Thus, even in the elderly, phase advances are more disruptive to sleep than phase delays. While both nortriptyline and interpersonal psychotherapy are superior to placebo in preventing recurrence of major depressive episodes in elderly patients, the best three-year outcome was associated with combined treatment using nortriptyline and interpersonal therapy. Both the Apolipoprotein E4 allele and increased PMF appear to be independent risk factors associated with developing AD among relatives of AD sufferers. Initial studies show that cholinergic enzymes are not decreased in the cortex of patients with either MCI or early mild AD, suggesting an extended window for therapy. Thus, hypothermia or other therapies that decrease cytokines may need to compensate for the suppressed effects of lost neurotrophin activities, one of which is probably to up-regulate antioxidants.
Neurotrophin activities are a major protective response of the brain against injury.