How Early Can We Observe Alzheimer's Disease Developing?

Considering that the Alzheimer's disease process begins as much as 20 years before the onset of Alzheimer's dementia, you'd think that people would want to know if it's in their future.  But not really.  Americans, especially seniors, often refuse screening tests, apparently in recognition that we have no pharmacological cure.  So what's the use?  Most have not heard that lifestyle changes can at least delay the advance of the disease, or they are unwilling to make the changes.  (They should read Beating the Dementia Monster.) 

But we still want to know if the disease process has begun in someone, if for no other reason than we need people with pre-clinical (presymptomatic) Alzheimer's disease for drug trials and other trial interventions.  There is a growing belief that strategies, like targeting the accumulation of beta amyloid, only have hope of success if they begin very early in the disease progression.  And so we look for ways of diagnosing the disease in those very early stages.  And so we need test subjects reliably diagnosed with pre-clinical Alzheimer's disease.

I believe that within a year we will have a reliable blood test that can identify amyloid abnornalities that may signal pre-clinical Alzheimer's disease, but we are nevertheless looking for other diagnostic tools.

Last week's issue of the journal Alzheimer's and Dementia published research on using information from three existing studies that contained information connecting both cognitive test performance and accumulation of beta amyloid.  These studies included people with Alzheimer's dementia, mild cognitive impairment, and people with no evidence of cognitive impairment.

The research article was "Clinical meaningfulness of subtle cognitive decline on longitudinal testing in preclinical AD."  The researchers wanted to see how pre-clinical Alzheimer's disease could be identified by following test subjects and seeing what became of people with certain test results at different ages.

The upshot was that subjects with passing but subtly declining cognitive test scores who also showed amyloid accumulation in PET scans, were much more likely to develop mild cognitive impairment (MCI).  The MCI likely preceded Alzheimer's dementia.

What does this mean?  I will speculate.  Recall that a diagnosis of Alzheimer's disease requires both evidence of cognitive decline and biomarker evidence together.  If someone does poorly on cognitive tests, brain imaging biomarkers may also show accumulation of amyloid plaques, or an MRI may show certain patterns of brain atrophy.  It appears to me that the blood tests that are emerging may show abnormalities in amyloids in the body, but this would not be sufficient for a diagnosis.  If at the same time cognitive test scores are beginning to decline in a certain fashion, these two indicators may then be sufficient for a diagnosis.  The test scores may still be in the normal range, but this research seems to have identified a rate of decline that signals pre-clinical Alzheimer's disease.

As a footnote, I may have participated in one of the three studies supplying data for the research.  This was the Alzheimer's Disease Neuroimaging Initiative.  In February 2017 I was asked to submit to an MRI at the University of Washington, but I don't recall much about it.  They probably had me sign a bunch of papers and gave me documents describing what they were doing.  But I can't find them now, and I don't remember what they said.  The research people just told that they wanted lots of MRIs of people with MCI.  They were nice enough to send the results to my neurologist.

The same week I had another MRI in the same facility for the SNIFF study we discuss in Beating the Dementia Monster.  It might have been on the same machine.  Both images were read by the same radiologist, and the results were consistent with each other.