Dementia prevention, intervention, and care.

Biochemical, electrophysiological, and pharmacological evidence supporting a role for cholinergic dysfunction in age-related memory disturbances is critically reviewed. An attempt has been made to identify pseudoissues, resolve certain controversies, and clarify misconceptions that have occurred in the literature. Significant cholinergic dysfunctions occur in the aged and demented central nervous system, relationships between these changes and loss of memory exist, similar memory deficits can be artificially induced by blocking cholinergic mechanisms in young subjects, and under certain tightly controlled conditions reliable memory improvements in aged subjects can be achieved after cholinergic stimulation. Conventional attempts to reduce memory impairments in clinical trials hav not been therapeutically successful, however. Possible explanations for these disappointments are given and directions for future laboratory and clinical studies are suggested.

Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and early Alzheimer's disease. In a double-blind study, we evaluated subjects with the amnestic subtype of mild cognitive impairment. Subjects were randomly assigned to receive 2000 IU of vitamin E daily, 10 mg of donepezil daily, or placebo for three years. The primary outcome was clinically possible or probable Alzheimer's disease; secondary outcomes were cognition and function. A total of 769 subjects were enrolled, and possible or probable Alzheimer's disease developed in 212. The overall rate of progression from mild cognitive impairment to Alzheimer's disease was 16 percent per year. As compared with the placebo group, there were no significant differences in the probability of progression to Alzheimer's disease in the vitamin E group (hazard ratio, 1.02; 95 percent confidence interval, 0.74 to 1.41; P=0.91) or the donepezil group (hazard ratio, 0.80; 95 percent confidence interval, 0.57 to 1.13; P=0.42) during the three years of treatment. Prespecified analyses of the treatment effects at 6-month intervals showed that as compared with the placebo group, the donepezil group had a reduced likelihood of progression to Alzheimer's disease during the first 12 months of the study (P=0.04), a finding supported by the secondary outcome measures. Among carriers of one or more apolipoprotein E epsilon4 alleles, the benefit of donepezil was evident throughout the three-year follow-up. There were no significant differences in the rate of progression to Alzheimer's disease between the vitamin E and placebo groups at any point, either among all patients or among apolipoprotein E epsilon4 carriers. Vitamin E had no benefit in patients with mild cognitive impairment. Although donepezil therapy was associated with a lower rate of progression to Alzheimer's disease during the first 12 months of treatment, the rate of progression to Alzheimer's disease after three years was not lower among patients treated with donepezil than among those given placebo. Copyright 2005 Massachusetts Medical Society.

It is unclear to what extent poor social relationships are related to the development of dementia. A comprehensive systematic literature search identified 19 longitudinal cohort studies investigating the association between various social relationship factors and incident dementia in the general population. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled using random-effects meta-analysis. Low social participation (RR: 1.41 (95% CI: 1.13-1.75)), less frequent social contact (RR: 1.57 (95% CI: 1.32-1.85)), and more loneliness (RR: 1.58 (95% CI: 1.19-2.09)) were statistically significant associated with incident dementia. The results of the association between social network size and dementia were inconsistent. No statistically significant association was found for low satisfaction with social network and the onset of dementia (RR: 1.25 (95% CI: 0.96-1.62). We conclude that social relationship factors that represent a lack of social interaction are associated with incident dementia. The strength of the associations between poor social interaction and incident dementia is comparable with other well-established risk factors for dementia, including low education attainment, physical inactivity, and late-life depression.