The subjects were patients examined as outpatients at a general hospital in Okayama between 1999 and 2008. The inclusion criteria included the following: (1) a diagnosis of dementia of the Alzheimer's type according to DSM-IV criteria, early in their course of treatment; (2) the availability of more than six years of follow-up data. Patients were excluded if they had other obvious neurological or psychiatric diseases such as cerebrovascular disease or major depression. Seventy-seven patients fulfilled the above criteria.
The MMSE scores recorded at the first medical examination (T0) and at the one-year (T1), three-year (T2), and six-year (T3) follow-up examinations were analyzed retrospectively. A two-way analysis of variance (ANOVA) was conducted to test whether time (T0-T3), medication, sex, age at T0, severity of cognitive impairment at T0, or residential state affected the MMSE scores.
Fifty-eight of the subjects (19 men and 39 women; mean age, 75.5 years) were continuously treated with donepezil, whereas nineteen (4 men and 15 women; mean age, 80.6 years) were not. The most frequent reason for non-medication was gastrointestinal side effects. Table 1 shows the patients' MMSE scores. In the medication group, the mean MMSE score fell 6.9 points during the six-year period (annual rate of decline was 1.2). In the non-medication (control) group, the corresponding value was 11.4 points (annual rate of decline was 1.9). An ANOVA revealed significant main effects for both time and medication. The interaction between time and medication was also significant, indicating that the medication group exhibited a slower rate of decline.