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Senior Lecturer and Deputy Head Department of Neurology Edith Wolfson Medical Center Sackler Faculty of Medicine Tel Aviv University Holon 58100, Israel fax 972-3-502-8681 y_lampl{at}hotmail.com
Professor and Head Department of Neurology Edith Wolfson Medical Center
Senior Lecturer and Head Department of Nuclear Medicine Edith Wolfson Medical Center
Published Online, October 12, 2004. www.theannals.com, DOI 10.1345/aph.1D445
We report the clinical outcome of 9 patients suffering from FTD. Five of these patients had shown improvement after treatment with acetylcholinesterase inhibitors. The inclusion criteria used were according to the Consensus on Clinical Diagnostic Criteria and the report of work groups on FTD and Pick's disease.2 Each patient underwent a complete workup that excluded other causes of dementia.
Each patient was randomly treated with either donepezil or rivastigmine, both acetylcholinesterase inhibitors, immediately after diagnosis for FTD. None of the patients was treated with medications with significant anticholinergic properties. The follow-up examination was performed once monthly during the first 3 months after the initiation of treatment and once every 2 months thereafter during this trial period. The parameters for outcome were based on the Lund–Manchester Research Criteria.3 A repeat single photon emission computed tomography (SPECT) study was performed after 6 months.
Nine patients (4 men) were examined. Mean age ± SD was 68.3 ± 4.6 years (men: 64.2 ± 2.2, women: 71.6 ± 2.9). All 4 male patients had a clinically significant improvement that was also demonstrated on the SPECT imaging. In 3 female patients, there was only a very slight improvement for the first 3 months. The other 2 women showed continuous deterioration of their condition. The clinical data are shown in Table 1.
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The patients showed 2 different types of therapeutic responses to the acetylcholinesterase inhibitors. One group, mainly males with an average younger age, showed impressive improvement with this therapy. Another group, mostly women with an average older age, showed no significant beneficial effect with this treatment strategy.
It is well established that not all patients suffering from FTD are of homogeneous origin. The classical lobar atrophy and cellular changes, which were described by Pick as characteristic histologic findings, are not associated with the larger percentage of the patients classified as FTD. This fact leads to the assumption that the neurochemical changes of enzymes in the frontal neocortex in Pick's disease are not identical in all patients with FTD.
Various authors have described normal levels of cholinacetyltransferase in brain specimens of patients with Pick's disease, but reduced levels in the brains of patients with Alzheimer's disease.4,5 However, unlike in Alzheimer's disease, studies have shown varying results of Pick's disease. The decrease of neural cells in FTD was found to be nonsignificant, moderately significant, or up to severely significant. These findings stress the assumption that the decrease of acetylcholine receptor binding sites is nonhomogeneous and reflects different subgroups of populations.
The dramatic beneficial effect of acetylcholinesterase inhibitors in a subgroup of our patients appears very promising. It seems that a prospective study with a larger cohort of FTD patients should be performed to test the effect of acetylcholinesterase inhibitors, taking into account the various characteristics of the FTD subgroups.
Footnotes
We extend our appreciation to Ms. Judy Brandt for her skillful English editing, word processing expertise, and contributions.
References
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