Aging alters numerous aspects of circadian biology, including the amplitude of rhythms generated by the suprachiasmatic nuclei (SCN) of the hypothalamus, the site of the central circadian pacemaker in mammals, and the response of the pacemaker to environmental stimuli such as light. Although previous studies have described molecular correlates of these behavioral changes, to date only 1 study in rats has attempted to determine if there are age-related changes in the expression of genes that comprise the circadian clock itself. We used in situ hybridization to examine the effects of age on the circadian pattern of expression of a subset of the genes that comprise the molecular machinery of the circadian clock in golden hamsters. Here we report that age alters the 24-h expression profile of Clock and its binding partner Bmal1 in the hamster SCN. There is no effect of age on the 24-h profile of either Per1 or Per2 when hamsters are housed in constant darkness. We also found that light pulses, which induce smaller phase shifts in old animals than in young, lead to decreased induction of Per1, but not of Per2, in the SCN of old hamsters.

Mianserin HCI (1&60 mg/day) was administered orally before bedtime to 46 patients (mean age: 63 years) with delirium at Kurume University Hospital. The therapeutic effects of mianserin were assessed pre-and post-treatment using the Delirium Rating Scale (DRS: Trzepacz et al., 1988). The mean pre-treatment DRS score was 21. This score decreased significantly (p <0-05) to 14 on treatment day 1 and 10 on day 3. Mianserin was observed to be effective in 85 per cent of the cases (marked improvement in 67 per cent of the patients and slight improvement in 17 per cent). Of the 46 patients, 28 were classified with delirium due to direct causes such as a brain turnour or cerebrovascular disease, and 18 due to facilitating factors such as hospitalization or physical restraint. In the former group, marked improvement was observed in 54 per cent of the patients, and slight improvement in 21 per cent. The latter group demonstrated marked improvement in 89 per cent of the patients, and slight improvement in 11 per cent. In control subjects receiving haloperidol, marked improvement was observed in 62 per cent of I7 delirious patients. The plasma concentration of mianserin reached a therapeutic level within 24 h of the initiation of treatment. Hence, based on these clinical results and on measurements of plasma mianserin concentrations, mianserin can be considered effective in the treatment of delirium in elderly patients due to its rapid onset and few side-effects. Mianserin may offer an efficacy similar to that of haloperidol in the treatment of delirium while being safer.

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