Saturday, January 19, 2008

Failed the Test? Blame Homocysteine!

Recently there was an article which raised some red flags for me. It explains why we can't be jumping to all sorts of conclusions about genes and their effects.
From Medical News Today:

"UMaine psychology professors Merrill F. "Pete" Elias, Michael A. Robbins and Penelope K. Elias, in collaboration with colleagues in Syracuse, N.Y., England and Australia, studied the relationships among the gene ApoE, homocysteine concentrations, and cognitive performance"

This prompts me to ask what variants did they study and what do they mean by cognitive performance?

Nine hundred eleven dementia-free and stroke-free subjects (59% women) from the Maine-Syracuse study (26–98 years old) were stratified into no-ApoE-4 (n = 667) and ApoE-4 carrier (n = 244) cohorts

The clinical diagnosis of dementia was determined from cognitive data, self-report, and medical records, using the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria

This is quite a few people, but they do not eliminate those patients who may have had a TIA or separated them by IQ. Which is probably a better way to assess this. In addition, Self report is a notoriously poor way for dementia patients to identify themselves. Remember these people who have dementia frequently deny that they have dementia.

Participants completed the Center for Epidemiological Studies Depression Scale (CES-D [34]) within one week prior to neuropsychological testing. Following a fast from midnight, a blood sample was drawn and a light breakfast was served. A physical examination and neuropsychological testing followed.

Probably some of the best testing so far....

What did they find?

With adjustment for the Expanded model (Basic +CVD+ B-vitamin covariates), we found that persons with high, as versus low, plasma tHcy in the presence of an ApoE-4 allele performed 0.30S.D. and 0.40S.D. lower on the Global composite and the MMSE, respectively. Deficits of this magnitude are of considerable importance at the population level and constitute a risk factor for dementia

Here's where the researchers make a huge error! They state "But there is hope for prevention and reversal of cognitive deficit related to elevated homocysteine by reducing homocysteine levels."

Great! If you have Apo-E4 you should take folate? No!

Hope? Listen, this same old story was thought to be true for cardiovascular disease. "We'll give you folate to lower your risk for heart attack" What happened? Nothing. In fact recently there is literature hinting that folate may actually increase your risk of colon cancer growth!

The Sherpa Says:
So where does this leave us? Is Folate good for those with APO-E4? Don't starting taking it yet. Nutrigenomics is coming, but the data, much like in Personalized Genomic testing, is not there yet. In Folate's case, what you don't know might actually kill you. Or At least give you colon cancer. That's why you need the Sherpas, to guide you through the study trail!


drmerrill said...

Go back and read the paper more carefully doctor.

This is an interesting comment regarding our paper on ApoE, homocysteine and congnitive performance, but you do not describe the tudy accurately. We used extensive measures of cognitive performance to define dementia, not just self-report; futher our procedures for diagnosing dementia are highly similar to those employed in the Framingham Heart Study, and used well-established medical criteria as the diagnostic criteria.

We excluded clinical stroke in the paper, but not TIA; TIA is difficult to diagnose in a community-based study and the symptoms are often reflective of other health issues. Nevertheless, we find the same results with respct when we exclude TIA.

Elias et al. comments with regard to how to deal with high homocysteine were made in a news interview, not in the research paper.

The paper did not deal with remediation via folic acid or any other treatment issue.

The authors.

M. F. Elias, PhD MPH

Anonymous said...

Dr. Sherpas fials reading test.

My reading of the ApoE, homocysteine, cognition news release from the Univeristy of Maine indicates that Elias et al. recommended that persons taking folic acid, or B vitamins, consult their physician before doing so.

Concerns over some cancers may be justified [clinical trials are ongoing] and that is apparently why this recommendation was made.

Futher, the published paper itself does not deal with treatment of high levels of homocysteine.

Elias et al. used standard medical criteria for diagnosing dementia, not self report.

Steve Murphy MD said...

I will re-review. The quote I inculded is from the news. I don't mean to delude anyone. But I still maintain that the jury of folic acid is still out.
I apologize for any misrepresentation and will re-review and re-publish.