Fronto-striatal atrophy correlates of neuropsychiatric dysfunction in frontotemporal dementia (FTD) and Alzheimer's disease (AD)

Yi, Dong Seok; Bertoux, Maxime; Mioshi, Eneida; Hodges, John R.; Hornberger, Michael

doi:10.1590/S1980-57642013DN70100012

ABSTRACT

Behavioural disturbances in frontotemporal dementia (FTD) are thought to reflect mainly atrophy of cortical regions. Recent studies suggest that subcortical brain regions, in particular the striatum, are also significantly affected and this pathology might play a role in the generation of behavioural symptoms.

Objective:

To investigate prefrontal cortical and striatal atrophy contributions to behavioural symptoms in FTD.

Methods:

One hundred and eighty-two participants (87 FTD patients, 39 AD patients and 56 controls) were included. Behavioural profiles were established using the Cambridge Behavioural Inventory Revised (CBI-R) and Frontal System Behaviour Scale (FrSBe). Atrophy in prefrontal (VMPFC, DLPFC) and striatal (caudate, putamen) regions was established via a 5-point visual rating scale of the MRI scans. Behavioural scores were correlated with atrophy rating scores.

Results:

Behavioural and atrophy ratings demonstrated that patients were significantly impaired compared to controls, with bvFTD being most severely affected. Behavioural-anatomical correlations revealed that VMPFC atrophy was closely related to abnormal behaviour and motivation disturbances. Stereotypical behaviours were associated with both VMPFC and striatal atrophy. By contrast, disturbance of eating was found to be related to striatal atrophy only.

Conclusion:

Frontal and striatal atrophy contributed to the behavioural disturbances seen in FTD, with some behaviours related to frontal, striatal or combined fronto-striatal pathology. Consideration of striatal contributions to the generation of behavioural disturbances should be taken into account when assessing patients with potential FTD.

Key words:
frontotemporal dementia; Alzheimer's disease; neuropsychiatric symptoms; striatum

RESUMOObjetivo:

Distúrbios de comportamento na demência frontotemporal (DFT) parecem refletir principalmente atrofia de regiões corticais. Estudos recentes sugerem que regiões cerebrais subcorticais, em particilar o estriado, são também são significativamente afetados e esta patologia pode ter um papel na geração dos sintomas comportamentais.

Investigar a contribuição da atrofia cortical prefrontal e estriatal para os sintomas da DFT.

Métodos:

182 participantes (87 pacienjtes com DFT, 39 pacientes com DA e 56 controles) foram incluídos. Os perfis cognitivos foram estabelecidos usando o Cambridge Behavioural Inventory Revised (CBI-R) e Frontal System Behaviour Scale (FrSBe). Atrofia nas regiões prefrontal (VMPFC, DLPFC) e estriatal (caudado e putamen) foi estabelecida através de uma escala visual de 5 pontos nas imagens de ressonância magnética. Os escores de comportamento foram correlacionados aos escores de atrfoia.

Resultados:

Os resultados comportamentais e de atrofia demonstraram que os pacientes estavam significativamente mais comprometidos do que os controles, com os pacientes com DFT mais gravemente afetados. As correlações anátomo-comportamentais revelaram que a atrofia do VMPFC foi intimamente relacionada ao comportamento anormal e distúrbios de motivação. Comportamentos estereotipados estiveram associados com atrofia do VMPFC e estriatal. Em contraste, distúrbios da alimentação foram relacionados somente a atrofia estriatal.

Conclusão:

A atrofia frontal e estriatal contribuíram para os distúrbios vistos na DFT, com alguns comportamentos relacionados a patologia frontal, estriatal ou combinadas. Considerações quanto à contribuição estriatal na gênese dos distúrbios de comportamento devem ser levados em conta quando se avalia pacientes com DFT em potencial.

Palavras-chave:
demência fronto-temporal; doença de Alzheimer; sintomas neuropsiquiátricos; estriado

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REFERENCES

Seeley WW, Crawford R, Rascovsky K, et al. Frontal Paralimbic Network Atrophy in Very Mild Behavioural Variant Frontotemporal Dementia. Arch Neurol 2008;65:249-255.
Whitwell JL, Przybelski SA, Weigandet SD, et al. Distinct anatomical subtypes of the behavioural variant of frontotemporal dementia: a cluster analysis study. Brain 2009;132:2932-2946.
Seelaar H, Rohrer JD, Pijnenburg YAL, Fox NC, van Swieten JC. Clinical, genetic and pathological heterogeneity of frontotemporal dementia: a review. J Neurol Neurosurg Psychiatry 2010;82:476-486.
Rosen HJ, Gorno-Tempini ML, Goldmanet WP, et al. Patterns of brain atrophy in frontotemporal dementia and semantic dementia. Neurology 2002;58:198-208.
Hodges JR, Patterson K. Semantic dementia: a unique clinicopathological syndrome. Lancet Neurol 2007;6:1004-1014.
Nestor PJ. Neuroimaging and other investigative findings: Cambridge University Press; 2007.
Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology2011;76:1006-1014.
Gorno-Tempini ML, Brambati SM, Ginexet V, et al. The logopenic/phonological variant of primary progressive aphasia. Neurology2008;71: 1227-1234.
Broe M, Hodges JR, Schofield E, Shepherd CE, Kril JJ, Halliday GM. Staging disease severity in pathologically confirmed cases of frontotemporal dementia. Neurology2003;60:1005-1011.
Chow TW, Izenberg A, Binnset MA, et al. Magnetic resonance imaging in frontotemporal dementia shows subcortical atrophy. Dement Geriatr Cogn Disord 2008;26:79-88.
Looi JC, Lindberg O, Zandbelt BB, et al. Caudate nucleus volumes in frontotemporal lobar degeneration: differential atrophy in subtypes. AJNR Am J Neuroradiol 2008;29:1537-1543.
Looi JC, Svensson L, Lindberg O, et al. Putaminal volume in frontotemporal lobar degeneration and Alzheimer disease: differential volumes in dementia subtypes and controls. AJNR Am J Neuroradiol2009; 30:1552-1560.
Garibotto V, Borroni B, Agosti C, et al. Subcortical and deep cortical atrophy in Frontotemporal Lobar Degeneration. Neurobiol Aging 2011; 32:875-884.
Halabi C, Halabi A, Dean DL, et al. Patterns of Striatal Degeneration in Frontotemporal Dementia. Alzheimer Dis Assoc Disord 2013;27: 74-83.
Rosen HJ, Allison SC, Schauer GF, Gorno-Tempini ML, Weiner MW, Miller BL. Neuroanatomical correlates of behavioural disorders in dementia. Brain2005;128:2612-2625.
Woolley JD, Gorno-Tempini ML, Seeleyet WW, et al. Binge eating is associated with right orbitofrontal-insular-striatal atrophy in frontotemporal dementia. Neurology2007;69:1424-1433.
Zamboni G, Huey ED, Krueger F, Nichelli PF, Grafman J. Apathy and disinhibition in frontotemporal dementia: Insights into their neural correlates. Neurology2008;71:736-742.
Eslinger PJ, Moore P, Antani S, Anderson C, Grossman M. Apathy in frontotemporal dementia: behavioral and neuroimaging correlates. Behav Neurol 2012;25:127-136.
Rankin KP, Gorno-Tempini ML, Allison SC, et al. Structural anatomy of empathy in neurodegenerative disease. Brain2006;129:2945-2956.
Josephs KA, Whitwell JL, Jack Jr. CR, Anatomic correlates of stereotypies in frontotemporal lobar degeneration. Neurobiol Aging2008; 29:1859-1863.
Raczka KA, Becker G, Seese A, et al. Executive and behavioral deficits share common neural substrates in frontotemporal lobar degeneration - a pilot FDG-PET study. Psychiatry Res 2010;182:274-280.
Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain2011;134:2456-2477.
Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol2007;6:734-746.
Mioshi E, Hsieh S, Savage S, Hornberger M, Hodges JR. Clinical staging and disease progression in frontotemporal dementia. Neurology2010;74:1591-1597.
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. International Journal of Geriatric Psychiatry 2006;21:1078-1085.
Wear HJ, Wedderburn CJ, Mioshi E, et al. The Cambridge Behavioural Inventory Revised. Dement Neuropsychol 2008;2:102-107.
Malloy P, Grace J. A review of rating scales for measuring behavior change due to frontal systems damage. Cog Behav Neurol2005;18: 18-27.
Davies RR., Scahill VL, Graham A, Williams GB, Graham KS, Hodges JR.Development of an MRI rating scale for multiple brain regions: comparison with volumetrics and with voxel-based morphometry. Neuroradiology 2009;51:491-503.
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 Disord2010; 30:547-552.
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 Disord2007; 23:334-342.
Miller BL, Boeve BE (editors). The Behavioural Neurologyof Dementia. Cambridge: Cambridge University Press; 2009.
Prioni S, Fetoni V, Barocco F, et al. Stereotypic behaviors in degenerative dementias. J Neurol 2012; 259:2452-2459.
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 Psychiatry2003;74:1398-1402.
Hornberger M, Geng J, Hodges JR.Convergent grey and white matter evidence of orbitofrontal cortex changes related to disinhibition in behavioural variant frontotemporal dementia. Brain2011;134:2502- 2512.
Looi JC, Walterfang M, Styner M, et al. Shape analysis of the neostriatum in subtypes of frontotemporal lobar degeneration: neuroanatomically significant regional morphologic change. Psychiatry Res2011; 191:98-111.
Viskontas IV, Possin KL, Miller BL. Symptoms of frontotemporal dementia provide insights into orbitofrontal cortex function and social behavior. Ann N Y Acad Sci 2007;1121:528-545.
Zald DH, Rauch SL. The orbitofrontal cortex: Oxford University Press; 2006.
Piguet O, Petersen A, Yin Ka Lam B, et al. Eating and hypothalamus changes in behavioral-variant frontotemporal dementia. Ann Neurol 2011;69:312-319.

Publication Dates

Publication in this collection
Jan-Mar 2013

History

Received
16 Dec 2012
Accepted
20 Feb 2013

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

[1] Seeley WW, Crawford R, Rascovsky K, et al. Frontal Paralimbic Network Atrophy in Very Mild Behavioural Variant Frontotemporal Dementia. Arch Neurol 2008;65:249-255.

[2] Whitwell JL, Przybelski SA, Weigandet SD, et al. Distinct anatomical subtypes of the behavioural variant of frontotemporal dementia: a cluster analysis study. Brain 2009;132:2932-2946.

[3] Seelaar H, Rohrer JD, Pijnenburg YAL, Fox NC, van Swieten JC. Clinical, genetic and pathological heterogeneity of frontotemporal dementia: a review. J Neurol Neurosurg Psychiatry 2010;82:476-486.

[4] Rosen HJ, Gorno-Tempini ML, Goldmanet WP, et al. Patterns of brain atrophy in frontotemporal dementia and semantic dementia. Neurology 2002;58:198-208.

[5] Hodges JR, Patterson K. Semantic dementia: a unique clinicopathological syndrome. Lancet Neurol 2007;6:1004-1014.

[6] Nestor PJ. Neuroimaging and other investigative findings: Cambridge University Press; 2007.

[7] Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology2011;76:1006-1014.

[8] Gorno-Tempini ML, Brambati SM, Ginexet V, et al. The logopenic/phonological variant of primary progressive aphasia. Neurology2008;71: 1227-1234.

[9] Broe M, Hodges JR, Schofield E, Shepherd CE, Kril JJ, Halliday GM. Staging disease severity in pathologically confirmed cases of frontotemporal dementia. Neurology2003;60:1005-1011.

[10] Chow TW, Izenberg A, Binnset MA, et al. Magnetic resonance imaging in frontotemporal dementia shows subcortical atrophy. Dement Geriatr Cogn Disord 2008;26:79-88.

[11] Looi JC, Lindberg O, Zandbelt BB, et al. Caudate nucleus volumes in frontotemporal lobar degeneration: differential atrophy in subtypes. AJNR Am J Neuroradiol 2008;29:1537-1543.

[12] Looi JC, Svensson L, Lindberg O, et al. Putaminal volume in frontotemporal lobar degeneration and Alzheimer disease: differential volumes in dementia subtypes and controls. AJNR Am J Neuroradiol2009; 30:1552-1560.

[13] Garibotto V, Borroni B, Agosti C, et al. Subcortical and deep cortical atrophy in Frontotemporal Lobar Degeneration. Neurobiol Aging 2011; 32:875-884.

[14] Halabi C, Halabi A, Dean DL, et al. Patterns of Striatal Degeneration in Frontotemporal Dementia. Alzheimer Dis Assoc Disord 2013;27: 74-83.

[15] Rosen HJ, Allison SC, Schauer GF, Gorno-Tempini ML, Weiner MW, Miller BL. Neuroanatomical correlates of behavioural disorders in dementia. Brain2005;128:2612-2625.

[16] Woolley JD, Gorno-Tempini ML, Seeleyet WW, et al. Binge eating is associated with right orbitofrontal-insular-striatal atrophy in frontotemporal dementia. Neurology2007;69:1424-1433.

[17] Zamboni G, Huey ED, Krueger F, Nichelli PF, Grafman J. Apathy and disinhibition in frontotemporal dementia: Insights into their neural correlates. Neurology2008;71:736-742.

[18] Eslinger PJ, Moore P, Antani S, Anderson C, Grossman M. Apathy in frontotemporal dementia: behavioral and neuroimaging correlates. Behav Neurol 2012;25:127-136.

[19] Rankin KP, Gorno-Tempini ML, Allison SC, et al. Structural anatomy of empathy in neurodegenerative disease. Brain2006;129:2945-2956.

[20] Josephs KA, Whitwell JL, Jack Jr. CR, Anatomic correlates of stereotypies in frontotemporal lobar degeneration. Neurobiol Aging2008; 29:1859-1863.

[21] Raczka KA, Becker G, Seese A, et al. Executive and behavioral deficits share common neural substrates in frontotemporal lobar degeneration - a pilot FDG-PET study. Psychiatry Res 2010;182:274-280.

[22] Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain2011;134:2456-2477.

[23] Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol2007;6:734-746.

[24] Mioshi E, Hsieh S, Savage S, Hornberger M, Hodges JR. Clinical staging and disease progression in frontotemporal dementia. Neurology2010;74:1591-1597.

[25] 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. International Journal of Geriatric Psychiatry 2006;21:1078-1085.

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

[27] Malloy P, Grace J. A review of rating scales for measuring behavior change due to frontal systems damage. Cog Behav Neurol2005;18: 18-27.

[28] Davies RR., Scahill VL, Graham A, Williams GB, Graham KS, Hodges JR.Development of an MRI rating scale for multiple brain regions: comparison with volumetrics and with voxel-based morphometry. Neuroradiology 2009;51:491-503.

[29] 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 Disord2010; 30:547-552.

[30] 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 Disord2007; 23:334-342.

[31] Miller BL, Boeve BE (editors). The Behavioural Neurologyof Dementia. Cambridge: Cambridge University Press; 2009.

[32] Prioni S, Fetoni V, Barocco F, et al. Stereotypic behaviors in degenerative dementias. J Neurol 2012; 259:2452-2459.

[33] 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 Psychiatry2003;74:1398-1402.

[34] Hornberger M, Geng J, Hodges JR.Convergent grey and white matter evidence of orbitofrontal cortex changes related to disinhibition in behavioural variant frontotemporal dementia. Brain2011;134:2502- 2512.

[35] Looi JC, Walterfang M, Styner M, et al. Shape analysis of the neostriatum in subtypes of frontotemporal lobar degeneration: neuroanatomically significant regional morphologic change. Psychiatry Res2011; 191:98-111.

[36] Viskontas IV, Possin KL, Miller BL. Symptoms of frontotemporal dementia provide insights into orbitofrontal cortex function and social behavior. Ann N Y Acad Sci 2007;1121:528-545.

[37] Zald DH, Rauch SL. The orbitofrontal cortex: Oxford University Press; 2006.

[38] Piguet O, Petersen A, Yin Ka Lam B, et al. Eating and hypothalamus changes in behavioral-variant frontotemporal dementia. Ann Neurol 2011;69:312-319.

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