By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for GlaxoSmithKline and is on the speaker's bureau of GlaxoSmithKline, 3M, Wyeth-Ayerst, Pfizer, Novartis, Bristol-Myers Squibb, AstraZeneca, Jones Pharma, and Boehringer Ingelheim.
Cognitive Impairment Progression Blunted by Exercise
Source: Lautenschlager NT, et al. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: A randomized trial. JAMA 2008;300:1027-1037.
Clinical trials of pharmacotherapy to prevent progression of cognitive decline in those with mild cognitive impairment (MCI) have been disappointing; neither cholinesterase inhibitors (donepezil, rivastigmine, galantamine), vitamin E, nor COX-2 inhibitors has demonstrated any clinically meaningful benefit in placebo-controlled MCI trials.
Observational data are consistent that regular physical activity, even if started late in life, is associated with reduced risk of dementia. Whether exercise might prevent progression in persons with MCI was the subject of this first randomized trial to address the issue.
Subjects (n = 170) with MCI between the ages of 50-77 (mean age, 68.6 years) were randomized to receive either 50-min sessions of moderate-intensity exercise (e.g., brisk walking, ballroom dancing, and swimming) three times weekly vs control (general education about health, including physical activity, diet, alcohol, and stress management). All educational materials were also provided to the intervention group. All participants (control and intervention) wore a pedometer and provided diaries of daily total number of steps. Physical activity and cognitive function were assessed at 6, 12, and 18 months after randomization.
At each assessment point, cognitive scores for the intervention group were better than the control group. The intervention group averaged approximately 6000 more steps/week than the control group. Exercise, averaging as little as 21 min/day, reduces cognitive decline in persons with MCI.
Pramlintide as a Weight-Loss Adjunct
Source: Smith SR, et al. Sustained weight loss following 12-month pramlintide treatment as an adjunct to lifestyle intervention in obesity. Diabetes Care 2008;3:1816-1823.
Something that neither mother nor medical school taught us was that more than one hormone is secreted from the beta cells of the pancreas in response to rising glucose. In conjunction with insulin, the hormone amylin is released. Pramlintide is a synthetic form of amylin. The physiologic effects of amylin include slowed gastric emptying (thereby slowing the rate of glucose delivery to the intestine), suppression of glucagon, and centrally mediated satiety. For addressing obesity, there is great conceptual appeal to an agent that improves satiety.
Smith et al performed a double-blind, placebo-controlled trial of various doses of subcutaneous pramlintide (bid to tid) in obese, nondiabetic subjects, who were also receiving intensive lifestyle (diet/exercise) intervention. The initial 4-month double-blind phase was followed by a 4-month single-blind extension (for those who completed the initial phase without protocol violation).
Weight loss was dose-proportional: At 360 mg twice daily the placebo-corrected weight loss was 3.3 kg at month 4 and 7.2 kg at month 12. No safety concerns were seen. Nausea, which is also the most common adverse event seen in diabetic subjects, was mostly mild to moderate, and improved over time. Nausea is not the mechanism of action, since weight reduction was similar in those who did and did not experience nausea. These initial data are encouraging that pramlintide may find a role in enhancing weight loss when used in conjunction with lifestyle intervention.
Hormone Replacement and Skin Health in Menopausal Women
Source: Phillips TJ, et al. Does hormone therapy improve age-related skin changes in postmenopausal women? J Am Acad Dermatol 2008;59:397-404.
As little as a decade ago, menopausal status alone was the ticket of admission to advocate hormone replacement therapy (HRT). The "story line" went that HRT prevented cognitive decline, improved symptoms, enhanced cardiovascular health, and preserved cutaneous health, i.e., reduced age-related wrinkles, dryness, and laxity. Unfortunately, HRT has failed to live up to many of its hopeful claims.
To study the effects of HRT on menopausal women's skin, 485 subjects were randomly assigned to placebo or two different HRT doses in double-blind fashion. Dermatologists evaluated skin wrinkling, laxity, and texture (as did the patients) over a 48-week interval. The mean age of the women was 54 years.
At study end, there were no statistically significant differences in any primary endpoint of the trial. When the data were analyzed for impact of baseline levels of estradiol, race, or age, no meaningful differences were found. During the trial, all study groups enjoyed some skin improvements attributable to daily application of moisturizing cream and sunscreen, but HRT added nothing to this. Claims that HRT provides reduced risk of age-related skin changes are not supported by this trial.