The aim of this controlled study was to evaluate the effects of a long-term program of formal didactic group therapy [class reality orientation therapy (ROT)] in Alzheimer disease. The study was conducted in the day hospital of an Alzheimer Dementia Research and Care Unit (Brescia, Italy), a multidisciplinary care center providing diagnostic evaluation and treatment for elderly patients with cognitive impairment. The criteria for the inclusion of patients in the study were mild to moderate cognitive impairment [Mini Mental Status Examination (MMSE) between 11 and 24/30] and absence of major aphasia, blindness, and overt behavioral disturbances such as wandering or agitation. Sixteen patients constituted the experimental group and 12 the control group. The last cognitive, functional, and affective evaluation in the experimental and control group was performed 8.2 and 8.5 months after baseline assessment, respectively. The experimental group had repeated cycles of 1-month ROT classes, and 5-7 weeks was allowed between each cycle. Differential change for MMSE score between the two groups was significant. In the experimental group, there was mild improvement in MMSE score (0.68 point) at the last assessment, whereas the control group declined (-2.58 points). This treatment effect on MMSE score (3.27 points) was controlled for potential confounders in a multiple regression analysis. Adjusted treatment effect, including age, education, baseline MMSE, disease duration, disease severity, number of diseases other than Alzheimer, and time elapsing from baseline to last assessment, was very slightly lower: 3.12. In the experimental group, treatment effect was evaluated by comparing ROT cycle changes and resting period changes. A clearly significant treatment effect was found for MMSE and verbal fluency.