Alzheimer’s Disease (AD) and other causes of dementia in later life are growing problems in our aging population. Over the past half century, many of the most common causes of premature death have been, if not eliminated, then at least markedly reduced. Infections, lung disease, cardiovascular disease and many cancers are now far less frequent causes of death, and the average lifespan of people living in the industrialized world continues to increase. Unfortunately, we have been less successful in preventing or effectively treating diseases of the aging brain. (Improvements in the control of hypertension and cardiovascular disease have somewhat reduced the risk of developing so-called vascular dementia, which develops following a series of mini-strokes that cumulatively result in progressive cognitive decline and dementia.) Since the much publicized revelation of the Reagan family that our 40th President was suffering from AD, funding for AD research has increased dramatically. However, despite extensive ongoing research into the causes of AD, we are still only beginning to understand the biological underpinnings of this devastating disease. At the present time, there are no good therapies for AD. Even estrogen/progestin hormone replacement therapy, which was once thought to reduce the risk of AD, now appears more likely to increase the risk of dementia with long-term use.

Several previous studies have suggested that the aging brain responds well to continued stimulation, and that “exercising” your squash in your later years may at least mildly reduce your risk of developing dementia. However, as is frequently the case, other similar studies have not been able to reproduce this finding. A new study in this week’s New England Journal of Medicine looked at 469 volunteers who were all older than 79 years of age. All study volunteers lived in their own homes, none of the study participants had any clinical evidence of dementia at the onset of the study. Over the course of this 5-year study, 146 study participants developed dementia (AD in 61 subjects, vascular dementia in another 30 volunteers, and other types of dementia in 8 other subjects). When the study’s authors looked at the leisure activities of the study volunteers, they found that reading, playing board games, playing musical instruments, and dancing were all associated with a significant reduction in the risk of developing dementia. However, the overall level of physical activity did not appear to affect the risk of developing dementia. Thus, this study appears to confirm previous animal and human studies that show a reduction in dementia associated with frequent involvement in cognitively challenging leisure activities later in life (who would’ve thought that dancing would be identified as a cognitively challenging leisure activity…?). These results are also in line with animal research, dating back to the 1960s, that revealed an increase in the complexity of neuronal circuitry in the brain, and overall brain size, in animals that were placed in environments that provided cognitively stimulating recreational activities. More recently, this phenomenon has also been confirmed to occur in the brains of older animals as well.

The old maxim, “use it or lose it,” appears to apply to the brain as much as it does to any other organ of the body. Perhaps board game manufacturers will take a page from the food industry’s recent habit of placing pro-health statements on containers of oatmeal and orange juice, among other food products:

“Playing this game may reduce your risks of developing Alzheimer’s Disease or other causes of dementia.”

New MRI Detects Tiny Prostate Cancer Lymph Node Metastases

The current generation of CT and MRI scanners are able to detect clusters of tumor cells measuring about 5 to 10 millimeters in diameter, or about two-tenths to four-tenths of an inch. By the time a 10 millimeter (1 centimeter) tumor has formed, however, approximately 1 billion cells are already present. Thus, even the most sensitive scanners are still relatively crude instruments for detecting tumors cells at the earliest stages of cancer. In my own area of research, we are working with powerful diagnostic tests that amplify, hundreds of thousands of times, the genetic material of occult tumor cells floating unseen in the blood, bone marrow and lymph nodes of patients with cancer. Using this RT-PCR technique, we can identify the presence of a single tumor cell floating in a sea of more than a million normal surrounding cells. However, RT-PCR is expensive, time-consuming, and requires a huge investment in equipment and highly trained personnel.

A new method of performing MRI scans may now significantly increase the ability of physicians to detect very small clumps of tumor cells in the lymph nodes of patients with prostate cancer, and perhaps with other cancers as well. Unlike CT (Computed Tomography) scans, which use x-rays, MRI (Magnetic Resonance Imaging) relies upon a powerful magnetic field to slightly and reversibly alter the atoms of our bodies, resulting in exquisitely detailed anatomic images. Currently, the element Gadolinium is injected into patients undergoing MRI cancer imaging, resulting in improved image quality and resolution. However, as I’ve already mentioned, conventional Gadolinium-enhanced MRI scans have a maximum resolution of only 5 to 10 millimeters. A high-resolution MRI scanner has recently been developed to take advantage of a newly developed image enhancer known as lymphotropic superparamagnetic nanoparticles. (Drop that mouthful at your next cocktail party!) These iron-based nanoparticles are extremely fine, and are injected into the bloodstream. Unlike other MRI enhancing agents that are too large to filter into and through the body’s lymph nodes, the nanoparticles are able to freely permeate lymph nodes and, in the process, dramatically improve the MRI scanner’s ability to detect tiny deposits of tumor cells within the nodes.

A new study that employed nanoparticle-enhanced MRI to evaluate 80 patients with prostate cancer is being reported in the current issue of the New England Journal of Medicine. All patients underwent enhanced MRI scans, both with and without nanoparticles, prior to undergoing surgery for their cancers. The results of the preoperative MRI scans were then compared to the pathologists’ findings after surgery. A total of 334 lymph nodes were recovered from the 80 patients during their operations, and 63 of these lymph nodes, from 33 patients (41%), were positive under the microscope for involvement with tumor cells. Using conventional MRI scanning techniques, 45 (71%) of these 63 histopathologically-positive lymph nodes were abnormal on the preoperative MRI scans . However, the nanoparticle-enhanced preoperative MRI confirmed the presence of metastatic tumor in the lymph nodes of all 33 patients who were subsequently confirmed, postoperatively, to have tumor spread to their lymph nodes. When the study’s authors analyzed all 334 lymph nodes recovered from the 80 patients during surgery, they found that the nanoparticle-enhanced MRI scans picked-up a rather amazing 90.5% of all tumor-involved lymph nodes, whereas the conventional MRI scans picked up only 35.4% of involved nodes. These are very impressive results, and may allow physicians to more accurately stage their patients’ cancers before the patients go to the operating room. This knowledge, in many cases, might alter patient care plans by identifying those patients who might benefit from chemotherapy, radiation, or other so-called adjuvant treatments prior to undergoing surgery. Additional study of this new MRI technology should also be directed at other types of tumors that have a propensity to spread through the lymph nodes, including cancers of the lung, breast, colon, stomach, pancreas; and melanomas and lymphomas, to name a few.

Soy Intake & Breast Cancer Risk in Japan

The role of isoflavones, soy-derived compounds, in cancer prevention is unclear at this time. There are good research data that support both a positive and a negative impact of isoflavones on the risk of developing breast cancer. Some of the more recent research, including studies performed recently in the laboratory of the “other Dr. Wascher” (my lovely wife), suggest a dose-dependant effect of isoflavones on breast cancer risk. Very high doses of soy-derived isoflavones in the laboratory appear to stimulate normal breast cells to divide excessively, which increases the risk for cancer development. On the other hand, lower doses of isoflavones in the lab appear to have a potentially protective effect on breast cell proliferation. Unfortunately, the jury is still out on the clinically relevant effects of dietary soy products on breast cancer risk in human beings (often, what happens to a culture of a single type of cells in the laboratory does not accurately reflect the more complex biology of a living human being).

The proposed breast-protective effects of dietary soy were originally based upon the purely anecdotal observation that Japanese women living in their native country experienced a much lower incidence of breast cancer than American women. The dietary soy intake among Japanese living in Japan is indeed considerably higher than is found in the typical American diet. When you look at the breast cancer incidence among Japanese women who emigrate to the United States, the protective effect of being a Japanese woman in Japan is gradually lost after relocation to the US, and continues to decline over time. Moreover, the American-born daughters of Japanese immigrants have breast cancer rates that approximate those of other American-born women without a Japanese heritage. However, no solid research evidence has yet been presented that elevates this conjectural linkage between dietary soy in Japan and breast cancer risk to the level scientific fact. A new study in the current issue of the Journal of the National Cancer Institute attempts to clarify this soy/breast cancer debate.

In this Japan Public Health Center prospective study, 21,852 Japanese women (aged 40 to 59 years) completed a questionnaire that included detailed questions about dietary soy intake. During the 9-year course of the study, 179 of the study participants were diagnosed with breast cancer. The study’s authors then analyzed the self-reported dietary intake of miso soup (a soy-derived food that contains high levels of isoflavones) and other soy-rich foods, comparing the soy, isoflavone and miso soup intakes of patients who developed breast cancer with those of volunteers who did not develop breast cancer. The study found that women who reported the highest frequency of miso soup in their diets, and the highest intake of isoflavones in general, experienced a reduction in the risk of breast cancer by as much as 54% (relative risk). Interestingly, high levels of foods containing soybeans did not appear to decrease the risk of developing breast cancer. Thus, this large-scale prospective study does appear to give some validity to the proposed breast cancer reduction properties of dietary isoflavones, including those found in miso soup. Now, if someone could make tofu actually taste good, that would be a true miracle…

Prozac & Premature Ejaculation

Quite apart from the amusing depictions of premature ejaculation (PE) in teen-themed movies, PE is a condition that causes considerable distress to many men and their partners, and is the most commonly diagnosed male sexual dysfunction (poor libido is the most common dysfunction diagnosed in women). The incidence of premature ejaculation among men aged 18 to 59 years has been estimated to be approximately 20% (Journal of the American Medical Association, 1992), although the definition of PE is subjective and somewhat arbitrary. Unfortunately, the tender sexual psyche of most of us men can render this problem a source of major anxiety and concern. In addition to the traditional desensitizing methods first popularized by Masters & Johnson, the antidepressant drug Prozac has recently been advocated to treat PE. (Prozac, it seems, can improve almost any medical disease or condition….)

In the current issue of the Journal of Urology, the standard 20 mg per day dose of Prozac was compared to a single weekly 90 mg dose for patients suffering from PE. All patients were first evaluated to exclude physical causes of PE, such as diabetes and cardiovascular disease. Eighty volunteers with an average age of 36 years were randomized into two groups: 20 mg of Prozac each day versus 90 mg per week. The average time to ejaculation was assessed for all patients at the beginning of the study, and again, 3 months later, at the conclusion of the study. The average time to ejaculation prior to beginning Prozac therapy was about 30 seconds for the 80 study participants. After 3 months of either daily or weekly Prozac therapy, the average time to ejaculation increased to 3.37 and 3.57 minutes, respectively. Partner satisfaction and time-to-ejaculation tended to be superior with the 90 mg per week dose, although this trend was not statistically significant. Nausea, insomnia and headache were the most commonly reported side effects, but did not vary between the two treatment groups.

Thus, this study shows that a single weekly dose of 90 mg of Prozac was as effective in treating PE as a 20 mg daily dose, and without any observed difference in side effects profiles as well. I find this to be an interesting application of Prozac, the granddaddy of the selective seretonin uptake inhibitor (SSRI) class of antidepressants. Ironically, one of the most common reasons that patients discontinue SSRI drugs is because of reduced libido and difficulty in obtaining erections. However, the anxiety-reducing effects of Prozac appear to provide therapeutic benefit to patients with PE that compensates for any potentially detrimental effects on sexual function that are known to be associated with this medication.

Dr. Robert A. Wascher