Effects of rivastigmine on cognitive function in patients with traumatic brain injury.

OBJECTIVE: To compare the efficacy and safety of rivastigmine (3 to 6 mg/day) vs placebo over 12 weeks in patients with traumatic brain injury and persistent cognitive impairment. METHODS: This prospective, randomized, double-blind, placebo-controlled study was conducted in 157 patients at least 12 months after injury. The primary efficacy measures were the Cambridge Neuropsychological Test Automated Battery (CANTAB) Rapid Visual Information Processing (RVIP) A' subtest and the Hopkins Verbal Learning Test (HVLT). The primary efficacy outcome was the proportion of patients who demonstrated 1.0 SD or greater improvement from baseline at week 12 on CANTAB RVIP A' or HVLT. RESULTS: The percentage of responders at week 12 on either the CANTAB RVIP A' or HVLT was 48.7% for rivastigmine and 49.3% for placebo (p = 0.940). Furthermore, for the overall study population, there were no significant differences for any of the secondary efficacy variables. In a subgroup of patients with moderate to severe memory impairment (n = 81), defined as 25% impairment or greater on HVLT at baseline, rivastigmine was significantly better than placebo for a number of measures, including the proportion of HVLT responders and CANTAB RVIP mean latency. CONCLUSIONS: Rivastigmine was safe and well tolerated in patients with traumatic brain injury with cognitive deficits. Rivastigmine shows promising results in the subgroup of patients with traumatic brain injury with moderate to severe memory deficits.

Behavioral and psychological signs and symptoms of dementia: a practicing psychiatrist's viewpoint.

Alzheimer's disease typically presents with two often overlapping syndromes, one cognitive, the other behavioral. The behavioral syndrome is characterized by psychosis, aggression, depression, anxiety, agitation, and other common if less well-defined symptoms subsumed under the umbrella entity "behavioral and psychological symptoms of dementia" (BPSD), itself divided into a number of subsyndromes: psychosis, circadian rhythm (sleepwake) disturbance, depression, anxiety, and agitation, it is BPSD with its impact on care providers that ultimately precipitates the chain of events resulting in long-term institutional care. The treatment challenge involves eliminating unmet medical needs (undiagnosed hip fracture and asymptomatic urinary tract infection or pneumonia). Pharmacologic intervention relies on risperidone and, increasingly cholinesterase inhibitors for the control of psychosis (but with response rates of only 65% at tolerable doses), olanzapine and risperidone for anxiety, and carbamazepine and valproic acid for agitation. However, evidence increasingly favors nonpharmacologic interventions, to the extent that these should now be considered as the foundation of BPSD treatment. Problem behaviors are viewed as meaningful responses to unmet needs in the therapeutic milieu. Because the progression and impact of BPSD varies between patients, interventions must be explored, designed, implemented, and assessed on an individual basis. They include: family support and education, psychotherapy reality orientation, validation therapy, reminiscence and life review, behavioral interventions, therapeutic activities and creative arts therapies, environmental considerations (including restraint-free facilities), behavioral intensive care units, and workplace design and practices that aid the ongoing management of professional caregiver stress.

Fenfluramine challenge test as a marker of serotonin activity in patients with Alzheimer's dementia and agitation.

BACKGROUND: Changes in serotonin (5-HT) have been described in both Alzheimer's disease (AD) and aggressive/agitated behaviors. This paper explores a possible association between 5-HT deficits and agitation in AD, using prolactin response to d,1-fenfluramine administration as a probe for 5-HT activity. METHODS: Five AD patients with agitation and 5 without agitation received a 60-mg oral dose of d,1-fenfluramine. Prolactin levels were obtained at baseline, and 2 and 3 hours following administration. RESULTS: Change in prolactin levels from baseline to 3 hours was significantly larger among the agitated than the nonagitated Alzheimer's patients. Further, there was a positive and significant correlation between change in prolactin levels from baseline and level of agitation. CONCLUSIONS: These findings suggest an association between 5-HT responsiveness and agitation in AD.

Treatment of agitation in patients with dementia.

This article attempts to summarize some of the pertinent literature in the context of the authors' clinical experience and suggests that a comprehensive psychiatric and medical evaluation, as well as a combined behavioral/environmental approach together with appropriate pharmacotherapy, are important tools in the management of this complicated clinical challenge.