Acute treatment with the PDE4 inhibitor roflumilast improves verbal word memory in healthy old individuals: a double-blind placebo-controlled study

Arjan Blokland, Marlies A. Van Duinen, Anke Sambeth, Pim R.A. Heckman, Max Tsai, Gezim Lahu, Tolga Uz, Jos Prickaerts

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

There is ample evidence that phosphodiesterase 4 (PDE4) inhibition can improve memory performance in animal studies. In the present study, we examined the acute effects of the PDE4 inhibitor roflumilast on memory performance in healthy individuals (60-80 years of age). We tested the effects of acute roflumilast administration (100, 250, 1000 μg) in a double-blind, placebo-controlled, 4-way crossover design. Participants were first screened for their verbal word memory performance to ensure normal memory performance (within 0.5 standard deviation from norm score; n = 20) Drug effects on memory performance were tested in a verbal memory test and a spatial memory test. Reported side effects of drug treatment were registered. Roflumilast (100 μg) improved the delayed recall performance of the participants (Cohen's d, 0.69). No effects were observed in the spatial memory task. Roflumilast was well tolerated at this low dose. Although no clear adverse side effects were reported at the low dose, mild adverse events (including headache, dizziness, insomnia, and diarrhea) were reported after the 1000 μg dose. The present study provides first evidence that the PDE4 inhibitor roflumilast improves verbal memory performance in old participants. The current data encourage further development of PDE4 inhibitors for improving memory.

Original languageEnglish
Pages (from-to)37-43
Number of pages7
JournalNeurobiology of Aging
Volume77
Early online date26 Jan 2019
DOIs
Publication statusPublished - May 2019

Keywords

  • AGE
  • Aging
  • CAMP
  • COGNITION
  • Cognition enhancement
  • DISEASE
  • EDUCATION
  • ENHANCEMENT
  • LONG-TERM-MEMORY
  • N-OXIDE
  • NORMATIVE DATA
  • PHOSPHODIESTERASE-4 INHIBITOR
  • ROLIPRAM
  • Verbal memory

Cite this

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title = "Acute treatment with the PDE4 inhibitor roflumilast improves verbal word memory in healthy old individuals: a double-blind placebo-controlled study",
abstract = "There is ample evidence that phosphodiesterase 4 (PDE4) inhibition can improve memory performance in animal studies. In the present study, we examined the acute effects of the PDE4 inhibitor roflumilast on memory performance in healthy individuals (60-80 years of age). We tested the effects of acute roflumilast administration (100, 250, 1000 μg) in a double-blind, placebo-controlled, 4-way crossover design. Participants were first screened for their verbal word memory performance to ensure normal memory performance (within 0.5 standard deviation from norm score; n = 20) Drug effects on memory performance were tested in a verbal memory test and a spatial memory test. Reported side effects of drug treatment were registered. Roflumilast (100 μg) improved the delayed recall performance of the participants (Cohen's d, 0.69). No effects were observed in the spatial memory task. Roflumilast was well tolerated at this low dose. Although no clear adverse side effects were reported at the low dose, mild adverse events (including headache, dizziness, insomnia, and diarrhea) were reported after the 1000 μg dose. The present study provides first evidence that the PDE4 inhibitor roflumilast improves verbal memory performance in old participants. The current data encourage further development of PDE4 inhibitors for improving memory.",
keywords = "AGE, Aging, CAMP, COGNITION, Cognition enhancement, DISEASE, EDUCATION, ENHANCEMENT, LONG-TERM-MEMORY, N-OXIDE, NORMATIVE DATA, PHOSPHODIESTERASE-4 INHIBITOR, ROLIPRAM, Verbal memory",
author = "Arjan Blokland and {Van Duinen}, {Marlies A.} and Anke Sambeth and Heckman, {Pim R.A.} and Max Tsai and Gezim Lahu and Tolga Uz and Jos Prickaerts",
note = "Copyright {\circledC} 2019 Elsevier Inc. All rights reserved.",
year = "2019",
month = "5",
doi = "10.1016/j.neurobiolaging.2019.01.014",
language = "English",
volume = "77",
pages = "37--43",
journal = "Neurobiology of Aging",
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Acute treatment with the PDE4 inhibitor roflumilast improves verbal word memory in healthy old individuals : a double-blind placebo-controlled study. / Blokland, Arjan; Van Duinen, Marlies A.; Sambeth, Anke; Heckman, Pim R.A.; Tsai, Max; Lahu, Gezim; Uz, Tolga; Prickaerts, Jos.

In: Neurobiology of Aging, Vol. 77, 05.2019, p. 37-43.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Acute treatment with the PDE4 inhibitor roflumilast improves verbal word memory in healthy old individuals

T2 - a double-blind placebo-controlled study

AU - Blokland, Arjan

AU - Van Duinen, Marlies A.

AU - Sambeth, Anke

AU - Heckman, Pim R.A.

AU - Tsai, Max

AU - Lahu, Gezim

AU - Uz, Tolga

AU - Prickaerts, Jos

N1 - Copyright © 2019 Elsevier Inc. All rights reserved.

PY - 2019/5

Y1 - 2019/5

N2 - There is ample evidence that phosphodiesterase 4 (PDE4) inhibition can improve memory performance in animal studies. In the present study, we examined the acute effects of the PDE4 inhibitor roflumilast on memory performance in healthy individuals (60-80 years of age). We tested the effects of acute roflumilast administration (100, 250, 1000 μg) in a double-blind, placebo-controlled, 4-way crossover design. Participants were first screened for their verbal word memory performance to ensure normal memory performance (within 0.5 standard deviation from norm score; n = 20) Drug effects on memory performance were tested in a verbal memory test and a spatial memory test. Reported side effects of drug treatment were registered. Roflumilast (100 μg) improved the delayed recall performance of the participants (Cohen's d, 0.69). No effects were observed in the spatial memory task. Roflumilast was well tolerated at this low dose. Although no clear adverse side effects were reported at the low dose, mild adverse events (including headache, dizziness, insomnia, and diarrhea) were reported after the 1000 μg dose. The present study provides first evidence that the PDE4 inhibitor roflumilast improves verbal memory performance in old participants. The current data encourage further development of PDE4 inhibitors for improving memory.

AB - There is ample evidence that phosphodiesterase 4 (PDE4) inhibition can improve memory performance in animal studies. In the present study, we examined the acute effects of the PDE4 inhibitor roflumilast on memory performance in healthy individuals (60-80 years of age). We tested the effects of acute roflumilast administration (100, 250, 1000 μg) in a double-blind, placebo-controlled, 4-way crossover design. Participants were first screened for their verbal word memory performance to ensure normal memory performance (within 0.5 standard deviation from norm score; n = 20) Drug effects on memory performance were tested in a verbal memory test and a spatial memory test. Reported side effects of drug treatment were registered. Roflumilast (100 μg) improved the delayed recall performance of the participants (Cohen's d, 0.69). No effects were observed in the spatial memory task. Roflumilast was well tolerated at this low dose. Although no clear adverse side effects were reported at the low dose, mild adverse events (including headache, dizziness, insomnia, and diarrhea) were reported after the 1000 μg dose. The present study provides first evidence that the PDE4 inhibitor roflumilast improves verbal memory performance in old participants. The current data encourage further development of PDE4 inhibitors for improving memory.

KW - AGE

KW - Aging

KW - CAMP

KW - COGNITION

KW - Cognition enhancement

KW - DISEASE

KW - EDUCATION

KW - ENHANCEMENT

KW - LONG-TERM-MEMORY

KW - N-OXIDE

KW - NORMATIVE DATA

KW - PHOSPHODIESTERASE-4 INHIBITOR

KW - ROLIPRAM

KW - Verbal memory

U2 - 10.1016/j.neurobiolaging.2019.01.014

DO - 10.1016/j.neurobiolaging.2019.01.014

M3 - Article

C2 - 30776650

VL - 77

SP - 37

EP - 43

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

ER -