Characterizing impaired functional alertness from diphenhydramine in the elderly with performance and neurophysiologic measures.
OBJECTIVE
Psychometric task performance measures can be highly sensitive to manipulations that impair functional alertness in young adults; such measures have been shown to be less sensitive to reduced alertness in older adults. The purpose of this study is to determine whether neurophysiologic measures can aid in the detection and characterization of impairments in functional alertness in the elderly.


METHODS
Double-blind, placebo-controlled, counter-balanced, crossover study.


METHODS
Research laboratory.


METHODS
Twelve healthy older adults (62-75 years of age).


METHODS
Diphenhydramine, 50 mg.


RESULTS
Behavioral performance and electroencephalogram measures were obtained while participants completed spatial working memory and word recognition episodic memory tasks in a baseline interval before drug ingestion and in 4 hourly test intervals following drug ingestion. Relative to placebo, diphenhydramine had marginal effects on task performance yet was effective in reducing alertness, as evidenced by subjective ratings and objective neurophysiologic (electroencephalogram) markers. Diphenhydramine significantly reduced the amplitude of alertness-sensitive event-related potentials recorded during working memory task performance, including the N160 and P300. It also affected neurophysiologic processes underlying episodic memory, as evidenced by a reduction in the difference in event-related potentials between old and new words in the word recognition task. Discriminant analyses incorporating neurophysiologic measures showed that the time course of the central effects of diphenhydramine in older subjects was similar to that previously observed in young adults.


CONCLUSIONS
These results demonstrate that diphenhydramine has adverse neurocognitive effects in elderly individuals and highlights the utility of incorporating direct measures of brain function into assessments of functional alertness.
McEvoy
Linda K
LK
San Francisco Brain Research Institute & SAM Technology, CA 94108, USA. linda@eeg.com
Smith
Michael E
ME
Fordyce
Moira
M
Gevins
Alan
A
D000368:Aged; D001143:Arousal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D018592:Cross-Over Studies; D004155:Diphenhydramine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects; D018913:Event-Related Potentials, P300 / Q000187:drug effects*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D008875:Middle Aged; D011594:Psychometrics; D011597:Psychomotor Performance / Q000187:drug effects*; D021641:Recognition, Psychology / Q000187:drug effects; D013067:Speech Perception / Q000187:drug effects*; D014825:Vocabulary
D006993:Hypnotics and Sedatives; D004155:Diphenhydramine