Increased mental slowing associated with the APOE epsilon4 allele after trihexyphenidyl oral anticholinergic challenge in healthy elderly.
OBJECTIVE
The objectives of this study were to examine the relationship between APOE epsilon4 and subjective effects of trihexyphenidyl on measures reflecting sedation and confusion and to investigate the relationship between trihexyphenidyl-induced subjective effects and objective memory performance.


METHODS
This study comprised 24 cognitively intact, health elderly adults (12 APOE epsilon4 carriers) at an outpatient geriatric psychiatry research clinic. This was a randomized, double blind, placebo-controlled, three-way, crossover experimental design. All participants received 1.0 mg or 2.0 mg trihexyphenidyl or placebo administered in counterbalanced sequences over a period of three consecutive weeks. Bond and Lader's visual analog scales and alternate versions of the Buschke Selective Reminding Test were administered in a repeated measures design at baseline, 1, 2.5, and 5 hours postdrug administration.


RESULTS
A 2.0-mg oral dose of trihexyphenidyl resulted in increased subjective ratings of mental slowness in carriers of the APOE epsilon4 allele only. Drug effects as determined by difference scores between 2.0 mg trihexyphenidyl and placebo on ratings of mental slowness significantly correlated with total and delayed recall on the Buschke Selective Reminding Test in carriers of the APOE epsilon4 allele only. However, no significant effects were found with other visual analog scales reflecting subjective sedation and clear-headedness.


CONCLUSIONS
The epsilon4 allele in healthy elderly was associated with increased subjective mental slowing after trihexyphenidyl anticholinergic challenge.
Pomara
Nunzio
N
Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA. pomara@nki.rfmh.org
Belzer
Ken
K
Hernando
Raymundo
R
De La Pena
Corazon
C
Sidtis
John J
JJ
D000284:Administration, Oral; D000368:Aged / Q000523:psychology*; D000483:Alleles; D053327:Apolipoprotein E4 / Q000235:genetics*; D001364:Awareness / Q000187:drug effects; D018680:Cholinergic Antagonists / Q000009:adverse effects / Q000494:pharmacology; D003072:Cognition Disorders / Q000139:chemically induced / Q000175:diagnosis* / Q000523:psychology; D018592:Cross-Over Studies; D003625:Data Collection; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006304:Health Status; D006579:Heterozygote; D006801:Humans; D008569:Memory Disorders / Q000139:chemically induced / Q000145:classification / Q000175:diagnosis; D018727:Muscarinic Antagonists / Q000009:adverse effects / Q000494:pharmacology; D010865:Pilot Projects; D010919:Placebos; D012307:Risk Factors; D014282:Trihexyphenidyl / Q000009:adverse effects / Q000494:pharmacology
D053327:Apolipoprotein E4; D018680:Cholinergic Antagonists; D018727:Muscarinic Antagonists; D010919:Placebos; D014282:Trihexyphenidyl