Brain Advance Access published online on October 5, 2009
Brain, doi:10.1093/brain/awp248
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Semantic dementia: demography, familial factors and survival in a consecutive series of 100 cases
1 Prince of Wales Medical Research Institute (POWMRI), University of New South Wales, Randwick, Sydney, NSW 2031, Australia 2 University Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge, UK 3 Department of Pathology, University of Cambridge, UK 4 MRC Cognition and Brain Sciences Unit, Cambridge, UK
Correspondence to:
Prof. John R. Hodges, Prince of Wales Medical Research Institute, Cnr Barker & Easy Street, Randwick, NSW 2031, Sydney, Australia E-mail: j.hodges{at}powmri.edu.au
A great deal has been written about cognitive aspects of semantic dementia but little is known about the demography or prognosis. We describe these features in a consecutive series of 100 patients seen over a 17-year period; all cases were assessed and followed up in a specialist clinic. The mean age at diagnosis was 64.2 (±7.1) range 40–79 years, but 46 presented after age 65 and 7 after 75; a higher proportion than the existing literature might predict. Fifteen had a first-degree relative with dementia, but in seven this was almost certainly unrelated. Only two had relatives with young-onset dementia. There were no families with more than two affected members. The familial rate was estimated at between 2% and 7% (95% confidence interval 0–12%). Kaplan–Meier analyses indicated a 50% survival of 12.8 years (95% confidence interval 11.9–13.7); a more benign course than suggested by neuropathologically based studies. We were unable to identify any factors influencing survival. Of the 100, 34 have died, with pathological confirmation in 24; 18 had frontotemporal lobar degeneration with ubiquitin-positive inclusions (13 of 13 confirmed TAR DNA binding protein-43 positive), and 3 had classic tau-positive Pick bodies and 3 had Alzheimer's pathology. The age at diagnosis or death across the pathological subgroups was equivalent. Although semantic dementia has a strong statistical association with ubiquitin-positive pathology, it does not have the signature of familial frontotemporal lobar degeneration with ubiquitin-positive inclusions, notably the presence of intranuclear lentiform TAR DNA binding protein-43 inclusions. The age of onset is older than predicted and the course more slowly progressive than suggested by earlier studies of small groups of subjects.
Key Words: frontotemporal dementia; semantic dementia; ubiquitin pathology; TDP43
Abbreviations: ACE, Addenbrooke's cognitive examination; CDR, clinical dementia rating; FTD, frontotemporal dementia; FTLD, frontotemporal lobar degeneration; FTLD-tau, classic tau-positive Pick body frontotemporal dementia; FTLD-U, frontotemporal lobar degeneration with ubiquitin-positive tau-negative inclusions; MMSE, mini-mental state examination; NPI, the neuropsychiatric inventory; TDP, TAR DNA binding protein
Received June 1, 2009. Revised July 30, 2009. Accepted August 22, 2009.