Faculty Bibliography

The authors evaluated the safety, tolerability, and efficacy of risperidone in 103 elderly patients (mean age, 71 years) with schizophrenia (75%) or schizoaffective disorder (25%). Using the Extrapyramidal Symptoms Rating Scale (ESRS), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression (CGI) scale, they conducted a prospective, open-label, 12-week trial in 14 psychiatric centers in the United States. Patients' symptoms were assessed at baseline and over a 12-week period. At endpoint, ESRS scores were significantly reduced, as were PANSS total and subscale scores. There were no clinically significant changes in electrocardiograms, laboratory test results, or vital signs. Risperidone was well tolerated and efficacious in elderly patients with schizophrenia or schizoaffective disorder

This report examines plasma amyloid beta proteins A beta 40 and A beta 42 and apolipoprotein E (apoE) levels and their relationships with age in non-demented older adults with (N = 32) or without the apoE-epsilon 4 allele (N = 94). A beta levels did not differ between the groups whereas the epsilon 4 allele was associated with a significant reduction in plasma apoE. In subjects with the epsilon 4 allele, increasing age was associated with significant reduction in plasma A beta 40. Subjects without the epsilon 4 allele showed a significant positive correlation between A beta 40 and A beta 42 levels. There was also a significant correlation between plasma A beta 40 and apoE levels in all subjects

We examined the acute performance and sedative effects of single high and low doses of alprazolam and lorazepam, both before and after chronic, 3-week b.i.d. treatment in elderly adults. The effects of chronic treatment also were examined in this parallel, double-blind, placebo-controlled study. Initial acute low doses significantly impaired total recall and increased intrusion errors. High doses also impaired delayed recall and critical flicker fusion threshold (CFF). Only chronic treatment with high-dose alprazolam increased intrusions and self-rated sedation. Single-dose rechallenge after chronic treatment was associated with significantly less impairment than the initial challenge in memory tasks but not in the discriminant reaction time (DRAT) task. For most memory measures, the development of tolerance was only partial; rechallenge still produced significant deficits in relation to placebo. The development of tolerance was task-specific and depended on drug type and dosage. Despite impairments in various memory functions, CFF, and DRAT, volunteers did not report significant drug-induced changes in sedation

Complement activation is present in the brain in Alzheimer's disease (AD), and C1q concentrations are decreased in AD cerebrospinal fluid (CSF). To determine whether concentrations of other complement proteins are also altered in AD CSF, we measured concentrations of C3a and SC5b-9 in CSF from patients with probable AD (n = 19), normal aged controls (n = 11), and normal younger controls (n = 15). C3a concentrations were similar between AD and aged controls, but threefold higher than in younger controls (p < 0.05 vs. both groups). A similar pattern was found with SC5b-9, though the increase was only twofold and statistically significant only for AD vs. younger controls. These results suggest that an increased generation of complement proteins in localized areas of the AD brain does not result in elevated concentrations of these proteins in CSF, compared with age-matched controls. Increased C3a (and, to a lesser extent, SC5b-9) in aged controls may be due to increased complement activation, increased central nervous system production, and/or blood-brain barrier leakage of these proteins

Immunocytochemical staining was performed to investigate the presence of anti-hippocampal antibodies in cerebrospinal fluid (CSF) from patients with probable Alzheimer's disease (AD) (n = 19), aged normal controls (n = 9), and young normal controls (n = 10). Marked staining of neurons in the granule cell layer of the dentate gyrus and in pyramidal neurons in CA1-3 of the rat hippocampus was observed in 5 AD CSF samples (26%), 1 aged control sample (11%), and 1 young control sample (10%). These differences were not statistically significant. One of the immunoreactive AD CSF specimens also contained high concentrations of C5b-9, the membrane attack complex. The infrequent occurrence of anti-hippocampal antibodies in AD CSF, and the detection of similar immunoreactivity in control CSF specimens, suggest that these antibodies are unlikely to play a role in the neurodegenerative process in most individuals with AD. However, elevated C5b-9 concentration in an AD CSF specimen with marked immunoreactivity to hippocampal neurons suggests the possibility that anti-neuronal antibodies may contribute to complement activation in some AD patients