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Increased mental slowing associated with the APOE epsilon4 allele after trihexyphenidyl oral anticholinergic challenge in healthy elderly.
Am J Geriatr Psychiatry. 2008 Feb; 16(2):116-24.AJ

Abstract

OBJECTIVES

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.

CONCLUSION

The epsilon4 allele in healthy elderly was associated with increased subjective mental slowing after trihexyphenidyl anticholinergic challenge.

Authors+Show Affiliations

Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA. pomara@nki.rfmh.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18239197

Citation

Pomara, Nunzio, et al. "Increased Mental Slowing Associated With the APOE Epsilon4 Allele After Trihexyphenidyl Oral Anticholinergic Challenge in Healthy Elderly." The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry, vol. 16, no. 2, 2008, pp. 116-24.
Pomara N, Belzer K, Hernando R, et al. Increased mental slowing associated with the APOE epsilon4 allele after trihexyphenidyl oral anticholinergic challenge in healthy elderly. Am J Geriatr Psychiatry. 2008;16(2):116-24.
Pomara, N., Belzer, K., Hernando, R., De La Pena, C., & Sidtis, J. J. (2008). Increased mental slowing associated with the APOE epsilon4 allele after trihexyphenidyl oral anticholinergic challenge in healthy elderly. The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry, 16(2), 116-24. https://doi.org/10.1097/JGP.0b013e31815aff75
Pomara N, et al. Increased Mental Slowing Associated With the APOE Epsilon4 Allele After Trihexyphenidyl Oral Anticholinergic Challenge in Healthy Elderly. Am J Geriatr Psychiatry. 2008;16(2):116-24. PubMed PMID: 18239197.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased mental slowing associated with the APOE epsilon4 allele after trihexyphenidyl oral anticholinergic challenge in healthy elderly. AU - Pomara,Nunzio, AU - Belzer,Ken, AU - Hernando,Raymundo, AU - De La Pena,Corazon, AU - Sidtis,John J, PY - 2008/2/2/pubmed PY - 2008/5/15/medline PY - 2008/2/2/entrez SP - 116 EP - 24 JF - The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry JO - Am J Geriatr Psychiatry VL - 16 IS - 2 N2 - OBJECTIVES: 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. CONCLUSION: The epsilon4 allele in healthy elderly was associated with increased subjective mental slowing after trihexyphenidyl anticholinergic challenge. SN - 1064-7481 UR - https://www.unboundmedicine.com/medline/citation/18239197/Increased_mental_slowing_associated_with_the_APOE_epsilon4_allele_after_trihexyphenidyl_oral_anticholinergic_challenge_in_healthy_elderly_ L2 - https://linkinghub.elsevier.com/retrieve/pii/16/2/116 DB - PRIME DP - Unbound Medicine ER -