New Alzheimer's Drug on Horizon? A Solid Maybe...

 

Contributed by: Dennis Fortier, President, Medical Care Corporation
________________________________________________

A new Alzheimer's drug, being co-developed by Biogen and Easai, has completed a Phase II FDA trial with seemingly positive results. The drug (BAN2401) is a monoclonal antibody that binds to certain forms of amyloid protein, which is considered by many in the field to be a key culprit in the onset and progression of Alzheimer's disease. When the antibody is flushed out of the system, it takes the harmful amyloid protein with it. Over the past five years, several similar drugs have shown glimmers of promise before ultimately failing in Phase III FDA trials.

For perspective, Phase II studies are generally smaller (fewer people enrolled) with the purpose of determining safety for various doses of a drug along with any possible side-effects at each dose of the drug. Phase III studies are generally larger, often longer, and usually a final step prior to "market approval".

Biogen recently presented a snapshot of the data from their Phase II FDA trial at the Alzheimer's Association International Conference in Chicago. While the results showed a reduction in amyloid among subjects receiving the higher doses and a possible slowing of cognitive decline at some stages, the presentation lacked details and many questions remain unanswered.

The primary questions were related to the trial design which appeared to have lower-risk patients in the high dose group and higher risk patients in the untreated (placebo) group. If this was the case, then it would be easier to show that the treatment group fared better (perhaps on both amyloid deposition and cognition) than the placebo group. In defense of this approach, it was taken as a safety measure, not as an attempt to show efficacy through some deceptive trial design. With that in mind, the results are encouraging.

Secondarily, some in the field questioned the validity of the instrument used to measure cognition. The instrument (the ADCOMS) is a composite measure that pulls certain items from various other, well-validated instruments and combines them in a new instrument specifically designed to detect subtle changes. Given the well-documented mediocrity of the instruments historically used to measure cognitive change in FDA clinical trials,  concerns about the ADCOMS should be somewhat tempered because the new instrument may not be significantly better than previous instruments, but it is probably no worse either. With this perspective, lingering angst about the ADCOMS may possibly be over-blown.

Overall, the trial results are both PROMISING and PREMATURE. While there is reason for a fair amount of optimism, one should not carry that optimism with an unrealistic amount of conviction.

Is Memory Loss Normal as You Age?

Contributed by: Dennis Fortier, President, Medical Care Corporation

 Is it normal to have memory loss as you age?

This is a question I see posed on a regular basis in the press.  It is clearly a topic of intense interest to the aging population, and it is worthy of a careful answer.  As a starting point, it is useful to consider the three component parts of human memory:

1. Working memory is sometimes called attention span, and refers to information to which you have been exposed during the last minute or two.  This information is held in the frontal lobe of the brain and, as far as we know, not stored for later retrieval.  Recalling a phone number just long enough to dial it is a good example of working memory.

2. Short-term memory refers to information that you find novel or interesting, and store for later retrieval.  This memory lasts from a few minutes to a couple of weeks, and is processed in the medial temporal lobe of your brain.  Short term memory is used to recall your room number during a week-long stay in a hotel.

3. Long-term memory can last up to a lifetime.  The name of your home town, the color of your first bike, and the name of your first pet are likely to be stored in long term memory.

We still have much to learn about memory formation, storage, and retrieval.  However, with regards to memory loss, here are a few things we know:

• It is never normal to experience severe or sudden changes in memory capacity.  Any decline severe enough to interfere with your normal, daily activities is likely due to some underlying medical condition.
• Working memory declines slowly with time, starting at around age 40.  As such,  a person who can read a ten-digit phone number and then successfully recall it for dialing, might someday need to break that phone number into three short chunks, and dial each separately.  This does not indicate the presence of an illness.
• Both long-term and short-term memory processing tends to slow with age.  This means that you might search longer for the right word or for a person's name as you get older.  This is true even for a healthy brain.
• Hearing and vision can both decline with age and, when this happens, the brain may need to devote more resources to deciphering what it sees and hears.  This additional activity distracts from storing information, so some perceived memory loss is actually due to  distraction.

Healthy Brain Checklist
If you are concerned about your memory, you might be interested in a free questionnaire called the Healthy Brain Checklist that you can download from Medical Care Corporation.   It allows you to tick off the types of memory concerns you have, and see if they are likely to be caused by an underlying medical condition, or if they are more likely due to the normal aging process.

Remember, many conditions can cause memory loss, including thyroid malfunction, sleeping disorders, medicines, depression, infections, and vitamin deficiencies.  Of course more serious problems like Alzheimer's disease, stroke, and head trauma can also cause memory loss, but all can be treated best if detected early.  So if you have a concern that seems correlated with a medical condition, be sure to discuss it with your physician.

Also, if your physician does not take your concern seriously, and your symptoms do not seem to be correlated with normal aging as described above, seek a second opinion from a different physician.