Expert: Mary Gordon - 10/23/2006

Question
We began to notice my mom's symptoms at 59/60 years of age. Her mother also had AD. I am sending a list of questions to her Dr. via my father. My objective is to determine if she has early-onset AD. Is it definitive that when symptoms begin before age 65, this is considered FAD and hence genetic? Any suggestions for questions?

Thanks

Answer
Hi Daughter!

Here is a good explanation of the current understanding of the genetics of Alzheimer's

http://ghr.nlm.nih.gov/condition=alzheimerdisease

Certainly your mother was young to get AD, but relatively young age at onset does not necessarily mean the familial type. I don't know if you have ever tried to do a family tree, but it is necessary to do up a pedigree, and you will need one to discuss your concerns with the doctors. Do yourself up a tree for your mother's family, and go back as far as you can - and find out as much as you can about the ages people died and what they died from - which will be difficult information to get -listen to the stories you might get from older relatives who might say someone went funny, or crazy, was put away, or had to retire early for some vague reason -and not realize that the person may have had Alzheimer's.  You may have to ask a lot of questions to get the idea that someone might have actually had a dementia, especially with the cultural stigma about "insanity" in years gone by.

A very small minority of families have a strongly inheritable form (i.e. the 50-50 inheritable), but if that is in your family, it should be easy to track in at least recent generations (i.e. it should pop out at you). If you think this pattern may exist in your background (keeping in mind that this is rare), ask the doctor about genetic counselling.

If there is a positive family history of early-onset dementia, and pedigree analysis suggests "autosomal dominant" AD, your mother and other family members can likely be referred to a clinician with an interest in familial dementia for confirmation of the diagnosis. Your family would then be  managed by a multidisciplinary team of experts in genetic neurodegenerative disorders (such as Huntington's disease) and predictive gene testing. Genetic testing is approprialtely only offered in a comprehensive program where mutations in PS1, PS2 and APP are looked for. Gene testing is not recommended for sporadic cases of early-onset AD without a definite family history. You can appreciate that there are a lot of ethical dilemnas around the testing, if that is something appropriate for your family.

The problem with the pure genetic theory is that some persons with the gene combinations associated with certain forms of AD do not develop AD while some persons who appear to be lower risk do.  It is for this reason that research is investigating potential environmental factors which may be triggers of the disease.  Except for the families where the strongly inheritable form runs, there is nothing which can be proved or disproved with certainty at the present time.  It may be that familial AD and sporatic AD are actually entirely separate illnesses with similar pathology.  

All of our chances of developing AD increase with age to an almost one in two probability after the age of 85 (that is, if we are lucky enough to live that long).  We all face this probability.  Studies, for example, have shown a correlation between level of schooling and AD.  Should persons who did not complete high school worry about the risk of developing AD?  Other studies show that persons who smoke have a lesser risk.  Should non-smokers worry?  

I do understand your fears, particularly if you are a mother yourself. If you are really worried, why not book some time to see your mother's doctor WITH your father.

Odds are, she has a sporatic form and has just been incredibly unlucky. Hang tight, cross bridges when you come to them.

Hope this helps. I do apologise for the wait.

Mary G.