WAIT-AND-SEE APPROACH FOR MS

“The longer the duration of multiple sclerosis [MS] and the lower the disability, the more likely a patient is to remain stable and not progress to a greater level of disability,” said Sean J. Pittock, MD. Dr. Pittock and colleagues reached this conclusion after conducting a 10-year follow-up study of patients considered to have benign MS. The findings were reported in the August Annals of Neurology.

Only 7% of patients with an Expanded Disability Status Scale (EDSS) score of 2.0 or lower in 1991 attained an EDSS score of 4.0 or higher. “Patients with an EDSS score of 2 or lower for longer than five years were much less likely than those with EDSS 2.5 to 4 for a similar disease duration to progress to EDSS score higher than 4,” they said. “Patients with EDSS score of 2 or lower and disease duration of at least 10 years have a 93% chance of continuing to have low disability an additional decade later.” However, they admitted that forecasting the course of MS in a patient prior to the five-year mark is difficult.

Coauthor Brian G. Weinshenker, MD, said this study “flies in the face of the commonly held belief that MS is never benign and that every person should be started on lifelong interferon therapy before we get a feel of how the natural course of their illness will behave.” The researchers suggested that rather than taking medication to ward off a potential attack, patients diagnosed with MS may want to take a conservative approach and wait watchfully with their doctors for the first few years to see how the disease progresses.

Moses Rodriguez, MD, another coauthor, said, “If we treat everyone early, we would treat some people who never needed treatment. And, if they don’t need treatment, we can save society hundreds of millions of dollars, and the patients with benign MS can avoid major side effects.”

Pittock SJ, McClelland RL, Mayr WT, et al. Clinical implications of benign multiple sclerosis: a 20-year population-based follow-up study. Ann Neurol. 2004;56:303-306.

PHYSICAL ACTIVITY AND COGNITIVE FUNCTION

Walking, and physical activity in general, is associated with a reduced risk of cognitive decline in elderly men and women, according to two studies in the September 22/29 JAMA. Both studies are consistent with previous findings that physical activity is associated with better cognitive function and less cognitive decline.

In the first study, Robert D. Abbott, PhD, of the University of Virginia School of Medicine, Charlottesville, and colleagues found that older men who walked the least in a comparison group were twice as likely to have dementia as men who walked the most.

The study examined 2,257 men between the ages of 71 and 93. Researchers assessed the distance walked each day from 1991 to 1993. The participants were then assessed for dementia in two follow-up examinations between 1994 and 1999. Researchers identified 158 cases of dementia. They also found that men who walked less than a quarter mile per day were 1.8 times more likely to have dementia than men who walked more than two miles per day. Similarly, those who walked a quarter mile to one mile per day had a 71% increased risk of dementia compared with those who walked more than two miles per day.

The men who walked more were, on average, younger than those who walked less. The men who walked the most also had higher physical performance scores and were more educated.

The researchers offered “no clear explanations for the relation between walking and dementia.” However, they noted that “people who are active tend to adhere to a healthier lifestyle and a better diet than those who are inactive.” These factors could contribute to overall vitality and health. “There is also the possibility that people who walk are less likely to get diseases later in life that could lead to dementia versus people who are inactive.”

Jennifer Weuve, ScD, of the Harvard School of Public Health, Boston, and colleagues conducted a similar study involving 18,766 women ages 70 to 81. They surveyed the women on their physical activity in biennial questionnaires beginning in 1986. The “women were asked to estimate the average amount of time per week during the past year spent on the following physical activities: running, jogging, walking or hiking outdoors, racquet sports, lap swimming, bicycling, aerobic dance or use of exercise machines,” and other vigorous activities. They were also asked to indicate their usual outdoor walking pace. From 1995 to 2001, trained nurses conducted telephone interviews with the participants to test general cognition, verbal memory, category fluency, and attention.

Results indicated that higher levels of physical exercise were associated with better cognitive performance. Women who had the greatest amount of physical activity had a 20% lower risk of cognitive impairment compared with women with the lowest amount of physical activity. Furthermore, researchers found that “women who walked at an easy pace for at least 1.5 hours per week had higher cognitive scores than those who walked less than forty minutes per week.” The researchers said “the apparent cognitive benefits of greater physical activity were similar in extent to being about three years younger in age.”

The researchers offered several explanations for the relationship between physical activity and cognitive function. They suggested that physical activity “sustains the brain’s vascular health by lowering blood pressure, improving lipoprotein profiles, promoting endothelial nitric oxide production, and ensuring adequate cerebral perfusion.” They also noted that aerobic activities might have a beneficial effect on insulin resistance and glucose intolerance, thereby delaying or preventing cognitive decline. Another possibility is that physical activity affects the brain directly, “potentially preserving neuronal structure and promoting the expansion of neural fibers, synapses, and capillaries.”

Abbott RD, White LR, Ross GW, et al. Walking and dementia in physically capable elderly men. JAMA. 2004;292:1447-1453.
Weuve J, Kang JH, Manson JE, et al. Physical activity, including walking, and cognitive function in older women. JAMA. 2004;292:1454-1461.

MONOAMINE OXIDASE TYPE B INHIBITORS FOR PARKINSON’S DISEASE

The use of monoamine oxidase type B inhibitors (MAOBIs) for the treatment of early Parkinson’s disease is not associated with an increased risk of mortality, according to Natalie J. Ives and colleagues. Their study appeared in the September 11 BMJ.

The researchers analyzed data on mortality, motor complications, side effects, treatment compliance, and clinician-rated disability from 17 trials involving 3,525 patients—13 trials examined selegiline, three examined lazabemide, and one examined rasagiline—and found no significant difference in mortality between patients taking MAOBIs and control patients.

Patients taking MAOBIs “had significantly better total scores, motor scores, and activities of daily living scores on the unified Parkinson’s disease rating scale at three months compared with patients taking placebo; they were also less likely to need additional levodopa or to develop motor fluctuations.” Patients taking MAOBIs experienced a 25% reduction in motor fluctuations. The incidence of dyskinesia was similar in both groups.

Based on the findings of their study, the researchers noted that MAOBIs “could be one of the most clinically effective and cost effective treatments available for early Parkinson’s disease.”

In an accompanying editorial, Yoav Ben-Shlomo and Kailash Bhatia critiqued the analysis by Ives et al. Although the study shows that MAOBIs are not associated with an increased risk of mortality, the editorialists “doubt that it has totally closed this debate.”

To check the study for bias, the editorialists “used the mortality odds ratios and confidence intervals provided by Ives et al … to generate a funnel plot.” They found “six imprecise studies to the left of the pooled estimate and none to the right, which implies that the analysis may underestimate the adverse effect on mortality.” Furthermore, they point out that most of the data for mortality in the analysis were extracted from two studies—the US DATATOP study and the UK-PDRG study. In addition, the studies analyzed by Ives et al did not examine dopamine agonists, which are “believed to be the most efficacious drugs in preventing motor complications.”

The editorialists concluded that although “these drugs clearly provide symptomatic benefit and probably entail no risk of increased mortality if they are used as monotherapy and in younger and otherwise healthy patients … data on comparative efficacy with other first line drugs, particularly dopamine agonists, is lacking.”

Ives NJ, Stowe RL, Marro J, et al. Monoamine oxidase type B inhibitors in early Parkinson’s disease: meta-analysis of 17 randomised trials involving 3525 patients. BMJ. 2004;329:593-596.
Ben-Shlomo Y, Bhatia K. Using monoamine oxidase type B inhibitors in Parkinson’s disease. BMJ. 2004;329:581-582.

COGNITIVE IMPAIRMENT IN OLDER WOMEN WITH DIABETES OR PREDIABETES

Elderly women with diabetes or prediabetes are at an increased risk for mild cognitive impairment and dementia, according to Kristine Yaffe, MD, of the University of California, San Francisco, and colleagues. They studied 7,027 older women and found that among women with diabetes or impaired fasting glucose, the risk of developing cognitive impairment increased almost twofold.

According to their study, which was published in the August 24 Neurology, 267 women had diabetes and 297 had impaired fasting glucose. Participants completed six cognitive tests at baseline and then annually for four years. “Women with impaired fasting glucose had worse baseline cognitive scores compared to women with normal glucose but better scores than diabetics,” the researchers reported.

Throughout the four-year study, women with diabetes had greater decline in mental function than women without diabetes. “For every increase in glucose level group, there was a 40% increase in risk of developing cognitive impairment.” Of 4,961 women who participated in the dementia assessment, 48 were diagnosed with dementia and 173 were diagnosed with mild cognitive impairment.

The investigators indicated “several mechanisms whereby diabetes may cause cognitive impairment.” Renal disease, stroke, hypertension, hyperlipidemia, and ischemic heart disease are all thought to provoke impaired cognitive performance. In addition, chronic hyperglycemia, cerebral vessel atherosclerosis, hyperinsulinemia, and insulin resistance are all thought to be associated with an increased risk of cognitive impairment.

The researchers stressed that “interventions aimed at early diagnosis and treatment of abnormal glucose metabolism and their effects on prevention of cognitive impairment need to be undertaken.”

NR

Yaffe K, Blackwell T, Kanaya AM, et al. Diabetes, impaired fasting glucose, and development of cognitive impairment in older women. Neurology. 2004;63:658-663.

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