Six and 18-month changes in mild to moderate Alzheimer's patients treated with acetylcholinesterase inhibitors: what can we learn for clinical outcomes of therapeutic trials?

BACKGROUND

Clinical trials in Alzheimer's disease (AD) include patients benefiting from recent improvements in AD management.

OBJECTIVE

To observe the progression of Alzheimer's disease (AD) after 6 and 18 months in patients treated with acetylcholinesterase inhibitors (AChEI) in order to determine the best duration of follow-up necessary to demonstrate the impact of new drugs.

METHODS

Six hundred and eleven patients included in the REAL.FR cohort were treated with AChEI at baseline. We describe the cognitive, functional, behavioural, nutritional and global changes in the 509 and 364 patients who completed 6 and 18 months of follow-up, respectively, and who did not discontinue treatment.

RESULTS

After 6 and 18 months, we observed a statistically significant change in the MMSE (-0.54 +/- 3.13 at 6 months and -2.90 +/- 4.10 at 18 months), ADAS-cog (1.58 +/- 5.23 and 4.02 +/- 6.83), ADL (-0.30 +/- 0.79 and -0.84 +/- 1.20), IADL (-0.31 +/- 0.95 and -0.94 +/- 1.20), CDR sum of boxes (0.75 +/- 2.03 and 2.65 +/- 3.18) and MNA scores (-0.42 +/- 2.89 and -0.95 +/- 3.57), demonstrating the progression of AD. But on examining these changes, it appears that even if they were statistically significant at 6 months, they do not appear to be clinically relevant or sufficient to allow the observation of the effect of a new drug at this time, whereas such observation would be possible after 18 months. Similar results were obtained in a subgroup of patients who answer to the inclusion criteria of disease modifying trials which confirms the need for having 18 months of follow-up.

CONCLUSION

Changes in AD in patients under AChEI treatment are not sufficient to demonstrate the effect of a new treatment at 6 months. However, 18-month trials appear to have the potential to demonstrate clearly the effect of a new drug.