Recent News No benefit of Ginkgo biloba in preventing dementia November 19, 2008 ST LOUIS (MD Consult) - Ginkgo biloba extract does not reduce the risk of Alzheimer's disease or dementia in older adults with normal or mildly impaired cognition (MCI), reports a trial in the November 19 issue of The Journal of the American Medical Association. The randomized, double-blind "Ginkgo Evaluation of Memory" (GEM) study included 3,069 community-dwelling elderly subjects aged 75 years or older. At baseline, 2,587 had normal cognition and 482 had MCI. The subjects were enrolled at six US academic medical centers. One group received G. biloba extract, 120 mg twice daily, while the control group received placebo. Rates of incident dementia and Alzheimer's disease were compared at a median follow-up of 6.1 years. The lead author was Dr Steven T. DeKosky of University of Pittsburgh. Based on expert panel consensus, there were 523 cases of incident dementia during follow-up: 277 in the G. biloba group and 246 in the placebo group. Ninety-two percent of cases were classified as possible or probable Alzheimer's disease or as Alzheimer's disease with evidence of vascular disease. Follow-up data were available for nearly 94% of subjects. There was no significant difference in the rate of dementia between groups: 3.3 per 100 person-years in the G. biloba group and 2.9 per 100 person-years in the placebo group. Hazard ratios for progression to all-cause dementia or Alzheimer's disease were nonsignificant, including among subjects with MCI. Supplementation with G. biloba is widely used in the hope of preserving memory function. Most efficacy trials of G. biloba have focused on patients who already have dementia; no previous studies have evaluated the use of G. biloba for primary prevention of dementia. This 6-year follow-up study finds no benefit of G. biloba extract in preventing the development of dementia in people aged 75 or older. Treatment with G. biloba has no effect on the incidence of all-cause dementia or Alzheimer's disease; there is no evidence of benefit for cognitively normal older adults or those with MCI. The investigators conclude, "Based on the results of this trial, G. biloba cannot be recommended for the purpose of preventing dementia." JAMA. 2008;300:2253-2262. Smoking linked to reduced quality of life in old age October 13, 2008 ST LOUIS (MD Consult) - Very long-term follow-up data on middle-aged smokers show reductions in health-related quality of life as well as survival, reports a study in the October 13 Archives of Internal Medicine. The researchers analyzed 26-year follow-up data on subjects enrolled in the Helsinki Businessmen Study. The prospective cohort study included 1,658 men—all white and of similar socioeconomic status—aged 40 to 55 years and healthy at baseline in 1974. Follow-up information was obtained from questionnaires mailed in 2000, including the RAND 36-Item Health Survey to assess health-related quality of life. Subjects who died were identified using Finnish mortality data. The effects of baseline smoking on mortality and health-related quality of life were assessed. The lead author was Dr Arto Y. Strandberg of University of Helsinki. Mortality during follow-up was 22.4%, and increased along with number of cigarettes smoked. Smokers had significantly shorter survival: the 614 men who never smoked lived a mean of 10 years longer than the 188 men who smoked more than 20 cigarettes per day. Never-smokers also had the best scores on all health-related quality of health scales. Differences between never-smokers versus heavy smokers ranged from 4 points for social functioning to 14 points for physical functioning. The difference in physical functioning was equivalent to an age difference of 10 years, compared to the age- and sex-matched population. Physical component summary score decreased in graded fashion as the daily number of cigarettes increased. In addition to increasing morbidity, smoking is related to several factors that may reduce quality of life. This suggests a possible smoking-related decrease in health-related quality of life. However, it cannot be assumed that the additional years gained by not smoking are associated with better quality of life. The new findings in a socioeconomically homogeneous population of men suggest that smoking in middle age is associated with reduced quantity and quality of life. On average, heavy smokers die 10 years sooner than heavy smokers. Smokers who survive have reductions in health-related quality of life, particularly in physical functioning. The investigators conclude, "Never-smokers lived longer than heavy smokers, and their extra years were of better quality." Arch Intern Med. 2008;168:1968-1974. Creatine supplementation does not affect health markers in soccer players September 30, 2008 By Mark S. Lesney Creatine monohydrate supplementation for 8 weeks led to no negative effects on blood and urinary clinical health markers in a small, randomized study of soccer players. Supplementation did, however, lead to a gain of total body mass, a significant increase in total creatine kinase activity, a tendency to decreased uric acid, and a significant decrease in serum glucose, according to a study reported in the September issue of the British Journal of Sports Medicine. Creatine monohydrate (CrM) is a widely used nutritional supplement, and its intake has previously been reported to improve soccer-specific exercise performance in soccer players. There are fears, however, that because it is a nitrogen-rich compound, CrM may cause renal or liver damage, calling supplementation into question, according to Dr. Paula Cancela and colleagues at the Universidad de la República, Uruguay, and the University of North Carolina, Chapel Hill. A total of 14 male soccer players were randomized in a double-blinded fashion to CrM supplementation (7 players) or a placebo control (7 players). Creatine supplementation consisted of 4.4 g of Cr (5.0 g of CrH2O) 3 times per day for 7 days, followed by 2.6 g CrM (3.9 g of CrH2O) for 49 days. The placebo group received maltodextrin on the same regimen. Blood and urine samples were taken after a 12-hour fast pre- and post-supplementation, as well as 48 hours after game participation. Total body mass significantly increased in the CrM group (mean of 64.8 kg vs. 66.2 kg), but not in the placebo group (70.0 kg vs. 71 kg). Similarly, postsupplementation serum glucose concentrations decreased in the CrM group (5.27 mmol/L vs. 4.61 mmol/L). Blood measurements analyzed were all within normal reference values for healthy athletes and no significant change was seen in estimated creatine clearance between the two groups. This included blood urea nitrogen, serum creatine, total protein, albumin, and the ratio of albumin to globulin concentrations after supplementation. Liver enzymes were not affected and no significant differences were seen in urinary markers (Br. J. Sports Med. 2008;42:731-5). “It should be remembered that [creatine] pharmacokinetics depends on individuals and on a set of different conditions, and it may be necessary to adjust the doses to achieve the best possible results and prevent potentially adverse effects on health,” they concluded. The authors recognized that small sample size was a key limitation of the study, but they still concluded that creatine supplementation in soccer players appeared to have no bad short-term metabolic consequences and did improve performance. They reported no competing interests. Lifestyle factors account for 55% of deaths in US women September 26, 2008 ST LOUIS (MD Consult) - More than half of deaths among middle-aged women in the United States may be attributable to a combination of smoking, overweight, low physical activity, and poor diet, suggests a study published September 27, 2008 by the British Medical Journal. The researchers analyzed the mortality impact of lifestyle risk factors in a sample of 77,782 female registered nurses enrolled in the Nurses' Health Study. At the time of enrollment in 1980, the women were between 34 and 59 years old and free of cardiovascular disease. Mortality was assessed through 24 years' follow-up. The contributions of five lifestyle factors were assessed: cigarette smoking, overweight, low levels of moderate to vigorous physical activity, more than light to moderate alcohol use, and low diet quality score. The lead author was Rob M. van Dam of Harvard School of Public Health. Of 8,882 deaths occurring during follow-up, 1,790 were from cardiovascular disease and 4,527 from cancer. All five of the lifestyle factors investigated were significant and independent predictors of mortality. For women with all five risk factors, the relative risk of death from any cause was 4.31, compared to women with no risk factors. Relative risks were 3.26 for death from cancer 8.17 for death from cardiovascular causes. The population attributable risks of mortality for cigarette smoking was estimated at 28%. For the combination of smoking, overweight, lack of physical activity, and low diet quality, the estimated population attributable risks were 55% for overall mortality, 44% for cancer mortality, and 72% for cardiovascular mortality. Including alcohol use led to only a small increase in the population attributable risks. Information on the health impact of lifestyle factors, individually and combined, is essential to prioritizing clinical and public health efforts. Previous studies of this issue have addressed an elderly, mostly male population. It is unclear whether the findings apply to younger patients and women. The new results suggest that the combination of smoking, overweight, low physical activity, and poor diet account for most deaths among middle-aged American women. For cardiovascular disease mortality, the population attributable risk exceeds 70%. "These findings underscore the importance of intensifying both efforts to eradicate cigarette smoking and those aimed at improving diet and physical activity," the investigators conclude. BMJ 2008;337:a1440. Fish oil cut heart failure morbidity and mortality in large study September 3, 2008 By Bruce Jancin MUNICH (EGMN) – Supplementation with a single daily low-dose fish oil capsule in patients with chronic heart failure resulted in modest but clinically meaningful reductions in mortality and cardiovascular hospitalization in a nearly 7,000-patient randomized trial presented at the annual congress of the European Society of Cardiology. In a surprise finding, the same Italian study, known as GISSI-HF, concluded that rosuvastatin at 10 mg/day had no effect on mortality or hospital admission for cardiovascular events, suggesting that patients with chronic heart failure should not be started on statins. In GISSI-HF, 6,975 patients with New York Heart Association class II-IV chronic heart failure were randomized in double-blind fashion to 1 g/day of omega-3 polyunsaturated fatty acids (n-3 PUFA) in the form of eicosapentaenoic acid and docosahexaenoic acid or to placebo. The participants were on standard background therapy with the agents of proven efficacy in heart failure. All-cause mortality after a median 3.9 years of follow-up was 27% in the n-3 PUFA group and 29% in controls, for a significant adjusted 9% relative risk reduction in the n-3 PUFA group, reported Dr. Luigi Tavazzi, chair of the GISSI-HF steering committee and professor of cardiology at the University of Pavia (Italy). The co–primary end point in GISSI-HF was death or cardiovascular hospitalization, which occurred in 57% of the n-3 PUFA cohort and in 59% of those on placebo, for an 8% relative risk reduction that did not reach statistical significance. In all, 44 patients needed to be treated with n-3 PUFA for 3.9 years to prevent one additional death or cardiovascular hospitalization, whereas 56 patients needed to be treated to prevent one death. Those are fairly high numbers, but it’s a trouble-free therapy, according to Dr. Tavazzi. Among the nearly 5,000 patients who remained compliant with their assigned treatment for the full study duration, the n-3 PUFA benefits were more pronounced: an absolute 3% difference in mortality equating to a 14% relative risk reduction, compared with placebo, and a 12% relative risk reduction in the combined end point, he added. The benefits of n-3 PUFA supplementation were seen across the board regardless of the cause of heart failure, which was ischemia in half of subjects, dilated cardiomyopathy in 30%, and hypertension in 15%. The benefits were also consistent in the 9% who had heart failure with preserved systolic function and in the vastly greater number of patients with a low ejection fraction. The study was undertaken in large part based upon the earlier favorable GISSI-Prevenzione trial by the same group, which showed markedly reduced mortality – mainly because of a decrease in sudden death – in patients randomized to 1 g/day of n-3 PUFA after an acute MI (Lancet 1999;354:447-55). In addition, numerous epidemiological studies have linked fish consumption to a reduced risk of cardiovascular death. In an interview, Dr. Tavazzi attributed the high long-term compliance rate with the n-3 PUFA regimen in GISSI-HF with the simple, once-daily, 1-g dosing, which was essentially devoid of side effects. “If you take a large population with many elderly people, who are often frail, and all of them are already on many heart failure medications, and then you prescribe the new drug forever, you need to have a very well-tolerated dose, and this was exceptionally well tolerated,” he said. Other studies of n-3 PUFA supplementation in cardiovascular medicine have used daily dosages of up to 24 g/day, with 3-6 g/day being most typical – and they’ve generally been brief trials that begged the issue of long-term compliance, the cardiologist continued. “In the last 10 years or so, no new life-prolonging drugs have appeared on the scene in heart failure. The therapeutic approach to chronic heart failure has been rather static. A new drug, even if it gives only moderate benefit on top of optimal therapy, like n-3 PUFA, might be important for physicians to consider,” Dr. Tavazzi added. New ESC President-elect Dr. Michel Komajda predicted that the GISSI-HF findings could end up having a significant impact on daily practice. “Those of us who have the responsibility to draw up the next version of chronic heart failure guidelines will pay a lot of attention to the results of the GISSI-HF trial. We will weigh on the one side that the benefit observed is modest and that the outcome curves diverge only after 2 years, but on the other side that this benefit was significant statistically, that the product is well tolerated, it is cheap, and the context is that we have very little to offer at the moment to our heart failure patients in terms of additional medications to improve their outcome,” explained Dr. Komajda of Pierre and Marie Curie University, Paris. Nevertheless, he added, there remains “a bit of mystery” regarding the mechanism of benefit, as there was no significant reduction in sudden cardiac death or presumed arrhythmic death in the n-3 PUFA group. And the optimal dosage has yet to be defined; if 1 g/day is good, perhaps more is better, Dr. Komajda suggested. GISSI-HF was simultaneously published online (Lancet 2008 Aug. 31 [doi:10.1016/50140-6736(08)61239-8]). Running linked to increased survival, decreased disability in older men August 11, 2008 ST LOUIS (MD Consult) - Running is associated with reduced disability and longer survival in middle-aged and older men, according to a study in the August 11/25 Archives of Internal Medicine. Dr Eliza F. Chakravarty and colleagues of Stanford University School of Medicine analyzed questionnaire responses from 538 members of a nationwide running club. Beginning in 1984, annual questionnaires were sent to club members aged 50 or older and to a sample of 423 healthy controls. Respondents provided information on the frequency of running and other exercise and body mass index. The Health Assessment Questionnaire Disability Index (HAQ-DI) was used to rate disability on a scale of 0 (no difficulty) to 3 (unable to perform). Complete 21-year follow-up information was available for 284 runners and 156 controls. The National Death Index was used to gather data on causes of death through 2003. Mortality and disability rates were compared for runners and controls by multivariate regression analysis. At baseline, the runners were younger (58 versus 62 years), leaner, and less likely to smoke than controls. Education and alcohol use were similar between groups. Throughout follow-up, runners had a higher mean HAQ-DI score than controls. While disability increased with age in both groups, the mean increase in HAQ-DI score was 0.17 in runners versus 0.36 in controls. On multivariate analysis, runners were less likely to reach an HAQ-DI score of 0.50—hazard ratio 0.61. By 2003, 15% of the runners had died, compared to 34% of controls. The hazard ratio for mortality among runners was 0.62, after adjustment for covariates. The between-group difference in survival curves was still increasing in 2005, as the surviving respondents entered their eighties. The health benefits of exercise are well documented across age groups. Regular exercise may be an important part of recommendations to improve functioning and quality of life in an aging population. Long-term follow-up data are needed to confirm the disability and survival advantages of exercise for older adults. This study supports the long-term benefits of vigorous exercise, such as running, for men aged 50 and older. Running in older men is associated with reduced disability and increased survival, after adjustment for other factors. The findings "further support recommendations to encourage moderate to vigorous physical activity at all ages," the researchers write. "Increasing healthy lifestyle behaviors may not only improve length and quality of life but also hopefully lead to reduced health care expenditures associated with disability and chronic diseases." Arch Intern Med. 2008;168:1638-1646. Mediterranean diet linked to reduced diabetes risk June 13, 2008 ST LOUIS (MD Consult) - Healthy people who follow a "Mediterranean diet" are at lower risk of developing type 2 diabetes, according to a study published June 14, 2008 by the British Medical Journal. The prospective study included 13,380 graduates of a Spanish university, all of whom were free of diabetes at enrollment. Responses to a validated food frequency questionnaire were used to calculate how closely the participants adhered to the so-called Mediterranean diet. Over a median follow-up of 4.4 years, there were 33 new confirmed cases of type 2 diabetes. Associations between adherence to the Mediterranean diet and risk of diabetes were assessed, with adjustment for a wide range of other factors. The lead author was Dr M.Á. Martinez-González of University of Navarra, Pamplona, Spain. The closer the subjects adhered to the Mediterranean diet, the lower their risk of diabetes. Age- and sex-adjusted incidence rate ratios were 0.41 for subjects with moderate adherence to the Mediterranean diet (score of 3 to 6 on a 9-point index) and 0.17 for those with high adherence (score of 7 to 9), compared with those at the lowest level of adherence. The relationship between diet and diabetes risk remained the same on fully adjusted analysis, which included body mass index, physical activity, smoking, and family history of diabetes. For each 2-point increase in the dietary index, there was a 35% relative reduction in diabetes risk. Multivariate analysis showed a significant inverse linear trend. Studies have linked the traditional Mediterranean diet—high in olive oil, fruits and vegetables, nuts, cereals, legumes, and fish but low in meat and dairy products—to a reduced risk of cardiovascular disease. There is reason to believe that this diet may also have a protective effect against the development of diabetes. This prospective follow-up study demonstrates a lower incidence of confirmed type 2 diabetes among subjects with moderate to high adherence to the Mediterranean diet. The protective effects are apparent even in subgroups with key diabetes risk factors, including increased body weight, family history of diabetes, and high blood pressure. Because of the limited number of diabetes cases reported, larger studies will be needed to confirm the study findings. BMJ. 2008;336:1348-1351. Prebiotics show promise in Crohn’s and ulcerative colitis January 17, 2008 By Heidi Splete ROCKVILLE, Md. (EGMN) - Prophylactic use of dietary prebiotics could benefit patients with ulcerative colitis and Crohn’s disease, based on data from preliminary but promising studies, said Dr. Leo Dieleman of the division of gastroenterology at the University of Alberta, Edmonton. In contrast to probiotics, which are live microorganisms that benefit their hosts, prebiotics are nondigestible fermentable dietary oligosaccharides that affect the growth and activity of certain types of protective bacteria found in the gastrointestinal tract. Previous studies of probiotics have shown that adding probiotic bacteria to the diets of patients with inflammatory bowel disease (IBD) improved their symptoms, Dr. Dieleman said. Specifically, certain types of probiotics such as Lactobacilli and Bifidobacteria species, when added to the diet, can be protective against IBD, he added. But for probiotics to be effective, patients must consume large amounts of them, which can be difficult and inconvenient, Dr. Dieleman said at a meeting sponsored by the National Institutes of Health. Prebiotics might be a viable alternative because they are inexpensive, easy to administer in the diet - in powder form, for example - and they have been shown to be safe, he said. Based on the promising results of probiotic research, investigators have begun to study prebiotics for treating IBD patients. “Everyone has a unique intestinal microbiotic profile,” Dr. Dieleman said. But inflammation tends to reduce the diversity of microflora in the gut, and studies have shown that a subset of Crohn’s disease and ulcerative colitis patients have distinctly abnormal microflora, compared with non-IBD controls. Patients with IBD tend to have a microbiotic profile that is deficient in firmicutes and bacteroidetes, organisms that are thought to be associated with a healthy gastrointestinal tract. Sometimes ingesting probiotics can help these patients. “But not all probiotics are effective for each patient,” Dr. Dieleman said. Because prebiotics stimulate the growth of several different intestinal protective bacteria, there may a place for prebiotics in IBD treatment. Dr. Dieleman identified three criteria that make prebiotics potentially useful for treating gastrointestinal disorders. First, prebiotics are nondigestible ingredients. As such, they transfer unchanged into the large intestine. Second, prebiotics are fermented by colonic bacteria that already exist in the large intestine. Third, prebiotics induce selective stimulation of bacterial growth and activity. Studies have shown that prebiotics change the profile of intestinal microflora by increasing the growth of specific protective intestinal bacteria. After ingestion of prebiotics, there will be more protective bacteria in the gut. The prebiotics that have been used most often in clinical trials completed to date are the compounds inulin and oligofructose. Studies of other compounds are ongoing, Dr. Dieleman said. Data from a randomized pilot study of 20 adults with ulcerative colitis showed that those who took Synergyl, an oral combination of oligofructose and inulin, at a dose of 12 g/day for 2 weeks, showed significant improvement in disease activity scores and significant reductions in levels of fecal calprotectin (a calcium-binding inflammatory protein found in feces), compared with those who took a placebo (Aliment. Pharmacol. Ther. 2007;25:1061-7). Prebiotics also have shown positive effects on adults with Crohn’s disease, Dr. Dieleman said. The results from a recent open-label study of 10 patients with mild to moderate Crohn’s disease showed that treatment for 3 weeks with 15 g/day of a 30% inulin/70% oligofructose combination supplement was associated with improved disease activity and increased expression of the anti-inflammatory interleukin-10, which is expressed in dendritic cells (Gut 2006;55:348-55). Dr. Dieleman also described an ongoing open-label study at his institution, the University of Alberta, in which 25 patients with active ulcerative colitis are being treated with oligofructose-enriched inulin when they experience flaring on a stable dose of 5-aminosalicylate. The patient evaluations will include assessment of disease activity, including endoscopy results, and analyses of microflora and mucosal cytokines. “Animal models have taught us a lot about the pathogenesis of IBD,” Dr. Dieleman said. However, larger studies in humans are needed to better characterize the role of prebiotics in treating GI disorders such as IBD, he added. Vitamin D inadequacy may play role in chronic pain November 5, 2007 By Sherry Boschert SAN FRANCISCO (EGMN) - In what may be the first study of the prevalence of vitamin D inadequacy in patients seeking treatment for chronic pain, those who were on opioids used significantly higher doses and had been taking opioids significantly longer if they had vitamin D inadequacy than if they had adequate vitamin D levels, Dr. W. Michael Hooten reported at the annual meeting of the American Society of Anesthesiologists. Inadequate levels of vitamin D were detected in 26% of 267 patients admitted to a multidisciplinary pain rehabilitation center at a tertiary referral medical center from February through December of 2006. Of the 140 patients who were using opioids, 27% had inadequate levels of vitamin D, Dr. Hooten of the Mayo Clinic, Rochester, Minn., and his associates reported in a poster presentation. “Vitamin D inadequacy may represent an underrecognized source of nociception and impaired neuromuscular functioning among patients with chronic pain,” he said. In previous studies, inadequate levels of vitamin D have been associated with medication-refractory musculoskeletal pain and neuromuscular dysfunction. In the current retrospective study, patients underwent vitamin D testing at admission, were questioned about opioid use, and completed the Short Form-36 Health Status Questionnaire (SF-36). Serum 25-hydroxyvitamin D levels of 20 ng/mL or higher were considered adequate, and levels below 20 ng/mL were considered inadequate. Both the adequate and inadequate vitamin D groups were nearly evenly split between opioid users and nonusers. Among 69 patients with vitamin D inadequacy, 38 were using opioids, and 31 were not. Among 198 patients with adequate vitamin D, 102 were using opioids and 96 were not. Patients taking opioids used a mean morphine equivalent dose of 134 mg/day in the subgroup with vitamin D inadequacy and 70 mg/day in the subgroup with adequate vitamin D. Opioid users with inadequate vitamin D had been taking the medications for a mean of 71 months, compared with 44 months for opioid users with sufficient vitamin D. Opioid users with inadequate vitamin D reported significantly worse health perceptions and physical functioning on the SF-36. Scores did not differ significantly between the vitamin D groups for “bodily pain” or “role emotional.” Prospective trials of vitamin D therapy are needed to assess effects on pain outcomes and physiological measures of neuromuscular functioning in patients with chronic pain and vitamin D inadequacy, Dr. Hooten said. Studies show exercise delays onset of dementia June 28, 2007 By Timothy F. Kirn SEATTLE (EGMN) – While it might not seem probable, evidence is starting to suggest that exercise can at least forestall Alzheimer’s disease, Dr. Eric B. Larson said at the annual scientific meeting of the American Geriatrics Society. “We now see association studies of physical activity showing a pretty convincing relationship with a delayed onset of dementia,” said Dr. Larson, the executive director of the Center for Health Studies of the Group Health Cooperative, Seattle. “I don’t think we are preventing this disease from ever happening,” he added. “What we’re doing is delaying it.” Four observational studies have now shown, with consistency, a 30%-40% reduction in the incidence of Alzheimer’s disease when people get regular exercise, noted Dr. Larson. Some might find it implausible that physical exercise could affect the brain, cognitive function, and decline, since it has been thought that the brain does not develop after a young age, Dr. Larson noted. But, it turns out that animal experiments show that new neurons do form in the adult brain. “Neurogenesis is possible at almost any phase of development, at least in animals,” he said. And then, there is the human study. In a study of individuals who used functional magnetic resonance imaging, the investigators found that aerobic physical fitness measured on a treadmill correlated with frontal, parietal, and temporal lobe tissue density, such that better fitness meant higher density, which indicates less age-related loss (J. Gerontol. A Biol. Sci. Med. Sci. 2003;58:176-80). In his own study, Dr. Larson looked at 2,581 individuals, who were aged 65 years or older, without dementia. They were tested for cognitive functioning and interviewed about exercise habits every 2 years, starting in 1994-1996. For the analysis, the investigators threw out those individuals who scored in the bottom quartile of subjects on the cognitive testing, on the grounds that they might be persons already showing some dementia-associated decline (Ann. Intern. Med. 2006;144:73-81). With an average follow-up of 6.2 years, during which time 158 subjects developed dementia, the researchers found that those subjects who exercised three or more times per week had a 40% reduction in the risk of developing dementia, compared with those who exercised less than three times per week. The incidence rates of dementia were 13/1,000 person-years for those who exercised three or more times per week, compared with 19.7/1,000 person-years for those who exercised less than three times per week. Exercise was defined as the number of days during the past year that the subjects had engaged in walking, hiking, bicycling, aerobics or calisthenics, swimming, water aerobics, weight training, stretching, or other exercise, for at least 15 minutes at a time. About 60% of those who developed dementia had developed Alzheimer’s disease. The interesting part of the findings was that those subjects who had the lowest physical performance benefited the most from exercise, Dr. Larson said. All of the prevention was in the people in the lowest third on physical performance measures.