Frontal presentation of Alzheimer's disease: A series of patients with biological evidence by CSF biomarkers

Souza, Leonardo Cruz de; Bertoux, Maxime; Funkiewiez, Aurélie; Samri, Dalila; Azuar, Carole; Habert, Marie-Odile; Kas, Aurélie; Lamari, Foudil; Sarazin, Marie; Dubois, Bruno

doi:10.1590/S1980-57642013DN70100011

ABSTRACT

Besides its typical amnesic presentation, focal atypical presentations of Alzheimer's disease (AD) have been described in neuropathological studies. These phenotypical variants of AD (so-called "atypical AD") do not follow the typical amnestic pattern and include non-amnestic focal cortical syndromes, such as posterior cortical atrophy and frontal variant AD. These variants exhibit characteristic histological lesions of Alzheimer pathology at post-mortem exam. By using physiopathological markers, such as cerebrospinal fluid markers, it is now possible to establish in vivo a biological diagnosis of AD in these focal cortical syndromes. We report a series of eight patients who were diagnosed with behavioural variant frontotemporal dementia based on their clinical, neuropsychological and neuroimaging findings, while CSF biomarkers showed an AD biological profile, thus supporting a diagnosis of frontal variant of AD.

Key words:
Alzheimer's disease; frontotemporal dementia; CSF biomarkers

RESUMO

Além da típica forma amnésica, apresentações focais atípicas da doença de Alzheimer (DA) foram descritas em estudos anatomopatológicos. Essas variantes fenotípicas da DA ("DA atípica") não seguem o padrão amnésico convencional e incluem síndromes corticais focais não amnésicas, tais como a atrofia cortical posterior e a variante frontal da DA. Essas variantes apresentam lesões histológicas características da DA ao exame patológico post-mortem . O uso de marcadores fisiopatológicos da DA, como os biomarcadores do líquido cefalorraquidiano, permite estabelecer in vivo um diagnóstico biológico de DA nessas síndromes corticais focais. Reportamos uma série de oito pacientes que foram clinicamente diagnosticados como portadores da variante comportamental da demência frontotemporal (de acordo com critérios clínicos, neuropsicológicos e de neuroimagem), mas nos quais a investigação dos biomarcadores do líquor mostrou um perfil biológico de DA, de modo que o diagnóstico da variante frontal de DA foi finalmente estabelecido.

Palavras-chave:
doença de Alzheimer; demência frontotemporal; biomarcadores do líquor

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Querfurth HW, LaFerla FM. Alzheimer's disease. N Engl J Med 2010;362: 329-344.
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34:939-944.
Alladi S, Xuereb J, Bak T, et al. Focal cortical presentations of Alzheimer's disease. Brain. 2007;130:2636-2645.
Galton CJ, Patterson K, Xuereb JH, Hodges JR. Atypical and typical presentations of Alzheimer's disease: a clinical, neuropsychological, neuroimaging and pathological study of 13 cases. Brain2000;123:484-498.
Snowden JS, Thompson JC, Stopford CL, et al. The clinical diagnosis of early-onset dementias: diagnostic accuracy and clinicopathological relationships. Brain2011;134:2478-2492.
Murray ME, Graff-Radford NR, Ross OA, Petersen RC, Duara R, Dickson DW. Neuropathologically defined subtypes of Alzheimer's disease with distinct clinical characteristics: a retrospective study. Lancet Neurol 2011;10:785-796.
Dubois B, Feldman HH, Jacova C, et al. Revising the definition of Alzheimer's disease: a new lexicon. Lancet Neurol2010;9:1118-1127.
Grossman M, Libon DJ, Forman MS, et al. Distinct antemortem profiles in patients with pathologically defined frontotemporal dementia. Arch Neurol 2007;64:1601-1609.
Mendez MF, Joshi A, Tassniyom K, Teng E, Shapira JS. Clinicopathologic differences among patients with behavioral variant frontotemporal dementia. Neurology2013;80:561-568.
de Souza LC, Corlier F, Habert MO, Uspenskaya O, Maroy R, Lamari F, et al. Similar amyloid-{beta} burden in posterior cortical atrophy and Alzheimer's disease. Brain2011;134:2036-2043.
de Souza LC, Lamari F, Belliard S, et al. Cerebrospinal fluid biomarkers in the differential diagnosis of Alzheimer's disease from other cortical dementias. J Neurol Neurosurg Psychiatry 2011;82:240-246.
Rosenbloom MH, Alkalay A, Agarwal N, et al. Distinct clinical and metabolic deficits in PCA and AD are not related to amyloid distribution. Neurology2011;76:1789-1796.
Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology1998; 51:1546-1554.
McKhann GM, Albert MS, Grossman M, Miller B, Dickson D, Trojanowski JQ. Clinical and pathological diagnosis of frontotemporal dementia: report of the Work Group on Frontotemporal Dementia and Pick's Disease. Arch Neurol2001;58:1803-1809.
Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain2011;134:2456-2477.
de Souza LC, Volle E, Bertoux M, et al. Poor creativity in frontotemporal dementia: a window into the neural bases of the creative mind. Neuropsychologia 2010;48:3733-3742.
Bertoux M, Delavest M, de Souza LC, et al. Social Cognition and Emotional Assessment differentiates frontotemporal dementia from depression. J Neurol Neurosurg Psychiatry2012;83:411-416.
Grober E, Buschke H, Crystal H, Bang S, Dresner R. Screening for dementia by memory testing. Neurology1988;38:900-903.
Reitan R. Validity of the Trail Making test as an indicator of organic brain damage. Percept Mot Skills 1958;8:271-276.
Nelson HE. A modified card sorting test sensitive to frontal lobe defects. Cortex 1976;12:313-324.
Liberman J, Stewart W, Seines O, Gordon B. Rater agreement for the Rey-Osterrieth Complex Figure Test. J Clin Psychol 1994;50:615-624.
Peigneux P, Van der Linden M. Présentation d'une batterie neuropsychologique et cognitive pour l'évaluation de l'apraxie gestuelle. Rev Neuropsychol 2000;10:311-362.
Richard-Mornas A, Dirson S, Perret-Liaudet A, Decousus M, Thomas-Anterion C. Diagnosis contribution of biomarkers in Alzheimer disease: A case of frontotemporal dementia. Rev Neurol (Paris) 2011;167:160-163.
Raux G, Gantier R, Thomas-Anterion C, et al. Dementia with prominent frontotemporal features associated with L113P presenilin 1 mutation. Neurology2000;55:1577-1578.
Johnson JK, Head E, Kim R, Starr A, Cotman CW. Clinical and pathological evidence for a frontal variant of Alzheimer disease. Arch Neurol1999;56:1233-1239.
Taylor KI, Probst A, Miserez AR, Monsch AU, Tolnay M. Clinical course of neuropathologically confirmed frontal-variant Alzheimer's disease. Nat Clin Pract Neurol 2008;4:226-232.
Piguet O, Hornberger M, Mioshi E, Hodges JR. Behavioural-variant frontotemporal dementia: diagnosis, clinical staging, and management. Lancet Neurol2011;10:162-172.
Seelaar H, Rohrer JD, Pijnenburg YA, Fox NC, van Swieten JC. Clinical, genetic and pathological heterogeneity of frontotemporal dementia: a review. J Neurol Neurosurg Psychiatry2011;82:476-486.
Kertesz A, McMonagle P, Blair M, Davidson W, Munoz DG. The evolution and pathology of frontotemporal dementia. Brain2005;128:1996-2005.
de Souza LC, Lehericy S, Dubois B, Stella F, Sarazin M. Neuroimaging in dementias. Curr Opin Psychiatry 2012;25:473-479.
Bian H, Van Swieten JC, Leight S, et al. CSF biomarkers in frontotemporal lobar degeneration with known pathology. Neurology2008;70:1827-1835.
Weiner MF, Hynan LS, Bret ME, White C 3rd. Early behavioral symptoms and course of Alzheimer's disease. Acta Psychiatr Scand 2005; 111:367-371.
Yew B, Alladi S, Shailaja M, Hodges JR, Hornberger M. Lost and Forgotten? Orientation versus Memory in Alzheimer's Disease and Frontotemporal Dementia. J Alzheimers Dis 2013;33:473-481.
Graham A, Davies R, Xuereb J, et al. Pathologically proven frontotemporal dementia presenting with severe amnesia. Brain2005;128:597-605.
Hornberger M, Piguet O. Episodic memory in frontotemporal dementia: a critical review. Brain2012;135:678-692.
Hornberger M, Piguet O, Graham AJ, Nestor PJ, Hodges JR. How preserved is episodic memory in behavioral variant frontotemporal dementia? Neurology2010;74:472-479.
Hodges JR, Davies RR, Xuereb JH, et al. Clinicopathological correlates in frontotemporal dementia. Ann Neurol 2004;56:399-406.
Hornberger M, Wong S, Tan R, et al. In vivo and post-mortem memory circuit integrity in frontotemporal dementia and Alzheimer's disease. Brain2012;135:3015-3025.
Frisoni GB, Laakso MP, Beltramello A, Geroldi C, Bianchetti A, Soininen H, et al. Hippocampal and entorhinal cortex atrophy in frontotemporal dementia and Alzheimer's disease. Neurology1999;52:91-100.
Laakso MP, Frisoni GB, Kononen M, et al. Hippocampus and entorhinal cortex in frontotemporal dementia and Alzheimer's disease: a morphometric MRI study. Biol Psychiatry 2000;47:1056-1063.
Lindberg O, Walterfang M, Looi JC, et al. Hippocampal shape analysis in Alzheimer's disease and frontotemporal lobar degeneration subtypes. J Alzheimers Dis2012;30:355-365.
Davatzikos C, Resnick SM, Wu X, Parmpi P, Clark CM. Individual patient diagnosis of AD and FTD via high-dimensional pattern classification of MRI. Neuroimage 2008;41:1220-1227.
Albert MS, Dekosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011;7:270-279.
Jack CR, Jr., Albert MS, Knopman DS, et al. Introduction to the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement2011;7:257-262.
Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 2010;6: 131-144.
Tapiola T, Overmyer M, Lehtovirta M, et al. The level of cerebrospinal fluid tau correlates with neurofibrillary tangles in Alzheimer's disease. Neuroreport 1997;8:3961-3963.
Tapiola T, Alafuzoff I, Herukka SK, et al. Cerebrospinal fluid {beta}-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain. Arch Neurol2009;66:382-389.
Seppala TT, Nerg O, Koivisto AM, et al. CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings. Neurology2012;78:1568-1575.
Buerger K, Ewers M, Pirttila T, et al. CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer's disease. Brain2006;129:3035-3041.
Strozyk D, Blennow K, White LR, Launer LJ. CSF Abeta 42 levels correlate with amyloid-neuropathology in a population-based autopsy study. Neurology2003;60:652-656.
Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L. Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol2006;5:228-2234.
Mattsson N, Zetterberg H, Hansson O, et al. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA 2009;302:385-393.
Leyton CE, Villemagne VL, Savage S, et al. Subtypes of progressive aphasia: application of the international consensus criteria and validation using {beta}-amyloid imaging. Brain2011;134:3030-3043.
Baumann TP, Duyar H, Sollberger M, et al. CSF-tau and CSF-Abeta(1-42) in posterior cortical atrophy. Dement Geriatr Cogn Disord 2010; 29:530-533.
Rabinovici GD, Jagust WJ, Furst AJ, et al. Abeta amyloid and glucose metabolism in three variants of primary progressive aphasia. Ann Neurol2008;64:388-401.
Seguin J, Formaglio M, Perret-Liaudet A, et al. CSF biomarkers in posterior cortical atrophy. Neurology2011;76:1782-1788.
Kas A, Uspenskaya O, Lamari F, et al. Distinct brain perfusion pattern associated with CSF biomarkers profile in progressive aphasia J Neurol Neurosurg Psychiatry2012;83:695-698.
Rabinovici GD, Rosen HJ, Alkalay A, et al. Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD. Neurology2011;77:2034-2042.
Rowe CC, Ng S, Ackermann U, et al. Imaging beta-amyloid burden in aging and dementia. Neurology2007;68:1718-1725

Publication Dates

Publication in this collection
Jan-Mar 2013

History

Received
07 Dec 2012
Accepted
08 Feb 2013

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

[1] Querfurth HW, LaFerla FM. Alzheimer's disease. N Engl J Med 2010;362: 329-344.

[2] McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34:939-944.

[3] Alladi S, Xuereb J, Bak T, et al. Focal cortical presentations of Alzheimer's disease. Brain. 2007;130:2636-2645.

[4] Galton CJ, Patterson K, Xuereb JH, Hodges JR. Atypical and typical presentations of Alzheimer's disease: a clinical, neuropsychological, neuroimaging and pathological study of 13 cases. Brain2000;123:484-498.

[5] Snowden JS, Thompson JC, Stopford CL, et al. The clinical diagnosis of early-onset dementias: diagnostic accuracy and clinicopathological relationships. Brain2011;134:2478-2492.

[6] Murray ME, Graff-Radford NR, Ross OA, Petersen RC, Duara R, Dickson DW. Neuropathologically defined subtypes of Alzheimer's disease with distinct clinical characteristics: a retrospective study. Lancet Neurol 2011;10:785-796.

[7] Dubois B, Feldman HH, Jacova C, et al. Revising the definition of Alzheimer's disease: a new lexicon. Lancet Neurol2010;9:1118-1127.

[8] Grossman M, Libon DJ, Forman MS, et al. Distinct antemortem profiles in patients with pathologically defined frontotemporal dementia. Arch Neurol 2007;64:1601-1609.

[9] Mendez MF, Joshi A, Tassniyom K, Teng E, Shapira JS. Clinicopathologic differences among patients with behavioral variant frontotemporal dementia. Neurology2013;80:561-568.

[10] de Souza LC, Corlier F, Habert MO, Uspenskaya O, Maroy R, Lamari F, et al. Similar amyloid-{beta} burden in posterior cortical atrophy and Alzheimer's disease. Brain2011;134:2036-2043.

[11] de Souza LC, Lamari F, Belliard S, et al. Cerebrospinal fluid biomarkers in the differential diagnosis of Alzheimer's disease from other cortical dementias. J Neurol Neurosurg Psychiatry 2011;82:240-246.

[12] Rosenbloom MH, Alkalay A, Agarwal N, et al. Distinct clinical and metabolic deficits in PCA and AD are not related to amyloid distribution. Neurology2011;76:1789-1796.

[13] Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology1998; 51:1546-1554.

[14] McKhann GM, Albert MS, Grossman M, Miller B, Dickson D, Trojanowski JQ. Clinical and pathological diagnosis of frontotemporal dementia: report of the Work Group on Frontotemporal Dementia and Pick's Disease. Arch Neurol2001;58:1803-1809.

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

[16] de Souza LC, Volle E, Bertoux M, et al. Poor creativity in frontotemporal dementia: a window into the neural bases of the creative mind. Neuropsychologia 2010;48:3733-3742.

[17] Bertoux M, Delavest M, de Souza LC, et al. Social Cognition and Emotional Assessment differentiates frontotemporal dementia from depression. J Neurol Neurosurg Psychiatry2012;83:411-416.

[18] Grober E, Buschke H, Crystal H, Bang S, Dresner R. Screening for dementia by memory testing. Neurology1988;38:900-903.

[19] Reitan R. Validity of the Trail Making test as an indicator of organic brain damage. Percept Mot Skills 1958;8:271-276.

[20] Nelson HE. A modified card sorting test sensitive to frontal lobe defects. Cortex 1976;12:313-324.

[21] Liberman J, Stewart W, Seines O, Gordon B. Rater agreement for the Rey-Osterrieth Complex Figure Test. J Clin Psychol 1994;50:615-624.

[22] Peigneux P, Van der Linden M. Présentation d'une batterie neuropsychologique et cognitive pour l'évaluation de l'apraxie gestuelle. Rev Neuropsychol 2000;10:311-362.

[23] Richard-Mornas A, Dirson S, Perret-Liaudet A, Decousus M, Thomas-Anterion C. Diagnosis contribution of biomarkers in Alzheimer disease: A case of frontotemporal dementia. Rev Neurol (Paris) 2011;167:160-163.

[24] Raux G, Gantier R, Thomas-Anterion C, et al. Dementia with prominent frontotemporal features associated with L113P presenilin 1 mutation. Neurology2000;55:1577-1578.

[25] Johnson JK, Head E, Kim R, Starr A, Cotman CW. Clinical and pathological evidence for a frontal variant of Alzheimer disease. Arch Neurol1999;56:1233-1239.

[26] Taylor KI, Probst A, Miserez AR, Monsch AU, Tolnay M. Clinical course of neuropathologically confirmed frontal-variant Alzheimer's disease. Nat Clin Pract Neurol 2008;4:226-232.

[27] Piguet O, Hornberger M, Mioshi E, Hodges JR. Behavioural-variant frontotemporal dementia: diagnosis, clinical staging, and management. Lancet Neurol2011;10:162-172.

[28] Seelaar H, Rohrer JD, Pijnenburg YA, Fox NC, van Swieten JC. Clinical, genetic and pathological heterogeneity of frontotemporal dementia: a review. J Neurol Neurosurg Psychiatry2011;82:476-486.

[29] Kertesz A, McMonagle P, Blair M, Davidson W, Munoz DG. The evolution and pathology of frontotemporal dementia. Brain2005;128:1996-2005.

[30] de Souza LC, Lehericy S, Dubois B, Stella F, Sarazin M. Neuroimaging in dementias. Curr Opin Psychiatry 2012;25:473-479.

[31] Bian H, Van Swieten JC, Leight S, et al. CSF biomarkers in frontotemporal lobar degeneration with known pathology. Neurology2008;70:1827-1835.

[32] Weiner MF, Hynan LS, Bret ME, White C 3rd. Early behavioral symptoms and course of Alzheimer's disease. Acta Psychiatr Scand 2005; 111:367-371.

[33] Yew B, Alladi S, Shailaja M, Hodges JR, Hornberger M. Lost and Forgotten? Orientation versus Memory in Alzheimer's Disease and Frontotemporal Dementia. J Alzheimers Dis 2013;33:473-481.

[34] Graham A, Davies R, Xuereb J, et al. Pathologically proven frontotemporal dementia presenting with severe amnesia. Brain2005;128:597-605.

[35] Hornberger M, Piguet O. Episodic memory in frontotemporal dementia: a critical review. Brain2012;135:678-692.

[36] Hornberger M, Piguet O, Graham AJ, Nestor PJ, Hodges JR. How preserved is episodic memory in behavioral variant frontotemporal dementia? Neurology2010;74:472-479.

[37] Hodges JR, Davies RR, Xuereb JH, et al. Clinicopathological correlates in frontotemporal dementia. Ann Neurol 2004;56:399-406.

[38] Hornberger M, Wong S, Tan R, et al. In vivo and post-mortem memory circuit integrity in frontotemporal dementia and Alzheimer's disease. Brain2012;135:3015-3025.

[39] Frisoni GB, Laakso MP, Beltramello A, Geroldi C, Bianchetti A, Soininen H, et al. Hippocampal and entorhinal cortex atrophy in frontotemporal dementia and Alzheimer's disease. Neurology1999;52:91-100.

[40] Laakso MP, Frisoni GB, Kononen M, et al. Hippocampus and entorhinal cortex in frontotemporal dementia and Alzheimer's disease: a morphometric MRI study. Biol Psychiatry 2000;47:1056-1063.

[41] Lindberg O, Walterfang M, Looi JC, et al. Hippocampal shape analysis in Alzheimer's disease and frontotemporal lobar degeneration subtypes. J Alzheimers Dis2012;30:355-365.

[42] Davatzikos C, Resnick SM, Wu X, Parmpi P, Clark CM. Individual patient diagnosis of AD and FTD via high-dimensional pattern classification of MRI. Neuroimage 2008;41:1220-1227.

[43] Albert MS, Dekosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011;7:270-279.

[44] Jack CR, Jr., Albert MS, Knopman DS, et al. Introduction to the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement2011;7:257-262.

[45] Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 2010;6: 131-144.

[46] Tapiola T, Overmyer M, Lehtovirta M, et al. The level of cerebrospinal fluid tau correlates with neurofibrillary tangles in Alzheimer's disease. Neuroreport 1997;8:3961-3963.

[47] Tapiola T, Alafuzoff I, Herukka SK, et al. Cerebrospinal fluid {beta}-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain. Arch Neurol2009;66:382-389.

[48] Seppala TT, Nerg O, Koivisto AM, et al. CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings. Neurology2012;78:1568-1575.

[49] Buerger K, Ewers M, Pirttila T, et al. CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer's disease. Brain2006;129:3035-3041.

[50] Strozyk D, Blennow K, White LR, Launer LJ. CSF Abeta 42 levels correlate with amyloid-neuropathology in a population-based autopsy study. Neurology2003;60:652-656.

[51] Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L. Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol2006;5:228-2234.

[52] Mattsson N, Zetterberg H, Hansson O, et al. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA 2009;302:385-393.

[53] Leyton CE, Villemagne VL, Savage S, et al. Subtypes of progressive aphasia: application of the international consensus criteria and validation using {beta}-amyloid imaging. Brain2011;134:3030-3043.

[54] Baumann TP, Duyar H, Sollberger M, et al. CSF-tau and CSF-Abeta(1-42) in posterior cortical atrophy. Dement Geriatr Cogn Disord 2010; 29:530-533.

[55] Rabinovici GD, Jagust WJ, Furst AJ, et al. Abeta amyloid and glucose metabolism in three variants of primary progressive aphasia. Ann Neurol2008;64:388-401.

[56] Seguin J, Formaglio M, Perret-Liaudet A, et al. CSF biomarkers in posterior cortical atrophy. Neurology2011;76:1782-1788.

[57] Kas A, Uspenskaya O, Lamari F, et al. Distinct brain perfusion pattern associated with CSF biomarkers profile in progressive aphasia J Neurol Neurosurg Psychiatry2012;83:695-698.

[58] Rabinovici GD, Rosen HJ, Alkalay A, et al. Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD. Neurology2011;77:2034-2042.

[59] Rowe CC, Ng S, Ackermann U, et al. Imaging beta-amyloid burden in aging and dementia. Neurology2007;68:1718-1725

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