Apr 122017
 

Perhaps your grandmother had Alzheimer’s disease; maybe your mom or dad is currently living with the disease. You may be concerned that you are seeing signs of the disease in yourself or a loved one. Whatever the situation, if your family has been touched by Alzheimer’s, it is natural to be curious if a genetic test is valuable in predicting the likelihood of developing the disease. Although the cause of Alzheimer’s is still unknown, scientists have identified a number of genes that impact your risk of developing the disease.

On Thursday, April 6, the U.S. Food and Drug Administration (FDA) announced that they have approved at-home genetic testing through the 23andMe Personal Genome Service Genetic Health Risk (GHR) test, which tests for genes associated with risk of 10 diseases or conditions, including late-onset Alzheimer’s. People will be able to send 23andMe a saliva sample and receive their genetic data back through the mail.

We spoke with Keith Fargo, Ph.D., Director of Scientific Programs and Outreach at the Alzheimer’s Association, about what you need to know about this type of testing – and what the results tell (and don’t tell) you.

Two categories of genes influence whether a person develops a disease: risk genes and deterministic genes. Alzheimer’s genes have been found in both categories. Can you explain the difference between these types of genes?

Risk genes increase the likelihood of developing a disease, but do not guarantee it will happen. Deterministic genes directly cause a disease; they guarantee that anyone who inherits one will develop the disorder.

23andMe says their genetic test evaluates more than 500,000 genes and gene variants. Regarding Alzheimer’s, it evaluates whether you have the APOE-e4 Alzheimer’s risk gene. It was the first Alzheimer’s risk gene identified and remains the one with strongest impact. Having one copy of the APOE-e4 gene increases your risk – having two copies increases it more – but it is hard to say exactly how much for any individual.

There are two other variations of APOE, known as e2 and e3. The e3 variation is relatively neutral and the e2 variation may provide some protection against Alzheimer’s dementia. The newly approved test does not evaluate for these variants. Plus, there are nearly 30 other genes that have been identified to also affect risk of late-onset Alzheimer’s, but (a) those genes don’t impact risk as much as APOE-e4, and (b) this test does not evaluate for them.

There are three more genes that have misspelling in their DNA or mutations where, if you have one, it’s a virtual certainty that you will develop Alzheimer’s dementia. These are the deterministic genes. The 23andMe test does not look for these gene mutations, either.

Part of the challenge with understanding the value of the newly approved test is that many people who have APOE-e4 never experience Alzheimer’s dementia symptoms, and many who do develop the disease do not have any copies of APOE-e4.

For this reason, and because of the current lack of proven preventive strategies, the Alzheimer’s Association does not recommend genetic testing for Alzheimer’s disease for the general population. If you are concerned about Alzheimer’s disease or memory changes in yourself or a loved one, the Association encourages you to have a frank conversation about your risk with your healthcare provider.

If someone’s parent or sibling had or has Alzheimer’s, is he or she at a higher risk of developing the disease?

The fact is this: everyone is already at risk. Of people 85 and older, one third of them have Alzheimer’s dementia. And having a family history of Alzheimer’s is not necessary for someone to develop the disease.

That being said, people who have a parent, brother or sister with Alzheimer’s are more likely to develop the disease, and those who have more than one first-degree relative with the disease are at even higher risk. But, again, it is hard to say exactly how much an individual’s risk may be.

If someone is interested in having genetic testing done, what are the first steps he or she should take?

The Alzheimer’s Association suggests that you talk to a genetic counselor before deciding to take the test and, if you decide to get genetic testing for Alzheimer’s, again after you receive the results. The National Society of Genetic Counselors website provides a searchable directory to locate a counselor by location and specialty.

What are the benefits of speaking with a genetic counselor?

A genetic counselor can help you understand what the test does and does not do. He or she can help you work through making a decision that is best for you in terms of ordering the genetic testing kit. Once you get the results back, he or she can help you determine what the results really mean.

Some people think that this is a diagnostic test for Alzheimer’s, but it’s not. It is a test for the presence of one or two copies of the APOE-e4 Alzheimer’s risk gene. It’s not going to answer the question most people have, which is: “Will I get Alzheimer’s disease?” You can have two copies of APOE-e4 and never develop Alzheimer’s disease. Conversely, you can have no copies of the gene and still develop the disease.

Do you believe that taking a genetic test is a proactive step in controlling one’s health?

For some people, yes. It may give them the motivation they need to make lifestyle changes that can reduce their risk of cognitive decline as they age, and possibly even reduce their risk of dementia. In fact, there are behaviors that we should all be doing to keep our brain healthy as we age. As a starting point, the Alzheimer’s Association has research-based brain health tips that we call 10 Ways to Love Your Brain. You can find them at www.alz.org.

That said, at the Alzheimer’s Association, we are concerned that people who receive results that confirm they don’t carry APOE-e4 will assume that means they won’t develop Alzheimer’s. The truth is that these people are still at risk.

With an unsupervised at-home test, there is a real possibility of people misunderstanding their results, which could result in making misinformed decisions about their health. A genetic counselor can be helpful in making informed decisions. If you choose to take a genetic test, discuss it with a genetic counselor before and after so that you are educated about the process, the test and what the results mean. And if you are already experiencing symptoms of cognitive decline, see a healthcare professional for a full evaluation.

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Aug 202015
 

My mother told me, when I was rather young, that no one’s soul ever dies. I imagine that each memory is a small flame, burning amidst so many others. They eventually create a swirling, shimmering glow, illuminated by love, flying up, up, up, until they light the sky with a brilliant glow.

As we walked through the halls of the clinic, I spotted a ninety-year-old woman on her bed, eyes wide, mouth open as if trying to scream. No sound came out. Her breath came in heavy gasps. A shriek, as a patient slumped over in his wheelchair. His orange juice splattered across his white t-shirt. A moan, as patients cast slow, lingering glances at random objects, their tennis-balled walkers gliding slowly across the cold, tile ground. A yell. A patient’s flare of anger at an invisible phantom, lurking behind the humming refrigerator. A groan. Patients forget, their old minds giving way beneath the weight of their disease. A cry. Another memory casually fizzled into the air. Wearing a red uniform, a nurse guided us into another depressing room, then another, and it seemed like the corridors and rooms were endless. Dark beige walls and dim lamps created a somber, gloomy effect, which is probably an understatement. Finally, we reached the hallway which led to where my grandmother was. Maliha, my grandmother.haris2

Silently, we walked to the television room, where there was a large group of elderly, white haired men and women, each focusing on the TV, although it was clear to me that they had no idea where they were or what was playing on that strange, small sound omitting box. Scanning the room, I finally located my grandmother in the crowd, sitting and chatting with another patient in her native language, Farsi. Because she was the only one in the entire room who was saying anything, we walked over towards her. Once she looked up at us, my mother and father bent down and kissed her on the cheek, and, as usual, there was not a significant sign of recognition radiating from her. However, she did say hello and converse with us; some friendly habits die hard. My sister gave me the usual quizzical looks whenever my grandmother would address her, due to my grandmother’s no longer sensical or straightforward phrases. Then, she looked me in the eyes, an unfamiliar look on her face. Studying her very closely, I noticed a food stain her collar. Her hair was turning gray. Her eyes, though, were the same as ever. She said to me, “What is your name, honey?” Each word came out with a struggle; she was slowly losing her English. I remember the precise way she said those four words: Long, drawn out syllables and consonants fighting, clawing their way out of her quivering lips. This question was common. I usually simply replied and told her my name over and over. However, it was as if suddenly, I could not speak; my whole body went rigid. Tears welled up in my eyes, and my throat constricted. Slowly, my palms went damp, and, in a long, reluctant, moment, I quietly mumbled my name to her. Distractedly, she nodded and smiled, clearly having no clue as to who I was. She continued to speak nonsensically, but I could not take it anymore. Feeling suffocated, I excused myself, and I burst out of the room and went to the bathroom.

Perhaps I should not admit it. Maybe I should hide it out of fear of being judged, but I will not. I will tell everyone: I cried.

harisNever again would my grandmother recognize me. It is not fair that someone who was once a kindergarten teacher, who had done so much for me and my mother, was now robbed of what was so rightfully hers, her memory. Nothing belongs to one person more than their own thoughts and memories, but hers were taken from her. I could not, perhaps still cannot, understand why she was chosen, why she was the one to lose her own beliefs, theories. It is one of the questions I would ask God, or whoever or whatever took my grandmother from me.

When I felt more relaxed and slightly less distraught, I walked back out. Quietly strolling down the hall, I stopped at her room. No one was there because my parents, sister, and grandmother were in the television room. So, slowly, I crept inside and sat on the bed. Reaching under her bedside table, I brought out a box my mother made for her, filled with pictures of my grandma, mother, uncles, aunts, cousins, and friends. As I looked, I suddenly stopped. In front of me was a picture of my grandmother. Standing in front of a tree, she looked to be in her mid thirties, with long black hair. All my life, I had been told that my grandmother was a beauty, so I was not surprised by her striking appearance. Instead, I was transfixed by the depth of her calm, knowing gaze, and the picture revealed a profoundly subtle side of her that I had never seen in other pictures. Her smile showed no teeth, just a small upward curve of her thin lips, and there was, somewhere, a shimmering inward beauty radiating from her. That image woke something, it illuminated something, a rare acceptance that I had not experienced since before my grandmother was diagnosed.

Out of nowhere, I remembered a quotation from her favorite poet, Hafiz, that she would always recite: “Even after all this time The sun never says to the earth, “You owe Me.” Look what happens with A love like that, It lights the Whole Sky.”

Looking at the picture of my grandmother, a flood of memories of how she was before the disease rushed back to me. How her eyes twinkled when telling a story, how she would hum when music was playing, how delicious her cooking was, how much she loved me and my sister and my mother, and not once did she ever say, “You owe me”. Not when she raised and cared for my mother, nor did she say it when she watched and gave advice to me and my sister. Now, she was the vulnerable, weak one, who needed our love more than anything in the world. So, we gave our love, as freely and plentily as she had given her love to us. Hiding the picture in my back pocket, I carefully closed the lid of the picture box. Stowing it beneath the table once more, I walked out to the television room.

Everyone was preparing to leave, so I followed them. When we left, I looked behind me, and for just a brief second, I saw that familiar look of understanding, that twinkle in her eye, the calm smile. It was like old times, when she would tell stories and throw her head back and laugh with me. In an instant, she was Maliha again. But, as all things do, it left.

I am glad, if not relieved, that the last image I can conjure of that day is of my grandmother’s eyes. They are sincere, genuine, and tender, welcoming me into her warm, loving embrace. They are not from a picture, or any clear memory I have of her. Just a figment of my imagination. Sunlight brightens the right side of her face, and I can tell she is outside.  I can almost smell the Earth around her and hear the grass rustle with the soft breeze as the sun slowly sets. I cannot say the image is clear. In fact, it is almost a blur in my memory, like an unsteady camera took the picture, only seen through an unclear, perfect haze. A slight glare from the sunlight taints the view. My grandmother’s deep, brown eyes are wrinkled at the edges, hinting to a smile somewhere else. The image just cuts off abruptly, so I cannot see her thin lips, her smile.

But I am not sad. No, no, all is well. No sadness or grief burdens me. She is there, my grandmother, still there, somewhere. That image makes me happy, not sad, because I know, even though I cannot see it, that she is smiling at me, a majestic, radiant smile.

About the Author: Haris Hosseini, 14, won a top prize in the National Council of Teachers of English Promising Young Writers Program with this essay. He and his family participate in Walk to End Alzheimer’s on Team Kayoumy. They walk in support of his grandmother Maliha Kayoumy, as well as countless others living with Alzheimer’s disease.

Haris’s father is New York Times best-selling author Khaled Hosseini, author of The Kite RunnerA Thousand Splendid Suns and And the Mountains Echoed.


Learn more:
Walk to End Alzheimer’s
Alzheimer’s Information for Kids & Teens
Inside the Brain: An Interactive Brain Tour

Jan 112012
 

As 2012 begins, I would like to review some of the highlights of the Alzheimer’s Disease world this past year, and the new directions that we will likely be heading toward in 2012.

  • This year we saw the publication of new diagnostic guidelines for Alzheimer’ s disease formulated by committees sponsored by the National Institute on Aging and the Alzheimer’s Association. The National Institute on Aging and the Alzheimer’s Association also published guidelines for diagnosis of mild cognitive impairment due to Alzheimer’s disease and for preclinical Alzheimer’s disease. These guidelines will be important tools for clinicians to diagnose Alzheimer’s in its earliest stages, and represent the first revision in 25 years.
  • An FDA advisory committee gave preliminary approval of the PET amyloid imaging ligand AV-45, citing work to be done to ensure consistency in reading PET scans. Full approval is expected sometime in 2012, if a uniform training program is implemented for radiologists interpreting the scans.
  • The European Medicines Agency announced the likely approval of hippocampal atrophy as a marker of early Alzheimer’s disease for the purpose of clinical trials. Much work has gone into linking hippocampal atrophy visualized by MRI  as an early and specific biomarker of neurodegeneration seen in Alzheimer’s disease.
  • IGAP—the International Genomics of Alzheimer’s Project, a transatlantic collaboration to create the most detailed map of genetic variants that link to Alzheimer’s disease was also launched in 2011. Meta analysis of genome-wide association studies (GWAS) revealed four new genetic risk variants for Alzheimer’s disease.
  • In terms of clinical trials, Gantenerumab, an antibody against beta-amyloid, was shown to clear plaques when given intravenously, according to results from a Phase 1 trial. The drug seems to be one of the most potent developed thus far in reducing plaques. A Phase 2 gene therapy trial for Parkinson’s disease was deemed a success. A similar Phase II gene therapy trial for Alzheimer’s disease, called the Nerve Growth Factor Study, is currently ongoing and recruiting. Multiple clinical trials, including the ADCS Phase III Resveratrol and Roche Phase II Gantenerumab trial are launching in 2012.
  • A very important paper by the Holtzman group at Washington University further established the relationship between ApoE4 genotype and decreased clearance of beta-amyloid from brain, both in humans and animal models. The idea that ApoE4 is less effective in removing beta-amyloid from the brain is not necessarily novel, per se, and had been previously shown. However, it had never been proven so convincingly and in such a complete manner in humans and animal models of Alzheimer’s disease. Together, the data suggest that ApoE variants contribute to a person’s risk for Alzheimer’s by affecting the clearance of beta-amyloid from the brain long before amyloid plaque deposition begins. Later in the year, the same group reported that, in mice, lowering the levels of ApoE4 results in fewer amyloid plaques. The results imply that ApoE-lowering treatments have a place among proposed Alzheimer’s therapies, including immunotherapy, gene therapy, and beta- and gamma- secretase inhibitors.
  • Results published in the Journal of the American Medical Association showed that women with sleep-disordered breathing (SDB)— pauses in breathing or reduced ventilation quality during sleep — are more likely to develop cognitive impairment five years later. The biology behind this finding may include hypoxia, or decreased oxygen delivery to certain parts of the brain, including the hippocampus which is critical in memory function. In addition, sleep fragmentation, which can interfere with memory consolidation, which occurs during certain stages of sleep, may also lead to cognitive problems. This study has really brought much needed attention to the evaluation of sleep as part of the work-up in individuals with Mild Cognitive Impairment.

We anticipate further progress in understanding the progression of the earliest stages of Mild Cognitive Impairment and Alzheimer’s disease with the Alzheimer’s Disease Neuroimaging Initiative (ADNI2), The Dominantly Inherited Alzheimers Network (DIAN) study and the Alzheimer’s Prevention Initiative (API) during 2012.

By Michael Rafii, M.D., Ph.D.
Director, Memory Disorders Clinic
Associate Medical Core Director
Alzheimer’s Disease Cooperative Study
University of California, San Diego

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