I, like many of my patients, have elderly parents. Years ago, my mother started having balance problems and over time developed short term memory loss. Both symptoms are now severe. My father has been her caretaker but as he turned 90 developed multiple medical problems. Even though he is a theoretical physicist and writes and publishes articles in prestigious journals (in which the only words I truly understand are “the” and “or”), he too has what I call “cognitive slow down”. So when I came across an article about early Alzheimer’s disease in the clinical practice section of The New England Journal of Medicine I paid special attention. The author described a 72 year-old business man who was seen by a physician at the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at Columbia University. This individual had occasional lapses of memory and his wife was concerned that this indicated early Alzheimer’s disease.

We all have memory lapses, so how do we or our family know when to seek help? How is a definitive diagnosis made?

First, let me list some of the statistics that were reviewed in the article…”Alzheimer’s is the most frequent cause of dementia in Western countries affecting an estimated 5 million people in the US and 17 million worldwide.” It affects about 1% of the population between the ages of 60 and 70,  this increases to 6 to 7% at the age of 85 and in countries were survival to the age of 80 is not uncommon it is present in up to 30% of these older individuals!

When pathologists look at the brain of patients who had Alzheimer’s disease, they find plaques of a specific protein (beta-amyloid) and deposits of tau protein that cause tangles at the ends of neurons. These plaques and deposits then disconnect and destroy the brain cells. A family history seems to be one of the most important risk factors for Alzheimer’s disease. First degree relatives of those who had late-onset disease have twice the usual lifetime risk of developing Alzheimer’s disease. A single mutation can sometimes be found in rare families with early–onset Alzheimer’s.  More frequently there is a genetic change or variant that codes for a protein called APOE e4 which is associated with late onset Alzheimer’s. If a person inherits one allele (i.e. this variant is on one of 2 chromosomes they get from their parents) they have a double to triple risk of lifetime disease. If they have inherited 2 of these alleles (one from each parent), the risk increases by a factor of 5!  (Note a test for this allele can be done but many individuals who are positive don’t develop the disease hence it’s not a part of general screening tests…no I haven’t done it on myself.)

So how do clinicians make a diagnosis of Alzheimer’s disease? We all start complaining about trouble recalling names (as in “who was the actor in that movie about, you know?” …or “I know I met that person at what’s her names event”… or recent events; “Did I have chicken or fish for dinner yesterday? Or more commonly; “Where did I put my reading glasses?”  In the early stages of Alzheimer’s, there is an increasing inability to retain recently acquired information whereas memory of remote events is usually spared until the disease has progressed. There may be a decline in verbal memory and the ability to perform sequential tasks. (The more medical term is “executive function”…with no specificity for MBA’s). As the disease progresses, this is followed by a reduced independence in daily activities.

Clinicians can administer a test that measures functional cognitive status; it’s called the Clinical Dementia Rating scale; the higher the score the greater the severity of impairment. (Note the test takes 30 to 45 minutes and often will require a special referral). And as memory declines, patients may have changes in mood, suffer delusions or can exhibit psychotic behavior. The latter can make dealing with Alzheimer’s patients difficult. (I know this from very upsetting personal circumstances and have to tell myself that I can’t argue this behavior away) Brain imaging has come a long way in helping identify early Alzheimer’s. Radiologists can detect areas of atrophy (inactive and “shrunken”) with MRI that occur in certain areas of the brain in patients who are likely to go from mild cognitive impairment to full blown Alzheimer’s. But there is no standard technique for doing this and these scans are too expensive to become the routine for diagnosis. Pet scans that look at metabolism, blood flow as well as ameloid binding of specific injected substances in certain areas of the brain, have also been used to predict progression of the disease but this too is costly and not widely available. There are also tests that measure levels of specific plaque associated proteins in the fluid that surrounds the spine and the brain, but this requires a lumbar puncture (“spinal tap”) and obviously is not done as a first line diagnostic test. Often the diagnosis is made by exclusion of other causes of dementia.

So what treatments are available? We have all seen the ads about medications that will help our loved ones keep their memory for longer and retain function (usually around the beach or on vacation). The author of the NEJM article lists 4 medications that are FDA approved for drug therapy for Alzheimer’s. They are Aricept, Exelon. Razadyne and Namenda. He states that “randomized , placebo-controlled clinical trials of cholinesterase inhibitors (I won’t go into that phrase but it includes the first three drugs) for  mild-to-moderate Alzheimer’s  have shown significant but clinically marginal benefits with respect to cognition, daily function and behavior. The rate of decline of patients on these meds was slower than untreated patients. He then went on to state that 27 studies showed no clinical difference on cognitive performance between the drugs but on the basis of 14 studies that measured daily function, Aricept was modestly more effective than Exelon. (Note they all have side effects so one may cause less for a particular patient than another.) Nemanda was also found to have marginal benefit for 6 months and has been used in patients with severe disease in combination with Aricept.

Since none of these therapies seem to “cure” Alzheimer’s and at best can stall progression for an all too short a time. What about alternative therapies…vitamins, statins hormones or anti-inflammatory drugs? Unfortunately, randomized trials have not shown any consistent benefit. And ginko biloba, carnitine, lecithin, curcumin, periwinkle and phosphtidylserine (that are touted by the salespeople in the health food sites and stores) have likewise not been shown to help in randomized trials.

So what can be done for that 72-year-old patient (and our relatives)? The diagnosis may be difficult, and  the clinician has to try to establish  that there are no mini strokes, no vitamin B12 deficiency, central nervous infection, substance abuse, medication reactions, HIV infection or cancer (with brain metastases). Mental exams should be done and, if necessary, a brain MRI. One of the above mentioned medications might help….but ultimately it is the caregiver who with patience and understanding will have to ensure that the patient is kept safe and loved for as long as possible. The author (and I) can’t offer much more advice. I wish I could end this article on a more positive note…I am currently trying to get my parents to agree to have a full time caretaker live with them. So far they refuse.

I keep a mental dietary list which I review at the end of each day…”Let’s see, I had juice in the morning, salad at lunch, two vegetables at dinner and fruit for dessert. OK, now I’ve had my five or more fruits and vegetables and have done my nutritional duty to ward off cancer.” It turns out I am giving myself inadequately proven anti-cancer food advice.

The largest prospective study to date, the European Prospective Investigation into Cancer and Nutrition study (wisely acronymed the EPIC study), followed 478,478 individuals aged 25 to 70 years in 10 European countries for a median of 8.7 years. (How they got to a number that has those matching numerals is a mystery.) Unlike many large studies, women comprised the predominant gender (335,873 women vs. 142,605 men). The overall cancer incidence rates were 7.9 per 1000 person –years for men and 7.1 per thousand-person years for women. When the researchers analyzed the impact of daily veggies, they found that an increase of 100 grams (the equivalent of a serving of broccoli) reduced cancer risk by only 2% while a comparable intake of fruit (less than an apple) reduced cancer risk by just 1%. These were very low percentages…and were restricted to women; they didn’t even apply to men who gained no cancer protection.

I would like to remind you of a previous website article in which I cited articles that discourage women from drinking more than 10 grams (one drink) at any time. Well, the researchers that reviewed the EPIC data found that intake of fruit and vegetables did decrease cancer risk by 10% in heavy drinkers (more than 30 g daily for women and 60 grams for men). But considering all the damage that excessive alcohol consumption does to our health, proclaiming that the right foods will prevent certain cancers is not appropriate medical advice.

The American Cancer Society (ACS) still advises that we consume 5 servings of a variety of fruits and vegetables on a daily basis to help reduce cancer risk both directly as well as indirectly by helping maintain a healthy weight. In 2005, ACS made “the 5 rule” the third priority after healthy weight maintenance throughout life and adoption of a physically active lifestyle. The ACS meets to update its recommendations later this summer and will probably change them based on the EPIC study.

But before I encourage you to stop that “5-a-day” nutritional count let’s remember that cardiovascular disease is the number one cause of mortality in women (not cancer). There are many prospective studies that have shown that 5 servings of fruit and vegetables a day reduce cardiovascular risk by as much as 12%.  These foods contain nutrients and vitamins that are essential for all of our bodies’ functions. They most certainly help us maintain a healthy weight and a lower weight  (or more precisely, lack of obesity) will diminish our risk of diabetes, heart disease and many cancers. We have to eat something, and substitutions for fruits and/or veggies usually carry excess calories, sugar, salt and bad fats. (Think processed or junk food.)

I may stop computing those servings in the hope that I will reduce my risk of cancer, but I’ll keep up the count to maintain my heart, weight and future health and well being.

I routinely ask my new patients: “How much, on average, do you drink each week?” In order to make this question slightly less accusatory, I also add “do you usually have wine with dinner or a cocktail before?” If the answer is “yes, one or two glasses”, I then feel obligated to discuss the pros and cons of women’s alcohol consumption. I was therefore delighted to find an article under the heading of “Clinical  Crossroads” in last week’s JAMA which dealt with the question of whether a person (in this case, a 42 year old man) should drink for his health. The authors were kind enough to also consider the health implications of drinking for women. Here are some of the facts that they presented:

The estimated ethanol (alcohol) content per serving of various alcoholic beverages is similar, although their caloric content may vary. Twelve ounces of beer have 14 grams of ethanol and 150 calories, light beer contains 11 grams of ethanol but about 50 calories less; 5 ounces of wine contain 15 grams of ethanol and 120 -125 calories and finally 1.5 ounces of “hard alcohol” or spirits have 14 to 15 grams of ethanol and 100 calories.

Because women have a smaller volume of distribution in which to dilute the alcohol, overall smaller body size, and a different first –pass metabolism (alcohol is not as quickly metabolized by the liver), we experience the toxic effects of alcohol at approximately half the daily dose of alcohol as do men. One glass of  wine, serving of beer or “a drink” for a woman is like two for a man….so ( and I don’t meant to insult your intelligence, but  want to write this for emphasis)….two drinks at dinner would be the equivalent of four for a man. And that’s a number that would cause concern to most of their female companions.

Alcoholism has been ranked the third most important preventable cause of death in the United States. The National Institute on Alcohol Abuse and Alcoholism has issued the following guidelines for safe drinking:

* Up to 2 drinks for men younger than 65
* Up to one drink per drinking day (I’m not sure what constitutes a drinking day, but it’s their wording) for non-pregnant women and older adults

No alcohol for

* Women who are pregnant or trying to become pregnant
* Persons with medical conditions that could be made worse by drinking
* Persons who plan to engage in activities that require alertness and skill (such as driving a car)
* Persons taking certain over-the-counter or prescription medications (think sleeping medications, ant anxiety meds, antihistamines or anything that effects brazen chemistry)
* Persons recovering from alcoholism
*  Persons younger than 21

In order not to sound like an abolitionist, let me also proffer the data that was cited on the “biochemical effects of light to moderate alcohol consumption in short term feeding studies”. (Actually they were drinking studies). Researchers looked at certain biomarkers for cardiac disease and the effect of ethanol on these markers. HDL or high density lipoprotein (the good cholesterol) was minimally increased, but a lot of alcohol was needed to do this (60 grams per day in men and 35 grams in women). Alcohol seemed to work best on HDL if the levels were low to begin with. (Before menopause most women have fairly high HDL levels, perhaps due to their production of estrogen.) Triglycerides were increased in men who drank moderately but may have decreased in women (although beer with more carbohydrates seems to erase this phenomenon). Fibrinogen which is involved in clot production was lowered. Adiponectin which increases insulin sensitivity (a good thing) did minimally increase and as such may have lowered the risk of diabetes.

Now here is the concern for women: Light to moderate drinking increases the bodies own sex steroid hormones by 5% to 20% and can increase risk of breast cancer! This translates to an approximate 1% increase in the relative risk for each one gram a day of alcohol.   It also has an adverse effect on other cancers in men and women. Malignancies of the mouth, larynx and esophagus are increased in all moderate drinkers. The relative risk of developing these cancers (compared to nondrinkers) is approximately 1.4 to 1.7 with “just” 2 drinks a day.

So should we drink for our hearts or abstain for our breasts? Studies dating back at least 25 years have shown that 10 grams of ethanol per day among women (and 25 grams for men) lowered risk of coronary heart disease by 20 to 30%. The authors calculated that this conferred a 1% lower absolute 10 year risk for a 50 year old man who was deemed “average”, but remember our 10 year average risk at 50 is usually less than that of men.

It sounds like that one drink is a draw…but the authors go on to state that the typically high HDL levels in premenopausal women would appear to make any clinical benefit for alcohol limited at best, “and since the risk of breast cancer is increased, it is unlikely that premenopausal women would profit from drinking”.

There is so much more that we can do to prevent heart disease…not smoking, exercising, maintaining a reasonable body weight and if necessary treating elevated lipids (LDL cholesterol and triglyceride).

Alcohol is not a medicine. If you love it and want to drink a glass of wine with dinner or have that drink before….limit it to one.  Your choice to imbibe is similar to your desire for desert, but without the “nose”….it tastes good, you enjoy it and it adds to your meal. The toast “l’haim” (to life) that accompanies that drink is a wish, not a medical certainty.

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