Sunday, August 23, 2020

A New Diagnostic Tool for Alzheimer’s Disease: What Does It Tell Us?



You may have read recently about a new, more accurate test for identifying people with Alzheimer’s disease (AD).  Finding a reliable marker of the disease has long been a goal of researchers.  The ability to confirm diagnosis would help improve research of all kinds, but especially drug trials, because there would be more certainty that participants in the trials had Alzheimer’s and not another form of dementia.  An early marker of AD would also be enormously helpful for designing prevention studies.  We know, however, that many stories about Alzheimer’s disease in the media exaggerate or misinterpret the findings of studies. So we decided to take a look at the article about the new diagnostic tool, which has been published on-line in JAMA.

 

The paper reports on findings from three studies of people with and without Alzheimer’s.  The goal of the three studies was to test how well a marker found in blood samples, P-tau217, distinguished between people with a confirmed diagnosis of Alzheimer’s disease and people without the disease. Tau, as you may know, is a protein normally found in nerve cells that can become twisted, forming one of the primary markers of Alzheimer’s disease, neurofibrillary tangles.  P-tau217 is a marker of those abnormal cells.  

 

Study 1 consisted of people with and without dementia who had volunteered to be followed over time until their death.  Plasma samples of P-tau217 were obtained prior to death and compared with postmortem findings in the brain as well as with prior diagnosis.  

 

Study 2 was part of a large Swedish study that was following people with Alzheimer’s Disease and other neuropathological disorders and well as persons without dementia.  Amounts of P-tau217 were compared to other markers of the disease as well as to diagnosis.

 

Study 3 used a sample from an ongoing study in communities in Colombia, where many people have an autosomal dominant gene for Alzheimer’s disease that leads to the disease at early ages, typically when carriers of the gene are in their 40s.  Blood samples were obtained from people with and without the gene who were part of the study.

 

What did they find?

 

Across the three studies, P-tau217 from blood and plasma differentiated between cases of Alzheimer’s disease and non-disease subjects better than or as well as other markers, including findings from PET and MRI scans and samples of P-tau217 from cerebral spinal fluid.  P-tau217 was highly correlated with the amount of tau (tau density) found in the brain at autopsy in Study 1 and with estimates of tau in the brain from PET scans in the other two samples.  In Study 3, people with the dominant gene for Alzheimer’s disease began showing increased P-tau217 in their mid-20s, or about 20 years before symptoms typically occur.

 

What are the implications?

 

            The main take away from the study is that P-tau217 is a reliable marker of Alzheimer’s disease and of one of the main pathologies in AD, neurofibrillary tangles.  The blood test for P-tau217 is easier to administer and less painful than tests using cerebral spinal fluid, and more readily available and less expensive than PET scans, but just as accurate for determining diagnosis as either of the other methods.

 

            But does P-tau217 predict Alzheimer’s among people who are not symptomatic?  Here the media loudly proclaimed that P-tau217 could detect AD up to 20 years prior to symptoms.  This was based on the finding that people in their 20s in the Colombia sample who carried to dominant gene for AD and could expect to become symptomatic in their 40s had elevated levels of P-tau217.  It remains to be determined higher levels of P-tau217 are found years before onset of symptoms only in certain genetic variants of the disease, or if they can be detected early across most or all cases of AD.  That’s a big “if.”

 

Is P-tau217 ready for widespread use for diagnosis?

 

            No.  There are two hurdles that are by no means easy to overcome.  First, there needs to be a reliable cut-off score, that is, how much P-tau217 indicates a disease process.  The cut-off used in this research worked well in differentiating people already characterized as having AD from controls without the disease, but whether that score would work as well in community samples where people may have early symptoms remains to be seen.  Every effort to push diagnosis earlier in the disease process runs the risk of increasing false positive diagnoses.    

 

            The second hurdle is how far ahead can P-tau217 reliably predict AD.  P-tau217 may predict in a sample with a strong genetic determinant, where we know that people holding the gene will develop the disease, but may not do as well as a predictor for other forms of the disease.  Studies to determine how far ahead a P-tau217 score might predict symptoms would take considerable time to conduct—doing the test today and waiting a few years or more to find out who gets the disease and who does not.

 

Do you want to know your risk for Alzheimer’s?

 

            This is, of course, the key question.  Would you want to know?  One reason to consider the test is if one of the rare, dominant gene forms of AD runs in your family.  In that case, getting a genetic test would be more definitive than the P-tau217.  For cases that occur in later life,  60+,  the APO E4 allele has been linked to AD.  The APO E4 is not a dominant gene so having one copy of it does not mean you will get AD, and even having two copies may not result in AD.  Genetic tests can identify if you have one or two copies of the APO E4 allele. 

 

            The other reason to consider the P-tau217 test is if you think you are having symptoms.  Having occasional memory lapses is not reliably a symptom of AD.  Everyone forgets.  But if memory and other cognitive abilities seem to worsen, then the P-tau217 test could help clarify what is behind the cognitive problems. 

 

            But the question still remains – would you want to know?  If you tested positive for a gene associated with AD or for P-tau217, what would you do differently?   What changes would you make in your life?

 

            Growing older has been described by our friend Bo Malmberg as “sooner or later.”  Sooner or later, something bad will happen.  The implication is to live a full life now.  

 

            

 

Reference:  Palmqvist, S., et al. (2020).  Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders.  JAMA, doi:10.1001/jama.2020.12134 (published on-line with free access).  

 

 

 

 

            

 

 

 

 

 

 

Wednesday, August 12, 2020

Celebrating National Chocolate Chip Cookie Day

 


You may have missed it but Tuesday, August 4, was National Chocolate Cookie Day.  What a wonderful idea!  Our grandson Sam was spending the day with us, and Judy decided that some Grandma-Grandson baking was in order.  They had great fun and the cookies turned out perfectly.  The bowl they were using is the same one Judy used with the kids when they were young, too.  And as you can see in the photos, Sam and Judy were able to be safely masked during the baking.  Just so you know he wasn’t left out, Steve was also safely masked during the cleanup.  

 

Cooking and baking are ways we have connected with our grandkids.  They all like to help out, and they all love eating the results.  

 

While helping Sam, Judy realized she has been making this recipe for chocolate chip cookies for 53 years.  The only change has been to use better quality ingredients which she couldn’t afford or weren’t available when she was young—Penzey’s Vanilla, Kerrygold Irish butter, and Guittard chocolate chips.  Our kids have their favorite recipes from when they were growing up, and that led Judy to put many of the family favorites on her cooking blog.  Steve also makes a few recipes from his mother, including a very tasty Poppy Seed Biscuit.  Making family favorites for our children and grandchildren helps us convey something about the past to our family. 

 

You can find the recipe for chocolate chip cookies on Judy’s blog at http://jzcooks.blogspot.com/2012/09/   The recipe follows the section on baking and cooking measures.  Or browse through for other recipes for cookies and brownies.

 

Wednesday, August 5, 2020

Is the Pandemic an Opportunity for Improving Support to Caregivers

 







The New York Times recently ran an opinion piece titled “Biden’s Quietly Radical Plan.”  The column by Bryce Covert describes plans announced by Mr. Biden that would provide universal pre-school and improve long-term care services for older people.  

 

The COVID pandemic has brought into the open how important caregiving is to our society, whether it is care for young children or for older adults.  As COVID restrictions were gradually being lifted, parents of young children could not return to work because child care and pre-school programs remained closed.  With the school year approaching, parents are facing the dilemma of what to do with their school age kids if their schools go to remote learning.  

 

For older adults, the pandemic revealed how poorly prepared many nursing homes and other residential facilities are for protecting the health of residents.  But trying to keep someone at home where they may be safe poses its own problems, particularly, difficulties finding and retaining qualified caregivers who are virus-free to help out in the home.  Mr. Biden’s proposal would improve wages for home care workers and also improve their work situation.  

 

We need to remember that life before the pandemic was already hard and getting harder for many people.  Needs such as affordable child care and services to support older people to remain at home are routinely addressed in almost all other advanced economic countries, but the US has remained mired in outdated beliefs about care.  There was a time when most women didn’t work outside the home and could care for children or parents at home.  And that was a time, too, when most people did not live to advanced age, so there were not as many older people who needed care.  The idea that families should do it all is as antiquated as a statue of Robert E. Lee. 

 

So maybe we have an opportunity.  The impact of the COVID pandemic and the utter incompetence of the Trump administration have made people more aware of how backward our country has become in so many ways.  This can be the time when we start taking the steps to make caring for young and old more manageable and humane.  We are not likely to become Denmark overnight, but there is much that we can borrow from the Danes and other countries about providing for basic needs for children and older adults and other individuals with special needs.

 

You can find Bryce Covert’s article, “Biden’s Quietly Radical Plan,” at this link:

https://www.nytimes.com/2020/08/02/opinion/biden-child-care.html?action=click&module=Opinion&pgtype=Homepage