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Frontotemporal lobar degeneration: Study of a clinicopathological cohort

  • María José Gil
    Correspondence
    Corresponding author at: Institution/Organization, Hospital Universitario de Torrejón, Servicio de Neurología, Calle Mateo Inurria, s/n. 28850, Torrejón de Ardoz, Madrid, Spain. Facultad de Ciencias de la Salud, Universidad Francisco de Vitoria (UFV), Edicio E. Carretera M-515 Pozuelo-Majadahonda, mm 1.899. 28223, Pozuelo de Alarcón, Madrid, Spain.
    Affiliations
    Servicio de Neurología, Hospital Universitario de Torrejón, Facultad de Ciencias de la Salud, Universidad Francisco de Vitoria (UFV), Madrid, Spain

    Banco de Tejidos, Departamento de Neuropatología, Fundación Centro de Investigación en Enfermedades Neurológicas, Instituto de Salud Carlos III (FCIEN-ISCIII), Madrid, Spain
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  • María Sagrario Manzano
    Affiliations
    Servicio de Neurología, Hospital Universitario Infanta Cristina, Parla, Madrid, Spain
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  • María Luz Cuadrado
    Affiliations
    Servicio de Neurología, Hospital Clínico San Carlos, Departamento de Medicina, Universidad Complutense de Madrid (UCM), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
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  • Cristina Fernández
    Affiliations
    Unidad de Gestión Clínica de Medicina Preventiva, Hospital Clínico San Carlos, Facultad de Enfermería, Universidad Complutense de Madrid (UCM), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
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  • Elena Góméz
    Affiliations
    Banco de Tejidos, Departamento de Neuropatología, Fundación Centro de Investigación en Enfermedades Neurológicas, Instituto de Salud Carlos III (FCIEN-ISCIII), Madrid, Spain
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  • Carmen Matesanz
    Affiliations
    Departamento de Biología Molecular, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
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  • Miguel Calero
    Affiliations
    Banco de Tejidos, Departamento de Neuropatología, Fundación Centro de Investigación en Enfermedades Neurológicas, Instituto de Salud Carlos III (FCIEN-ISCIII), Madrid, Spain

    Departamento de Biología Molecular, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
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  • Alberto Rábano
    Affiliations
    Banco de Tejidos, Departamento de Neuropatología, Fundación Centro de Investigación en Enfermedades Neurológicas, Instituto de Salud Carlos III (FCIEN-ISCIII), Madrid, Spain
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Published:October 19, 2018DOI:https://doi.org/10.1016/j.jocn.2018.10.024

      Highlights

      • Frontotemporal dementia (FTD) has been considered as a disease with onset below age 65 but diagnosis at higher ages is increasingly common.
      • Cardiovascular risk factor and other medical history traditionally related to the FTD were not relevant in our series.
      • Subjective memory impairment was the most frequent initial symptom. Language alteration was related to an earlier age at onset and death.
      • Behavioral variant of the FTD was associated with TDP pathology and with Pick’s disease. Semantic dementia and MND-FTD to DP pathology.
      • An inversely proportional relation between the encephalic weight and the duration of the disease was observed.
      • Argyrophilic grain disease increased with age and was more frequent in PSP cases.
      • Low percentage of APOE4 was detected and it was related to a shorter time of disease and to the presence of ß-amyloid pathology.
      • H1/H1 haplotype of the MAPT gene was the most frequent and appeared in relationship with 4R tauopathies. A different clinical initial phenotype was observed according to the MAPT haplotype.
      • This study shows that there are biologically significant differences between the different types of FTLD.

      Abstract

      Frontotemporal dementia results from different neurodegenerative diseases heterogeneous from a clinical, neuropathological and genetic point of view.
      Our main objective was to analyze the sociodemographic, clinical, neuropathological and molecular characteristics of cases with frontotemporal lobar degeneration from different Neurological Tissue Banks.
      FTD has been considered as a disease with onset below 65. However, diagnosis at higher ages is increasingly common. In our study, there was a correlation between symptoms and disease course with certain neuropathological diagnoses, with different distribution depending on age and sex. Combined pathology with Alzheimer’s and vascular pathology was observed and presence of argyrophilic grains, with a different distribution in the different subgroups and a particular clinical and progression phenotype. Low percentage of APOE4 was detected. H1/H1 haplotype of the MAPT gene was the most frequent and appeared in relationship with 4R tauopathies.
      These results point to biologically significant differences between the different types of FTLD.

      Keywords

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      References

        • Neary D.
        • Snowden J.S.
        • Gustafson L.
        • Passant U.
        • Stuss D.
        • Black S.
        • et al.
        Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria.
        Neurology. 1998; 51: 1546-1554
        • Bak T.H.
        • Hodges J.R.
        Motor neurone disease, dementia and aphasia: coincidence, co-occurrence or continuum?.
        J Neurol. 2001; 248: 260-270
        • Cairns N.J.
        • Bigio E.H.
        • Mackenzie I.R.A.
        • Hatanpaa K.J.
        • White C.L.
        • Schneider J.A.
        • et al.
        Neuropathological diagnostic criteria and nosology of the frontotemporal lobar degenerations: consensus criteria of the Consortium for frotntotemporal lobar degeneration.
        Acta Neuropathol. 2007; 114: 5-22
        • Hutton M.
        • Lendon C.L.
        • Rizzu P.
        • Baker M.
        • Froelich S.
        • Houlden H.
        • et al.
        Association of missense and 5’-splice-site mutations in tau with the inherited dementia FTDP-17.
        Nature. 1998; 393: 702-705
        • Braak H.
        • Alafuzoff I.
        • Arzberger T.
        • Krestzschemar H.
        • Del Tredici K.
        Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry.
        Acta Neuropathol. 2006; 112: 389-404
        • Watts G.D.
        • Wymer J.
        • Kovach M.J.
        • Mehta S.G.
        • Mumm S.
        • Darvish D.
        • et al.
        Inclusion body miopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein.
        Nat Genet. 2004; 36: 377-381
        • Brown J.
        • Ashworth A.
        • Gydesen S.
        • Sorensen A.
        • Rossor M.
        • Hardy J.
        • et al.
        Familial non-specificic maps to chromosome 3.
        Hum Mol Genet. 1995; 4: 1625-1628
        • Yan J.
        • Deng H.X.
        • Siddique N.
        • Fecto F.
        • Chen W.
        • Yang Y.
        • et al.
        Frameshift and novel mutations in FUS in familial amyotrophic lateral sclerosis and ALS/dementia.
        Neurology. 2010; 75: 807-884
        • Benajiba L.
        • Le Ber I.
        • Camuzat A.
        • Lacoste M.
        • Thomas-Anterion C.
        • Couratier P.
        • et al.
        TARDBP mutations in motoneuron disease with frontotemporal lobar degeneration.
        Ann Neurol. 2009; 65: 470-473
        • DeJesus-Hernández M.
        • Mackenzie I.R.
        • Boeve B.F.
        • Boxer A.L.
        • Baker M.
        • Rutherford N.J.
        • et al.
        Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS.
        Neuron. 2011; 72: 245-256
        • Martínez-Martín P.
        • Avila J.
        Alzheimer Center Reina Sofia Foundation: fighting the disease and providing overall solutions.
        J Alzheimers Dis. 2010; 21: 337-348
        • Montine T.
        • Phelps C.
        • Beach T.
        • Bgio E.
        • Cairns J.
        • Dickson D.
        • et al.
        National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach.
        Acta Neuropathol. 2012; 123: 1-11
        • Mirra S.S.
        • Heyman A.
        • McKeel D.
        • Sumki S.M.
        • Crain B.J.
        • Brownlee L.M.
        • et al.
        The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part II. Standarization of the neuropathologic assessment of Alzheimer’s disease.
        Neurology. 1991; 41: 479-486
        • Deramecourt V.
        • Slade J.Y.
        • Oakley A.E.
        • Perry R.H.
        • Ince P.G.
        • Maurage C.A.
        • et al.
        Staging and natural history of cerebrovascular pathology in dementia.
        Neurology. 2012; 78: 1043-1050
        • Zea-Sevilla M.A.
        • Fernández-Blázquez M.A.
        • Calero M.
        • Bemejo-Velasco P.
        • Rábano A.
        Combined Alzheimer’s disease and cerebrovascular staging explains advanced dementia cognition.
        Alzheimers Dement. 2015; 11: 1358-1366
        • Thal D.R.
        • Schultz C.
        • Botez G.
        • Del Tredici K.
        • Mrak R.E.
        • Griffin W.S.
        • et al.
        The impact of argyrophilic grain disease on the development of dementia and its relationship to concurrent Alzheimer’s disease-related pathology.
        Neuropathol Appl Neurobiol. 2005; 31: 270-279
        • Bullido M.J.
        • Aldudo J.
        • Frank A.
        • Coria F.
        • Avila J.
        • Valdivieso F.
        A polymorphism in the tau gene associated with risk for Alzheimer’s disease.
        Neurosci Lett. 2000; 278: 49-52
        • Combarros O.
        • Rodero L.
        • Infante J.
        • Palacio E.
        • Llorca J.
        • Fernández-Viadero C.
        • et al.
        Age-dependent association between the Q7R polymorphism in the Saitohin gene and sporadic Alzheimer’s disease.
        Dement Geriatr Cogn Disord. 2003; 16: 132-135
        • Calero O.
        • Hortiguela R.
        • Bullido M.J.
        • Calero M.
        Apolipoprotein E genotyping method by real time PCR, a fast and cost-effective alternative to the TaqMan and FRET assays.
        J Neurosci Methods. 2009; 183: 238-240
        • Ratnavalli E.
        • Brayne C.
        • Dawson K.
        • Hodges J.
        The prevalence of frontotemporal demencia.
        Neurology. 2002; 11: 1615-1621
        • Hodges J.
        • et al.
        Frontotemporal dementia syndromes.
        Cambridge University Press, Cambridge2007
        • Wolfson C.
        • Wolfson D.B.
        • Asgharian M.
        • et al.
        A reevaluation of the duration of survival after the onset of dementia.
        N Engl J Med. 2001; 344: 1111-1116
        • Laakso M.
        Hipoccampus and entorhinal cortex in frontotemporal dementia and Alzheimer’s disease: a morphometric MRI study.
        Biological Psiquiatry. 2000; 47: 1056-1063
        • Rosen H.J.
        • Hartikainen K.M.
        • Jagust W.
        • et al.
        Utility of clinical cirteria in differentiating frontotemporal lobar degeneration (FTLD) from AD.
        Neurology. 2002; 58: 1608-1614
        • Josephs K.A.
        • Whitwell J.L.
        • Weigand S.D.
        • Senjem M.L.
        • Boeve B.V.
        • Knopman D.S.
        • et al.
        Predicting functional decline in behavioural variant frontotemporal dementia.
        Brain. 2011; 134: 432-448
        • Fernández-Matarrubia M.
        • Matías-Guiu J.A.
        • Moreno-Ramos T.
        • Matías-Guiu J.
        Behavioral variant frontotemporal dementia.
        Neurologia. 2014 Oct; 29: 464-472
        • Hodges J.
        • Davies R.
        • Xuereb J.
        • Casey B.
        • Broe M.
        • Back T.
        • et al.
        Clinicopathological correlates in frontotemporal dementia.
        Ann Neurol. 2004; 56: 399-406
        • Hodges J.R.
        • Mitchell J.
        • Dawson K.
        • Spillantini M.G.
        • Xuereb J.H.
        • McMonagle P.
        • et al.
        Semantic dementia: demography, familial factors and survival in a consecutive series of 100 cases.
        Brain. 2010; 133: 300-306
        • Cairns N.J.
        • Neumann M.
        • Bigio E.H.
        • Holm I.E.
        • Troost D.
        • Hatanpaa K.J.
        • et al.
        TDP-43 in familial and sporadic frontotemporal lobar degeneration with ubiquitin inclusions.
        Am J Pathol. 2007; 171: 227-240
        • Osaki Y.
        • Ben-Shlomo Y.
        • Lees A.J.
        • et al.
        Accuracy of clincial diagnosis of progressive supranuclear palsy.
        Mov Disord. 2004; 19: 181-189
        • Yokota O.
        • Tsuchiya K.
        • Terada S.
        • Ishizu H.
        • Uchikado H.
        • Ikeda M.
        • et al.
        Basophilic inclusion body disease and neuronal intermediate filament inclusion disease: a comparative clinicopathological study.
        Acta Neuropathol. 2008; 115: 561-575
        • Seilhean D.
        • Le Ber I.
        • Sarazin M.
        • Lacomblez L.
        • Millecamps S.
        • Salachas F.
        • et al.
        Fronto-temporal lobar degeneration: neuropathology in 60 cases.
        J Neural Transm. 2011; 118: 753-764
        • Braak H.
        • Thal D.R.
        • Ghebremedhin E.
        • Del Tredici K.
        Stages of the pathological process in Alzheimer’s disease: age categories 1 year to 100 years.
        J Neuropathol Exp Neurol. 2011; 70: 960-969
        • Dhikav V.
        • Anand K.S.
        Are vascular factors linked to the development of hippocampal atrophy in Alzheimer's disease?.
        J Alzheimers Dis. 2012; 32: 711-718
        • Togo T.
        • Cookson N.
        • Dickson D.W.
        Argyrophilic grain disease: neuropathology, frequency in a dementia brain bank and lack of relationship with apolipoprotein E.
        Brain Pathol. 2002; 12: 45-52
        • Josephs K.A.
        • Whitwell J.L.
        • Parisi J.E.
        • Knopman D.S.
        • Boeve B.F.
        • Geda Y.E.
        • et al.
        Argyrophilic grains: a distinct disease or an additive pathology?.
        Neurobiol Aging. 2008; 29: 566-573
        • Tolnay M.
        • Monsch A.U.
        • Probst A.
        Argyrophilic grain disease. A frequent dementing disorder in aged patients.
        Adv Exp Med Biol. 2001; 487: 39-58
        • Williams D.R.
        • de Silva R.
        • Paviour D.C.
        • Pittman A.
        • Watt H.C.
        • Kilford L.
        • et al.
        Characteristics of two distinct clinical phenotypes in pathologically proven progressive supranuclear palsy: Richardson’s syndrome and PSP-parkinsonism.
        Brain. 2005; 128: 1247-1258
        • Togo T.
        • Isojima D.
        • Aktsu H.
        • Suzuki K.
        • Uchikado H.
        • Katsuse O.
        • et al.
        Clinical features of Argyrophilic grain disease: a retrospective survey of cases with neuropsychiatric symptoms.
        Am J Geriatr Psychiatry. 2005; 13: 1083-1091
        • Thal D.R.
        • von Armin C.
        • Griffil S.
        • Mrak R.
        • Walker L.
        • Attems J.
        • et al.
        Frontotemporal lobar degeneration FTLD-tau: preclininical lesions, vascular, and Alzheimer-related co-pathologies.
        J Neural Transm. 2015; 122: 1007-1118
        • Srinivasan R.
        • Davidson Y.
        • Gibbons L.
        • Payton A.
        • Richardson A.M.
        • Varma A.
        • et al.
        The apolipoprotein E epsilon4 allele selectively increases the risk of frontotemporal lobar degeneration in males.
        J Neurol Neurosurg Psychiatry. 2006; 77: 154-158
        • Borroni B.
        • Grassi M.
        • Agosti C.
        • Premi E.
        • Archetti S.
        • Alberici A.
        • et al.
        Establishing short-term prognosis in Frontotemporal Lobar Degeneration spectrum: role of genetic background and clinical phenotype.
        Neurobiol Aging. 2010; 31: 270-279
        • Engelborghs S.
        • Dermaut B.
        • Mariën P.
        • Symons A.
        • Vloeberghs E.
        • Maertens K.
        • et al.
        Dose dependent effect of APOE epsilon4 on behavioral symptoms in frontal lobe dementia.
        Neurobiol Aging. 2006; 27: 285-292
        • Mann D.M.
        • McDonagh A.
        • Pickering-Brown S.
        • Kowa H.
        • Iwatsubo T.
        Amyloid beta protein deposition in patients with frontotemporal lobar degeneration: relationship to age and apolipoprotein E genotype.
        Neurosci Lett. 2001; 304: 161-164
        • Verpillat P.
        • Camuzat A.
        • Hannequin D.
        • Thomas-Anterion C.
        • Puel M.
        • Belliard S.
        • et al.
        Association between the extended tau haplotype and frontotemporal dementia.
        Arch Neurol. 2002; 59: 935-939
        • Borroni B.
        • Yancopoulou D.
        • Tsuitsui M.
        • Padovani A.
        • Sawcer S.J.
        • Hodges J.R.
        • et al.
        Association between tau H2 haplotype and age at onset in frontotemporal dementia.
        Arch Neurol. 2005; 62: 1419-1422
        • Baba Y.
        • Tsuboi Y.
        • Baker M.C.
        • Uitti R.J.
        • Hutton M.L.
        • Dickson D.W.
        • et al.
        The effect of tau genotype on clinical features in FTDP-17.
        Parkinsonism Relat Disord. 2005; 11: 205-208