Expert: Mary Gordon - 9/18/2009

Question
Hello Mary,

My brother-in-law has been slipping into some form of dementia for around 6 years now.  He's been repeatedly tested for all sorts of things, but nothing definite has come of all the testing.  

Over this past year, his condition has worsened to the point in which he doesn't know his address, doesn't know what day it is, etc.  So, he had an MRI recently, and it came back completely normal.  His doctor says that means he doesn't have AD.  But, since everything else has also been ruled out... is it possible to have AD and yet still have a normal MRI?  There is a strong family history of EOAD.  

Thanks for your time.  

Answer
Hi Justy, might be time for a new doctor! And I'm not entirely kidding.

A significant proportion of early-onset Alzheimer's is linked to three genes labelled PS1, PS2 and APP. Past research suggests that mutations on PS1 may be responsible for as much as 30% to 60% of early-onset Alzheimer's cases. Newer research is inconclusive regarding the exact prevalence of specific mutations, but confirms that a PS1 gene is the mutation most commonly linked to FAD

These three genes are different from the APOE gene — the gene that can increase your risk of Alzheimer's in general.   Hereare a couple of overview blurbs about the genetics
http://en.wikipedia.org/wiki/Early-onset_Alzheimer's_disease
http://alzheimers.about.com/lw/Health-Medicine/Conditions-and-diseases/Early-Ons...

Has your brother in law been tested for these genes? Check with the insurance company first, just in case his coverage doesn't pay for it, or only covers part. He definitely has some sort of progressive dementia. If they find the genes, that would be a pretty solid indicator of EOAD - but if they can't or won't do the test, essentially you diagnose it by ruling out everything else it can be. The only definitive test is a brain biopsy on autopsy.

Sadly, your brother in law's situation is not unusual, and many people with early onset spend years trying to get a diagnosis. Doctors don't always take seriously the possibility of AD in people younger than their senior years. I don't know where your brother in law has been seen, but I'd seek help at a university hospital with an AD research center or a specialized memory clinic. Alternately the family may want to ask their local chapter of the Alzheimer Association for recommendations of physicians with a special interest in dementia.

With him deteriorating, I'd go on the working assumption it IS a progressive incurable dementia, and very likely Alzheimers. If it walks like duck and quacks like a duck, and just about everything else is ruled out...  And to point of fact...MRIs are usually used to rule out other causes, like strokes, tumors etc. A negative MRI doesn't mean much.

Here's a good article about the process http://www.alzforum.org/eFAD/diagenetics/essay3.asp

This doctor is NOT helping the family cope by shrugging at them. They need some firmer guidance and decisions, so they can move on and make good plans. A good doctor will also steer the family to supports and resources to help them through this.

Hope this helps.

Mary G.