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Pathological correlates of frontotemporal lobar degeneration in the elderly

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Abstract

Frontotemporal lobar degeneration (FTLD) is generally recognised as a disorder with presenile onset (that is before 65 years of age) with only occasional cases presenting later than this. We set out to determine what proportion of cases of FTLD had late onset of disease and whether such cases of FTLD had distinctive clinical and neuropathological features as compared to cases with presenile onset. Within a combined Manchester and Newcastle autopsy series of 117 cases with pathologically confirmed FTLD (109/117 cases also met Lund Manchester clinical criteria for FTLD), we identified 30 cases (onset age range 65–86 years), comprising 25% of all FTLD cases ascertained in these two centres over a 25-year period. Neuropathologically, the 30 elderly cases presented features of several FTLD histological subgroups [FTLD-TDP (types 1, 2 and 3, 19 cases (63%)], FLTD-tau [MAPT, PiD and CBD, 10 cases (33%)] and FTLD-UPS (1 case), similar in range of phenotypes to that seen in the presenile group, though patients with MAPT, but not PGRN, mutation, or FUS pathology, were notably absent or fewer in the elderly group. Hippocampal sclerosis (HS) was present in 13/30 of the elderly FTLD cases (43%) compared with 14/79 (18%) (P = 0.012) in the presenile FTLD patients. Lobar atrophy present in most of the younger patients was prominent in only 25% of the elderly subjects. Prospective and retrospective psychiatric and medical case note analysis showed that the majority of the elderly FTLD patients, like their younger counterparts, had behavioural features consistent with frontotemporal dementia. FTLD is common amongst elderly persons and all or most of the major clinical and histological subtypes present in younger individuals can be seen in the older group.

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Acknowledgments

We thank all staff at the Neuropathology Department, Newcastle General Hospital, and Histopathology Department, Salford Royal Hospitals NHS Foundation Trust for technical assistance, particularly Andrew Brown and Janet Thompson at Newcastle for cutting and staining of the sections and Lynne Ramsay for the TDP43 staining. Dr E. Jaros, Andrew Brown and Lynne Ramsay have been supported by the UK NIHR Biomedical Research Centre for Ageing and Age-related disease award to the Newcastle upon Tyne Hospitals NHS Foundation Trust. We also acknowledge the support of Alzheimers Research Trust and Alzheimer’s Society through their funding of the Manchester Brain Bank under the Brains for Dementia Research initiative. DMAM and SPB also receive funding from MRC and Wellcome Trust which partially supported this study.

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Authors and Affiliations

  1. Department of Neuropathology, Walton Centre for Neurology and Neurosurgery, Lower Lane, Liverpool, L9 7LJ, UK

    Atik Baborie

  2. Cognitive Neurology Clinic, Newcastle General Hospital, Newcastle University, Newcastle upon Tyne, NE4 6BE, UK

    Timothy D. Griffiths

  3. Neuropathology/Cellular Pathology, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne, NE1 4LP, UK

    Evelyn Jaros & Robert Perry

  4. Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK

    Evelyn Jaros, Ian G. McKeith, David J. Burn & Robert Perry

  5. Neurodegeneration and Mental Health Research Group, Greater Manchester Neurosciences Centre, Hope Hospital, University of Manchester, Salford, M6 8HD, UK

    Anna Richardson, Daniel Duplessis, Piyali Pal, Jennifer C. Thompson, David Neary, Julie S. Snowden & David M. A. Mann

  6. Department of Internal Medicine 4C101/4C160/4C127, Texas Tech University Health Sciences Center, Stop 9410, 3601 4th St., Lubbock, TX, 79430, USA

    Raffaele Ferrari, Jorge Moreno & Parastoo Momeni

  7. Neurodegeneration and Mental Health Research Group, A V Hill Building, University of Manchester, Salford, M13 9PL, UK

    Sara Rollinson & Stuart Pickering-Brown

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  1. Atik Baborie
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  2. Timothy D. Griffiths
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  18. David M. A. Mann
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Correspondence to David M. A. Mann.

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401_2010_765_MOESM1_ESM.xls

FTLD pathological classification according to Mackenzie et al. 2010 [18]. FTD = Frontotemporal Dementia, PNFA = progressive non-fluent aphasia, PAX = Progressive apraxia, SD = Semantic dementia, CBD = Corticobasal degeneration, PSP = Progressive Supranuclear Palsy, MND = Motor Neurone Disease, AD = Alzheimer’s Disease, DLB = Dementia with Lewy Bodies, RTA = Road Traffic Accident, FTLD = Frontotemporal lobar degeneration, HS = Hippocampal sclerosis, GGI = Granular Globular Inclusions, Pi = Pick bodies (XLS 44 kb)

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Baborie, A., Griffiths, T.D., Jaros, E. et al. Pathological correlates of frontotemporal lobar degeneration in the elderly. Acta Neuropathol 121, 365–371 (2011). https://doi.org/10.1007/s00401-010-0765-z

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  • DOI: https://doi.org/10.1007/s00401-010-0765-z

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