Neural correlates of behavioural symptoms in behavioural variant frontotemporal dementia and Alzheimer's disease: Employment of a visual MRI rating scale

Go, Christopher; Mioshi, Eneida; Yew, Belinda; Hodges, John R.; Hornberger, Michael

doi:10.1590/S1980-57642012DN06010003

ABSTRACT

Frontotemporal dementia (FTD) patients often present with severe behavioural disturbances and concomitant lack of insight. The underlying neural correlates of these disturbances are mostly attributed to prefrontal cortex dysfunction, but are still poorly understood.

Objectives:

The current study explores whether a simple visual magnetic resonance imaging (MRI) rating scale in combination with the Frontal System Behaviour Scale (FrSBe) can be used to identify the prefrontal correlates of behavioural symptoms in behavioural variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD).

Methods:

Forty-eight patients with a clinical diagnosis of bvFTD and AD participated in the study. Their behavioural profiles were assessed using the Frontal System Behaviour Scale (FrSBe) and cross-correlated to the atrophy of the sub-regions in the prefrontal cortex using a 5-point visual rating scale of MRI scans.

Results:

Patients with bvFTD showed higher incidence of behavioural disturbances than AD with apathy being the most significant. BvFTD patients also showed the highest incidence of atrophy in the orbital frontal cortex and this atrophy was correlated with the apathetic features.

Conclusions:

Employment of a simple visual MRI rating scale can be used in combination with a behavioural screening test to identify reliably the behavioural symptoms in bvFTD and AD. These findings will inform the diagnostic accuracy of the neural correlates of behavioural dysfunction in bvFTD in the future.

Key words:
behavioural symptoms; apathy; magnetic resonance imaging; behavioural variant frontotemporal dementia; Alzheimer's disease

RESUMO.

Pacientes com demência frontotemporal (DFT) frequentemente se apresentam com graves distúrbios comportamentais e concomitante falta de insight. Os correlatos neurais subjacentes a estes distúrbios são em sua maioria atribuídos a disfunção do córtex pré-frontal, porém, ainda são pouco compreendidos.

Objetivos:

O presente estudo explora se uma escala de mensuração visual de ressonância magnética (RM) em combinação com a Escala Comportamental do Sistema Frontal podem ser usadas para identificar os correlatos pré-frontais de sintomas comportamentais na variante comportamental da DFT (cDFT) e na doença de Alzheimer (DA).

Métodos:

Quarenta e oito pacientes com diagnóstico clínico de cDFT e DA participaram do estudo. Seus perfis comportamentais foram avaliados usando a Escala Comportamental do Sistema Frontal (ECSF) e correlacionada a atrofia das sub-regiões no córtex pré-frontal utilizando uma escala de mensuração visual de 5 pontos na RM.

Resultados:

Os pacientes com cDFT mostraram uma maior incidência de distúrbios comportamentais do que os com DA, sendo a apatia o sintoma mais significativo. Os pacientes com cDFT também demonstraram uma maior incidência de atrofia no córtex orbito-frontal e esta atrofia correlacionou-se às características apáticas.

Conclusões:

O emprego de uma escala simples de mensuração visual de RM pode ser usada em combinação a um teste de rastreio comportamental para identificar de forma confiável os sintomas comportamentais na cDFT e DA. Estes achados informarão a acurácia diagnóstica dos correlatos neurais da disfunção comportamental na cDFT no futuro.

Palavras-chave:
sintomas comportamentais; apatia; ressonância magnética; variante comportamental da demência frontotemporal; doença de Alzheimer

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REFERENCES

Ratnavalli EC, Brayne K, Dawson K, Hodges JR, The prevalence of frontotemporal dementia. Neurology 2002 58:1615-1621.
Velakoulis D, Walterfang M, Mocellin R, Pantelis C, McLean C. Frontotemporal dementia presenting as schizophrenia-like psychosis in young people: clinicopathological series and review of cases. Br J Psychiatry 2009;194:298-305.
Rascovsky K, Hodges JR, Kipps CM, et al. Diagnostic criteria for the behavioral variant of frontotemporal dementia (bvFTD): current limitations and future directions. Alzheimer Dis Assoc Disord. 2007;21:S14-S8.
Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308-2314.
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.
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.
Williams GB, Nestor PJ, Hodges JR. Neural correlates of semantic and behavioural deficits in frontotemporal dementia. Neuroimage 2005; 24:1042-1051.
Rosen HJ, Allison SC, Schauer GF, Gorno-Tempini ML, Weiner MW, Miller BL. Neuroanatomical correlates of behavioural disorders in dementia. Brain 2005;128:2612-2625.
Peters F, Perani D, Herholz K, et al. Orbitofrontal dysfunction related to both apathy and disinhibition in frontotemporal dementia. Dement Geriatr Cogn Disord 2006;21:373-379.
Grossman M. Frontotemporal dementia: a review. J Int Neuropsychol Soc 2002;8:566-583.
Snowden J, Neary D, Mann D (Editors). Fronto-temporal lobar degeneration: fronto-temporal dementia, progressive aphasia, semantic dementia. Edinburgh: Churchill Livingstone; 1996.
Zamboni G, Huey E, Krueger F, Nichelli P, Grafman J, Apathy and disinhibition in frontotemporal dementia: insights into their neural correlates. Neurology 2008;71:736.
Neary D, Snowden J, Gustafson L, et al. Frontotemporal lobar degeneration: A consensus on clinical diagnostic criteria. Neurology 1998; 51:1546-1554.
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.
Tierney MC, Fisher RH, Lewis AJ, et al. The NINCDS-ADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer's disease: a clinicopathologic study of 57 cases. Neurology 1988;38:359-364.
Mioshi E, Hsieh S, Savage S, Hornberger M, Hodges JR, Clinical staging and disease progression in frontotemporal dementia. Neurology 2010;74:1591-1597.
Malloy P, Grace J. A review of rating scales for measuring behavior change due to frontal systems damage. Cog Behav Neurol 2005;18:18-27.
Malloy P, Tremont G, Grace J, Frakey L. The Frontal Systems Behavior Scale discriminates frontotemporal dementia from Alzheimer's disease. Alzheimers Dement 2007;3:200-203.
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.
Wear HJ, Wedderburn CJ, Mioshi E, et al. The Cambridge Behavioural Inventory Revised. Dement Neuropsychol 2008;2:102-107.
Kipps CM, Davies RR, Mitchell J, Kril JJ, Halliday GM, Hodges JR. Clinical significance of lobar atrophy in frontotemporal dementia: application of an MRI visual rating scale. Dement Geriatr Cogn Disord . 2007; 23:334-342
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.
Hornberger M, Savage S, Hsieh S, Mioshi E, Piguet O, Hodges JR. Orbitofrontal Dysfunction Discriminates Behavioral Variant Frontotemporal Dementia from Alzheimer's Disease. Dement Geriatr Cogn Disord . 2010;30:547-552.
Piguet O, Hornberger M, Shelley BP, Kipps CM, Hodges JR. Sensitivity of current criteria for the diagnosis of behavioral variant frontotemporal dementia. Neurology 2009;72:732-737.
Ruby P, Schmidt C, Hogge M, D'Argembeau A, Collette F, Salmon E. Social mind representation: where does it fail in frontotemporal dementia? J Cogn Neurosci 2007;19:671-683.
van der Meer L, Costafreda S, Aleman A, David AS. Self-reflection and the brain: a theoretical review and meta-analysis of neuroimaging studies with implications for schizophrenia. Neurosci Biobehav Rev 2010; 34:935-946.
Zamboni G, Huey ED, Krueger F, Nichelli PF, Grafman J. Apathy and disinhibition in frontotemporal dementia: insights into their neural correlates. Neurology 2008 ;71:736-742.

Publication Dates

Publication in this collection
Jan-Mar 2012

History

Received
05 Dec 2011
Accepted
16 Feb 2012

This is an open-access article distributed under the terms of the Creative Commons Attribution License

[1] Ratnavalli EC, Brayne K, Dawson K, Hodges JR, The prevalence of frontotemporal dementia. Neurology 2002 58:1615-1621.

[2] Velakoulis D, Walterfang M, Mocellin R, Pantelis C, McLean C. Frontotemporal dementia presenting as schizophrenia-like psychosis in young people: clinicopathological series and review of cases. Br J Psychiatry 2009;194:298-305.

[3] Rascovsky K, Hodges JR, Kipps CM, et al. Diagnostic criteria for the behavioral variant of frontotemporal dementia (bvFTD): current limitations and future directions. Alzheimer Dis Assoc Disord. 2007;21:S14-S8.

[4] Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308-2314.

[5] 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.

[6] 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.

[7] Williams GB, Nestor PJ, Hodges JR. Neural correlates of semantic and behavioural deficits in frontotemporal dementia. Neuroimage 2005; 24:1042-1051.

[8] Rosen HJ, Allison SC, Schauer GF, Gorno-Tempini ML, Weiner MW, Miller BL. Neuroanatomical correlates of behavioural disorders in dementia. Brain 2005;128:2612-2625.

[9] Peters F, Perani D, Herholz K, et al. Orbitofrontal dysfunction related to both apathy and disinhibition in frontotemporal dementia. Dement Geriatr Cogn Disord 2006;21:373-379.

[10] Grossman M. Frontotemporal dementia: a review. J Int Neuropsychol Soc 2002;8:566-583.

[11] Snowden J, Neary D, Mann D (Editors). Fronto-temporal lobar degeneration: fronto-temporal dementia, progressive aphasia, semantic dementia. Edinburgh: Churchill Livingstone; 1996.

[12] Zamboni G, Huey E, Krueger F, Nichelli P, Grafman J, Apathy and disinhibition in frontotemporal dementia: insights into their neural correlates. Neurology 2008;71:736.

[13] Neary D, Snowden J, Gustafson L, et al. Frontotemporal lobar degeneration: A consensus on clinical diagnostic criteria. Neurology 1998; 51:1546-1554.

[14] 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.

[15] Tierney MC, Fisher RH, Lewis AJ, et al. The NINCDS-ADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer's disease: a clinicopathologic study of 57 cases. Neurology 1988;38:359-364.

[16] Mioshi E, Hsieh S, Savage S, Hornberger M, Hodges JR, Clinical staging and disease progression in frontotemporal dementia. Neurology 2010;74:1591-1597.

[17] Malloy P, Grace J. A review of rating scales for measuring behavior change due to frontal systems damage. Cog Behav Neurol 2005;18:18-27.

[18] Malloy P, Tremont G, Grace J, Frakey L. The Frontal Systems Behavior Scale discriminates frontotemporal dementia from Alzheimer's disease. Alzheimers Dement 2007;3:200-203.

[19] 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.

[20] Wear HJ, Wedderburn CJ, Mioshi E, et al. The Cambridge Behavioural Inventory Revised. Dement Neuropsychol 2008;2:102-107.

[21] Kipps CM, Davies RR, Mitchell J, Kril JJ, Halliday GM, Hodges JR. Clinical significance of lobar atrophy in frontotemporal dementia: application of an MRI visual rating scale. Dement Geriatr Cogn Disord . 2007; 23:334-342

[22] 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.

[23] Hornberger M, Savage S, Hsieh S, Mioshi E, Piguet O, Hodges JR. Orbitofrontal Dysfunction Discriminates Behavioral Variant Frontotemporal Dementia from Alzheimer's Disease. Dement Geriatr Cogn Disord . 2010;30:547-552.

[24] Piguet O, Hornberger M, Shelley BP, Kipps CM, Hodges JR. Sensitivity of current criteria for the diagnosis of behavioral variant frontotemporal dementia. Neurology 2009;72:732-737.

[25] Ruby P, Schmidt C, Hogge M, D'Argembeau A, Collette F, Salmon E. Social mind representation: where does it fail in frontotemporal dementia? J Cogn Neurosci 2007;19:671-683.

[26] van der Meer L, Costafreda S, Aleman A, David AS. Self-reflection and the brain: a theoretical review and meta-analysis of neuroimaging studies with implications for schizophrenia. Neurosci Biobehav Rev 2010; 34:935-946.

[27] Zamboni G, Huey ED, Krueger F, Nichelli PF, Grafman J. Apathy and disinhibition in frontotemporal dementia: insights into their neural correlates. Neurology 2008 ;71:736-742.

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