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Measuring progression in frontotemporal dementia

Implications for therapeutic interventions

From the Department of Clinical Neurosciences, University of Cambridge (C.M.K., P.J.N., C.E.D., J.M., J.R.H.), Cambridge, UK.

Address correspondence and reprint requests to Prof Hodges, Prince of Wales Medical Research Institute, Barker St., Randwick, Sydney NSW 2031, Australia j.hodges{at}powmri.edu.au

Background: There is a need for instruments which can measure progression of disease in frontotemporal dementia (FTD), particularly with respect to the assessment of potential therapeutic agents.

Methods: The Cambridge Early Onset Dementia Clinic database was reviewed for all prospectively enrolled cases of FTD with documented scores on the Mini-Mental State Examination (MMSE) or Addenbrooke’s Cognitive Examination (ACE) on at least two occasions. We identified 50 cases fulfilling these criteria: pathologic confirmation was present in 11 of 16 patients who had died, 12 of the remainder had imaging abnormalities on their initial scans, and 22 had structural scans no different from controls. We compared these groups to a cohort with early AD (n = 25) and healthy controls (n = 10).

Results: There was clear cognitive decline (measured by the MMSE and ACE) in patients who had died, and those with documented atrophy on initial MRI scan. In contrast, patients with FTD with normal scans showed no change in cognitive scores over a much longer interval, and serial ACE measurements paralleled those of controls. Power calculations showed that the inclusion of these patients with FTD would significantly increase the number of cases needed in any therapeutic trial.

Conclusion: Addenbrooke’s Cognitive Examination is a simple monitoring tool which can detect progression of disease in frontotemporal dementia over a 1- to 2-year interval without the need for serial imaging. We estimated that a clinical trial that enrolled subjects with abnormal MR scans would require 135 subjects per group to detect a small effect, and 35 for a medium effect.

Abbreviations: ACE = Addenbrooke’s Cognitive Examination; ANOVA = analysis of variance; bvFTD = behavioral variant of frontotemporal dementia; CBI = Cambridge Behavioral Inventory; CDR = Clinical Dementia Rating; DLDH = dementia lacking distinctive histology; FTD = frontotemporal dementia; FTDc = clinically similar FTD cases; FTDp = patients with FTD who have imaging abnormalities and require increasing levels of care or institutionalization; FTDp+ = FTP cases pathologically verified at postmortem; MMSE = Mini-Mental State Examination.

Disclosure: The authors report no disclosures.

Received June 17, 2007. Accepted in final form February 25, 2008.