Alzheimer's Drugs Little Used, Unevenly Effective, Study Finds

FDA-approved medications for Alzheimer’s disease are not widely used, but show particular promise for female patients.

Cholinesterase inhibitors and the NMDA receptor antagonist memantine have been found to moderately delay Alzheimer’s disease (AD) progression in approximately 40% of patients. In a study published online February 3 in Alzheimer’s & Dementia, researchers looked into whether individual AD patient characteristics could predict better outcomes. The medications included in their study were memantine and the cholinesterase inhibitors donepezil, rivastigmine, and galantamine, all of which have been approved by the FDA to treat AD.

The researchers examined data from the Cache County Dementia Progression Study, which followed 327 AD patients for up to 9 years. Of these, only 69 (21.1%) had ever regularly taken a cholinesterase inhibitor or memantine. Those who did tended to be younger, more educated, and more likely to have an APOE E4 allele, which predisposes one to develop AD. Patients who took the medications were no more or less likely to have medical comorbidities than patients who did not.

The researchers also found the following trends:

• Patients with an APOE E4 allele were almost twice as likely to have taken dementia medications.
• Among women who possessed an APOE E4 allele, longer periods of cholinesterase inhibitor use were associated with slower disease progression.
• Among men, longer periods of cholinesterase inhibitor use were associated with faster disease progression, particularly if they had an APOE E4 allele.
• Because claims data such as that used in the study often underestimate the prevalence of dementia, the portion of people with AD who were taking dementia medication is probably less than the 21% identified in the study.

Given the considerable side-effect profiles associated with FDA-approved AD medications, more study is needed to determine which sub-populations benefit most from these treatments. Gender-specific differences have been found for nearly all cholinergic markers, and testosterone may interfere with cholinesterase inhibitors by decreasing the amount of drug that reaches the brain or by modifying the interaction of the cholinesterase inhibitor with cholinesterase. Men either may benefit less overall from the drugs or need higher doses.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy and a freelance writer from Virginia.