No abstract

To evaluate the safety of the peroxisome proliferator-activated receptor gamma agonist pioglitazone in nondiabetic patients with Alzheimer disease (AD) and to explore treatment effect sizes on clinical outcomes. Design: Double-blind, placebo-controlled randomized controlled trial of 18-month duration. Setting: Two academic medical center outpatient clinics. Patients: Nondiabetic patients meeting research criteria for probable AD were enrolled. Twenty-five of 29 subjects completed the study; no withdrawals were attributable to adverse effects. Intervention: Subjects received pioglitazone (Actos), titrated to 45 mg daily, or matching placebo, and 200 IU of vitamin E daily. Patients maintained treatment with cholinesterase inhibitors and could begin memantine therapy when it became available during the study. Main Outcome Measures: The primary outcome was frequency of reported adverse effects (AEs). Secondary outcomes were measures of cognition, activities of daily living, neuropsychiatric symptoms, and global function. Results: Peripheral edema was the principal AE occurring more frequently in subjects taking pioglitazone than placebo (28.6% vs 0%). This is consistent with the known AE profile of pioglitazone. No group differences in laboratory measures were identified. No significant treatment effect was observed on exploratory analysis of clinical efficacy. Conclusions: Pioglitazone was generally well tolerated in this pilot study. There were no serious or unanticipated adverse events or clinical laboratory changes attributable to pioglitazone over a long-term exposure in nondiabetic patients with AD. The tolerability of pioglitazone in this population and peroxisome proliferator-activated receptor gamma effects in laboratory models of AD support further study of this drug class in earlier disease stages.

ComputerLink was a computer support network for family caregivers of people with Alzheimer's disease. In a 12-month experiment, 102 caregivers were randomly assigned to an experimental group that had access to ComputerLink or to a control group that did not. This investigation examined whether caregivers in the experimental group had greater reductions in four types of care-related strain by the end of the 1-year study. ComputerLink reduced certain types of strain if caregivers also had larger informal support networks, were spouses, or did not live alone with their care receivers. More frequent use of the communication function was related to significantly reduced strain for caregivers who were initially more stressed and for non-spouse caregivers. Greater use of the information function was related to significantly lower strain among caregivers who lived alone with care receivers. Overall, ComputerLink appeared to be an effective tool for reducing strain for some caregivers.

Our study suggests that reserve is dynamic, but it is most amenable to change in early life. We conclude that an active, engaged lifestyle, emphasizing mental activity and educational pursuits in early life, can have a positive impact on cognitive functioning in late life.

The authors' results may indicate a relatively early influence of Alzheimer disease neuropathology on capacity to pursue mentally demanding occupations. However, results also are consistent with the notion that mentally demanding occupations have a direct influence on Alzheimer disease neuropathology.