Mixed neuropathology in frontotemporal lobar degeneration

Abstract

Aim: Frontotemporal lobar degeneration (FTLD) is a significant cause of dementia in mid-life and older adults. The extent of interactions between FTLD and other neurodegenerative pathologies is unclear. We reviewed the occurrences of mixed pathology in cases of neuropathologically diagnosed FTLD from the UK Brain Bank Network. Materials and methods: Clinicopathological details of cases of FTLD were extracted from the UK Brain Bank Network database. Results: Of 515 cases, 30.10% had mixed neuropathology. Concordance between clinical and neuropathological diagnosis was lower in these cases (38.71% vs. 59.17%). Alzheimer’s spectrum pathology was the commonest additional finding. Age at death was higher in mixed neuropathology cases (mean 76.7 years vs. 72.59.0 years, p < 0.005), increasing in tandem with the number of neuropathologies present. Conclusion: Mixed neuropathology is common in FTLD and associated with increased age at death. Our findings suggest that mixed neuropathology influences age at onset and clinical phenotype in FTLD and makes accurate antemortem diagnosis more difficult. Further investigation of interactions between neuropathologies and phenotype is warranted, particularly in view of the potential impact on clinical diagnosis and patient selection for clinical trials.

Key points

• Mixed neurodegenerative neuropathologies commonly occur with frontotemporal lobar degeneration.

• The likelihood of mixed neuropathology with FTLD increases with older age at death.

• Mixed neuropathology could influence the clinical phenotype of frontotemporal lobar degeneration.

Keywords:

• FTLD
• frontotemporal
• tauopathy
• TDP-43
• Pick’s disease
• dementia

Acknowledgements

The authors acknowledge all those who have contributed to UK brain banks and their families. The authors thank the members of the MRC UK Brain Banks Network, namely: Cambridge Brain Bank; Edinburgh Brain and Tissue Bank; Manchester Brain Bank; MRC London Neurodegenerative Diseases Brain Bank; the Multiple Sclerosis and Parkinson’s Tissue Bank; Newcastle Brain Tissue Resource; Oxford Brain Bank; Queen Square Brain Bank; Sheffield Brain Tissue Bank; and South West Dementia Brain Bank.

Ethical approval

This work was ethically approved by the UK Brain Bank Network, and the authors would like to thank the Network for making this resource available.

Authors’ contributions

Study design was determined by Dr Pennington and Professor Love. Data extraction and analysis was performed by Dr Pennington and Dr Marini. Manuscript writing was carried out by Dr Pennington. Manuscript review and editing was performed by all authors.

Declaration of interest

The authors have no competing interests to declare.

Additional information

Funding

Dr. Pennington is funded by a grant from the BRACE charity.