Faculty Bibliography

OBJECTIVE: This study compared the relation between negative mood states and memory in young and elderly subjects. METHOD: Forty-five normal, healthy young volunteers (ages 19-35 years) and 45 normal, healthy elderly volunteers (ages 60-78 years) were administered a verbal list-learning task and self-rated scales of affective states. RESULTS: The elderly group, but not the young group, consistently exhibited significant correlations between their performance on verbal recall measures and their ratings of their anxiety, depression, and withdrawal; i.e., within the elderly group, higher levels of negative affective states were associated with poorer memory. CONCLUSIONS: These findings indicate that aging modulates the relation between emotional state and memory functions, and they are consistent with the hypothesis that the elderly are more vulnerable than the young to the adverse effects of negative emotional states on memory. Therefore, even in normal elderly individuals without diagnosable psychopathology, negative affective states (such as anxiety and depression) may interfere with memory functioning

OBJECTIVE: Milacemide, a MAO-B inhibitor that is also a prodrug for glycine, was tested as a treatment for senile dementia of the Alzheimer type (SDAT) because of its potential for enhancing cognition in animal models of impaired learning and memory. DESIGN: Double-blind, placebo-controlled, randomized clinical trial. SETTING: Sixteen study sites, both university-affiliated and private. PATIENTS: A total of 228 outpatients (116 men and 112 women) with SDAT, ranging in age from 49-93 years. INTERVENTION: 1200 mg/day milacemide treatment for 1 month (113 patients received milacemide, and 115 patients received placebo). MAIN OUTCOME MEASURES: Alzheimer's Disease Assessment Scale and the Mini-Mental State Examination. RESULTS: Milacemide-treated SDAT patients did not show significant improvement in any of the outcome measures used. Significant elevations in liver enzymes in four subjects were of sufficient magnitude to necessitate withdrawal from the study. CONCLUSIONS: Milacemide does not appear to be an effective treatment in enhancing cognition in SDAT patients

The authors compared CSF amino acid levels of 10 patients with mild to moderate dementia and probable Alzheimer's disease who had never received antidepressant or neuroleptic medication with those of 10 normal subjects of similar age. The Alzheimer's patients had significantly higher levels of CSF glutamate. This finding was not related to age, sex, or severity of dementia. Elevated CSF glutamate may reflect greater glutamatergic activity early in the course of Alzheimer's disease. The authors speculate that the excitotoxic effects of glutamate may contribute to progressive neuronal loss in Alzheimer's disease

The effects of the muscarinic agonist, arecoline, on the concentration of homovanillic acid (HVA) in the cerebrospinal fluid of patients with Alzheimer's disease (AD) and controls were examined. Patients and controls received intravenous infusions of arecoline and a lumbar puncture was performed four hours after the infusion began. Arecoline induced a significant increase in the concentration of HVA in cerebrospinal fluid of Alzheimer's disease patients (p < .01) but not in controls. The differential HVA response to a muscarinic agonist in Alzheimer's disease is suggestive of an alteration in muscarinic receptor response. This finding may have potential implications for the pathophysiology and treatment of Alzheimer's disease

The failure of cholinesterase inhibitors to produce noticeable improvement in about half of patients with Alzheimer's disease (AD) may result from heterogeneity of neurotransmitter abnormalities in this disorder. This study examined whether pretreatment postural blood pressure (BP) drop, which presumably reflects sympathetic response, differed in patients who were responders or nonresponders to the cholinesterase inhibitor, HP 029. Twenty-three AD patients completed a double-blind dose-finding phase of a clinical trial in which four doses of HP 029 and placebo were administered. Evaluation for efficacy occurred after 7 days of treatment at each dose. Of the 23 patients, 12 were classified as responders in the dose-ranging phase of the study. Nonresponders demonstrated significantly greater decreases in pretreatment systolic postural BPs when going from a supine to sitting position than did responders. The greater postural BP drop in nonresponders may identify a subgroup of AD patients that responds poorly to cholinesterase inhibitors

This study evaluated the equivalence of five forms of the Selective Reminding Test, a widely used measure of verbal learning, 45 normal young and 45 normal elderly subjects were randomly administered three of the five test forms on three separate sessions. The five forms generally correlated well with one another and were of comparable difficulty, suggesting adequate test equivalence. Four of the five forms were particularly well matched