The development of Alzheimer's disease (AD) later in life may be reflective of environmental factors operating over the course of a lifetime. Educational and occupational attainments have been found to be protective against the development of the disease but participation in activities has received little attention. In a casecontrol study, we collected questionnaire data about 26 nonoccupational activities from ages 20 to 60. Participants included 193 people with probable or possible AD and 358 healthy controlgroup members. Activity patterns for intellectual, passive, and physical activities were classified by using an adaptation of a published scale in terms of ''diversity'' (total number of activities), ''intensity'' (hours per month), and ''percentage intensity'' (percentage of total activity hours devoted to each activity category). The control group was more active during midlife than the case group was for all three activity categories, even after controlling for age, gender, income adequacy, and education. The odds ratio for AD in those performing less than the mean value of activities was 3.85 (95% confidence interval: 2.65-5.58, P < 0.001). The increase in time devoted to intellectual activities from early adulthood (20 -39) to middle adulthood (40 -60) was associated with a significant decrease in the probability of membership in the case group. We conclude that diversity of activities and intensity of intellectual activities were reduced in patients with AD as compared with the control group. These findings may be because inactivity is a risk factor for the disease or because inactivity is a reflection of very early subclinical effects of the disease, or both.case-control study ͉ dementia ͉ epidemiology ͉ leisure ͉ recreation

Implementing the TS program in nursing facilities improves the care environment for PWDs. However, additional studies are needed to offer further insights into the mechanisms by which TS improves both staff and resident outcomes.

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.

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.

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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.

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Researchers have suggested that educational attainment and occupational status—indicators of cognitive and/or neurologic “reserve”—can help persons compensate for clinical manifestations of Alzheimer's disease (AD), such as the rates of cognitive and functional decline. The effects of educational attainment on rates of decline could be “direct” (independent of occupational status), “indirect” (working through occupational status), or both. We used multilevel analysis for repeated measures to study the effects of educational attainment and occupational status on rates of decline in cognition (Mini-Mental State Examination, MMSE) and function (Cleveland Scale for Activities of Daily Living). Subject included persons with “probable” or “possible” AD, drawn from our Alzheimer's Disease Research Center registry (N = 482 in the analysis of cognitive decline, and N = 450 in the analysis of functional decline). When controlling for year of birth, gender, ethinicity, and duration of illness, we found that there was an inverse relationship between number of years of education and rate of decline in MMSE, but effects of occupational status were not significant. This implies a “direct” effect of education on decline in MMSE, but no “indirect” effect through occupational status. Neither educational attainment nor occupational status affected rate of decline in functional ability. We conclude that education slows the rate of cognitive decline in persons with AD, but not through its impact on occupational status. Thus the protective effects of reserve may be established early in life, before people enter the workforce.