The Tangled Neuron

The MTHFR gene and Alzheimer's

One of the test results I found in Dad’s records was for a mutation in a gene called MHTFR. His medical records say:

Methylenetetrahydrofolate reductase (MHTFR) FRET genotype analysis to identify the C677T polymorphism. Genotype result: A/A (Normal)

The U.S. National Library of Medicine has a Genetics Home Reference site written for consumers who want to know more about genetic conditions. Information on that site says mutations in this gene are associated with cardiovascular disease and elevated levels of an amino acid called homocysteine. Elevated levels of homocysteine in the blood are thought to increase the risk for cerebrovascular disease and Alzheimer’s disease.

Some researchers have suggested a possible association between a particular mutation of the MHTFR gene and Alzheimer’s disease or vascular dementia, but recent studies have not found any strong association, except in Japanese and Chinese populations.

Even if this genetic mutation were a problem, Dad didn’t have it. His homocysteine levels were also normal. None of his doctors ever mentioned this genetic test or homocysteine levels, so I guess they didn’t feel this was likely to be a factor in his dementia.

Genetics, Alzheimer's and Dementia

Looking back through Dad’s medical records, I found the results of some genetic tests. Did his genes explain what happened to him? Were his dementia and death already set in stone the day he was born? Or maybe by the time this picture was taken?

 

I remember that one of his neurologists had said that my father didn’t have the gene that may increase the risk of developing Alzheimer’s. To see if I could get a better understanding, I thumbed through Dad’s records looking at all the pages with the words “gene” or “genotype”.

Here’s what I found:

• Apolipoprotein E Genotype: 2 and 3
• Methylenetetrahydrofolate reductase (MHTFR) FRET genotype analysis to identify the C677T polymorphism. Genotype result: A/A
• Analysis for C282Y mutation, H63D mutation and S65C mutation…

The Apoliprotein E Gene is the one the neurologist told me is associated with Alzheimer’s Disease. The C282Y, H63D and S65C mutations are associated with iron overload, which this same neurologist suspected might be a problem. But I have no idea with the C677T polymorphism is, or what all of this means. I’ll try to find some answers, and will post any results.

 

Keep copies of your medical records!

I’ve spent the last few months working to get copies of Dad’s records sent to my family or to various doctors who are interested in his case.   It took anywhere from three weeks to seven months to get any one set of records sent.  At first, I thought the delays and confusion I encountered were due to privacy concerns, but each doctor had written permission from my father to release his records to me or to anyone I requested.

 

It seems the real issue was outsourcing of the medical records function by doctors’ offices and health systems.  Every time there was a delay, the doctor’s office didn’t have any way to check the status of the requests they had made.  I had to call the medical records vendors to find out when they would send the records we needed.  There also didn’t seem to be a requirement that the records be sent promptly – I can’t count the number of times I heard “Your request is in process.”

 

In the case of the seven month delay, the health system where Dad was treated outsourced its records function to a medical records company, which outsourced collection of payment for copies of records to a third company. 

 

To speed the process up, I called the third company, and was able to pay over the phone using my credit card.  But that company failed to notify the medical records company that a payment had been made, so the records company refused to release the records.   “I hate it when they do that,” said the supervisor of the Medical Information Release Unit at the health system.  She finally copied the records for me and sent them out.

 

You might think that the problem was that this work was “offshored” or outsourced to companies somewhere across the world, but all of the companies I dealt with are based in the U.S.   

 

Patients and doctors need prompt and hassle-free access to these records.  I guess all of us should keep up-to-date copies of our own medical records and hand-carry them to our doctors as necessary.   I’d hate to think that someone’s treatment might be delayed because his records haven’t been sent.

 

I wonder if access to records is less of a problem in countries with nationalized health care...

 

 

Can loss of sense of smell predict Alzheimer's?

My father always hated chocolate, and so did I. No Snickers bars or chocolate chip cookies for us. Then at Christmas two years ago, Dad ate a piece of chocolate cake. “This is great,” he said happily as I watched in amazement. Mom later told me he had become less picky about what he ate.   She didn’t think he had much of a sense of smell left either.

I hadn’t given this much thought until I saw the March 22nd post on Brainblog about a Rush University Medical Center study that showed “impaired odor identification in old age is associated with impaired global cognition and more rapid decline in perceptual processing speed and episodic memory.” The blog’s author, a neuropsychologist named Anthony Risser, suggested I contact the University of Pennsylvania’s Smell and Taste Center for more information on how loss of the sense of smell may be related to Alzheimer’s and other dementias.

Richard Doty, PhD is a Professor at the University’s School of Medicine and Director of the Center. He co-authored a recent article about a study in which a brief 10-smell test was effective in predicting whether patients with “mild cognitive impairment” would develop Alzheimer’s Disease.

 

 

 

Richard Doty, PhD

 

Why are sense of smell and cognitive decline linked? “There is no consensus as to the reasons for the smell loss in AD [Alzheimer’s disease],” Dr. Doty says, “although AD-related neuropathology does show up relatively early in such structures as the olfactory bulb and anterior olfactory nucleus.”

Just because Dad couldn’t detect odors very well didn’t necessarily mean he had or would develop Alzheimer’s. Many factors, including illnesses other than Alzheimer’s, habits such as smoking, and even normal aging can diminish our ability to smell. So smell tests can’t be used to diagnose Alzheimer’s or other dementias, but they could be useful for identifying patients whose mild memory problems may develop into more serious dementia.

When Dad first complained of memory problems several years ago, I don’t think any of his doctors asked him about his sense of smell. I looked at the American Academy of Neurology practice guidelines for early detection of dementia and also at an American Academy of Family Physicians publication about early diagnosis of dementia . Neither document says anything about smell tests.

I asked Dr. Doty why doctors wouldn’t routinely use these tests for preliminary dementia screening. I wondered whether the tests are too expensive or time-consuming. It turns out Dr. Doty is involved with Sensonics , a company that manufactures smell test kits that could be used to screen for likelihood of developing dementia. “The 12-item test takes about 5 minutes,” he said.  “The cost of this test is $12.95 and it would seem to me reasonable for screening purposes.  But despite a relatively large literature on olfaction in the prediction of AD, there are few clinics that use such testing.”

Dr. Doty is sending me some smell kits so I can see what the tests are like. I’ll write more about this topic once I’ve tried them out.