Correlations in Frontotemporal Dementia: an Update on the Cambridge Series and Review of the Literature

The pathological basis of frontotemporal dementia is complex. Few studies have followed large groups prospectively to examine clinico-pathological correlations. Improved prediction is important for planning therapy with the advent of disease-modifying therapies. From a total of 250 brain donors recruited into the Cambridge Brain Bank between 1990 and 2010, 150 had a diagnosis of an FTD variant in life, of whom 132 had sufficient data for inclusion in this study, which examines the correlations between in vivo clinical diagnosis and pathology postmortem. Overall 50 patients had FTLD-U, 41 a form of FTLD tau, 33 Alzheimer’s disease (AD) and 8 other pathologies. There were numerous clear correlations. Of the 26 with semantic dementia (SD), 19 (73%) had FLTD-U. Patients with progressive nonfluent aphasia (n=26) had mainly tau deposition (43%) or AD (46%). In mixed aphasia (n=8), AD was present in 75%. Patients with FTD complicated by motor neurone disease (FTD-MND) showed FTLD-U in 100%. In behavioural variant FTD (n=40), the pathology was unpredictable and split equally between FTLD-tau and FTLD-U. In corticobasal syndrome (CBS n=19), the majority (58%) had AD pathology and the remainder FTLD-tau. The underlying pathology in patients diagnosed clinically with FTD is heterogeneous. Clear predictions can be made in SD, FTDMND (which are FTLD-U related) and to a lesser extent PNFA (which is largely tau related or secondary to AD) but not in bvFTD or CBS. Alzheimer’s disease is surprisingly common in patients with progressive nonfluent or mixed aphasia and CBS.