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Friday, June 10, 2011

Is It Memory Loss or Dementia?

A VIEW FROM THE OFFICE



Am I Just Forgetful or Am I Getting Dementia?

     This is a question that worries many of us as we creep above the age of 50. For some people it starts even younger. It is my personal observation that we have more brain fatigue in our population than ever in the history of the world just because we have so much information and media to digest and because we tend to be multi-tasking all the time and wired all the time. I can't believe this hyperarousal for the ordinary business of life is any good for us.
     So how many of you out there have had the experience of trying to pull up a word from your vocabulary for a common object, something you absolutely know you know, but you can't come up with it? How many of you have stepped into another room to get something and have forgotten what you were looking for before you even get half way into the room? How many of you when taking pills at night can remember whether you have already taken you vitamin pill?  How many of you have worried about an important lunch date for weeks then forgot all about it when the time came? How many of you have drawn a total blank on the PIN number for your ATM card and had to go home cashless?  These minor humiliations are happening all the time to more and more of us. It is also true that there are more cases of Alzheimer's disease in the general population than there ever has been before--most of this due just to the fact that we are living much longer than we used to.
     Generally, as soon as a middle aged person has repeated bouts of memory lapses of the kind described above they start to worry, "Could I have Alzheimer's?"
     The good news is that, if you have the presence of mind to ask yourself this question, you probably do not have Alzheimer's disease.  The other good news is that even if you did, it's not as bad as it once was. It is now possible to live 20 or more years of completely function life after the initial diagnosis of mild Alzheimer's.
     The New England Journal of Medicine has just published an article on "Mild Cognitive Impairment," which is the term for this kind of repetitive memory loss that is not Alzheimer's disease. (Petersen RC. Mild Cognitive Impairment. NEJM 2011; 364: 2227-34)
I thought it might be a worthwhile endeavor to illustrate the range of cognitive function between normal and full-blown Alzheimer's disease. Here the authors identify their subject, mild cognitive impairment, as "an intermediate state of cognitive function between the changes seen in aging and those fulfilling the criteria for dementia and often Alzheimer's disease. Most people undergo a gradual cognitive decline, typically with regard to memory, over their life span; the decline is usually minor, and although it may be a nuisance, it does not compromise the ability to function." Only about 1 in 100 people go through an entire lifespan with no signs of cognitive impairment. Currently it is estimated that the prevalence of mild cognitive impairment in population-based studies ranges from 10 to 20% among persons older than 65 years of age. In the US the incidence of dementia is 1-2% per year.
     The authors divide cognitive impairment into two categories:
     1. Amnestic mild cognitive impairment: "Typically, these patients and their families are aware of the increasing forgetfulness. However, other cognitive capacities, such as executive , use of language, and visuospatial skills, are relatively preserved, and functional activities are intact, except perhaps for some mild inefficiencies."
     2. "Non-amnestic mild cognitive impairment is characterized by a subtle decline in function not related to memory, affecting attention, use of language, or visuospatial skills." 

     The distinction between these two types of memory function is subtle and somewhat difficult. The memory loss is more severe in patients with the amnestic type. "Typically, they start to forget important information that they previously would have remembered easily  such as appointments, telephone conversations, or recent events that would normally interest them (e.g., for a sports fan, outcomes of sport events). However, virtually all other aspects of function are preserved. The forgetfulness is generally apparent to those close to the person but not to the casual observer." The big difference in dementia is that in dementia the cognitive deficits are affecting daily functioning to the extent that there is loss of independence in the community.
     What most people with mild cognitive impairment are worried about is whether it will progress to actual dementia. In reality, such progression occurs in only 10% of patients.

     If a diagnosis of "mild cognitive impairment" is made there is not much to do. While there are some fancy imaging techniques that are being use in research, they will not help an individual patient, particularly as there is no specific treatment for this condition. While medications offer no benefit as yet, there is some evidence of potential benefit from cognitive rehabilitation, including the use of mnemonics, association strategies, and computer-assisted training programs. One of the most important points for evaluation is to rule out the possibility of depression (from loss of significant others or diminished circumstances or chronic disease), as depression clearly causes major impairment of memory. For the purposes of prevention, traditional cardiac risk factors appear to be markers for a higher risk of this condition. Thus the most effective primary prevention is likely to be, as I have said so many times before, a healthy lifestyle. You know: 0 - 5 - 10 - 30 - 150. (0 cigarettes, 5 servings of fruits and vegetables daily, 10 minutes of relaxation daily, a BMI < 30, and 150 minutes of exercise each week)
     For the most part mild memory loss is a normal aspect of aging to which the kindly grace of age helps us to adjust.
     I do not expect you to remember any of this article.

Friday, June 3, 2011

The Lowdown on Cancer Screening

A View from the Office


The Lowdown on Cancer Screening:
How Much Cancer Screening Is Enough

     We are all concerned about cancer, but how concerned do you really need to be. 

     Of course, the first and best approach is just to live a healthy lifestyle.


     Fourteen major epidemiological studies suggest that this healthy lifestyle can prevent 36% to 64% of all cancers. When you look at the data, you will realize that this is a greater benefit than all of the Pap smear, mammogram, prostate screening, and colon cancer screening programs put together. It not only costs far less, but is actually tremendously cost-saving in the long run.

     The second sound approach is to do you own personal assessment of cancer risk. This practice is based on the fact that the majority of people (not all) who get cancer had clearly defined risk factors. Such obvious risk factors include smoking, asbestos exposure, working with solvents or toxic organic chemicals, etc. 

Self-Assessment of Cancer Risks

       Cancer is a concern to everyone. This is especially true if someone in your family or among your close friends has had cancer. The general risk of developing cancer in the US is about 0.4% per year. For the most part interventions against cancer and various attempts to prevent the different kinds have had only equivocal effectiveness. In fact, none of them have yet to be proven to actually increase life expectancy. This is an area in which it is particularly important to be an informed consumer. Essential in order to do anything intelligent to mitigate your personal cancer risk is to systematically appraise your personal situation and determine what factors may put you at increased risk for specific cancers.
A wonderfully practical article on this topic appeared in the British Medical Journal.(Jankowski J, Boulton E. 10-Minute Consultation: Cancer Prevention. British Medical Journal 2005; 331: 618) There Janusz Jankowski and Emma Boulton presented a systematic approach to assessing personal cancer risk with respect to a variety of cancers using an alphabet-based memory aid—
ABCDEFGHIJK. The point is, unless you are at specifically increased risk of developing a specific cancer, there is little point in aggressive general cancer screening technology.

Alcohol consumption > 3 units a day: predisposes to squamous cancers, especially cancer of the bladder and esophagus.

Body Mass Index > 25 and certainly > 30: predisposes to all solid cancers. If you don’t know your BMI, see the free calculator at: http://www.nhlbisupport.com/bmi/ .

Cigarette smoking at any level (even passive smoking): predisposes to bladder cancer, lung cancer, head and neck cancer, esophageal cancer, and oropharyngeal cancers.

Diet, especially one that is high in fat: predisposes to all solid cancers.

Exercising < 30 minutes a day: predisposes to all solid cancers.

Family history of cancer: (in at least one first degree relative (e.g., brother, sister, mother, father, son, daughter) and at least 3 people in two or more generations): predisposes to inherited cancer syndromes, including breast cancer, colorectal cancer, diffuse gastric cancer, ovarian cancer, prostate cancer, and uterine cancer.

Genital health (sexually transmitted infections): predisposes to cervical cancer and penile cancer.

Health promoting drugs that may decrease global cancer risks (but need a careful risk benefit analysis): colonic adenomas can be treated with low dose aspirin but can have serious side effects; hormone replacement therapy is linked with breast cancer)

Intense sunburn: predisposes to melanoma. Job related factors: lung cancer (exposure to asbestos and particulates), skin cancer (contact with arsenic)

Known disease associations: colorectal cancer has predisposing mucosal pathology– adenomas, celiac disease, ulcerative colitis.

The actions they recommend for physicians at the time of a routine check-up are:
1. Review history for any symptoms of cancers of concern (e.g. bleeding in the rectum, altered bowel habits, weight loss) [remembering, as discussed in a recent issue, that most of these red flags do NOT turn out to be cancer]

2. Educate the patient that early investigation of cancer symptoms increases the chances of cancer being successfully treated, but that most of such symptoms are not in fact due to cancer.

3. Emphasize the importance of a good diet. A patient should eat at least 5 portions of fruit and vegetables each day and cut down on fat, salt, and added sugar.

4. Explain that many cancers are preventable through lifestyle modification. Help the patient strategize as to what modification to tackle first–smoking, exercise, dietary modification, or alcohol consumption.

5. If the patient is serious about lifestyle modification, counsel about the advantages and options of various support methods for assisting behavioral change.

6. Offer objective advice about the risks of medical interventions such as x-rays, Pap smears, endoscopic examinations (sigmoidoscopy, colonoscopy, endoscopic esophagoscopy, gastroscopy and duodenoscopy (EGAD)), mammography, Pap smears and additional interventions (e.g. ThinPrep, HPV testing), and fecal occult blood testing (FOBT). The authors state, “Most people asking about the risk of cancer won’t develop it, and in about 10% of people anxiety levels will be raised needlessly.”

7. Provide as much objective (non-cancer society and non-specialty society sponsored) information and web-links as appropriate.


     The other obvious risk factor is your family history. Family history is most important when it comes to breast cancer. If any of a woman's first degree relatives (mother, sister, daughter) had breast cancer before the age of menopause, the individual risk is significantly increased. For the average woman for each decade after age 50, the decentennial risk is about 3%. This can be reduced by about 15% with a program of regular mammographic screening. A family history of colon cancer increases your risk by about 50%, but, in general, this means increasing your risk from about 100 cases per 100,000 persons to about 150 cases per 100,000 persons. It is not a big risk. A family history of melanoma increases one's risk, but since the baseline risk is low, approximately 15 per 100,000, even a doubling of risk is not that large a number. Family history is important in lung cancer, not for the genetic aspects, but because it usually means you were exposed to a fair amount of passive smoking while growing up, which increases your risk. 

     Here are some basic cancer facts for the most common cancers.

Breast cancer: The average risk about 3% per decade after 50; mammography decreases risk of dying about 16%; with currently available treatments, more than 50% of women will survive regardless of whether they received screening or not. While women who receive screening have a lower risk of dying of breast cancer, their overall risk of dying is not changed by mammographic screening. A reasonable recommendation is to undergo mammography every other year between the ages of 50 to 75. The US Preventive Services Task Force, our national expert group, recent stopped recommending routine mammograms for women under 50. They also concluded that a physician breast exam was unnecessary if the woman is going to receive a mammogram.

Colon Cancer:  Starting at age 50, the risk of colon cancer is about 57 per 100,000 for men and slightly lower for women. Over the next 30 years, the risk increases to a maximum of about 180 cases per 100,000 at age 80. Screening techniques can reduce the risk of dying of colon cancer about 15%. A healthy lifestyle has been shown to reduce the number of cases of colon cancer by about 24%. There is no clear agreement on what is the best form of screening. The generally recommended approach is to have an annual blood test from the stool for 5 years and then to have a sigmoidoscopy every 5 years; an alternative is to have colonoscopy every 10 years. This program is very expensive and the yield is relatively low. While adhering to a regular screening program after the age of 50 will reduce your risk of dying of colon cancer, there is no evidence that it will reduce your overall risk of dying. Experts agree that colon cancer screening can stop after age 70 or whenever any other medical condition reduces your life expectancy to less than 10 years.

Cervical cancer: The average risk of cervical cancer in women is about 8 cases per 10,000 women a year. Regular Pap smear screening has reduced the risk of dying of cervical cancer by 40-60%. Recent guidelines recommend Pap smear screening for women every year for 3 years after they become sexually active and then every 3 years after that unless they have an abnormal Pap smear in the mean time. The biggest problem with Pap smear screening is that there are a large number of false positive tests. For example, 7 out of 100 smears will show "ASCUS" which means atypical squamous cells of undetermined significance". These are not pre-cancer cells; in fact, as their name implies, we do not really know what they are. Nevertheless, most gynecologists recommend a procedure called colposcopy for this abnormality, the value of which is currently unknown. The other false positive is the finding of HPV virus. It is now known that cervical cancer is caused by the HPV virus, but the confounding factor is that more than 50% of women get exposed to this virus, and in over two-thirds of these cases the virus goes away all by itself. The experts recommendations state that a woman can stop getting Pap smears at age 65, if the last 3 Pap smears were normal. Women who have had a hysterectomy for a benign condition like bleeding or fibroids no longer need Pap smears. 
      While a new vaccine (in 3 doses) is available to prevent certain high-risk types of HPV infection, it cannot prevent all HPV related cancers. Even if you receive the vaccine, it is still recommended to get routine Pap smear testing. It is now being recognized that HPV can cause cancer in men (of the penis and the throat), but no definitive screening guidelines have yet been developed for men. While receiving routine Pap smear screening will significantly reduce your risk of dying of cervical cancer, there is no evidence that such screening will reduce overall mortality rates.

Melanoma: As mentioned above, the overall risk of melanoma in the US is about 15/100,000 persons. It is higher in patients who have a positive family history of melanoma, but it is still not very high. Since dermatologists and other medical groups have increased their efforts in advocating preventive measures for melanoma, the actual detection rate of melanoma has increased, but the rate of death from melanoma has remained essentially unchanged. [insert]  This indicates that screening is detecting more cases, mostly mild cases, but it does not demonstrate a clear benefit. Preventive measures have been advocated, principally avoidance of direct sun (which can be expected to lead to relative vitamin D deficiency) and sun screen application. In over 2 dozen studies on the effectiveness of sun screens to prevent melanoma, only 1 has shown a positive effect. The USPSTF recommends as the primary approach to melanoma prevention is to pay attention to the ABCDEFs of melanoma. Your risk of developing melanoma from a mole or other pigmented spot on your skin increases if:

A: the skin lesion is asymmetric. Benign moles are generally simple round spots.
B: the border of the skin lesion is irregular. Benign moles usually have smooth borders.
C: the skin lesion changes in color, becomes darker, and/or develops different shades of dark pigmentation.
D: the diameter of the skin lesion increases to greater than 1/2 of a centimeter (about the size of a pencil eraser). 
E: the skin lesion is enlarging significantly over a relatively short period of time.


A web site to help you calculate your own risk of melanoma can be found at: 
http://www.cancer.gov/melanomarisktool/. One last practical tip is to get in the habit of taking a photograph of any groups of moles or pigmented spots once a year on your birthday; your back is the special area of concern. This allows easy identification of when there has been a significant change.

Lung Cancer: Except for persons with rare genetic conditions like alpha-1-anti-trypsin deficiency or asbestos exposure, virtually all lung cancer is caused by smoking. There is no need for screening. The need is to stop smoking and to avoid passive smoking. Period. Routine chest x-rays will not reduce your risk of dying of lung cancer. Periodic scanning with a CT scan of the chest may detect lung cancer earlier leading to a better chance of survival.

Prostate cancer: Prostate cancer is very common in males and increases in risk every year after a man turns 50. The overall average risk is about 156 per 100,000 men. This increases to about 50,000 cases per 100,000 men at age 80. The fact is that half of men will develop prostate cancer over their lifetime, but the large majority of them will never have any symptoms and will die of some other cause like a car accident or a heart attack. So far, numerous studies have failed to show a significant benefit for prostate cancer screening with either a rectal exam or the PSA blood test. In fact, of the major screening expert groups, the AMA, the US Preventive Services Task Force, the American College of Physicians, and the Canadian Task Force on Preventive Medicine recommend against routine screening. Only the American Urological Association and the American Cancer Society recommend for it, and they have a vested interest. The problem with screening is that there are a large number of false positive tests. The major cause of a false positive test is simple prostate enlargement, which most men will experience as they get older. In fact, the scientist who invented the test recently testified before the US Congress that screening with the PSA test should stop because ultimately it cannot tell us what we want to know, namely who will die of their prostate cancer and who will not. 

Footnote: One of the biggest problems with the most commonly recommended cancer screening or prevention tests is that they are very expensive and need to be repeated over and over again. For example, Pap smears need to be done annually for 3 years, then every 3 years until age 65 for a typical total of 15 Pap smears. Breast cancer screening with mammography generally requires 20 or more mammograms over a lifetime. Colon cancer screening involves a stool blood test every year between ages 50 and 70, for 20 stool tests plus either 4 sigmoidoscopies or 3 colonoscopies. PSA testing is recommended every year between 50 and 70 for a total of 20 tests. In practice, the main problem with these strategies is that we do not yet have universal health insurance in this country. This means that poor people and people without insurance tend not to get these tests, when these are the people at highest risk who could most benefit. Most of these tests are obtained for those who can pay because they have good health insurance. It turns out that people with good insurance have the  lowest risk of cancer, so this is not a particularly effective strategy.
      Alternatively, everyone can lead a healthy lifestyle.

Summary: So putting all this information together, what is a reasonable minimalist approach to cancer prevention:

1. Live a healthy lifestyle. In particular this means not smoking, which is the single greatest cancer risk factor among the general population.
2. Perform your own cancer risk assessment.  
3. Utilize the best screening tests. For average risk women I recommend a Pap smear every 3 years until age 65 and a mammogram every 2 years between the ages of 50 and 65.
4. For colon cancer screening and prostate cancer screening, that is purely an individual choice. I don't specifically recommend them to my patients, but I do ask patients about their family history and their preferences.

And that's about it.