Skip to main content
AAN.com
Articles
May 17, 2010

Clinical staging and disease progression in frontotemporal dementia

May 18, 2010 issue
74 (20) 1591-1597

Abstract

Objective: We aimed to develop a novel tool capable of staging disease severity in frontotemporal dementia (FTD) based upon functional dependence and behavioral changes, and to assess change over time in the 3 main FTD variants (behavioral variant FTD [bvFTD]; progressive nonfluent aphasia [PNFA]; and semantic dementia [SemD]).
Methods: The Frontotemporal Dementia Rating Scale (FRS) was developed in a validation cohort of 77 consecutive clinic attendees (bvFTD = 29; PNFA = 20; SemD = 28) and applied to an independent sample of 75 patients (bvFTD = 28; PNFA = 21; SemD = 26) to establish intergroup differences. Assessments from 42 patients followed up after 12 months were used to determine annual progression. Finally, a combined sample (n = 152) was used to determine length of symptoms in each severity category.
Results: Six severity stages were identified and operationalized based upon a 30-item questionnaire (very mild to profound). The cross-sectional study revealed much greater levels of impairment in bvFTD than in the language variants, with limited correlation with general cognitive measures. Patients with SemD showed the closest association between length of symptoms and stage, taking, on average, 10 years to reach the severe stage. Patients with bvFTD appear to move most quickly between stages and patients with PNFA were intermediate. The FRS was capable of detecting functional deterioration in all 3 variants over 12 months.
Conclusions: Disease progression differs across frontotemporal dementia (FTD) variants. Patients with behavioral variant FTD progress rapidly whereas those with semantic dementia progress more slowly. The Frontotemporal Dementia Rating Scale can aid in staging and determining disease progression. Length of symptoms and global cognitive assessments alone do not reflect disease severity and progression in FTD.

Get full access to this article

View all available purchase options and get full access to this article.

Supplementary Material

File (appendix_e-1.doc)
File (figure_e-1.ppt)
File (mioshi.pdf)
File (table_e-1.doc)
File (table_e-2.doc)

REFERENCES

1.
Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998;51:1546–1554.
2.
Hodges JR. Frontotemporal dementia (Pick's disease): clinical features and assessment. Neurology 2001;56(11 suppl 4):S6–S10.
3.
Knibb JA, Xuereb JH, Patterson K, Hodges JR. Clinical and pathological characterization of progressive aphasia. Ann Neurol 2006;59:156–165.
4.
Bozeat S, Gregory CA, Ralph MA, Hodges JR. Which neuropsychiatric and behavioural features distinguish frontal and temporal variants of frontotemporal dementia from Alzheimer's disease? J Neurol Neurosurg Psychiatry 2000;69:178–186.
5.
Kertesz A, McMonagle P, Blair M, Davidson W, Munoz DG. The evolution and pathology of frontotemporal dementia. Brain 2005;128:1996–2005.
6.
Nyatsanza S, Shetty T, Gregory C, Lough S, Dawson K, Hodges JR. A study of stereotypic behaviours in Alzheimer's disease and frontal and temporal variant frontotemporal dementia. J Neurol Neurosurg Psychiatry 2003;74:1398–1402.
7.
Mioshi E, Kipps CM, Dawson K, Mitchell J, Graham A, Hodges JR. Activities of daily living in frontotemporal dementia and Alzheimer disease. Neurology 2007;68:2077–2084.
8.
Wicklund AH, Johnson N, Rademaker A, Weitner BB, Weintraub S. Profiles of decline in activities of daily living in non-Alzheimer dementia. Alzheimer Dis Assoc Disord 2007;21:8–13.
9.
Rosen HJ, Narvaez JM, Hallam B, et al. Neuropsychological and functional measures of severity in Alzheimer disease, frontotemporal dementia, and semantic dementia. Alzheimer Dis Assoc Disord 2004;18:202–207.
10.
Rascovsky K, Salmon DP, Lipton AM, et al. Rate of progression differs in frontotemporal dementia and Alzheimer disease. Neurology 2005;65:397–403.
11.
Mioshi E, Bristow M, Cook R, Hodges JR. Factors underlying caregiver stress in frontotemporal dementia and Alzheimer's disease. Dement Geriatr Cogn Disord 2009;27:76–81.
12.
Riedijk SR, De Vugt ME, Duivenvoorden HJ, et al. Caregiver burden, health-related quality of life and coping in dementia caregivers: a comparison of frontotemporal dementia and Alzheimer's disease. Dement Geriatr Cogn Disord 2006;22:405–412.
13.
Boutoleau-Bretonniere C, Vercelletto M, Volteau C, Renou P, Lamy E. Zarit burden inventory and activities of daily living in the behavioral variant of frontotemporal dementia. Dement Geriatr Cogn Disord 2008;25:272–277.
14.
Diehl-Schmid J, Pohl C, Perneczky R, Forstl H, Kurz A. Behavioral disturbances in the course of frontotemporal dementia. Dement Geriatr Cogn Disord 2006;22:352–357.
15.
Shinagawa S, Toyota Y, Ishikawa T, et al. Cognitive function and psychiatric symptoms in early- and late-onset frontotemporal dementia. Dement Geriatr Cogn Disord 2008;25:439–444.
16.
Morris JC. Clinical dementia rating: a reliable and valid diagnostic and staging measure for dementia of the Alzheimer type. Int Psychogeriatr 1997;9 suppl 1:173–176; discussion 177–178.
17.
Knopman DS, Kramer JH, Boeve BF, et al. Development of methodology for conducting clinical trials in frontotemporal lobar degeneration. Brain 2008;131:2957–2968.
18.
Mioshi E, Dawson K, Mitchell J, Arnold R, Hodges JR. The Addenbrooke's Cognitive Examination Revised (ACE-R): a brief cognitive test battery for dementia screening. Int J Geriatr Psychiatry 2006;21:1078–1085.
19.
Davies RR, Kipps CM, Mitchell J, Kril JJ, Halliday GM, Hodges JR. Progression in frontotemporal dementia: identifying a benign behavioral variant by magnetic resonance imaging. Arch Neurol 2006;63:1627–1631.
20.
Hornberger M, Piguet O, Kipps C, Hodges JR. Executive function in progressive and nonprogressive behavioral variant frontotemporal dementia. Neurology 2008;71:1481–1488.
21.
Kipps CM, Nestor PJ, Fryer TD, Hodges JR. Behavioural variant frontotemporal dementia: not all it seems? Neurocase 2007;13:237–247.
22.
Hodges JR, Miller B. The neuropsychology of frontal variant frontotemporal dementia and semantic dementia: introduction to the special topic papers: part II. Neurocase 2001;7:113–121.
23.
Hodges JR, Patterson K, Ward 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;13:31–40.
24.
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.
25.
Gelinas I, Gauthier L, McIntyre M, Gauthier S. Development of a functional measure for persons with Alzheimer's disease: the disability assessment for dementia. Am J Occup Ther 1999;53:471–481.
26.
Bond TG, Fox CM. Applying the Rasch Model: Fundamental Measurement in the Human Sciences, 2nd ed. Mahwah, NJ: Lawrence Erlbaum Associates; 2007.
27.
Linacre M. Rasch analysis and Winsteps. Available at: www.winsteps.com/index.htm. Accessed March 2, 2009.
28.
Clemson L, Bundy A, Unsworth C, Singh MF. Validation of the modified assessment of living skills and resources, an IADL measure for older people. Disabil Rehabil 2009;31:359–369.
29.
Bland JM, Altman DG. Cronbach's alpha. BMJ 1997;314:572.
30.
Gorno-Tempini ML, Dronkers NF, Rankin KP, et al. Cognition and anatomy in three variants of primary progressive aphasia. Ann Neurol 2004;55:335–346.
31.
Alladi S, Xuereb J, Bak T, et al. Focal cortical presentations of Alzheimer's disease. Brain 2007;130:2636–2645.
32.
Wadia PM, Lang AE. The many faces of corticobasal degeneration. Parkinsonism Relat Disord 2007;13 suppl 3:S336–S340.
33.
Hanna-Pladdy B, Heilman KM, Foundas AL. Ecological implications of ideomotor apraxia: evidence from physical activities of daily living. Neurology 2003;60:487–490.
34.
Sunderland A, Shinner C. Ideomotor apraxia and functional ability. Cortex 2007;43:359–367.
35.
Roberson ED, Hesse JH, Rose KD, et al. Frontotemporal dementia progresses to death faster than Alzheimer disease. Neurology 2005;65:719–725.
36.
Pasquier F, Richard F, Lebert F. Natural history of frontotemporal dementia: comparison with Alzheimer's disease. Dement Geriatr Cogn Disord 2004;17:253–257.
37.
Hodges JR, Mitchell J, Dawson K, et al. Semantic dementia: demography, familial factors and survival in a consecutive series of 100 cases. Brain 2010;133:300–306.
38.
Feldman H, Sauter A, Donald A, et al. The disability assessment for dementia scale: a 12-month study of functional ability in mild to moderate severity Alzheimer disease. Alzheimer Dis Assoc Disord 2001;15:89–95.
39.
Behl P, Lanctot KL, Streiner DL, Black SE. The effect of cholinesterase inhibitors on decline in multiple functional domains in Alzheimer's disease: a two-year observational study in the Sunnybrook dementia cohort. Int Psychogeriatr 2008;20:1141–1159.

Information & Authors

Information

Published In

Neurology®
Volume 74Number 20May 18, 2010
Pages: 1591-1597
PubMed: 20479357

Publication History

Published online: May 17, 2010
Published in print: May 18, 2010

Permissions

Request permissions for this article.

Notes

Authors

Affiliations & Disclosures

E. Mioshi, PhD
From the Prince of Wales Medical Research Institute (E.M., S.H., S.S., M.H., J.R.H.), Sydney, Australia; Department of Clinical Neurosciences (J.R.H.), University of Cambridge; MRC Cognition and Brain Sciences Unit (E.M.), Cambridge, UK; and School of Medical Sciences (M.H., J.R.H.), University of New South Wales, Sydney, Australia.
S. Hsieh, DCN/Msc
From the Prince of Wales Medical Research Institute (E.M., S.H., S.S., M.H., J.R.H.), Sydney, Australia; Department of Clinical Neurosciences (J.R.H.), University of Cambridge; MRC Cognition and Brain Sciences Unit (E.M.), Cambridge, UK; and School of Medical Sciences (M.H., J.R.H.), University of New South Wales, Sydney, Australia.
S. Savage, MClinNeuro
From the Prince of Wales Medical Research Institute (E.M., S.H., S.S., M.H., J.R.H.), Sydney, Australia; Department of Clinical Neurosciences (J.R.H.), University of Cambridge; MRC Cognition and Brain Sciences Unit (E.M.), Cambridge, UK; and School of Medical Sciences (M.H., J.R.H.), University of New South Wales, Sydney, Australia.
M. Hornberger, PhD
From the Prince of Wales Medical Research Institute (E.M., S.H., S.S., M.H., J.R.H.), Sydney, Australia; Department of Clinical Neurosciences (J.R.H.), University of Cambridge; MRC Cognition and Brain Sciences Unit (E.M.), Cambridge, UK; and School of Medical Sciences (M.H., J.R.H.), University of New South Wales, Sydney, Australia.
J.R. Hodges, FRCP
From the Prince of Wales Medical Research Institute (E.M., S.H., S.S., M.H., J.R.H.), Sydney, Australia; Department of Clinical Neurosciences (J.R.H.), University of Cambridge; MRC Cognition and Brain Sciences Unit (E.M.), Cambridge, UK; and School of Medical Sciences (M.H., J.R.H.), University of New South Wales, Sydney, Australia.

Notes

Address correspondence and reprint requests to Prof. John R. Hodges, Prince of Wales Medical Research Institute, Cnr Barker St. and Easy St., Randwick, NSW 2031 Sydney, Australia [email protected]

Metrics & Citations

Metrics

Citations

Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

Cited By
  1. Correlates of Functional Impairment in Patients with the Behavioral Variant of Frontotemporal Dementia: A PRISMA-Compliant Systematic Review, International Journal of Molecular Sciences, 24, 18, (13810), (2023).https://doi.org/10.3390/ijms241813810
    Crossref
  2. The cognitive and behavioral correlates of functional status in patients with frontotemporal dementia: A pilot study, Frontiers in Human Neuroscience, 17, (2023).https://doi.org/10.3389/fnhum.2023.1087765
    Crossref
  3. Apathy and functional disability in behavioral variant frontotemporal dementia, Neurology Clinical Practice, 8, 2, (120-128), (2023)./doi/10.1212/CPJ.0000000000000429
    Abstract
  4. Longitudinal change in everyday function and behavioral symptoms in frontotemporal dementia, Neurology Clinical Practice, 6, 5, (419-428), (2023)./doi/10.1212/CPJ.0000000000000264
    Abstract
  5. Cut-off scores for mild and moderate dementia on the Addenbrooke's Cognitive Examination-III and the Mini-Addenbrooke's Cognitive Examination compared with the Mini-Mental State Examination, BJPsych Bulletin, (1-7), (2023).https://doi.org/10.1192/bjb.2023.27
    Crossref
  6. Neuropsychiatric symptoms in genetic frontotemporal dementia: developing a new module for Clinical Rating Scales, Journal of Neurology, Neurosurgery & Psychiatry, 94, 5, (357-368), (2023).https://doi.org/10.1136/jnnp-2022-330152
    Crossref
  7. Syndromes associated with frontotemporal lobar degeneration change response patterns on visual analogue scales, Scientific Reports, 13, 1, (2023).https://doi.org/10.1038/s41598-023-35758-5
    Crossref
  8. The BrainLat project, a multimodal neuroimaging dataset of neurodegeneration from underrepresented backgrounds, Scientific Data, 10, 1, (2023).https://doi.org/10.1038/s41597-023-02806-8
    Crossref
  9. Error profiles of facial emotion recognition in frontotemporal dementia and Alzheimer’s disease, International Psychogeriatrics, (1-10), (2023).https://doi.org/10.1017/S1041610223000297
    Crossref
  10. Hemispheric contributions toward interoception and emotion recognition in left-vs right-semantic dementia, Neuropsychologia, 188, (108628), (2023).https://doi.org/10.1016/j.neuropsychologia.2023.108628
    Crossref
  11. See more
Loading...

View Options

Get Access

Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Personal login Institutional Login
Purchase Options

Purchase this article to access the full text.

Purchase Access, $39 for 24hr of access

View options

Full Text

View Full Text

Full Text HTML

View Full Text HTML

Media

Figures

Other

Tables

Share

Share

Share article link

Share