ABSTRACT
The observation of orthostatic hypotension in an index case of manganese toxicity lead to this prospective attempt to evaluate cardiovascular autonomic function and cognitive and emotional neurotoxicity in eight manganese alloy welders and machinists. The subjects consisted of a convenience sample consisting of an index case of manganese dementia, his four co-workers in a "frog shop" for gouging, welding, and grinding repair of high manganese railway track and a convenience sample of three mild steel welders with lesser manganese exposure also referred because of cognitive or autonomic symptoms. Frog shop air manganese samples 9.6-10 years before and 1.2-3.4 years after the diagnosis of the index case exceeded 1.0 mg/m3 in 29% and 0.2 mg/m3 in 62%. Twenty-four-hour electrocardiographic (Holter) monitoring was used to determine the temporal variability of the heartrate (RR' interval) and the rates of change at low frequency (0.04-0.15 Hz) and high frequency (0.15-0.40 Hz). MMPI and MCMI personality assessment and short-term memory, figure copy, controlled oral word association, and symbol digit tests were used. The five frog shop workers had abnormal sympathovagal balance with decreased high frequency variability (increased ln LF/ln HF). Seven of the eight workers had symptoms of autonomic dysfunction and significantly decreased heart rate variability (rMSSD) but these did not distinguish the relative exposure. Mood or affect was disturbed in all with associated changes in short-term memory and attention in four of the subjects. There were no significant correlations with serum or urine manganese. Power spectrum analysis of 24-h ambulatory ECG indicating a decrease in parasympathetic high frequency activation of heart rate variability may provide a sensitive index of central autonomic dysfunction reflecting increased exposure to manganese, although the contribution of exposures to solvents and other metals cannot be excluded. Neurotoxicity due to the gouging, welding, and grinding of mild steel and high manganese alloys (11-25%) merits air manganese and neuropsychologic surveillance including autonomic function by Holter monitoring of cardiovagal activation.
Subject(s)
Autonomic Nervous System/drug effects , Cardiovascular Physiological Phenomena/drug effects , Manganese/adverse effects , Occupational Exposure , Adult , Alloys , Cognition/drug effects , Electrocardiography , Emotions/drug effects , Heart Rate/drug effects , Humans , Male , Memory/drug effects , Middle Aged , Personality AssessmentABSTRACT
OBJECTIVE: To examine the cognitive and behavioral effects of L-deprenyl in persons with mild dementia of the Alzheimer type (DAT) over a 15-month period. DESIGN: A 15-month randomized, double-blind, placebo-controlled trial using a parallel-group design. PARTICIPANTS: 39 subjects with mild DAT (CDR 1) selected using NINCDS-ADRDA criteria. OUTCOME MEASURES: A battery of neuropsychological tests and clinical rating scales. RESULTS: The placebo and L-deprenyl subjects were similar at baseline on the clinical and neuropsychological tests. The total score on the Brief Psychiatric Rating Scale (BPRS) was significantly less after 15 months in subjects taking L-deprenyl. The only individual item of the BPRS which differed between groups was disorientation. There was no evidence of a L-deprenyl effect on any other clinical or neuropsychological measure after 2, 8, or 15 months. CONCLUSION: L-deprenyl did appear to have a slight effect on a single measure of psychopathology, the BPRS. It did not have a measurable impact on any other measure of behavior or cognitive function over a 15-month period in this group of subjects with mild DAT and did not appear to slow the progression of the disease.
Subject(s)
Alzheimer Disease/drug therapy , Selegiline/therapeutic use , Aged , Alzheimer Disease/classification , Alzheimer Disease/physiopathology , Alzheimer Disease/psychology , Analysis of Variance , Behavior/drug effects , Cognition/drug effects , Double-Blind Method , Female , Humans , Interview, Psychological , Male , Neuropsychological Tests , Orientation/drug effects , Psychiatric Status Rating Scales , Selegiline/pharmacology , Severity of Illness IndexABSTRACT
OBJECTIVE: To examine the short-term cognitive and behavioral effects of L-deprenyl in persons with mild dementia of the Alzheimer type (DAT) over a 2-month period. DESIGN: A 15-month randomized, double-blind, placebo-controlled trial using a parallel-group design. This report deals with the first 2 months of the trial. PARTICIPANTS: 39 subjects with mild DAT (CDR 1) selected using NINCDS-ADRDA criteria. MEASURES: A battery of neuropsychological tests and clinical rating scales. RESULTS: The placebo and L-deprenyl subjects were similar at baseline on the clinical and neuropsychological tests. There was no evidence of a L-deprenyl effect on any clinical or neuropsychological measures after 2 months. CONCLUSION: L-deprenyl did not have a measurable impact on behavior or cognitive function over a 2-month period in this group of subjects with mild DAT.
