Authors: Majid Fotuhi
* With aging, most elderly people accumulate some degree of plaques and tangles in their brain without having any symptoms; this is called “silent Alzheimer’s.” Some will accumulate a great deal more and experience serious brain atrophy and dementia. The more plaques and tangles, the more their brains shrink and the more likely they are to develop memory loss, confusion, or difficulty in managing their simple daily routine.
† When combined with other brain shrinkers—like diabetes, hypertension, obesity, sedentary lifestyle, depression, PTSD, TBI, and sleep apnea—the risk of brain atrophy escalates and the patient experiences dementia faster.
A diagnosis of mixed dementia, when properly applied, could open up new treatment options for patients who might otherwise be seen as untreatable. That’s especially true given that reducing cardiovascular risk factors and preventing future strokes are known to be important strategies for preventing or slowing the progression of mixed dementia, as one group of researchers recently noted in
JAMA.
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Diagnosis In Action
Although there’s no single test to determine if someone suffers from pure Alzheimer’s disease, new procedures do exist to identify the presence of Alzheimer’s pathology in living people. For now, such methods aren’t routinely employed by most doctors for diagnosis and are not recommended by the American Academy of Neurology.
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Doctors, instead, rely on a battery of tests—some cutting edge, some tried and true and decidedly low-tech. Those methods might include MRI scans, blood tests, and a variety of health measures to rule out other conditions, as well as cognitive testing to gauge a person’s level of impairment.
Here are some of the diagnostic tests now available:
CSF
Cerebrospinal fluid (CSF) tests can look for a specific ratio of tau to amyloid, which seems to be highly indicative of a high risk for Alzheimer’s disease. This test isn’t perfect, as some people with abnormal CSF may not have symptoms of dementia. In addition, it’s somewhat invasive, as it requires taking a sample of spinal fluid through lumbar puncture.
PET Scans
These are new brain imaging techniques that can detect, by using radioactively labeled ligands (or markers), the presence of specific proteins in the brain. Radiologists have developed new ligands to label and visualize the footprints of Alzheimer’s disease in a living patient. These ligands are:
•
FDG,
a marker for glucose. Low FDG in the temporal, parietal, and frontal lobes is indicative of low brain activity and may indicate damage caused by Alzheimer’s pathology.
•
Pittsburg compound B
(PiB), which allows us to see amyloid plaques in the brain. Unfortunately, this ligand only alerts us to the presence of amyloid; it doesn’t tell us about tangles and it doesn’t tell us who will develop dementia and how severe it will be. In fact, between 20 and 50 percent of elderly people might have a positive PiB test without showing clinical signs of dementia.
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•
Florbetapir,
a newer ligand that detects the presence of amyloid. It is now available to the general public, but Florbetapir suffers from the same disadvantage as PiB. Some 21 to 28 percent of cognitively healthy elderly people tested have Florbetapir results that indicate the presence of amyloid even though the person doesn’t have dementia.
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In addition, a third of the patients who have symptoms of Alzheimer’s disease have negative Florbetapir results.
•
FDDNP
(fluorine fluoroethyl [methyl] amino naphthyl ethylidene malononitrile), which detects both plaques and tangles.
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FDDNP may prove to be the best tool for diagnosing Alzheimer’s, but the downside is that its results aren’t specific to Alzheimer’s. It can also pick up other conditions that are known to cause plaques and tangles, such as in football players who have chronic traumatic encephalopathy (see
chapter 13
), leading to the possibility that a football player in his sixties (who had concussions in his twenties) might be misdiagnosed with Alzheimer’s disease.
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Boxers and soldiers with blast trauma would also likely have a positive result on this test.
Of course, a negative scan using any of these methods can be extremely helpful because it tells us amyloid and possibly tau
aren’t
present.
Brain MRI
Of all the tests currently available, I favor brain MRIs that measure hippocampal size and atrophy. These tests are noninvasive and the results are quite robust, thanks to the strong correlation between Alzheimer’s disease and shrinkage of the hippocampus. Still, they’re not perfect. Some people with TBI or depression may have small hippocampi. If their symptoms are caused by these factors, we wouldn’t want to diagnose them as having Alzheimer’s disease.
Based on the fact that no one test is 100 percent accurate, a group of experts has suggested that an Alzheimer’s diagnosis should be given only if a patient has dementia plus abnormal results on one or more of the tests above (CSF, PET, or MRI for hippocampal atrophy).
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This is a work in progress and I expect new developments in the near future.
Slowing the Slide?
If you were experiencing memory or other cognitive problems late in life and you knew or suspected you had Alzheimer’s disease, you and your loved ones would likely be eager to find a cure. Or at least a way to slow your decline. And your children would likely be anxious to see what they could do to prevent themselves from developing the disease in old age. Since Alzheimer’s pathology clearly plays a role, one option would be to seek out a cure that clears the brain of plaques and tangles or prevents their further accumulation. Unfortunately, though there’s been much research in this area, neuroscientists haven’t had a great deal of luck so far. Part of the reason is that plaques and tangles likely accumulate for decades before dementia appears, making late-life treatment “too little, too late.” So far, every clinical human trial aimed at removing amyloid plaques has failed to produce a cognitive benefit for patients. There is some hope, however. New trials show some positive results that we may build on in the future.
Another option would be to realize that Alzheimer’s pathology isn’t the only cause of late-life Alzheimer’s disease in most cases. This means you might be able to grudgingly accept its presence and focus instead on eliminating other brain-shrinking ingredients in the soup of dementia causes.
The scientific evidence for prevention is quite strong. Hundreds of research studies, some of which you’ve already read about, suggest modifying certain factors reduces the risk of developing Alzheimer’s disease late in life.
Those efforts almost always come down to boosting brain size. We know, for example, that having a large hippocampus greatly reduces your likelihood of experiencing the symptoms of dementia, even if you have the footprints of Alzheimer’s in your brain.
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Therefore, actions that boost hippocampal size are vital to remaining free of symptoms. Increasing BDNF, enhancing oxygen flow, and promoting healthy brain activity—as you’ll do in your twelve-week brain fitness program—will help add synapses and blood vessels, and bolster highways throughout the brain.
But could such interventions help people who already have MCI or Alzheimer’s disease? Although little can be done to reverse the damage of advanced Alzheimer’s disease, recent studies suggest that certain interventions may provide some help for MCI patients.
In one randomized controlled clinical trial in Seattle, for example, researchers enrolled thirty-three adults with MCI and assigned half to a stretching group and half to a high-intensity aerobics group.
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The aerobics group exercised under the supervision of a fitness trainer for forty-five to sixty minutes a day, four days a week, for six months. The control group, meanwhile, completed stretching activities on the same schedule. All participants underwent treadmill fitness testing and memory testing before and after the study. Six months after they’d started, those who’d engaged in aerobic exercise showed improvements on tests of executive function and had increased their levels of BDNF.
Resistance training may also help. In one study, researchers found that resistance training promoted cognitive and functional brain plasticity in patients with MCI.
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The study included eighty-six women between the ages of seventy and eighty. By the close of the six-month study period, those who’d engaged in resistance training showed improved performance on tests of executive function and functional changes in the frontal lobes, as captured by fMRI.
Cognitive stimulation has also been shown to bring with it subtle brain performance improvements in MCI patients. One randomized controlled pilot trial of forty-seven MCI patients, conducted by my colleague Dr. Kristine Yaffe, looked at the effects of intensive computer-based cognitive training.
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The training was specifically designed to improve auditory processing speed and accuracy and was given to patients for a hundred minutes a day, five days a week, over a period of six weeks. A control group, meanwhile, engaged in passive computer activities, such as reading or listening. Participants in the cognitive training group, whose average age was seventy-four, saw small improvements in their total testing scores. And, compared to the control group, they did slightly better on verbal learning and memory after training.
Another small randomized study of forty-three people with MCI and mild Alzheimer’s disease found that a group assigned to cognitive stimulation for six months saw improvements in memory and mood.
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A large systematic review of this literature, published in 2012, concluded that MCI patients do benefit from cognitive stimulation—and that positive changes can be detected on MRI.
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This review of twenty studies from different research centers around the world provides evidence that neuroplasticity is at work even in patients who have MCI.
Prevention and Treatment
You’ve no doubt heard talk about an epidemic of Alzheimer’s disease on the horizon. In 2007, the Johns Hopkins Bloomberg School of Public Health announced its prediction that the number of people suffering from Alzheimer’s disease worldwide would quadruple by 2050. Even now, the Alzheimer’s Association puts our risk of developing Alzheimer’s disease by the age of eighty-five at nearly 50 percent.
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Those are pretty grim statistics. But what do they mean for you? Can you prevent Alzheimer’s disease? The answer, once again, depends on what we mean by Alzheimer’s disease.
For early-onset Alzheimer’s disease the answer is no, at least for now. Researchers may one day discover a way to silence the gene mutation responsible for the disease or block the aggregation of plaques and tangles, but currently there isn’t much that can be done in the way of prevention. Three large clinical trials with anti-amyloid drugs are about to start, however, so we may learn more as they wrap up, beginning in 2016.
The news is much brighter for late-life Alzheimer’s disease. Researchers will continue their efforts to find a cure (my prediction is that there will never be a single cure), but in the meantime, preventive measures come down to building brain reserve and reducing the factors that shrink the brain. This was the basis of my first book,
The Memory Cure
(published in 2002), and though the notion was controversial at the time, now it is widely accepted.
This all, of course, comes with a caveat: even the most rigorous of efforts can’t prevent every case of late-life dementia. There will always be people who eat right, exercise, sleep well, and treat their health conditions and yet still go on to develop Alzheimer’s disease late in life. But for most people prevention is entirely possible. And as someone who sees the effects of Alzheimer’s disease every day, I can tell you it’s a worthwhile endeavor.
At my Brain Center, my goal is to help patients sharpen their brain performance and prevent any memory loss or further cognitive decline in the future. But the goal posts move depending on the patient’s situation, and the lines between treatment and prevention blur, since some treatments can act as prevention, helping to slow further decline.
For each patient in my brain fitness program, I develop an individualized treatment plan that is specific to them, their needs, and their families’ needs. As you’ve read throughout the book, the effects can be dramatic, even if the program is started in middle age or late life.
Back to the Party
Remember those questions from worried friends and family at social gatherings I attend? My immediate response, “It’s probably not Alzheimer’s,” always earns me a relieved smile. But as happy as my friends and family are to hear they’re not likely suffering from a dreaded disease, they’re not off the hook. In fact, the memory lapses and slowed thinking that prompted their concern are a powerful reminder of the importance of a brain-healthy lifestyle throughout life. Not only will these efforts yield nearly immediate results, but the brain reserve created in the process will also go a long way toward preventing, or at least delaying, development of the type of late-life dementia that’s often diagnosed as Alzheimer’s disease.