Review

Management of frontotemporal dementia: targeting symptom management in such a heterogeneous disease requires a wide range of therapeutic options

† Author for correspondence

Email the corresponding author at gajich2@email.uky.edu

Sanders-Brown Center on Aging, 101 Sanders-Brown Building, University of Kentucky, Lexington, KY 40536-0230, USA

University of Kentucky Alzheimer’s Disease Center, 101 Sanders-Brown Building, University of Kentucky, Lexington, KY 40536-0230, USA

Department of Neuropathology, University of Kentucky College of Medicine, Lexington, KY, USA

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Published Online:8 Apr 2011https://doi.org/10.2217/nmt.11.9

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Abstract

SUMMARY There are no US FDA-approved therapies for the management of frontotemporal dementia (FTD). Evidence-based medicine that would support a FDA indication for the treatment of FTD requires large-scale, randomized, double-blind, placebo-controlled trials that do not currently exist. Progress in obtaining approval and therapeutic indications for FTD has been severely hampered by the heterogeneity of clinical and pathological phenotypes seen in various FTD disease states. These issues are often misinterpreted by clinicians, caregivers and patients suggesting that potential treatment options are nonexistent for this devastating disease. This article discusses these issues in the context of recent studies and publications investigating therapeutic options in FTD, and further suggests a rationale for individualized therapy in FTD. Targeting the myriad of symptoms seen in FTD requires recognition of such symptoms that may play primary or secondary roles in the spectrum of deficits that lead to functional disability in FTD, and the availability of a wide range of therapeutic options that may be helpful in alleviating such symptomatology. Fortunately, agents targeting the many cognitive, behavioral, psychiatric and motor symptoms that can be seen in FTD are readily available, having been previously developed and approved for symptomatic benefit in other disease states. In contrast to the widespread belief that beneficial treatments are not available for FTD today, our therapeutic armament is stocked with pharmacological tools that may improve quality of life for those suffering from this devastating and incurable class of degenerative diseases.

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

Bibliography

1 Allain H, Bentue-Ferrer D, Tribut O, Merienne M, Belliard S: Drug therapy of frontotemporal dementia. Hum. Psychopharmacol.18,221–225 (2003).Crossref, Medline, CAS, Google Scholar
2 Arvanitakis Z: Update on frontotemporal dementia. Neurologist16,16–22 (2010).Crossref, Medline, Google Scholar
3 Bei H, Ross L, Neuhaus J: Off-label medication use in frontotemporal dementia. Am. J. Alzheimers Dis. Other Demen.25,128–133 (2010).▪▪ Novel exploration of off-label medication use by expert clinicians in the area of frontotemporal dementia (FTD) demonstrates that therapeutic options do exist, and are being used currently for symptomatic treatment of this devastating disease.Crossref, Medline, Google Scholar
4 Boxer AL, Boeve BF: Frontotemporal dementia treatment: current symptomatic therapies and implications of recent genetic, biochemical, and neuroimaging studies. Alzheimer Dis. Assoc. Disord.21,S79–S87 (2007).Crossref, Medline, Google Scholar
5 Chow TW: Treatment approaches to symptoms associated with frontotemporal degeneration. Curr. Psychiatry Rep.7,376–380 (2005).Crossref, Medline, Google Scholar
6 Galariotis V, Bodi N, Janka Z, Kalman J: Frontotemporal dementia – part III. Clinical diagnosis and treatment. Ideggyogy Sz58,292–297 (2005).Medline, Google Scholar
7 Galariotis V, Bodi N, Janka Z, Kalman J: Frontotemporal dementia – part I. History, prevalence, clinical forms. Ideggyogy Sz58,164–171 (2005).Medline, Google Scholar
8 Graff-Radford NR, Woodruff BK: Frontotemporal dementia. Semin. Neurol.27,48–57 (2007).Crossref, Medline, Google Scholar
9 Honig LS, Bell K, Chin SS: Frontotemporal dementia. Sci. Aging Knowledge Environ.2003(13),DN1 (2003).Crossref, Medline, Google Scholar
10 Kaye ED, Petrovic-Poljak A, Verhoeff NP, Freedman M: Frontotemporal dementia and pharmacologic interventions. J. Neuropsychiatry Clin. Neurosci.22,19–29 (2010).Crossref, Medline, CAS, Google Scholar
11 Kirshner HS: Frontotemporal dementia and primary progressive aphasia: an update. Curr. Neurol. Neurosci. Rep.10,504–511 (2010).Crossref, Medline, Google Scholar
12 Leger GC, Johnson N: A review on primary progressive aphasia. Neuropsychiatr. Dis. Treat.3,745–752 (2007).Medline, Google Scholar
13 Mendez MF: Frontotemporal dementia: therapeutic interventions. Front Neurol. Neurosci.24,168–178 (2009).Crossref, Medline, Google Scholar
14 Roberson ED: Frontotemporal dementia. Curr. Neurol. Neurosci. Rep.6,481–489 (2006).Crossref, Medline, Google Scholar
15 Sjogren M, Andersen C: Frontotemporal dementia – a brief review. Mech. Ageing Dev.127,180–187 (2006).Crossref, Medline, Google Scholar
16 Weder ND, Aziz R, Wilkins K, Tampi RR: Frontotemporal dementias: a review. Ann. Gen. Psychiatry6,15 (2007).Crossref, Medline, Google Scholar
17 Yeaworth RC, Burke WJ: Frontotemporal dementia: a different kind of dementia. Arch. Psychiatr. Nurs.14,249–253 (2000).Crossref, Medline, CAS, Google Scholar
18 Freedman M: Frontotemporal dementia: recommendations for therapeutic studies, designs, and approaches. Can. J. Neurol. Sci.34(Suppl. 1),S118–S124 (2007).▪▪ This represents an in-depth review and opinion on shortcomings of prior therapeutic studies in FTD and further presents rational suggestions for improving clinical trials of therapeutic agents in this heterogeneous disease state.Crossref, Medline, Google Scholar
19 Gozes I: Tau pathology and future therapeutics. Curr. Alzheimer Res.7(8),685–696 (2010).Crossref, Medline, CAS, Google Scholar
20 Trojanowski JQ, Duff K, Fillit H et al.: New directions for frontotemporal dementia drug discovery. Alzheimers Dement.4,89–93 (2008).▪ Review of emerging therapeutic options in FTD based on recent discoveries in the area of pathobiology and genetics provides a unique look forward at the future of FTD therapeutics undergoing preclinical exploration currently.Crossref, Medline, CAS, Google Scholar
21 Vossel KA, Miller BL: New approaches to the treatment of frontotemporal lobar degeneration. Curr. Opin. Neurol.21,708–716 (2008).▪ Review of emerging therapeutic options in FTD based on recent discoveries in the area of pathobiology and genetics provides a unique look forward at the future of FTD therapeutics undergoing preclinical exploration currently.Crossref, Medline, Google Scholar
22 Kertesz A: Frontotemporal dementia, Pick’s disease. Ideggyogy Sz63,4–12 (2010).Medline, Google Scholar
23 Kertesz A: Pick complex: an integrative approach to frontotemporal dementia: primary progressive aphasia, corticobasal degeneration, and progressive supranuclear palsy. Neurologist9,311–317 (2003).Crossref, Medline, Google Scholar
24 Pasquier F, Lebert F, Lavenu I, Guillaume B: The clinical picture of frontotemporal dementia: diagnosis and follow-up. Dement. Geriatr. Cogn. Disord.10(Suppl. 1),10–14 (1999).Crossref, Medline, Google Scholar
25 Pijnenburg YA, Mulder JL, van Swieten JC et al.: Diagnostic accuracy of consensus diagnostic criteria for frontotemporal dementia in a memory clinic population. Dement. Geriatr. Cogn. Disord.25,157–164 (2008).Crossref, Medline, Google Scholar
26 Rose DZ: Primary progressive aphasia. Cleve. Clin. J. Med.74,9 (2007).Crossref, Medline, Google Scholar
27 Froelich-Fabre S, Skoglund L, Ostojic J et al.: Clinical and molecular aspects of frontotemporal dementia. Neurodegener. Dis.1,218–224 (2004).Crossref, Medline, Google Scholar
28 Padovani A, Agosti C, Premi E, Bellelli G, Borroni B: Extrapyramidal symptoms in frontotemporal dementia: prevalence and clinical correlations. Neurosci. Lett.422,39–42 (2007).Crossref, Medline, CAS, Google Scholar
29 Reich SG, Grill SE: Corticobasal degeneration. Curr. Treat. Options Neurol.11,179–185 (2009).Crossref, Medline, Google Scholar
30 Galariotis V, Bodi N, Janka Z, Kalman J: Frontotemporal dementia – Part II. Differential diagnosis, genetics, molecular pathomechanism and pathology. Ideggyogy Sz58,220–224 (2005).Medline, Google Scholar
31 Liscic RM: Frontotemporal dementias: update on recent developments in molecular genetics and neuropathology. Arch. Hig. Rada Toksikol.60,117–122 (2009).Crossref, Medline, Google Scholar
32 Neumann M, Tolnay M, Mackenzie IR: The molecular basis of frontotemporal dementia. Expert Rev. Mol. Med.11,e23 (2009).Crossref, Medline, Google Scholar
33 D’Souza I, Schellenberg GD: Regulation of tau isoform expression and dementia. Biochim. Biophys. Acta1739,104–115 (2005).Crossref, Medline, Google Scholar
34 Hodges JR, Miller B: The classification, genetics and neuropathology of frontotemporal dementia. Introduction to the special topic papers: part I. Neurocase7,31–35 (2001).Crossref, Medline, CAS, Google Scholar
35 Schraen-Maschke S, Dhaenens CM, Delacourte A, Sablonniere B: Microtubule-associated protein tau gene: a risk factor in human neurodegenerative diseases. Neurobiol. Dis.15,449–460 (2004).Crossref, Medline, CAS, Google Scholar
36 Wilhelmsen KC, Clark LN, Miller BL, Geschwind DH: Tau mutations in frontotemporal dementia. Dement. Geriatr. Cogn. Disord.10(Suppl. 1),88–92 (1999).Crossref, Medline, CAS, Google Scholar
37 Yoshiyama Y, Lee VM, Trojanowski JQ: Frontotemporal dementia and tauopathy. Curr. Neurol. Neurosci. Rep.1,413–421 (2001).Crossref, Medline, CAS, Google Scholar
38 van Swieten JC, Heutink P: Mutations in progranulin (GRN) within the spectrum of clinical and pathological phenotypes of frontotemporal dementia. Lancet Neurol.7,965–974 (2008).Crossref, Medline, CAS, Google Scholar
39 Yu CE, Bird TD, Bekris LM et al.: The spectrum of mutations in progranulin: a collaborative study screening 545 cases of neurodegeneration. Arch. Neurol.67,161–170 (2010).Crossref, Medline, Google Scholar
40 Guinto JB, Ritson GP, Taylor JP, Forman MS: Valosin-containing protein and the pathogenesis of frontotemporal dementia associated with inclusion body myopathy. Acta Neuropathol.114,55–61 (2007).Crossref, Medline, CAS, Google Scholar
41 Kimonis VE, Fulchiero E, Vesa J, Watts G: VCP disease associated with myopathy, Paget disease of bone and frontotemporal dementia: review of a unique disorder. Biochim. Biophys. Acta1782,744–748 (2008).Crossref, Medline, CAS, Google Scholar
42 Weihl CC, Pestronk A, Kimonis VE: Valosin-containing protein disease: inclusion body myopathy with Paget’s disease of the bone and fronto-temporal dementia. Neuromuscul. Disord.19,308–315 (2009).Crossref, Medline, Google Scholar
43 Momeni P, Rogaeva E, Van Deerlin V et al.: Genetic variability in CHMP2B and frontotemporal dementia. Neurodegener. Dis.3,129–133 (2006).Crossref, Medline, CAS, Google Scholar
44 Skibinski G, Parkinson NJ, Brown JM et al.: Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. Nat. Genet.37,806–808 (2005).Crossref, Medline, CAS, Google Scholar
45 van der Zee J, Urwin H, Engelborghs S et al.: CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro. Hum. Mol. Genet.17,313–322 (2008).Crossref, Medline, CAS, Google Scholar
46 Borroni B, Bonvicini C, Alberici A et al.: Mutation within TARDBP leads to frontotemporal dementia without motor neuron disease. Hum. Mutat.30,E974–E983 (2009).Crossref, Medline, CAS, Google Scholar
47 Mackenzie IR, Rademakers R, Neumann M: TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia. Lancet Neurol.9,995–1007 (2010).Crossref, Medline, CAS, Google Scholar
48 Origone P, Caponnetto C, Bandettini Di Poggio M et al.: Enlarging clinical spectrum of FALS with TARDBP gene mutations: S393L variant in an Italian family showing phenotypic variability and relevance for genetic counselling. Amyotroph. Lateral Scler.11,223–227 (2010).Crossref, Medline, CAS, Google Scholar
49 Gabryelewicz T, Masellis M, Berdynski M et al.: Intra-familial clinical heterogeneity due to FTLD-U with TDP-43 proteinopathy caused by a novel deletion in progranulin gene (PGRN). J. Alzheimers Dis.22(4),1123–1133 (2010).Crossref, Medline, CAS, Google Scholar
50 Mackenzie IR: The neuropathology and clinical phenotype of FTD with progranulin mutations. Acta Neuropathol.114,49–54 (2007).Crossref, Medline, Google Scholar
51 Seelaar H, Rohrer JD, Pijnenburg YA, Fox NC, van Swieten JC: Clinical, genetic and pathological heterogeneity of frontotemporal dementia: a review. J. Neurol. Neurosurg. Psychiatry (2010) (Epub ahead of print).▪▪ Focuses on recent clinical, neuropsychological, imaging, genetic and pathological developments that have influenced our understanding of FTD as a complex and heterogeneous disorder.Google Scholar
52 van Swieten JC, Rosso SM, van Herpen E, Kamphorst W, Ravid R, Heutink P: Phenotypic variation in frontotemporal dementia and parkinsonism linked to chromosome 17. Dement. Geriatr. Cogn. Disord.17,261–264 (2004).Crossref, Medline, CAS, Google Scholar
53 Cairns NJ, Bigio EH, Mackenzie IR et al.: Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol.114,5–22 (2007).▪ The molecular and pathological heterogeneity of frontotemporal lobar dementia is explored with an emphasis on clarifying nomenclature and establishing a uniform nosology in the field.Crossref, Medline, Google Scholar
54 Kovari E: Neuropathological spectrum of frontal lobe dementias. Front Neurol. Neurosci.24,149–159 (2009).Crossref, Medline, Google Scholar
55 Kertesz A, Munoz D: Relationship between frontotemporal dementia and corticobasal degeneration/progressive supranuclear palsy. Dement. Geriatr. Cogn. Disord.17,282–286 (2004).Crossref, Medline, Google Scholar
56 Rosso SM, van Swieten JC: New developments in frontotemporal dementia and parkinsonism linked to chromosome 17. Curr. Opin. Neurol.15,423–428 (2002).Crossref, Medline, Google Scholar
57 Zhukareva V, Trojanowski JQ, Lee VM: Assessment of pathological tau proteins in frontotemporal dementias: qualitative and quantitative approaches. Am. J. Geriatr. Psychiatry12,136–145 (2004).Crossref, Medline, Google Scholar
58 Mackenzie IR: The neuropathology of FTD associated With ALS. Alzheimer Dis. Assoc. Disord.21,S44–S49 (2007).Crossref, Medline, Google Scholar
59 Back-Madruga C, Boone KB, Briere J et al.: Functional ability in executive variant Alzheimer’s disease and typical Alzheimer’s disease. Clin. Neuropsychol.16,331–340 (2002).Crossref, Medline, Google Scholar
60 Habek M, Hajnsek S, Zarkovic K, Chudy D, Mubrin Z: Frontal variant of Alzheimer’s disease: clinico–CSF–pathological correlation. Can. J. Neurol. Sci.37,118–120 (2010).Crossref, Medline, Google Scholar
61 Johnson JK, Head E, Kim R, Starr A, Cotman CW: Clinical and pathological evidence for a frontal variant of Alzheimer disease. Arch. Neurol.56,1233–1239 (1999).Crossref, Medline, CAS, Google Scholar
62 Kosunen O, Soininen H, Paljarvi L, Heinonen O, Talasniemi S, Riekkinen PJ Sr: Diagnostic accuracy of Alzheimer’s disease: a neuropathological study. Acta Neuropathol.91,185–193 (1996).Crossref, Medline, CAS, Google Scholar
63 Larner AJ: “Frontal variant Alzheimer’s disease”: a reappraisal. Clin. Neurol. Neurosurg.108,705–708 (2006).Crossref, Medline, Google Scholar
64 Perry RJ, Hodges JR: Differentiating frontal and temporal variant frontotemporal dementia from Alzheimer’s disease. Neurology54,2277–2284 (2000).Crossref, Medline, CAS, Google Scholar
65 Talbot K, Young RA, Jolly-Tornetta C, Lee VM, Trojanowski JQ, Wolf BA: A frontal variant of Alzheimer’s disease exhibits decreased calcium-independent phospholipase A2 activity in the prefrontal cortex. Neurochem. Int.37,17–31 (2000).Crossref, Medline, CAS, Google Scholar
66 Taylor KI, Probst A, Miserez AR, Monsch AU, Tolnay M: Clinical course of neuropathologically confirmed frontal-variant Alzheimer’s disease. Nat. Clin. Pract. Neurol.4,226–232 (2008).Crossref, Medline, Google Scholar
67 Gislason TB, Sjogren M, Larsson L, Skoog I: The prevalence of frontal variant frontotemporal dementia and the frontal lobe syndrome in a population based sample of 85 year olds. J. Neurol. Neurosurg. Psychiatry74,867–871 (2003).Crossref, Medline, CAS, Google Scholar
68 Downes JJ, Priestley NM, Doran M, Ferran J, Ghadiali E, Cooper P: Intellectual, mnemonic, and frontal functions in dementia with Lewy bodies: a comparison with early and advanced Parkinson’s disease. Behav. Neurol.11,173–183 (1998).Crossref, Medline, Google Scholar
69 Engelborghs S, Maertens K, Marien P et al.: Behavioural and neuropsychological correlates of frontal lobe features in dementia. Psychol. Med.36,1173–1182 (2006).Crossref, Medline, Google Scholar
70 Stewart JT: Psychiatric and behavioral manifestations of vascular dementia. Am. J. Geriatr. Cardiol.16,165–170 (2007).Crossref, Medline, Google Scholar
71 Odawara T, Shiozaki K, Iseki E, Hino H, Kosaka K: Alterations of muscarinic acetylcholine receptors in atypical Pick’s disease without Pick bodies. J. Neurol. Neurosurg. Psychiatry74,965–967 (2003).Crossref, Medline, CAS, Google Scholar
72 Procter AW, Qurne M, Francis PT: Neurochemical features of frontotemporal dementia. Dement. Geriatr. Cogn. Disord.10(Suppl. 1),80–84 (1999).Crossref, Medline, CAS, Google Scholar
73 Sparks DL, Markesbery WR: Altered serotonergic and cholinergic synaptic markers in Pick’s disease. Arch. Neurol.48,796–799 (1991).Crossref, Medline, CAS, Google Scholar
74 Uhl GR, Hilt DC, Hedreen JC, Whitehouse PJ, Price DL: Pick’s disease (lobar sclerosis): depletion of neurons in the nucleus basalis of Meynert. Neurology33,1470–1473 (1983).Crossref, Medline, CAS, Google Scholar
75 Weinberger DR, Gibson R, Coppola R et al.: The distribution of cerebral muscarinic acetylcholine receptors in vivo in patients with dementia. A controlled study with ¹²³IQNB and single photon emission computed tomography. Arch. Neurol.48,169–176 (1991).Crossref, Medline, CAS, Google Scholar
76 Wood PL, Etienne P, Lal S et al.: A post-mortem comparison of the cortical cholinergic system in Alzheimer’s disease and Pick’s disease. J. Neurol. Sci.62,211–217 (1983).Crossref, Medline, CAS, Google Scholar
77 Frisoni GB, Pizzolato G, Bianchetti A et al.: Single photon emission computed tomography with [⁹⁹Tc]-HM-PAO and [¹²³I]-IBZM in Alzheimer’s disease and dementia of frontal type: preliminary results. Acta Neurol. Scand.89,199–203 (1994).Crossref, Medline, CAS, Google Scholar
78 Kanazawa I, Kwak S, Sasaki H et al.: Studies on neurotransmitter markers of the basal ganglia in Pick’s disease, with special reference to dopamine reduction. J. Neurol. Sci.83,63–74 (1988).Crossref, Medline, CAS, Google Scholar
79 Rinne JO, Laine M, Kaasinen V, Norvasuo-Heila MK, Nagren K, Helenius H: Striatal dopamine transporter and extrapyramidal symptoms in frontotemporal dementia. Neurology58,1489–1493 (2002).Crossref, Medline, CAS, Google Scholar
80 Sjogren M, Minthon L, Passant U, Blennow K, Wallin A: Decreased monoamine metabolites in frontotemporal dementia and Alzheimer’s disease. Neurobiol. Aging19,379–384 (1998).Crossref, Medline, CAS, Google Scholar
81 Sparks DL, Woeltz VM, Markesbery WR: Alterations in brain monoamine oxidase activity in aging, Alzheimer’s disease, and Pick’s disease. Arch. Neurol.48,718–721 (1991).Crossref, Medline, CAS, Google Scholar
82 Ferrer I: Neurons and their dendrites in frontotemporal dementia. Dement. Geriatr. Cogn. Disord.10(Suppl. 1),55–60 (1999).Crossref, Medline, Google Scholar
83 Bowen DM, Procter AW, Mann DM et al.: Imbalance of a serotonergic system in frontotemporal dementia: implication for pharmacotherapy. Psychopharmacology (Berl.)196,603–610 (2008).Crossref, Medline, CAS, Google Scholar
84 Franceschi M, Anchisi D, Pelati O et al.: Glucose metabolism and serotonin receptors in the frontotemporal lobe degeneration. Ann. Neurol.57,216–225 (2005).Crossref, Medline, CAS, Google Scholar
85 Yang Y, Schmitt HP: Frontotemporal dementia: evidence for impairment of ascending serotoninergic but not noradrenergic innervation. Immunocytochemical and quantitative study using a graph method. Acta Neuropathol.101,256–270 (2001).Crossref, Medline, CAS, Google Scholar
86 Gordon E, Rohrer JD, Kim LG et al.: Measuring disease progression in frontotemporal lobar degeneration: a clinical and MRI study. Neurology74,666–673 (2010).Crossref, Medline, CAS, Google Scholar
87 Kipps CM, Nestor PJ, Dawson CE, Mitchell J, Hodges JR: Measuring progression in frontotemporal dementia: implications for therapeutic interventions. Neurology70,2046–2052 (2008).Crossref, Medline, CAS, Google Scholar
88 Mioshi E, Hsieh S, Savage S, Hornberger M, Hodges JR: Clinical staging and disease progression in frontotemporal dementia. Neurology74,1591–1597 (2010).Crossref, Medline, CAS, Google Scholar
89 Boxer AL, Lipton AM, Womack K et al.: An open-label study of memantine treatment in 3 subtypes of frontotemporal lobar degeneration. Alzheimer Dis. Assoc. Disord.23,211–217 (2009).Crossref, Medline, CAS, Google Scholar
90 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. Psychiatry23,754–759 (2008).Crossref, Medline, Google Scholar
91 FitzGerald DB, Crucian GP, Mielke JB et al.: Effects of donepezil on verbal memory after semantic processing in healthy older adults. Cogn. Behav. Neurol.21,57–64 (2008).Crossref, Medline, Google Scholar
92 Kertesz A, Morlog D, Light M et al.: Galantamine in frontotemporal dementia and primary progressive aphasia. Dement. Geriatr. Cogn. Disord.25,178–185 (2008).Crossref, Medline, CAS, Google Scholar
93 Mendez MF, Shapira JS, McMurtray A, Licht E: Preliminary findings: behavioral worsening on donepezil in patients with frontotemporal dementia. Am. J. Geriatr. Psychiatry15,84–87 (2007).Crossref, Medline, Google Scholar
94 Moretti R, Torre P, Antonello RM, Cattaruzza T, Cazzato G, Bava A: Rivastigmine in frontotemporal dementia: an open-label study. Drugs Aging21,931–937 (2004).Crossref, Medline, CAS, Google Scholar
95 Adler G, Teufel M, Drach LM: Pharmacological treatment of frontotemporal dementia: treatment response to the MAO-A inhibitor moclobemide. Int. J. Geriatr. Psychiatry18,653–655 (2003).Crossref, Medline, Google Scholar
96 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.)172,400–408 (2004).Crossref, Medline, CAS, Google Scholar
97 Lebert F, Stekke W, Hasenbroekx C, Pasquier F: Frontotemporal dementia: a randomised, controlled trial with trazodone. Dement. Geriatr. Cogn. Disord.17,355–359 (2004).Crossref, Medline, CAS, Google Scholar
98 Moretti R, Torre P, Antonello RM, Cazzato G, Bava A: Effects of selegiline on fronto-temporal dementia: a neuropsychological evaluation. Int. J. Geriatr. Psychiatry17,391–392 (2002).Crossref, Medline, Google Scholar
99 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.49,13–19 (2003).Crossref, Medline, CAS, Google Scholar
100 Swartz JR, Miller BL, Lesser IM, Darby AL: Frontotemporal dementia: treatment response to serotonin selective reuptake inhibitors. J. Clin. Psychiatry58,212–216 (1997).Crossref, Medline, CAS, Google Scholar
101 Curtis RC, Resch DS: Case of pick’s central lobar atrophy with apparent stabilization of cognitive decline after treatment with risperidone. J. Clin. Psychopharmacol.20,384–385 (2000).Crossref, Medline, CAS, Google Scholar
102 Czarnecki K, Kumar N, Josephs KA: Parkinsonism and tardive antecollis in frontotemporal dementia – increased sensitivity to newer antipsychotics? Eur. J. Neurol.15,199–201 (2008).Crossref, Medline, CAS, Google Scholar
103 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. Psychiatry8,123–126 (2007).Crossref, Medline, Google Scholar
104 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.18,205–214 (2003).Crossref, Medline, Google Scholar
105 Goforth HW, Konopka L, Primeau M et al.: Quantitative electroencephalography in frontotemporal dementia with methylphenidate response: a case study. Clin. EEG Neurosci.35,108–111 (2004).Crossref, Medline, Google Scholar
106 Rahman S, Robbins TW, Hodges JR et al.: Methylphenidate (‘Ritalin’) can ameliorate abnormal risk-taking behavior in the frontal variant of frontotemporal dementia. Neuropsychopharmacology31,651–658 (2006).Crossref, Medline, CAS, Google Scholar
107 Decker DA, Heilman KM: Steroid treatment of primary progressive aphasia. Arch. Neurol.65,1533–1535 (2008).Crossref, Medline, Google Scholar
108 Tobinick E: Perispinal etanercept produces rapid improvement in primary progressive aphasia: identification of a novel, rapidly reversible TNF-mediated pathophysiologic mechanism. Medscape J. Med.10,135 (2008).Medline, Google Scholar
109 Cruz M, Marinho V, Fontenelle LF, Engelhardt E, Laks J: Topiramate may modulate alcohol abuse but not other compulsive behaviors in frontotemporal dementia: case report. Cogn. Behav. Neurol.21,104–106 (2008).Crossref, Medline, Google Scholar
110 Huey ED, Putnam KT, Grafman J: A systematic review of neurotransmitter deficits and treatments in frontotemporal dementia. Neurology66,17–22 (2006).Crossref, Medline, CAS, Google Scholar
111 Hansen LA, Deteresa R, Tobias H, Alford M, Terry RD: Neocortical morphometry and cholinergic neurochemistry in Pick’s disease. Am. J. Pathol.131,507–518 (1988).Medline, CAS, Google Scholar
112 Reed DA, Johnson NA, Thompson C, Weintraub S, Mesulam MM: A clinical trial of bromocriptine for treatment of primary progressive aphasia. Ann. Neurol.56,750 (2004).Crossref, Medline, Google Scholar
113 Swanberg MM: Memantine for behavioral disturbances in frontotemporal dementia: a case series. Alzheimer Dis. Assoc. Disord.21,164–166 (2007).Crossref, Medline, Google Scholar
114 Anneser JM, Jox RJ, Borasio GD: Inappropriate sexual behaviour in a case of ALS and FTD: successful treatment with sertraline. Amyotroph. Lateral Scler.8,189–190 (2007).Crossref, Medline, CAS, Google Scholar
115 Mendez MF, Shapira JS: The spectrum of recurrent thoughts and behaviors in frontotemporal dementia. CNS Spectr.13,202–208 (2008).Crossref, Medline, Google Scholar
116 Prodan CI, Monnot M, Ross ED: Behavioural abnormalities associated with rapid deterioration of language functions in semantic dementia respond to sertraline. J. Neurol. Neurosurg. Psychiatry80,1416–1417 (2009).Crossref, Medline, CAS, Google Scholar
117 Dorsey ER, Rabbani A, Gallagher SA, Conti RM, Alexander GC: Impact of FDA black box advisory on antipsychotic medication use. Arch. Intern. Med.170,96–103 (2010).Crossref, Medline, Google Scholar
118 Jeste DV, Blazer D, Casey D et al.: ACNP White Paper: update on use of antipsychotic drugs in elderly persons with dementia. Neuropsychopharmacology33,957–970 (2008).▪▪ Thought leaders in the field of geriatric psychiatry wrestle with available data in light of the 2005 US FDA ‘black-box’ warning on the use of antipsychotic drugs in dementia. The authors keenly point out that behavioral and psychiatric symptoms are major problems that lack any approved therapies at present, suggest that antipsychotic therapy may still play an important role in the management of dementia, but also urge caution and the importance of shared decision-making when considering this therapeutic strategy.Crossref, Medline, CAS, Google Scholar
119 Kirshner HS: Controversies in behavioral neurology: the use of atypical antipsychotic drugs to treat neurobehavioral symptoms in dementia. Curr. Neurol. Neurosci. Rep.8,471–474 (2008).Crossref, Medline, CAS, Google Scholar
120 Recupero PR, Rainey SE: Managing risk when considering the use of atypical antipsychotics for elderly patients with dementia-related psychosis. J. Psychiatr. Pract.13,143–152 (2007).Crossref, Medline, Google Scholar
121 Salzman C, Jeste DV, Meyer RE et al.: Elderly patients with dementia-related symptoms of severe agitation and aggression: consensus statement on treatment options, clinical trials methodology, and policy. J. Clin. Psychiatry69,889–898 (2008).Crossref, Medline, Google Scholar
122 Wang PS, Brookhart MA, Setoguchi S, Patrick AR, Schneeweiss S: Psychotropic medication use for behavioral symptoms of dementia. Curr. Neurol. Neurosci. Rep.6,490–495 (2006).Crossref, Medline, Google Scholar
123 Chow TW, Binns MA, Cummings JL et al.: Apathy symptom profile and behavioral associations in frontotemporal dementia vs dementia of Alzheimer type. Arch. Neurol.66,888–893 (2009).Crossref, Medline, Google Scholar
124 Rosen HJ, Cummings J: A real reason for patients with pseudobulbar affect to smile. Ann. Neurol.61,92–96 (2007).Crossref, Medline, CAS, Google Scholar
125 Schiffer R, Pope LE: Review of pseudobulbar affect including a novel and potential therapy. J. Neuropsychiatry Clin. Neurosci.17,447–454 (2005).Crossref, Medline, CAS, Google Scholar
126 Brooks BR, Thisted RA, Appel SH et al.: Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial. Neurology63,1364–1370 (2004).Crossref, Medline, CAS, Google Scholar
127 Miller A: Pseudobulbar affect in multiple sclerosis: toward the development of innovative therapeutic strategies. J. Neurol. Sci.245,153–159 (2006).Crossref, Medline, Google Scholar
128 Panitch HS, Thisted RA, Smith RA et al.: Randomized, controlled trial of dextromethorphan/quinidine for pseudobulbar affect in multiple sclerosis. Ann. Neurol.59,780–787 (2006).Crossref, Medline, CAS, Google Scholar
129 Lillo P, Hodges JR: Frontotemporal dementia and motor neurone disease: overlapping clinic-pathological disorders. J. Clin. Neurosci.16,1131–1135 (2009).Crossref, Medline, Google Scholar
130 Mathuranath PS, Xuereb JH, Bak T, Hodges JR: Corticobasal ganglionic degeneration and/or frontotemporal dementia? A report of two overlap cases and review of literature. J. Neurol. Neurosurg. Psychiatry68,304–312 (2000).Crossref, Medline, CAS, Google Scholar
131 Mitsuyama Y, Inoue T: Clinical entity of frontotemporal dementia with motor neuron disease. Neuropathology29,649–654 (2009).Crossref, Medline, Google Scholar
132 Snowden J, Neary D, Mann D: Frontotemporal lobar degeneration: clinical and pathological relationships. Acta Neuropathol.114,31–38 (2007).Crossref, Medline, Google Scholar
133 Bedlack RS: Amyotrophic lateral sclerosis: current practice and future treatments. Curr. Opin. Neurol.23,524–529 (2010).Crossref, Medline, CAS, Google Scholar
134 Bellingham MC: A review of the neural mechanisms of action and clinical efficiency of riluzole in treating amyotrophic lateral sclerosis: what have we learned in the last decade? CNS Neurosci. Ther.17(1),4–31 (2011).Crossref, Medline, CAS, Google Scholar
135 Cheah BC, Vucic S, Krishnan AV, Kiernan MC: Riluzole, neuroprotection and amyotrophic lateral sclerosis. Curr. Med. Chem.17,1942–1199 (2010).Crossref, Medline, CAS, Google Scholar
136 Miller RG, Jackson CE, Kasarskis EJ et al.: Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology73,1218–1226 (2009).Crossref, Medline, CAS, Google Scholar
137 Blair IP, Williams KL, Warraich ST et al.: FUS mutations in amyotrophic lateral sclerosis: clinical, pathological, neurophysiological and genetic analysis. J. Neurol. Neurosurg. Psychiatry81,639–645 (2010).Crossref, Medline, Google Scholar
138 Engelborghs S, Vloeberghs E, Le Bastard N et al.: The dopaminergic neurotransmitter system is associated with aggression and agitation in frontotemporal dementia. Neurochem. Int.52,1052–1060 (2008).Crossref, Medline, CAS, Google Scholar
139 Sedaghat F, Gotzamani-Psarrakou A, Dedousi E et al.: Evaluation of dopaminergic function in frontotemporal dementia using I-FP-CIT single photon emission computed tomography. Neurodegener. Dis.4,382–385 (2007).Crossref, Medline, CAS, Google Scholar

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Published online 8 April 2011

Published in print April 2011

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Acknowledgements

The authors gratefully acknowledge the many subjects, caregivers, friends and families of persons with Alzheimer’s disease that have engaged in clinical research activities that allow discoveries to be made. We also thank P Thomason for critical review and editing of the manuscript.

Financial & competing interests disclosure

GA Jicha is supported by funding from the NIH/NIA 1 P30 AG028383 & 2R01AG019241–06A2, NIH LRP 1 L30 AG032934, and the Sanders-Brown Foundation. GA Jicha has also received research support for clinical trial activities from NIH/NIA ADCS U01AG010483, Pfizer, Elan, Janssen, Medivation and Baxter. PT Nelson is supported by funding from the NIH/NIA 1 P30 AG028383, R21AG036875, R01NS061933. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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