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Joel S. Ross, MD, FACP, AGSF, CMD President and Founder of Memory Enhancement Center of America
 

Joel S. Ross, MD
MD FACP AGSF CMD CPI
President and Founder
 
Memory Enhancement Center
of America, Inc.
4 Industrial Way West, 2nd Floor
Eatontown, New Jersey 07724
732.571.1535
 
August 2010 NJ Physician Article

ApoE4 testing

By Joel Ross | January 7, 2012

ApoE Genetic Testing To Estimate a Person’s Risk of Developing AD
By Gabrielle Strobel

Genetic and epidemiologic studies have confirmed ApoE to be the strongest known genetic risk factor for common late-onset AD. Having inherited a single ApoE ε4 variant increases one’s risk of developing AD by a factor of three in men and four in women, and having two copies increases risk up to 15-fold compared to persons without the ε4 variant. ApoE testing is not clinically available to predict AD risk in healthy people, though it is sometimes offered as part of a diagnosis of a person who already has AD symptoms. In academic research settings, ApoE susceptibility testing is being studied in people who have a parent with AD.

ApoE testing is relevant to a much larger segment of society than testing for the rare mutations in the PS1, PS2, and APP genes that cause early-onset familial AD in a deterministic fashion (for the latter, see Genetic Testing and Counseling for Early-onset Familial Alzheimer Disease). In contrast to the deterministic mutations, ApoE is a “susceptibility” polymorphism. This means that the presence of one or two ε4 alleles increases the risk but does not guarantee that someone will develop AD. Almost all deterministic mutation carriers develop mid-life AD, but many people with ApoE ε4 do not. Conversely, many people who have AD carry no ApoE ε4 gene variant.

Consequently, interpreting ApoE genotype information is more complex than when a person has inherited a deterministic mutation. Essentially, it requires that the doctor and the test-taker grapple with graded probabilities. For most people, the overall risk equation is a mix of genotype, gender, ethnicity, family history, and age. A challenge for the physician, then, is to help people understand what they are to make of, for example, a 40 percent remaining lifetime risk of developing AD when they are 48. Research has shown that many people in the general population have difficulty interpreting probabilistic risk assessments. Not all physicians have the training to calculate and communicate risk. For these reasons, it is wise to conduct genetic testing through a qualified medical center.

Soon after ApoE was discovered as an AD risk gene in 1993, a genetic test became available. Concern over widespread testing among a poorly informed populace prompted discussion among professional groups, and they put the brakes on its routine use for the time being. In the absence of a preventive treatment, these groups warned, rushing headlong into genetic testing would be unethical. Between 1995 and 1997, working groups drawn from the National Institute on Aging, the Alzheimer’s Association, the American College of Medical Genetics, and the American Society of Human Genetics threw their weight behind a message of caution. They recommended against ApoE testing to predict future AD in healthy people. They felt that science still knew too little about ApoE genotyping to weigh the benefits of knowing against its downsides. How about genetic privacy? Would the person’s insurability, social standing, psychological health suffer? What would genetic counselors have to do to cushion the blow? Who would even want to know their ApoE status? Clearly, more study was needed.

To shed more light on ApoE susceptibility testing, in 1999 the National Institutes of Health funded a multicenter study headed by Robert C. Green of Boston University, called Risk Evaluation and Education for Alzheimer’s Disease (REVEAL). In the meantime, matters have advanced on the therapeutic front, as well. Mechanism-based experimental drugs are wending their way through the clinical trial process. If any of them prove their worth, public demand for ApoE testing may increase.

For its part, the REVEAL Study has yielded some of the data needed to guide the process and associated counseling. The first phase of the REVEAL Study enrolled 162 healthy adult children of people with AD. It offered half of them genetic counseling based only on their family history and gender; the other half received counseling with ApoE testing. Not all results are published yet, but here are the main findings to date:

Why Do People Choose ApoE Genotyping? The top reasons people cited grouped around altruism and coping. People wanted to arrange personal affairs and long-term care; they wanted to contribute to research and hoped that treatments would come online in time. They wanted to prepare family members, to do things sooner than planned, and hoped for relief if they were ApoE4-negative. People knew that knowing their ApoE status would not improve their medical care but opted for the test because they thought they’d be better able to plan and to cope.

Who Chooses to Find Out? People younger than 60 and college-educated people wanted to know, and women did so more than men (a preponderance of women also turned up in several international studies of HD predictive testing). Of the people the scientists contacted, a quarter chose to participate; of the ones who heard about the study and contacted the study coordinators themselves, 64 percent did. Self-selection strongly showed its face, as it does with predictive testing for deterministic diseases.

Genes as Destiny? In the REVEAL study, people placed great stock—perhaps too much—in genetic information. There were two groups who had the same total risk, but one had that level of risk with an ApoE4-negative genetic test result. These latter people perceived their risk as less worrisome and expressed relief because they were genetically “off the hook” even though their total family- and gender-based risk was actually identical to that of the second group who did not have the ApoE information.

Insurance: In the year after the study ended, few participants made changes to their health, life, or disability insurance, but the ApoE4 carriers tended to take out long-term care insurance. Future discrimination by insurers is an area that may require public policy protections.

Health Behavior: A constant drumbeat of health reports urging people to eat well and exercise has shown little efficacy, as rates of obesity, diabetes, and sedentary lifestyle inexorably increase. In this group, however, participants who received high-risk estimates at least self-reported certain changes, such as dietary improvements and exercise.

Psychological Consequences: Fears of depression and hopelessness were a major driving force behind the field’s hesitation to embrace genetic testing. The REVEAL study has not found evidence to support this. Knowing their ApoE genotype did not hurt participants’ psychological well-being. Participants already were anxious about their risk because of their parents’ AD; those without ApoE4 expressed relief, those with it expressed more distress initially but not at later follow-up times.

Genetic Counseling: The counseling protocol used in REVEAL works but is too time-consuming to be practical if ApoE susceptibility testing were to become widely available. A second phase of the REVEAL study is testing whether condensed education and counseling would adequately support risk assessment and genotyping. The abbreviated approach did away with the personal pre-test sessions mandated by widely used, extensive genetic counseling protocols and instead mailed out an educational brochure. Early results suggest that people who received risk assessment through the condensed protocol did just as well as those who were in the longer protocol.

In the future, demand for genetic risk assessment with ApoE disclosure will likely grow, especially if disease-modifying drugs are developed and people with higher risk wish to use them presymptomatically. If any of the experimental drugs now undergoing clinical testing prove to work better or worse in people who are ApoE ε4 positive, such evidence would add further incentive because then the ApoE test result would help the physician choose the right medication for a given patient. In addition, societal expectations are changing as we enter the era of “personalized medicine.” Increasingly, as shown in the REVEAL Study, healthy adults view genetic testing as valuable for coping with the fears they already have from managing their parent’s disease.

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Alzheimer’s Association and Clinical Trials: Let’s take a “real look”

By Joel Ross | January 6, 2012

My research practice started in 1987, many years before the NJ Alzheimer’s Association Chapter even was in it’s planning stage. The biggest challenge facing me and the stuy enrollment was access to interested patients and their loved ones. Lecturing to community centers, being invited to talk at houses of worship, going to senior centers, assisted living facilities, long term care centers (nursing homes), adult day care centers as well as lectures to doctors and other health care professionals was just a small part of what I had done to spread the word about the need to educate the public about “clinical trials”.
In I believe 2009 the Alzheimer’s Association finally got around to offering an online “trialmatch”. This helps patients, doctors, caregivers and anyone else interested in helping Alzheimer’s Disease patients find a clinical research site nearby and links them to the government website known as www.clinicaltrials.gov where all the important details concerning the study requirements are listed.
In Chicago I asked the diretor of that program recently how many patients actually become enrolled in any of the studies that “trialmatch” “matche”. Answer, “At this time we do not have the figures”. As of today, Jan 6, 2012 the number is still a big unknown, I would wager very few despite the huge expenditure of donors money (including my donations to the Alzheimer’s Association).

For my readers who want to visit the website, which I do endorse, simply click on the following link: https://trialmatch.alz.org/default.asp?i_user_type=pwd&i_user_action=match

Please ask those who have memory loss/MCI/Alzheimer’s Disease to think about volunteering for a clinical study.

Dr Ross

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A World Without Alzheimer’s Disease

By Joel Ross | January 3, 2012

There might be very soon (perhaps in 2012) a new study which will try to reduce the hippocampus from shrinking in those individuals who carry ApoE4.
Such individuals with or without a family history of dementia are high risk to develop such shrinkage of their hippocampi (the area of the brain where new memories are formed).

I encourage all my readers to keep this “top of mind” for those who might want to help rid the world of AD.
Stay tuned for more information on this important/ground breaking study.

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Merck and its BACE inhibitor

By Joel Ross | December 2, 2011

This information below is taken from a link from Merck’s recent presentation on it’s AD pipeline.
A BACE inhibitor acts to inhibit the production of toxic amyloid beta peptides that are 42 amino long.
It is currently under intense debate whether there should be drugs targeting any amount of amyloid in the brain. I believe the cause is related to the inability of the brain of AD subjects to properly balance production and excretion of normally produced amyloid. Please read below for Merck’s neweset attempt to combat this catastrophic/cataclysmic disease we call Alzheimer’s.

One can only cross one’s fingers and hope that Merck is really onto something with its new potential drug for Alzheimer’s disease.

In a press briefing last week, the New Jersey-based pharmaceutical giant updated the media on some of its early test results regarding what is now called MK-8931, according to The Star-Ledger of Newark.

http://www.nj.com/business/index.ssf/2011/11/mercks_prospect_for_alzheimers.html

This potential drug inhibits the creation of the enzymes that lead up to “the build-up of amyloid plaque, a trademark of the irreversible, degenerative disease,” according to The Ledger story published Friday.

“What makes it different, researchers explained, was the way it targets the so-called BACE enzyme to stop the accumulation of amyloid plaque,” The Ledger wrote of MK-8931.

Merck has identified Alzheimer’s drugs as a priority, but it is a risky one, as The Ledger pointed out.

Right now there is no cure for Alzheimer’s disease, which has become the Baby Boomer generation’s worst nightmare. A number of drug makers have spent a lot of R&D money — to no avail — trying to find a drug that will combat this horrendous disease, which robs people of their dignity.

Whoever finds a drug that successfully treats Alzheimer’s will not only be preventing heartbreak for generations to come, it will be hitting the jackpot in terms of generating revenue and financial success.

In this particular case, if Merck’s new drug works it will be a Godsend for all, not just the company’s shareholders but the public.

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Humanitarian of the Year Award

By Joel Ross | December 1, 2011

Joel S. Ross, MD, FACP, AGSF, CMD President and Founder of Memory Enhancement Center of America

December 1, 2011
Ocean County –Dr. Joel S. Ross, President and Founder of Memory Enhancement Center of America, Inc., with offices in Toms River and Eatontown, has been named the “Alzheimer’s Respite Care Program (ARCP) 2011 Humanitarian of the Year” by Caregiver Volunteers of Central Jersey (CVCJ). The honor will be given at the Annual ARCP Volunteer Recognition Brunch, December 1st at Harrogate LifeCare, 400 Locust Street, Lakewood.
Dr. Ross, MD, FACP, AGSF, CMD, is a recognized leader in providing comprehensive care for the patient with Alzheimer’s disease and other illnesses associated with memory loss. The Memory Enhancement Center conducts research on the effectiveness of investigational medications that may alleviate the symptoms of Alzheimer’s disease and slow its progression. His work with the CVCJ clients have included surveys of family caregivers, measuring stress and anxiety behaviors at intake and at three-month subsequent sessions once clients begin receiving CVCJ services. The resulting research will be invaluable supporting documentation as CVCJ moves forward in seeking funding from private foundations and government sources to enhance and extend its program for Ocean County residents.
The ARCP Humanitarian Award was created in 2003 to recognize individuals for their devotion and dedication to the elderly residents of Ocean County, especially those with Alzheimer’s disease and related memory loss.

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