Diagnosing, monitoring and managing behavioural variant frontotemporal dementia

Piguet, Olivier; Kumfor, Fiona; Hodges, John

doi:10.5694/mja16.01458

ARTICLE
AUTHORS
REFERENCES

Topics

Nervous system diseases

Mental disorders

Summary

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, motivation and decision making.
The underlying pathology is heterogeneous and classified according to the presence of intraneuronal inclusions of tau, TDP-43 or, occasionally, fused in sarcoma proteins. Biomarkers to detect these histopathological changes in life are increasingly important with the development of disease-modifying drugs.
A number of gene abnormalities have been identified, the most common being an expansion in the C9orf72 gene, which together account for most familial cases.
The 2011 international consensus criteria propose three levels of diagnostic certainty: possible, probable and definite. Detailed history taking from family members to elicit behavioural features underpins the diagnostic process, with support from neuropsychological testing designed to detect impairment in decision making, emotion processing and social cognition. Brain imaging is important for increasing the level of diagnosis certainty over time. Carer education and support remain of paramount importance.

1 Brain and Mind Centre, University of Sydney, Sydney, NSW
2 School of Psychology, University of Sydney, Sydney, NSW
3 Sydney Medical School, University of Sydney, Sydney, NSW

Correspondence: olivier.piguet@sydney.edu.au

Acknowledgements:

Olivier Piguet is supported by a National Health and Medical Research Council (NHMRC) Senior Research Fellowship (APP1103258). Fiona Kumfor is supported by an NHMRC–Australian Research Council Dementia Research Development Fellowship (APP1097026).

Competing interests:

No relevant disclosures.

1. Ratnavalli E, Brayne C, Dawson K, et al. The prevalence of frontotemporal dementia. Neurology 2002; 58: 1615-1621.
2. Coyle-Gilchrist IT, Dick KM, Patterson K, et al. Prevalence, characteristics, and survival of frontotemporal lobar degeneration syndromes. Neurology 2016; 86: 1736-1743.
3. Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 2011; 134: 2456-2477.
4. Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology 2011; 76: 1006-1014.
5. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Washington, DC: APA, 2013.
6. Lillo P, Garcin B, Hornberger M, et al. Neurobehavioral features in frontotemporal dementia with amyotrophic lateral sclerosis. Arch Neurol 2010; 67: 826-830.
7. Lomen-Hoerth C, Anderson T, Miller B. The overlap of amyotrophic lateral sclerosis and frontotemporal dementia. Neurology 2002; 59: 1077-1079.
8. Lillo P, Mioshi E, Zoing MC, et al. How common are behavioural changes in amyotrophic lateral sclerosis? Amyotroph Lateral Scler 2011; 12: 45-51.
9. Kertesz A, McMonagle P, Blair M, et al. The evolution and pathology of frontotemporal dementia. Brain 2005; 128: 1996-2005.
10. Cummings JL, Mega M, Gray K, et al. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994; 44: 2308-2314.
11. Wedderburn C, Wear H, Brown J, et al. The utility of the Cambridge Behavioural Inventory in neurodegenerative disease. J Neurol Neurosurg Psychiatry 2008; 79: 500-503.
12. Kertesz A, Davidson W, Fox H. Frontal behavioral inventory: diagnostic criteria for frontal lobe dementia. Can J Neurol Sci 1997; 24: 29-36.
13. Ahmed RM, Irish M, Kam J, et al. Quantifying the eating abnormalities in frontotemporal dementia. JAMA Neurol 2014; 71: 1540-1546.
14. Liu W, Miller BL, Kramer JH, et al. Behavioral disorders in the frontal and temporal variants of frontotemporal dementia. Neurology 2004; 62: 742-748.
15. Diehl-Schmid J, Pohl C, Perneczky R, et al. Behavioral disturbances in the course of frontotemporal dementia. Dement Geriatr Cogn Disord 2006; 22: 352-357.
16. Srikanth S, Nagaraja AV, Ratnavalli E. Neuropsychiatric symptoms in dementia-frequency, relationship to dementia severity and comparison in Alzheimer’s disease, vascular dementia and frontotemporal dementia. J Neurol Sci 2005; 236: 43-48.
17. Pasquier F, Lebert F, Lavenu I, et al. The clinical picture of frontotemporal dementia: diagnosis and follow-up. Dement Geriatr Cogn Disord 1999; 10 Suppl 1: 10-14.
18. Snowden JS, Rollinson S, Thompson JC, et al. Distinct clinical and pathological characteristics of frontotemporal dementia associated with C9ORF72 mutations. Brain 2012; 135: 693-708.
19. Devenney E, Hornberger M, Irish M, et al. Frontotemporal dementia associated with the C9ORF72 mutation: a unique clinical profile. JAMA Neurol 2014; 71: 331-339.
20. Hsieh S, Schubert S, Hoon C, et al. Validation of the Addenbrooke’s Cognitive Examination III in frontotemporal dementia and Alzheimer’s disease. Dement Geriatr Cogn Disord 2013; 36: 242-250.
21. Kipps CM, Nestor PJ, Dawson CE, et al. Measuring progression in frontotemporal dementia: Implications for therapeutic interventions. Neurology 2008; 70: 2046-2052.
22. Hornberger M, Savage S, Hsieh S, et al. Orbitofrontal dysfunction discriminates behavioral variant frontotemporal dementia from Alzheimer’s disease. Dement Geriatr Cogn Disord 2010; 30: 547-552.
23. Leslie F, Foxe D, Daveson N, et al. FRONTIER Executive Screen: a brief executive battery to differentiate frontotemporal dementia and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2016; 87: 831-835.
24. Torralva T, Roca M, Gleichgerrcht E, et al. INECO Frontal Screening (IFS): a brief, sensitive, and specific tool to assess executive functions in dementia. J Int Neuropsychol Soc 2009; 15: 777-786.
25. Chiong W, Wood KA, Beagle AJ, et al. Neuroeconomic dissociation of semantic dementia and behavioural variant frontotemporal dementia. Brain 2016; 139: 578-587.
26. O’Callaghan C, Bertoux M, Irish M, et al. Fair play: social norm compliance failures in behavioural variant frontotemporal dementia. Brain 2016; 139: 204-216.
27. Hornberger M, Piguet O. Episodic memory in frontotemporal dementia: a critical review. Brain 2012; 135: 678-692.
28. Irish M, Hornberger M, Lah S, et al. Profiles of recent autobiographical memory retrieval in semantic dementia, behavioural-variant frontotemporal dementia, and Alzheimer’s disease. Neuropsychologia 2011; 49: 2694-2702.
29. Tu S, Wong S, Hodges JR, et al. Lost in spatial translation - a novel tool to objectively assess spatial disorientation in Alzheimer’s disease and frontotemporal dementia. Cortex 2015; 67: 83-94.
30. Kennedy DP, Adolphs R. The social brain in psychiatric and neurological disorders. Trends Cogn Sci 2012; 16: 559-572.
31. Kumfor F, Piguet O. Disturbance of emotion processing in frontotemporal dementia: a synthesis of cognitive and neuroimaging findings. Neuropsychol Rev 2012; 22: 280-297.
32. Sturm VE, Sollberger M, Seeley WW, et al. Role of right pregenual anterior cingulate cortex in self-conscious emotional reactivity. Soc Cogn Affect Neurosci 2013; 8: 468-474.
33. Hutchings R, Palermo R, Piguet O, et al. Disrupted face processing in frontotemporal dementia: a review of the clinical and neuroanatomical evidence. Neuropsychol Rev 2017; 27: 18-30.
34. Miller LA, Hsieh S, Lah S, et al. One size does not fit all: face emotion processing impairments in semantic dementia, behavioural-variant frontotemporal dementia and Alzheimer’s disease are mediated by distinct cognitive deficits. Behav Neurol 2012; 25: 53-60.
35. Bora E, Walterfang M, Velakoulis D. Theory of mind in behavioural-variant frontotemporal dementia and Alzheimer’s disease: a meta-analysis. J Neurol Neurosurg Psychiatry 2015; 86: 714-719.
36. Fernandez-Duque D, Hodges SD, Baird JA, et al. Empathy in frontotemporal dementia and Alzheimer’s disease. J Clin Exp Neuropsychol 2010; 32: 289-298.
37. Baez S, Manes F, Huepe D, et al. Primary empathy deficits in frontotemporal dementia. Frontiers Aging Neurosci 2014; 6: 262.
38. Oliver LD, Mitchell DG, Dziobek I, et al. Parsing cognitive and emotional empathy deficits for negative and positive stimuli in frontotemporal dementia. Neuropsychologia 2015; 67: 14-26.
39. Ibanez A, Manes F. Contextual social cognition and the behavioral variant of frontotemporal dementia. Neurology 2012; 78: 1354-1362.
40. McDonald S, Flanagan S, Rollins J, et al. TASIT: a new clinical tool for assessing social perception after traumatic brain injury. J Head Trauma Rehabil 2003; 18: 219-238.
41. Bertoux M, Volle E, Funkiewiez A, et al. Social Cognition and Emotional Assessment (SEA) is a marker of medial and orbital frontal functions: a voxel-based morphometry study in behavioral variant of frontotemporal degeneration. J Int Neuropsychol Soc 2012; 18: 972-985.
42. Kumfor F, Irish M, Leyton CE, et al. Tracking the progression of social cognition in neurodegenerative disorders. J Neurol Neurosurg Psychiatry 2014; 85: 1076-1083.
43. Boccardi M, Sabattoli F, Laakso MP, et al. Frontotemporal dementia as a neural system disease. Neurobiol Aging 2005; 26: 37-44.
44. Agosta F, Scola E, Canu E, et al. White matter damage in frontotemporal lobar degeneration spectrum. Cereb Cortex 2012; 22: 2705-2714.
45. Seeley WW. Selective functional, regional, and neuronal vulnerability in frontotemporal dementia. Curr Opin Neurol 2008; 21: 701-707.
46. Seeley WW, Crawford RK, Zhou J, et al. Neurodegenerative diseases target large-scale human brain networks. Neuron 2009; 62: 42-52.
47. Landin-Romero R, Kumfor F, Leyton CE, et al. Disease-specific patterns of cortical and subcortical degeneration in a longitudinal study of Alzheimer’s disease and behavioural-variant frontotemporal dementia. Neuroimage 2017; 151: 72-80.
48. Pereira JM, Williams GB, Acosta-Cabronero J, et al. Atrophy patterns in histologic vs clinical groupings of frontotemporal lobar degeneration. Neurology 2009; 72: 1653-1660.
49. Gordon E, Rohrer JD, Fox NC. Advances in neuroimaging in frontotemporal dementia. J Neurochem 2016; 138: 193-210.
50. Filippi M, Agosta F, Scola E, et al. Functional network connectivity in the behavioral variant of frontotemporal dementia. Cortex 2013; 49: 2389-2401.
51. Lam BY, Halliday GM, Irish M, et al. Longitudinal white matter changes in frontotemporal dementia subtypes. Hum Brain Map 2014; 35: 3547-3557.
52. Whitwell JL, Boeve BF, Weigand SD, et al. Brain atrophy over time in genetic and sporadic frontotemporal dementia: a study of 198 serial magnetic resonance images. Eur J Neurol 2015; 22: 745-752.
53. Whitwell JL, Weigand SD, Boeve BF, et al. Neuroimaging signatures of frontotemporal dementia genetics: C9ORF72, tau, progranulin and sporadics. Brain 2012; 135: 794-806.
54. Devenney E, Bartley L, Hoon C, et al. Progression in behavioral variant frontotemporal dementia: a longitudinal study. JAMA Neurol 2015; 72: 1501-1509.
55. Rohrer JD, Nicholas JM, Cash DM, et al. Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the Genetic Frontotemporal dementia Initiative (GENFI) study: a cross-sectional analysis. Lancet Neurol 2015; 14: 253-262.
56. Varma AR, Adams W, Lloyd JJ, et al. Diagnostic patterns of regional atrophy on MRI and regional cerebral blood flow change on SPECT in young onset patients with Alzheimer’s disease, frontotemporal dementia and vascular dementia. Acta Neurol Scand 2002; 105: 261-269.
57. Kanda T, Ishii K, Uemura T, et al. Comparison of grey matter and metabolic reductions in frontotemporal dementia using FDG-PET and voxel-based morphometric MR studies. Eur J Nucl Med Mol Imaging 2008; 35: 2227-2234.
58. Morris E, Chalkidou A, Hammers A, et al. Diagnostic accuracy of 18 F amyloid PET tracers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging 2016; 43: 374-385.
59. Villemagne VL, Fodero-Tavoletti MT, Masters CL, et al. Tau imaging: early progress and future directions. Lancet Neurol 2015; 14: 114-124.
60. 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 (Berl) 2007; 114: 5-22.
61. Mackenzie IR, Neumann M. Molecular neuropathology of frontotemporal dementia: insights into disease mechanisms from postmortem studies. J Neurochem 2016; 138 Suppl 1: 54-70.
62. Shi J, Shaw CL, Du Plessis D, et al. Histopathological changes underlying frontotemporal lobar degeneration with clinicopathological correlation. Acta Neuropathol 2005; 110: 501-512.
63. Seelaar H, Klijnsma KY, de Koning I, et al. Frequency of ubiquitin and FUS-positive, TDP-43-negative frontotemporal lobar degeneration. J Neurol 2010; 257: 747-753.
64. Wood EM, Falcone D, Suh E, et al. Development and validation of pedigree classification criteria for frontotemporal lobar degeneration. JAMA Neurol 2013; 70: 1411-1417.
65. Po K, Leslie FV, Gracia N, et al. Heritability in frontotemporal dementia: more missing pieces? J Neurol 2014; 261: 2170-2177.
66. Rohrer JD, Guerreiro R, Vandrovcova J, et al. The heritability and genetics of frontotemporal lobar degeneration. Neurology 2009; 73: 1451-1456.
67. 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: 245-256.
68. Renton AE, Majounie E, Waite A, et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 2011; 72: 257-268.
69. Hodges J. Familial frontotemporal dementia and amyotrophic lateral sclerosis associated with the C9ORF72 hexanucleotide repeat. Brain 2012; 135: 652-655.
70. Pottier C, Ravenscroft TA, Sanchez-Contreras M, et al. Genetics of FTLD: overview and what else we can expect from genetic studies. J Neurochem 2016; 138 Suppl 1: 32-53.
71. Boxer AL, Boeve BF. Frontotemporal dementia treatment: current symptomatic therapies and implications of recent genetic, biochemical, and neuroimaging studies. Alzheimer Dis Assoc Disord 2007; 21: S79-S87.
72. Moretti R, Torre P, Antonello RM, et al. Frontotemporal dementia: paroxetine as a possible treatment of behavior symptoms. A randomized, controlled, open 14-month study. Eur Neurol 2003; 49: 13-19.
73. Deakin JB, Rahman S, Nestor PJ, et al. Paroxetine does not improve symptoms and impairs cognition in frontotemporal dementia: a double-blind randomized controlled trial. Psychopharmacology (Berl) 2004; 172: 400-408.
74. 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: 205-214.
75. Moretti R, Torre P, Antonello RM, et al. Rivastigmine in frontotemporal dementia: an open-label study. Drugs Aging 2004; 21: 931-937.
76. Mendez MF, Shapira JS, McMurtray A, et al. Preliminary findings: behavioral worsening on donepezil in patients with frontotemporal dementia. Am J Geriatr Psychiatry 2007; 15: 84-87.
77. Boxer AL, Knopman DS, Kaufer DI, et al. Memantine in patients with frontotemporal lobar degeneration: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol 2013; 12: 149-156.
78. Gauthier S, Feldman HH, Schneider LS, et al. Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer’s disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial. Lancet 2016; 388: 2873-2884.
79. Mendez MF, Joshi A, Jimenez E. Virtual reality for the assessment of frontotemporal dementia, a feasibility study. Disabil Rehabil Assist Technol 2015; 10: 160-164.
80. O’Connor CM, Clemson L, Brodaty H, et al. Enhancing caregivers’ understanding of dementia and tailoring activities in frontotemporal dementia: two case studies. Disabil Rehabil 2016; 38: 704-714.
81. Mioshi E, Bristow M, Cook R, et al. Factors underlying caregiver stress in frontotemporal dementia and Alzheimer’s disease. Dement Geriatr Cogn Disord 2009; 27: 76-81.
82. Boutoleau-Bretonniere C, Vercelletto M, Volteau C, et al. Zarit burden inventory and activities of daily living in the behavioral variant of frontotemporal dementia. Dement Geriatr Cogn Disord 2008; 25: 272-277.
83. Miller LA, Mioshi E, Savage S, et al. Identifying cognitive and demographic variables that contribute to carer burden in dementia. Dement Ger Cogn Disord 2013; 36: 43-49.
84. Mioshi E, McKinnon C, Savage S, et al. Improving burden and coping skills in frontotemporal dementia caregivers : a pilot study. Alzheimer Dis Assoc Disord 2013; 27: 84-86.
85. Garcin B, Lilo P, Hornberger M, et al. Determinants of survival in behavioral variant frontotemporal dementia. Neurology 2009; 73: 1656-1661.
86. Chow TW, Fridhandler JD, Binns MA, et al. Trajectories of behavioural disturbance in dementia. J Alzheimers Dis 2012; 31: 143-149.

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Diagnosing, monitoring and managing behavioural variant frontotemporal dementia

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