Initially, I was excited to see a review article titled, “Efficacy and safety of cognitive enhancers for patients with mild cognitive impairment: a systematic review and meta-analysis” (Canadian Medical Association Journal, 2013, September 16).   However, I was disappointed after carefully reading the paper.  I had hoped to gain insight into whether cognitive enhancing medications (Aricept/donepezil, Exelon/rivastigmine, and Razadyne/galantamine – there were no cognitive data for Namenda) help those with Mild Cognitive Impairment but there are too few studies with too many limitations to get a clear answer to the question of benefits.

Mild Cognitive Impairment is usually characterized by mild memory/cognitive deficits in those without functional decline in everyday skills.  These are persons who do not meet the criteria for Alzheimer’s disease but are clearly at greater risk of obtaining the diagnosis in the future.  The question is whether treating such individuals with one of the cognitive enhancers changes their clinical course.

The findings from the review are fairly clear.

  1. There was a beneficial effect of treatment with cognitive enhancers between 12-84 weeks.  There was no difference between treated groups and placebo between 85-96 weeks.
  2. There was no difference in efficacy between the medications (e.g., donepezil vs. galantamine) despite different mechanisms of action.
  3. Treatment did not alter functional outcome when compared to placebo.
  4. There was no benefit from these medications when compared to placebo for treating behavioral/psychiatric symptoms.
  5. There was no increase in mortality for those taking these medications up to 156 weeks.
  6. Nausea, diarrhea, and vomiting were significant side effects compared to placebo.

The problem is that there are too few studies (eight) to generate reliable conclusions and the studies were not well designed or well reported.  Furthermore, the studies were too short in duration.  The “conversion” from Mild Cognitive Impairment to Alzheimer’s disease takes many years and the longest studies were too short.  There was inconsistent definition of Mild Cognitive Impairment.

In short, I was hoping to gain clear guidance on whether treatment with Aricept/donepezil, Exelon/rivastigmine, or Razadyne/galantamine provides benefits for those with Mild Cognitive Impairment.  After reading the review, I am dismayed with how few resources we have put into resolving this important treatment issue.  The best guidance I can give is that there appear to be mild long-term benefits for those who with Alzheimer’s disease who tolerate these medications.  The question of how early to start treatment is still open.