Science Fact: Alzheimer Disease, also known as Alzheimer’s Disease, is the scariest of all diseases for many people. It’s an mystery disease that robs you of your “self” and has no known cure.

Importance of Alzheimer Disease

Alzheimer’s ranks behind heart disease, cancer, airway/pulmonary disease, stroke and accident as a cause of death. Those other causes of death have visible causes and means of treatment and prevention. Alzheimer’s, on the other hand, has poorly-understood causes and currently cannot be cured.

Alzheimer Disease is a very specific type of dementia, accounting for 60 to 80% of all dementia cases. It is estimated that 115 million people worldwide suffer from dementia. Dementia accounted for 4.5% of all deaths in 1900 and Alzheimer’s, its modern face, is just as significant today, also amounting to 4.5% of all deaths. Alzheimer’s is increasing worldwide: by 2050, 1.2% of all people will be suffering from the disease.

Areas of Research on Alzheimer Disease

The mystery and the fear of Alzheimer’s has motivated lots of scientific work, which may be classified as follows:
– 1. Prevention
– 2. Diagnosis
– 3. Understanding
– 4. Cure
– 5. Alleviation of Symptoms
– 6. Support for Caregivers and Family Members

The middle two, Understanding and Cure, are interrelated: in order to find a cure we either need to get really lucky, or we need to understand how Alzheimer’s starts and progresses so we can learn how to interrupt its progress.

The last two, Alleviation and Support, are also related because they occur at the same time. Alzheimer Disease is very slow to develop and the patient may have the disease for many years before eventually succumbing to it. Medical science has found drugs that reduce the symptoms and improve the quality of life for the patient. More recently, studies have turned their attention to family members of the patient. Alzheimer’s is very difficult for the family: seeing a loved one deteriorate mentally is stressful and sorrowful; in addition, if family members are also caregivers there are additional physical and emotional burdens to bear. Both professional counseling and support groups are needed. The Alzheimer’s Association in the U.S. and many other organizations not only sponsor research toward a cure but also provide resources to help patients and their loved ones.

Added December 16, 2017: For a helpful infographic on early symptoms of Alzheimer Disease, as well as practical tips on talking with a person who has dementia, see Meredith Rogers’ November 2017 article.

Alzheimer Disease Prevention and Diagnosis

That leaves us with the first two steps in the sequence, Prevention and Diagnosis.

Today’s blog focuses specifically on these two areas. Why? Because:
– Many people have Alzheimer’s, but an even larger number hope to avoid it
– There is recent progress to report in both Prevention and Diagnosis
– Since we have no cure for Alzheimer’s, prevention becomes that much more important.

One conference is especially worth pointing out: the Alzheimer’s Association International Conference (AAIC), whose most recent meeting was held last month in Copenhagen, July 12-17, 2014. AAIC had a broad program of talks and many of the papers presented are summarized in articles at the Alzheimer’s Association website and on MedScape. Some of the research mentioned below was reported or confirmed at this conference.

Alzheimer Disease Prevention – Epidemiology

Obviously, an important goal is to prevent Alzheimer’s in the first place.

Many researchers have looked for correlations between Alzheimer Disease and various lifestyle factors. Since these studies were epidemiological rather than controlled experiments, we can’t be sure that these lifestyle factors caused Alzheimer’s. Nevertheless, that work has inspired recommendations in hopes of lowering the risk of contracting Alzheimer’s:
– Medications: Long-term use of NSAIDs (e.g. aspirin, ibuprofen and naproxen) is associated with a lower risk of developing Alzheimer’s; similar results have now been found for the diabetes drug pioglitazone (Actos).
– Mental & Physical Exercise: Mental stimulation, especially games and puzzles, and physical exercise seem to reduce Alzheimer’s risk.
– Diet: This website has previously remarked on the reduced risk of Alzheimer’s among coffee drinkers. A “Mediterranean diet” and light consumption of alcohol also seems to help.
– Sleep: We have previously commented that getting more deep sleep may slow the progression of Alzheimer’s. A new study of veterans has found that any kind of sleep disturbance increased dementia risk by 30%, increasing to 80% if they also suffered from posttraumatic stress disorder (PTSD).

Alzheimer Disease Prevention – Prospective & Controlled Studies

Epidemiological studies have the inherent limitation that they look at associations within a defined population. They can’t prove cause and effect. Thus, we can say that mental exercise is associated with a lower risk of Alzheimer Disease, but which came first? Does the mental exercise itself help stave off the mental decline associated with Alzheimer’s, as we might like to believe? Or is there some unknown factor that helps protect against Alzheimer’s and also predisposes a person to work crossword puzzles? The latter seems far-fetched, but can’t be ruled out without something more than an epidemiological study.

We can do somewhat better with a “prospective” study, in which a group of people is followed over a long period of time. Two prospective studies at the Mayo Clinic in Scottsdale, Arizona both showed that any level of physical exercise, as opposed to a sedentary life, reduces the risk of Alzheimer’s. One study looked at 1,830 normal adults for three years; the other followed 280 adults with “mild cognitive impairment” for an average of 2.3 years. In both cases, exercise protected against cognitive decline.

The most persuasive research, however, is to conduct a controlled blind study: different therapies are randomly assigned to participants, and the researchers themselves do not know which person received which therapy when they are analyzing the data. Results are now emerging from such a study by a 21-person research team with Dr. Miia Kivipelto as lead author. The published article attracted considerable attention and was reported by Time and TheWeek.

The study is called FINGER, for Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability. It involves 1,260 participants aged 60 to 77 who are believed to be “at risk of cognitive decline” based on standard tests. Half of the test subjects were randomly assigned to receive standard health advice. The other half were given an intensive program of nutritional advice, supervised strength training and aerobics, close medical supervision of cardiovascular health, computer-based mental stimulation and social support from their fellow participants.

Even prior to completion of the study in late 2014, there were already some significant results: the intensively supported participants scored 40% higher on tests of memory, executive function, and speed of thought; in addition, their risk factors for heart disease declined, indicating less risk of future dementia. It seems clear that an integrated program of nutrition, exercise, mental stimulation and social support is a good way to reduce the risk of Alzheimer’s and/or to postpone it.

Updated December 16, 2017: The completion of the Kivipelto study, published in 2015, confirmed the early results, that a combination of interventions and support can improve or maintain cognitive functioning in elderly people. A 2017 article summarizes what the Finnish researchers have learned about countering dementia. A 2018 report describes a world-wide initiative (WW-FINGERS) that will test these treatments in a variety of populations and settings, with participants being recruited starting in 2018.

What I conclude from all this work:
– Live Right Now. Lifestyle choices early in life can prevent or postpone Alzheimer Disease
– Live Right Later. Mental stimulation and exercise can delay mental decline even in those who already have Alzheimer’s
– Assess Your Risk. People who are at risk, or who have the earliest signs of Alzheimer’s, would be well advised to improve their lifestyle to stave off the disease.

Since right living can keep you healthy longer, it’s important to catch Alzheimer Disease early on, before it has led to mental decline. So diagnosis of Alzheimer’s is not just a concern for the physician or the researcher – it’s important to every one of us to help guide our personal lives. Which brings us to the remaining topic:

Alzheimer Disease Early Diagnosis

The discussion above should have made it clear that early diagnosis of Alzheimer’s, the earlier the better, is a worthy goal for many reasons.

Alzheimer Disease is characterized by, and may be caused by, the buildup of beta amyloid plaques and tau proteins in the fluid surrounding the brain cells.

The diagnosis of Alzheimer Disease in progress is generally done through mental testing; however, if the goal is to stave off a degenerative disease, that’s just too late. Therefore, there has been a concerted effort to detect Alzheimer’s at the earliest possible stage. This early diagnosis has typically relied on the analysis of cerebrospinal fluid for amyloids and tau proteins, using a spinal tap. Another technique directly images plaques in the brain using positron emission tomography (PET) imaging. Unfortunately, PET imaging is expensive and spinal taps are invasive, so better early diagnosis techniques are needed that can be widely used to identify people at risk.

Non-Invasive Testing for Alzheimer Disease

Less expensive and less invasive early diagnosis techniques are coming. Here are three that are in the news and that look very promising:

Sniff Test. One early sign of Alzheimer Disease is an impaired ability to smell caused by degeneration of the parts of the brain that process odors. A sniff test is very attractive: it’s completely non-invasive and so should be suitable even for people who are needle-averse. Two new studies used a 40-item scratch-and-sniff test, the University of Pennsylvania Smell Identification Test (UPSIT). UPSIT measures olfactory function, which is correlated with elevated brain amyloid and neurodegeneration. The researchers concluded that the sniff test was a useful early test for Alzheimer’s when used alone, and more conclusive when combined with a memory test. So it’s helpful, but not as powerful a test as we would like.

Blood Test. A blood test is not what you would call non-invasive, but nevertheless it would be valuable if it gave early diagnosis of Alzheimer Disease. After all, a blood draw is standard procedure in physicians’ offices, followed by in-office analysis or submission to a testing laboratory. A news article in Time and a press release summarize a research article by a 27-person team from universities in ten countries plus companies in UK and the US. Whew! The researchers identified a group of 10 proteins in the blood that can predict progression to Alzheimer’s with an accuracy of 87% – pretty darn good.

Eye Test. This test is the most surprising but could turn out to be the most reliable. It’s based on the fact that beta amyloid in the retina and the lens of the eye is strongly correlated with that in the brain. It’s easy to see why this should be true: the eye is practically an offshoot of the brain, with the retina performing some image processing functions and the optic nerve serving as a wide-bandwidth connection to the brain. In a sense, the eye is a transparent window to what’s going on in the brain. Whatever amyloid is in the retina diffuses throughout the eye and can also be detected in the lens.

OK, if the beta amyloid is there in the eye, how do we measure it? Two different approaches reported at the AAIC conference are summarized in an AAIC press release and a MedScape article.

In both studies, the researchers treated the eyes with a substance that would bind to the beta amyloid in the eye, and reveal its concentration by fluorescing under ultraviolet light. They state that this type of test could be performed routinely by ophthalmologists as part of an ordinary eye exam. In both cases, the optical measurements correlated well with PET scans of amyloid in the brain.

In the first study, CSIRO (Commonwealth Scientific and Industrial Research Organization) researchers had test subjects drink a liquid containing curcumin, which is the principal ingredient of the Asian spice known as turmeric. The curcumin, when treated with phospholipids, is absorbed into the bloodstream and when it reaches the retina, binds to any amyloid protein that is present. The curcumin fluoresces with green light when it is excited with violet or near-ultraviolet light. The fluorescence allows the amount of amyloid to be measured.

The other study was carried out at Cognoptix, a Massachusetts company. The patient is given a sterile eye ointment containing “a small molecule” (identity not specified) that is allowed to diffuse into the lens of the eye overnight. The molecule binds to beta amyloid in the lens and its fluorescence allows measurement of the amyloid present. The measured amyloid in the lens of the eye correlates well with the amount in the brain determined by PET imaging.

These research results are moving along rapidly, with commercial partners already participating in the studies. Therefore, we should see clinical trials of non-invasive or minimally invasive early tests for Alzheimer’s before long, I would hope within a couple of years.

Science Speculation: Two other recent research results did not fit into the above discussion, but are so striking that they deserve mention.

Widowhood Prevents Alzheimer Disease. A woman who loses her husband generally becomes more vulnerable to serious diseases, including cancer and cardiovascular disease. Therefore, it was assumed that widowhood would also accelerate the survivor’s mental decline. Surprisingly, the opposite was found: widows are less likely to get Alzheimer’s, and if they do get it, they contract it at a much later age. [The researchers do not recommend trying this prevention technique yourself.]

Cataract Surgery Helps Preserve Mental Functioning. When a person gets Alzheimer’s, sometimes physicians and family members are so concerned with treating the disease that other medical conditions are either not diagnosed or not properly treated. Researchers found that when patients have dementia and also have cataracts, cataract surgery not only improved the patents’ vision but also improved their dementia. In particular, patients who had cataract surgery showed a slower rate of cognitive decline, fewer neuropsychiatric symptoms, and reduced stress on their caregivers. Apparently cataracts not only affect vision, but they tend to isolate the dementia patient from his surroundings, and that accelerates his mental decline.

Both these studies help illustrate the complexity of Alzheimer Disease therapy and the breadth of research that is ongoing.

Do you have experience with Alzheimer’s in your family? Where does Alzheimer’s rank in your personal list of “dread diseases”?

Acknowledgement: I thank Charles South for directing my attention to Alzheimer’s in general and to the blood test work in particular.

Image Credit: “Brain” from The Print Shop 2 Collection. Not for download or reuse.