–830.
- Whitwell JL, Jack CR, Jr, Senjem ML, Josephs KA. Patterns of atrophy in pathologically confirmed FTLD with and without motor neuron degeneration. Neurology 2006 Jan 10; 66(1): 102–104.
- Murphy JM, Henry RG, Langmore S, Kramer JH, Miller BL, Lomen-Hoerth C. Continuum of frontal lobe impairment in amyotrophic lateral sclerosis. Arch Neurol 2007 April 1; 64(4): 530–534.
- Lomen-Hoerth C, Murphy J, Langmore S, Kramer JH, Olney RK, Miller B. Are amyotrophic lateral sclerosis patients cognitively normal? Neurology 2003 Apr 8; 60(7): 1094–1097.
- Rebeiz JJ, Kolodny EH, Richardson EP, Jr. Corticodentatonigral degeneration with neuronal achromasia. Arch Neurol 1968 Jan 1; 18(1): 20–33.
- Gorno-Tempini ML, Murray RC, Rankin KP, Weiner MW, Miller BL. Clinical, cognitive and anatomical evolution from nonfluent progressive aphasia to corticobasal syndrome: a case report. Neurocase 2004 Dec; 10(6): 426–436.
- Boeve BF, Maraganore DM, Parisi JE, Ahlskog JE, Graff-Radford N, Caselli RJ, et al. Pathologic heterogeneity in clinically diagnosed corticobasal degeneration. Neurology 1999 Sep 11; 53(4): 795–800.
- Hu WT, Rippon GW, Boeve BF, Knopman DS, Petersen RC, Parisi JE, et al. Alzheimer's disease and corticobasal degeneration presenting as corticobasal syndrome. Mov Disord 2009 Jul 15; 24(9): 1375–1379.
- Whitwell JL, Jack CR, Jr, Boeve BF, Parisi JE, Ahlskog JE, Drubach DA, et al. Imaging correlates of pathology in corticobasal syndrome. Neurology 2010 Nov 23; 75(21): 1879–1887.
- Lee SE, Rabinovici GD, Mayo MC, Wilson SM, Seeley WW, DeArmond SJ, et al. Clinicopathological correlations in corticobasal degeneration. Ann Neurol 2011 Aug; 70(2): 327–40.
- Brun A. Frontal lobe degeneration of non-Alzheimer type. I. Neuropathol Arch Gerontol Geriatr 1987 Sep; 6(3): 193–208.
- Knopman DS, Mastri AR, Frey WH, 2nd, Sung JH, Rustan T. Dementia lacking distinctive histologic features: a common non-Alzheimer degenerative dementia. Neurology 1990 Feb; 40(2): 251–256.
- Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006 Oct 6; 314(5796): 130–133.
- Snowden J, Neary D, Mann D. Frontotemporal lobar degeneration: clinical and pathological relationships. Acta Neuropathol 2007 Jul; 114(1): 31–38.
- Urwin H, Josephs KA, Rohrer JD, Mackenzie IR, Neumann M, Authier A, et al. FUS pathology defines the majority of tau- and TDP-43-negative frontotemporal lobar degeneration. Acta Neuropathol 2010 Jul; 120(1): 33–41.
- Weingarten MD, Lockwood AH, Hwo SY, Kirschner MW. A protein factor essential for microtubule assembly. Proc Natl Acad Sci U S A 1975 May; 72(5): 1858–1862.
- Cairns NJ, Bigio EH, Mackenzie IR, Neumann M, Lee VM, Hatanpaa KJ, et al. Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the consortium for frontotemporal lobar degeneration. Acta Neuropathol 2007 Jul; 114(1): 5–22.
- Buratti E, Baralle FE. Multiple roles of TDP-43 in gene expression, splicing regulation, and human disease. Front Biosci 2008 Jan 1; 13: 867–878.
- Mackenzie IR, Neumann M, Baborie A, Sampathu DM, Du Plessis D, Jaros E, et al. A harmonized classification system for FTLD-TDP pathology. Acta Neuropathol 2011 Jul; 122(1): 111–113.
- Sampathu DM, Neumann M, Kwong LK, Chou TT, Micsenyi M, Truax A, et al. Pathological heterogeneity of frontotemporal lobar degeneration with ubiquitin-positive inclusions delineated by ubiquitin immunohistochemistry and novel monoclonal antibodies. Am J Pathol 2006 Oct; 169(4): 1343–1352.
- Mackenzie IR, Baborie A, Pickering-Brown S, Du Plessis D, Jaros E, Perry RH, et al. Heterogeneity of ubiquitin pathology in frontotemporal lobar degeneration: classification and relation to clinical phenotype. Acta Neuropathol 2006 Nov; 112(5): 539–549.
- Mackenzie IRA, Bigio EH, Ince PG, Geser F, Neumann M, Cairns NJ, et al. Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations. Ann Neurol 2007; 61(5): 427–434.
- Neumann M, Rademakers R, Roeber S, Baker M, Kretzschmar HA, Mackenzie IR. A new subtype of frontotemporal lobar degeneration with FUS pathology. Brain 2009 Nov; 132(Pt 11): 2922–2931.
- Munoz DG, Neumann M, Kusaka H, Yokota O, Ishihara K, Terada S, et al. FUS pathology in basophilic inclusion body disease. Acta Neuropathol 2009 Nov; 118(5): 617–627.
- Neumann M, Roeber S, Kretzschmar HA, Rademakers R, Baker M, Mackenzie IR. Abundant FUS-immunoreactive pathology in neuronal intermediate filament inclusion disease. Acta Neuropathol 2009 Nov; 118(5): 605–616.
- Rohrer JD, Geser F, Zhou J, Gennatas ED, Sidhu M, Trojanowski JQ, et al. TDP-43 subtypes are associated with distinct atrophy patterns in frontotemporal dementia. Neurology 2010 Dec 14; 75(24): 2204–2211.
- Davies RR, Hodges JR, Kril JJ, Patterson K, Halliday GM, Xuereb JH. The pathological basis of semantic dementia. Brain 2005 Sep; 128(Pt 9): 1984–1995.
- Kertesz A, McMonagle P, Blair M, Davidson W, Munoz DG. The evolution and pathology of frontotemporal dementia. Brain 2005 Sep; 128(Pt 9): 1996–2005.
- Josephs KA, Whitwell JL, Parisi JE, Petersen RC, Boeve BF, Jack CR, Jr, et al. Caudate atrophy on MRI is a characteristic feature of FTLD-FUS. Eur J Neurol 2010 Jul; 17(7): 969–975.
- Forman MS, Farmer J, Johnson JK, Clark CM, Arnold SE, Coslett HB, et al. Frontotemporal dementia: clinicopathological correlations. Ann Neurol 2006; 59(6): 952–962.
- Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC, et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 1996 Jul; 47(1): 1–9.
- Irwin DJ, Trojanowski JQ, Grossman M. Cerebrospinal fluid biomarkers for differentiation of frontotemporal lobar degeneration from Alzheimer's disease. Front Aging Neurosci 2013 Feb 21; 5: 6.
- Rabinovici GD, Furst AJ, O'Neil JP, Racine CA, Mormino EC, Baker SL, et al. 11C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. Neurology 2007 Apr 10; 68(15): 1205–1212.
- Sanchez-Juan P, Ghosh PM, Hagen J, Gesierich B, Henry M, Grinberg LT, et al. Practical utility of amyloid and FDG-PET in an academic dementia center. Neurology 2014 Jan 21; 82(3): 230–238.
- Hu WT, Chen-Plotkin A, Grossman M, Arnold SE, Clark CM, Shaw LM, et al. Novel CSF biomarkers for frontotemporal lobar degenerations. Neurology 2010 Dec 7; 75(23): 2079–2086.
- Hu WT, Watts K, Grossman M, Glass J, Lah JJ, Hales C, et al. Reduced CSF p-Tau181 to Tau ratio is a biomarker for FTLD-TDP. Neurology 2013 Nov 26; 81(22): 1945–1952.
- Coppola G, Karydas A, Rademakers R, Wang Q, Baker M, Hutton M, et al. Gene expression study on peripheral blood identifies progranulin mutations. Ann Neurol 2008 Jul; 64(1): 92–96.
- Sleegers K, Brouwers N, Van Damme P, Engelborghs S, Gijselinck I, van der Zee J, et al. Serum biomarker for progranulin-associated frontotemporal lobar degeneration. Ann Neurol 2009 May; 65(5): 603–609.
- Ghidoni R, Benussi L, Glionna M, Franzoni M, Binetti G. Low plasma progranulin levels predict progranulin mutations in frontotemporal lobar degeneration. Neurology 2008 Oct 14; 71(16): 1235–1239.
- Foulds P, McAuley E, Gibbons L, Davidson Y, Pickering-Brown SM, Neary D, et al. TDP-43 protein in plasma may index TDP-43 brain pathology in Alzheimer's disease and frontotemporal lobar degeneration. Acta Neuropathol 2008 Aug; 116(2): 141–146.
- Scherling CS, Hall T, Berisha F, Klepac K, Karydas A, Coppola G, et al. Cerebrospinal fluid neurofilament concentration reflects disease severity in frontotemporal degeneration. Ann Neurol 2014 Jan; 75(1): 116–126.
- Goldman JS, Farmer JM, Wood EM, Johnson JK, Boxer A, Neuhaus J, et al. Comparison of family histories in FTLD subtypes and related tauopathies. Neurology 2005 Dec 13; 65(11): 1817–1819.
- Baker M, Litvan I, Houlden H, Adamson J, Dickson D, Perez-Tur J, et al. Association of an extended haplotype in the tau gene with progressive supranuclear palsy. Hum Mol Genet 1999 Apr; 8(4): 711–715.
- Houlden H, Baker M, Morris HR, MacDonald N, Pickering-Brown S, Adamson J, et al. Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype. Neurology 2001 Jun 26; 56(12): 1702–1706.
- Seelaar H, Kamphorst W, Rosso SM, Azmani A, Masdjedi R, de Koning I, et al. Distinct genetic forms of frontotemporal dementia. Neurology 2008 Oct 14; 71(16): 1220–1226.
- Whitwell JL, Jack CR, Jr, Boeve BF, Senjem ML, Baker M, Rademakers R, et al. Voxel-based morphometry patterns of atrophy in FTLD with mutations in MAPT or PGRN. Neurology 2009 Mar 3; 72(9): 813–820.
- Whitwell JL, Jack CR, Jr, Boeve BF, Senjem ML, Baker M, Ivnik RJ, et al. Atrophy patterns in IVS10+16, IVS10+3, N279K, S305N, P301L, and V337M MAPT mutations. Neurology 2009 Sep 29; 73(13): 1058–1065.
- Beck J, Rohrer JD, Campbell T, Isaacs A, Morrison KE, Goodall EF, et al. A distinct clinical, neuropsychological and radiological phenotype is associated with progranulin gene mutations in a large UK series. Brain 2008 March 01; 131(3): 706–720.
- Ward ME, Miller BL. Potential mechanisms of progranulin-deficient FTLD. J Mol Neurosci 2011 Nov; 45(3): 574–582.
- Perry DC, Lehmann M, Yokoyama JS, Karydas A, Lee JJ, Coppola G, et al. Progranulin mutations as risk factors for Alzheimer disease. JAMA Neurol 2013 Jun; 70(6): 774–778.
- Gass J, Cannon A, Mackenzie IR, Boeve B, Baker M, Adamson J, et al. Mutations in progranulin are a major cause of ubiquitin-positive frontotemporal lobar degeneration. Hum Mol Genet 2006 Oct 15; 15(20): 2988–3001.
- DeJesus-Hernandez M, Mackenzie I, Boeve B, Boxer A, Baker M, Rutherford N, et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 2011 Oct 20; 72(2): 245–256.
- Renton A, Majounie E, Waite A, Simón-Sánchez J, Rollinson S, Gibbs J, et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 2011 Oct 20; 72(2): 257–268.
- Simon-Sanchez J, Dopper EG, Cohn-Hokke PE, Hukema RK, Nicolaou N, Seelaar H, et al. The clinical and pathological phenotype of C9ORF72 hexanucleotide repeat expansions. Brain 2012 Mar; 135(Pt 3): 723–735.
- Sha SJ, Takada LT, Rankin KP, Yokoyama JS, Rutherford NJ, Fong JC, et al. Frontotemporal dementia due to C9ORF72 mutations: clinical and imaging features. Neurology 2012 Sep 4; 79(10): 1002–1011.
- Snowden JS, Rollinson S, Thompson JC, Harris JM, Stopford CL, Richardson AM, et al. Distinct clinical and pathological characteristics of frontotemporal dementia associated with C9ORF72 mutations. Brain 2012 Mar; 135(Pt 3): 693–708.
- Hsiung GY, Dejesus-Hernandez M, Feldman HH, Sengdy P, Bouchard-Kerr P, Dwosh E, et al. Clinical and pathological features of familial frontotemporal dementia caused by C9ORF72 mutation on chromosome 9p. Brain 2012 Mar; 135(Pt 3): 709–722.
- Khan BK, Yokoyama JS, Takada LT, Sha SJ, Rutherford NJ, Fong JC, et al. Atypical, slowly progressive behavioral variant frontotemporal dementia associated with C9ORF72 hexanucleotide expansion. J Neurol Neurosurg Psychiatry 2012 Apr; 83(4): 358–364.
- Al-Sarraj S, King A, Troakes C, Smith B, Maekawa S, Bodi I, et al. p62 positive, TDP-43 negative, neuronal cytoplasmic and intranuclear inclusions in the cerebellum and hippocampus define the pathology of C9orf72-linked FTLD and MND/ALS. Acta Neuropathol 2011 Dec; 122(6): 691–702.
- Murray ME, DeJesus-Hernandez M, Rutherford NJ, Baker M, Duara R, Graff-Radford NR, et al. Clinical and neuropathologic heterogeneity of c9FTD/ALS associated with hexanucleotide repeat expansion in C9ORF72. Acta Neuropathol 2011 Dec; 122(6): 673–690.
- Mori K, Weng SM, Arzberger T, May S, Rentzsch K, Kremmer E, et al. The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS. Science 2013 Mar 15; 339(6125): 1335–1338.
- Mackenzie IR, Arzberger T, Kremmer E, Troost D, Lorenzl S, Mori K, et al. Dipeptide repeat protein pathology in C9ORF72 mutation cases: clinico-pathological correlations. Acta Neuropathol 2013 Dec; 126(6): 859–879.
- Gydesen S, Brown JM, Brun A, Chakrabarti L, Gade A, Johannsen P, et al. Chromosome 3 linked frontotemporal dementia (FTD-3). Neurology 2002 Nov 26; 59(10): 1585–1594.
- Johnson JO, Mandrioli J, Benatar M, Abramzon Y, Van Deerlin VM, Trojanowski JQ, et al. Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron 2010 Dec 9; 68(5): 857–864.
- Borroni B, Ghezzi S, Agosti C, Archetti S, Fenoglio C, Galimberti D, et al. Preliminary evidence that VEGF genetic variability confers susceptibility to frontotemporal lobar degeneration. Rejuvenation Res 2008 Aug; 11(4): 773–780.
- Rademakers R, Eriksen JL, Baker M, Robinson T, Ahmed Z, Lincoln SJ, et al. Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia. Hum Mol Genet 2008 Dec 1; 17(23): 3631–3642.
- Ferrari R, Hernandez DG, Nalls MA, Rohrer JD, Ramasamy A, Kwok JB, et al. Frontotemporal dementia and its subtypes: a genome-wide association study. Lancet Neurol 2014 Jul; 13(7): 686–699.
- Van Deerlin VM, Sleiman PM, Martinez-Lage M, Chen-Plotkin A, Wang LS, Graff-Radford NR, et al. Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions. Nat Genet 2010 Mar; 42(3): 234–239.
- Veerappan CS, Sleiman S, Coppola G. Epigenetics of Alzheimer's disease and frontotemporal dementia. Neurotherapeutics 2013 Oct; 10(4): 709–721.
- Mendez MF, Shapira JS, McMurtray A, Licht E. Preliminary findings: behavioral worsening on donepezil in patients with frontotemporal dementia. Am J Geriatr Psychiatry 2007 Jan; 15(1): 84–87.
- Moretti R, Torre P, Antonello RM, Cattaruzza T, Cazzato G, Bava A. Rivastigmine in frontotemporal dementia: an open-label study. Drugs Aging 2004; 21(14): 931–937.
- Kertesz A, Morlog D, Light M, Blair M, Davidson W, Jesso S, et al. Galantamine in frontotemporal dementia and primary progressive aphasia. Dement Geriatr Cogn Disord 2008; 25(2): 178–185.
- Diehl-Schmid J, Forstl H, Perneczky R, Pohl C, Kurz A. A 6-month, open-label study of memantine in patients with frontotemporal dementia. Int J Geriatr Psychiatry 2008 Jul; 23(7): 754–759.
- Boxer AL, Lipton AM, Womack K, Merrilees J, Neuhaus J, Pavlic D, et al. An open-label study of memantine treatment in 3 subtypes of frontotemporal lobar degeneration. Alzheimer Dis Assoc Disord 2009 Jul–Sep; 23(3): 211–217.
- Vercelletto M, Boutoleau-Bretonniere C, Volteau C, Puel M, Auriacombe S, Sarazin M, et al. Memantine in behavioral variant frontotemporal dementia: negative results. J Alzheimers Dis 2011 Jan 1; 23(4): 749–759.
- Boxer AL, Knopman DS, Kaufer DI, Grossman M, Onyike C, Graf-Radford N, et al. Memantine in patients with frontotemporal lobar degeneration: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol 2013 Feb; 12(2): 149–156.
- Swartz JR, Miller BL, Lesser IM, Darby AL. Frontotemporal dementia: treatment response to serotonin selective reuptake inhibitors. J Clin Psychiatry 1997 May; 58(5): 212–216.
- Ikeda M, Shigenobu K, Fukuhara R, Hokoishi K, Maki N, Nebu A, et al. Efficacy of fluvoxamine as a treatment for behavioral symptoms in frontotemporal lobar degeneration patients. Dement Geriatr Cogn Disord 2004; 17(3): 117–121.
- Moretti R, Torre P, Antonello RM, Cazzato G, Bava A. Frontotemporal dementia: paroxetine as a possible treatment of behavior symptoms. A randomized, controlled, open 14-month study. Eur Neurol 2003; 49(1): 13–19.
- Deakin JB, Rahman S, Nestor PJ, Hodges JR, Sahakian BJ. Paroxetine does not improve symptoms and impairs cognition in frontotemporal dementia: a double-blind randomized controlled trial. Psychopharmacology (Berl) 2004 Apr; 172(4): 400–408.
- Lebert F, Stekke W, Hasenbroekx C, Pasquier F. Frontotemporal dementia: a randomised, controlled trial with trazodone. Dement Geriatr Cogn Disord 2004; 17(4): 355–359.
- Moretti R, Torre P, Antonello RM, Cazzato G, Griggio S, Bava A. 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 Jul–Aug; 18(4): 205–214.
- Fellgiebel A, Muller MJ, Hiemke C, Bartenstein P, Schreckenberger M. 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(2): 123–126.
- 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 Jun; 20(3): 384–385.
- Boxer AL, Lang AE, Grossman M, Knopman DS, Miller BL, Schneider LS, et al. Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol 2014; 13(7): 676–685.
