Is Functional Decline Necessary for a Diagnosis of Alzheimer's Disease?
Park KW, Pavlik VN, Rountree SD, Darby EJ, Doody RS;
Commented by , 9 Nov 2007
Aim of the study
To examine baseline differences and annualized cognitive and functional change scores in mild Alzheimer's disease (AD) patients with and without impaired activities of daily living (ADL).
Method
Cohort of 267 mild (MMSE ≥ 20) probable AD (NINCDS-ADRDA criteria) follow for at least one year. Based on initial ADL scores using the Lawton and Brody scales (PSMS and IADL), they were divided in unimpaired (N=40) and impaired ADL (N=227). Differences in annualized change scores on MMSE, ADAS-cog, ADL (using PSMS and IADL), and CDR-SB were compared between the 2 groups.
Results
Although the group with unimpaired ADL at baseline had a shorter symptom duration (p= 0.01) and better neuropsychological scores at baseline (p<0.001), there was no significant difference in the annualized cognitive and functional changes. After one year 56% of the initially unimpaired group and 6% of the initially impaired group reported no ADL impairment.
Professor Gauthier's comments
The authors argue that functional decline should not be required for the diagnosis of AD, but rather impaired memory and a second cognitive domain. A similar argument has also been put forward by Dubois et al. (ref. 1) in a landmark article in the Lancet Neurology 2007. In this article the proposal is that a diagnosis of AD is possible in the presence of a decline in episodic memory accompanied by a change in MRI, SPECT, PET, CSF or a genetic mutation (PS or APP).
The trend is thus to recognize AD as a disease and not as a dementia. The "pre-dementia" stage of AD may be the most responsive to disease-modifying treatments, and since there are no standard drug therapies at that stage, placebo-controlled clinical trials are possible. The efficacy outcomes in such trials will not be a diagnosis of AD (as was done in MCI clinical trials up to now) but rather a clinically meaningful delay in decline of cognition, autonomy and possibly of emerging behaviors.
This "pre-dementia" diagnosis of AD will create new challenges in terms of possibility of wrong diagnosis, impact on employment, catastrophic reactions with suicide gestures. It will thus be necessary to give additional support to individuals with this very early diagnosis of AD, including the possibility to join new clinical trials aiming at disease modification.
References
1. Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurology 2007; 6 (8); 734-746