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ARTICLES: K. Rascovsky, D. P. Salmon, A. M. Lipton, J. B. Leverenz, C. DeCarli, W. J. Jagust, C. M. Clark, M. F. Mendez, D. F. Tang-Wai, N. R. Graff-Radford, and D. Galasko Rate of progression differs in frontotemporal dementia and Alzheimer disease Neurology 2005; 65: 397-403 [Abstract] [Full text] [PDF]

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Rate of progression differs in frontotemporal dementia and Alzheimer disease

Andrew Kertesz, MD, FRCP(C), FAAN   (28 March 2006)

Reply from the authors

David P. Salmon, PhD, Douglas Galasko, MD; Katya Rascovsky, PhD (Department of Neurosciences, UCSD)   (28 March 2006)

Rate of progression differs in frontotemporal dementia and Alzheimer disease 28 March 2006
Andrew Kertesz, MD, FRCP(C), FAAN, University of Western Ontario St. Joseph's Hospital 268 Grosvenor St, London, Ontario N6A 4V2 Canada Send Correspondence to journal: Re: Rate of progression differs in frontotemporal dementia and Alzheimer disease Andrew.Kertesz{at}sjhc.london.on.ca Andrew Kertesz, MD, FRCP(C), FAAN	Rascovsky et al collected data from several Alzheimer's Disease Research Centers (ADRCs) on 70 autopsy diagnosed Frontotemporal dementia (FTD) and matching Alzheimer's Disease (AD) patients. [1] Their claim of the more “malignant” course of FTD echoes recent papers yet is contradicted by their own data such as the same course and duration of illness from onset to death in both groups. We found the same in a recent autopsy series [2] and so did others as cited in the paper. Rascovsky et al's emphasis on the shorter duration from initial assessment to death may be misplaced as they state, "...FTD patients were actually farther along in disease course than those with AD at the time of initial evaluation given the observed differences in functional impairment at baseline." They also discuss why the Mini-Mental State Examination (MMSE) may not be sensitive to the earliest changes and why the drop observed at a one-year follow-up could be related to the language deterioration commonly seen in FTD in middle stages. Motor Neuron Disease may shorten the duration of FTD substantially, but this did not seem to be the case here as it might have been in other series. The more severe ADL impairment at initial assessment reflects the clinical reality and the fundamental difference between the two conditions. FTD patients neglect their hygiene and dress and often have an eating disorder yet their memory and spatial function may remain intact. In contrast, AD patients are often well dressed, socially appropriate and yet incapacitated by memory and spatial loss at presentation. Which one is more "malignant" often depends on the caregiver’s point of view. References 1.Rascovsky K, Salmon DP, Lipton AM, et al. Rate of progression differs in frontotemporal dementia and Alzheimer disease. Neurology 2005;65:397-403. 2. Kertesz A, McMonagle P, Blair M et al, The evolution and pathology of frontotemporal dementia. Brain 2005;128:1996-2005. Disclosure: The author reports no conflicts of interest.
Reply from the authors 28 March 2006
David P. Salmon, PhD, University of California, San Diego 9500 Gilman Drive, La Jolla, CA 92093-0948, Douglas Galasko, MD; Katya Rascovsky, PhD (Department of Neurosciences, UCSD) Send Correspondence to journal: Re: Reply from the authors dsalmon{at}ucsd.edu David P. Salmon, PhD, et al.	We thank Dr. Kertesz for his interest in our article. [1] We agree with his point that behavioral symptoms may precede significant cognitive decline in FTD, making it difficult to precisely define disease onset. Time of disease onset is also difficult to accurately estimate in AD, so it is not surprising that comparisons of disease duration based upon these estimates have produced mixed results. This is exactly what led us to use both the relatively “soft” starting point of estimated onset and the known benchmark of initial clinic presentation in comparing survival in FTD and AD. Dr. Kertesz’s excellent manuscript [2] describing the chronology of clinical features and neuropathology in FTD sheds little additional light as it reports survival based only on estimated disease onset and compares FTD with a small group of atypical AD patients. It is worth noting, however, that our finding regarding survival has been replicated in a larger series [3] which reported that patients with FTD had significantly shorter survival from estimated onset of symptoms and from initial clinic presentation than did comparable patients with AD. This study also supported our findings that patients with tau pathology had longer survival than those without, and had sufficient patients with ALS-FTD to establish the expected poorer survival in that clinical subgroup. Although there is extensive literature on behavioral changes in FTD, the impact of the disease on functional abilities has not been widely studied. As Dr. Kertesz points out, FTD patients often neglect “hygiene” and may have eating disorders such as food cravings and difficulty controlling how much and what they eat. However, these and other behavioral changes do not necessarily translate into the loss of functional abilities common to FTD and AD. Our focus on specific activities such as toileting, eating, and dressing allowed us to show that functional decline, which likely adds to the burden (and concern) of a caregiver and “malignancy” of disease, is greater in FTD than in AD. Admittedly, the MMSE is far from ideal for tracking change in FTD. Nevertheless, we believe that our findings should stimulate attempts to develop better ways of detecting cognitive decline in FTD and draw attention to the importance of measuring both instrumental and basic ADL. Furthermore, we hope that our findings lead to future research on the relative contributions of cognitive decline and behavioral symptoms to functional decline in FTD. References 3. Roberson ED, Hesse JH, Rose KD, et al. Frototemporal dementia progresses to death faster than Alzheimer disease. Neurology 2005; 65:719-725. Disclosure: The authors report no conflicts of interest.