Are Your Little Memory Lapses Really As Innocuous As Your Doctor Claims They Are?

Let’s say you’re 55 and learned today that you’d definitely live to be at least 85.

That would be pretty good news, right? But what if you learned, at the same time, that you’d positively be in the 47 percent of the population over 85 that gets Alzheimer’s disease. Not such good news, you say.

Guess what? Chances are, as an American woman, you will live to be close to 85, according to life expectancy statistics from the World Health Organization. Sadly, there’s that ominous fact that in the living population, 85 and older, 50 percent have a chance of getting Alzheimer’s disease. Simply put, the longer we live, the greater our chance of getting this horrific disease that causes our brains to waste away. Since there’s no cure yet, this is a frightening fact, even if the grim prospect of affliction is decades away for you.

Happily, a breakthrough, non-invasive eye test may soon tell us, years before symptoms actually show up, whether we’ll likely get Alzheimer’s. Hopefully, it also will help the medical community to create a drug that can stop the progression of the disease once an early diagnosis is made.

I had the privilege recently to interview the man who led the team that invented this test, Dr. Keith L. Black, Chairman and Professor of the Department of Neurosurgery, Director of Maxine Dunitz Neurosurgical Institute and Director of Johnnie L. Cochran, Jr. Brain Tumor Center at Cedars-Sinai Medical Center in L.A. I urge you to read every word. Besides giving you a straightforward, no-nonsense understanding of Alzheimer’s, the doctor explains if there’s anything we can do to attack the disease before it irreversibly attacks us and whether our little memory lapses are as innocent as our friends, relatives, and doctors say they are.

The interview unsettled me, but it gave me essential knowledge about a disease that has taken many of our loved ones for generations, is now taking many of our parents and is painfully close to taking many of us. It’s knowledge I think we all need to know. I hope you agree.

FOF: As simply put as possible, what’s the difference between Alzheimer’s and Dementia?

Dr. Black: Dementia is the big circle. It’s a characterization of laws of cognitive function from a number of different causes, including vascular dementia (micro strokes that can occur as we age); dementia related to other diseases, like Parkinson’s, which has a dementia component; frontotemporal dementia (reduced function in the brain’s frontal and temporal lobes, which control planning and judgment; emotions, speaking and understanding speech, and certain types of movement); dementia from metabolic states, such as a metabolic imbalance, which is caused by heavy metal intoxication, to dementia caused by Alzheimer’s. Of the entire bucket of dementias, the most common is Alzheimer’s, which makes up about 70 percent of people with dementia.

How many people are diagnosed with Alzheimer’s each year?

That number is increasing because the population is living longer. The best way to think about it is how many people at a particular age will actually have the diagnosis of Alzheimer’s, because it’s a function of age, which can be different in different countries, depending on life expectancy and other factors. The longer we live, the higher the number of people who will have Alzheimer’s at a particular age. By the time you’re 85 and older, approximately 47 percent will have a diagnosis of Alzheimer’s.

What about younger people?

At 65 and older, 1 in 8 people will have Alzheimer’s. We used to think about it when people became symptomatic. When we could do a memory test and say you lost so much of your cognitive function, we’d give you a diagnosis of Alzheimer’s.

We now know that this is a naive view because the disease probably starts 20 to 30 years before patients actually become symptomatic, not when they become symptomatic.

It’s more complex, so the best way to think about it is on a spectrum. First, there’s the presymptomatic phase, when all the pathology that’s developing in the brain is occurring; then the patient progresses to an early symptomatic phase, which we characterize as MCI (mild cognitive impairment), and, finally, he or she experiences enough cognitive decline to meet the definition of Alzheimer’s disease.

What happens in the brain at the different stages?

• During the presymptomatic phase, there’s a build-up of protein plaques in the brain, called a beta-amyloid, which are dense, mostly insoluble clumps of protein fragments. They leave a highly damaging substance outside and around the brain’s nerve cells.
• Then, about 10 years before becoming symptomatic, a patient starts getting neurofibrillary tangles (insoluble, twisted fibers that clog the brain from the inside-out), followed by inflammatory pathology in the brain, difficulty with connectivity within the brain, and then loss of brain cells.
• The brain is redundant, so as all of this pathology is beginning to build up, your brain cells are dying. If you start off with 100 billion brain cells, by the time you become symptomatic you’ve lost 40 percent of your brain cells (60 billion) and that’s when you get the clinical diagnosis of Alzheimer’s.

Please explain, in layman’s terms, what your new eye test will reveal.

NeuroVision Imaging, a company I co-founded with Steven R. Verdooner, has invented a noninvasive optical imaging system which appears to detect changes associated with Alzheimer’s disease with a simple eye test.

Since Dr. Alzheimer first described the disease in 1906, we’ve known that the buildup of plaque and neurofibrillary tangles were the hallmarks of the disease. A brain biopsy was the only way to determine this early on. Recently, PET scans have been a good way to look at the amount of plaque buildup in the brain, without doing a brain biopsy, but they are 80 percent accurate because you don’t have the best resolution. A spinal tap also can measure the amount of the toxic protein. Blood tests aren’t very accurate.

Then we have our retinal test.

The retina is an extension
of the brain, and so looking through the eye is like looking through a window into the brain.

The test gives us the ability to see plaque in very exquisite detail, down to individual plaque at about 20 microns, versus a couple of millimeters detected by a PET scan.

Preliminary results of 40 patients showed that beta-amyloid levels detected in the retina with the eye test were significantly correlated with beta-amyloid levels in the brain that appeared using PET imaging. The retinal amyloid imaging test differentiated between Alzheimer’s and non-Alzheimer’s subjects with 100 percent sensitivity and 80.6 percent specificity.

If your eye test shows plaque build-up, how accurately can you predict when a patient will become symptomatic with Alzheimer’s?

The retinal test will give us the amount of plaque that you have; the rate of the buildup of the plaque could be a very important predictor, as well. If the level of your plaque is stable, you may have a lower probability of progressing quickly then if your plaque is building up very fast. You have to repeat the test over time to see the progression of the plaque. We haven’t looked at patients long enough to YET understand the implications.

What’s the advantage of being able to diagnose the build-up of protein plaques in the brain years before we become symptomatic, when there’s no cure for the disease?

There’s a growing body of scientific evidence that lifestyle changes can slow down the progression of the disease, that aerobic exercise, for example, can decrease the build-up of these plaques.

If someone is 60 and learns she has plaque build-up, will it help to start exercising?

Yes, it will help to slow down the progression of plaque if you start an exercise program at 60, when you’re asymptomatic, and have 10 or 15 years before becoming symptomatic. There’s growing evidence that the earlier you start exercising, the greater the benefit.

Would you have the test before 50?

Yes, if you’re in a family with a strong genetic predisposition for early Alzheimer’s (before 65). Some people can develop it in their 40s and 50s.

When will your test be approved by the FDA?

We’re looking at getting FDA approval within a year. Unlike the long process to get a therapeutic drug approved, this is a non-invasive, safe diagnostic, so we’re looking at getting approval sometime in 2015, assuming we don’t get any delays from the FDA. At that point, doctors can start using the test and discussing the results with their patients.

When would your test be most beneficial?

The test would be beneficial throughout. When you’re 50, you can try to change your lifestyle. When you’re 70, you can start planning if you know you’re starting to develop the disease. Who is going to manage your estate, your financial affairs, who is going to be your caretaker?

Drug companies now believe that many of
their clinical trials to treat Alzheimer’s failed because they were treating patients too late, when they already had Alzheimer’s and lost 40 percent of their brain cells and half of their brain weight.

The probability of successful treatment would be greater if you could start it earlier. So the most exciting clinical trials now are looking for patients before they actually have Alzheimer’s, at the presymptomatic stage.

The only way to get into clinical trials now is to have a screen with a PET scan to detect amyloids, but it’s not easy to get to one, it’s expensive, it’s radioactive and it’s not reimbursed by the insurance companies. So it’s unlikely you’d get a pet scan at 50. But if you had an inexpensive, non-radioactive, non-invasive test, and you tested positive after having this screen, you could be a candidate for some of the newer trials with drugs to prevent the onset of the disease.

The new retina test also will be able to see if the plaque is going up or decreasing as a result of your lifestyle changes. If you can modify the bad thing that’s causing the disease, early enough, then that could make a difference. The unfortunate reality today is that Alzheimer’s is detected far too late for patients and their loved ones. Having an easy exam that can detect disease sooner will pave the way for earlier interventions with new therapies.

What other lifestyle changes could have a beneficial effect?

The Mediterranean Diet tends to confer a protective effect from Alzheimer’s. Omega 3 fatty acids (DHA) may be beneficial in clinical trials, according to a number of reports. Clinical trials are looking at the active ingredient, cumin, in the Indian spice curry, which may be beneficial. Coffee may be protective.

We don’t know what the maximum benefits can be, but if you assume the plaque build up is slow, and lifestyle changes (starting at 50) could decrease the accumulation by half, you would essentially get Alzheimer’s at 95, instead of 75. So you could live out your life without becoming symptomatic.

What puts you at greater risk for Alzheimer’s?

If you have one first degree relative, it doubles your risk of getting Alzheimer’s. The most common genetic test looks for the apoe4 gene. If you carry one gene, your risk is twice that of the rest of the population; two genes, your risk is four times greater. It’s a simple saliva test. The longer you live, the greater your chance of getting Alzheimer’s.

Are there definitive signs that you have Alzheimer’s?

By the time you have any symptoms you’re at the advanced stage of the disease. If you live long enough, everyone will get Alzheimer’s eventually. We begin to lose cognitive function at age 30, but the brain has a nice reserve, so a 30-year-old is going to be quicker in learning new tasks than a 65 year old. There’s the normal aging process and there’s the accelerated process that occurs with dementias. Anyone who isn’t functioning quite as well at work as they used to, not remembering as well as they did, those could be early signs. When we hit our late 50s or 60s, we’ll all moving to that phase when we could see early signs.

You may not be classified as clinically symptomatic (where you score at a certain level on the memory or cognitive test), but you could fall into the worried memory loss or subjective memory loss group, if you begin to worry about your memory, let’s say at around 60. That’s the phase right before you go into mild cognitive impairment. If you have memory loss events, it could be another kind of dementia, but it’s most likely Alzheimer’s.

Of what is a patient with advanced Alzheimer’s aware?

At the early stages, you know what’s happening. At the advanced stages, you’re probably not aware and probably don’t care. Patients at advanced stages become apathetic to the fact that they have the disease. At the advanced stage they most likely have lost cognitive function to the point that they don’t understand they have the disease. The emotional impact at that stage is not so much on the patient but on the family and on the caregivers.

So you really don’t know definitely what someone with advanced Alzheimer’s is thinking?

We don’t know that with absolute certainty because we can’t get inside their head because they’re so impaired. There are probably little flashes that they have the disease, but mostly no.

why do we die from Alzheimer’s?

The brain basically wastes away. Patients are bedridden, they aren’t able to eat or hold their secretions, so they end up dying from pneumonia or blood clots to the lungs and things like that.

Why is Alzheimer’s such a big concern for us today?

My grandfather lived on a farm and died at about 89. I don’t know if he had Alzheimer’s or not. Towards his later years, he had multiple generations around him. Grandpa would walk around, sit in his rocking chair on the porch, go back in and have dinner and watch a little TV. A couple of generations ago, life was very simple. We can’t live like that in current society. Most of us are out working, and would have to pay for caregivers to watch our parents with Alzheimer’s. We have things in our house that are very dangerous. You can’t make a phone call without really knowing how to use a smartphone. Life is very complicated. We use our brains now more than ever. The ability to live in this society, with cognitive impairment, is becoming much more difficult than it was 30 years ago.

Do any of the brain tests and games that are heavily promoted on the internet help our cognitive ability?

Lumosity, probably not. Doing the New York Times crossword puzzle that you’ve been doing for 30 years, probably not. Engaging in mental activity that is different, outside your comfort zone, probably. If you’ve been terrible at languages all your life and you try to learn a foreign language at 70, that’s really good. If you’ve been terrible at music and now you try to learn to play the piano, that’s really good. What you really want to do is to increase connectivity between brain cells. Doing something that’s really easy for you, that you’re used to, like riding a bicycle, won’t do it.