The Effects of Donepezil on Postlearning Sleep EEG of Healthy Older Adults

Abstract

Introduction: Aging is associated with cholinergic hypofunction and memory decline. Cholinergic activity also plays a crucial role in sleep-dependent memory consolidation. The acetylcholinesterase inhibitor (AChE-I) donepezil has been found to increase sleep-related procedural memory consolidation in healthy older adults in a previous study.

Methods: Data of the former study were reanalyzed with regard to the effects of donepezil on the sleep EEG of healthy older adults. This analysis was conducted with a special focus on spectral parameters of sleep, which have previously been linked to plasticity-related processes during sleep, i.e., sigma and delta activity. Forty-two participants (aged: 60–77 years) received 5 mg of the AChE-I donepezil orally 30 min before bedtime in a placebo-controlled, double-blind design. Power values for EEG delta, theta, alpha1, alpha 2, sigma, beta and gamma frequency bands were calculated for stage 2 NREM sleep, SWS and REM sleep.

Results: In line with our hypotheses, the AChE-I donepezil led to an increase in sigma activity during stage 2 NREM sleep and delta activity during slow wave sleep.

Conclusion: These results suggest that an AChE-I facilitates processes of sleep-dependent memory consolidation in older adults.

References

• 1 Backhaus J, Born J, Hoeckesfeld R. et al . Midlife decline in declarative memory consolidation is correlated with a decline in slow wave sleep.  Learn Mem. 2007;  14 336-341
• 2 Bódizs R, Békésy M, Szucs A. et al . Sleep-dependent hippocampal slow activity correlates with waking memory performance in humans.  Neurobiol Learn Mem. 2002;  78 441-457
• 3 Buzsáki G. Memory consolidation during sleep: a neurophysiological perspective.  J Sleep Res. 1998;  7 17-23
• 4 Clemens Z, Fabó D, Halász P. Overnight verbal memory retention correlates with the number of sleep spindles.  Neuroscience. 2005;  132 529-535
• 5 Darchia N, Campbell IG, Feinberg I. Rapid eye movement density is reduced in the normal elderly.  Sleep. 2003;  26 973-977
• 6 Datta S, Mavanji V, Ulloor J. et al . Activation of phasic pontine-wave generator prevents rapid eye movement sleep deprivation-induced learning impairment in the rat: a mechanism for sleep-dependent plasticity.  J Neurosci. 2004;  24 1416-1427
• 7 Farlow MR, Cummings JL. Effective pharmacologic management of Alzheimer's disease.  Am J Med. 2007;  120 388-397
• 8 Gais S, Born J. Low acetylcholine during slow-wave sleep is critical for declarative memory consolidation.  Proc Natl Acad Sci USA. 2004;  101 2140-2144
• 9 Gais S, Mölle M, Helms K. et al . Learning-dependent increases in sleep spindle density.  J Neurosci. 2002;  22 6830-6834
• 10 Hasselmo ME. Neuromodulation: acetylcholine and memory consolidation.  Trends Cogn Sci. 1999;  3 351-359
• 11 Hedden T, Gabrieli JD. Insights into the ageing mind: a view from cognitive neuroscience.  Nat Rev Neurosci. 2004;  5 87-96
• 12 Hornung OP, Danker-Hopfe H, Heuser I. Age-related changes in sleep and memory: commonalities and interrelationships.  Exp Gerontol. 2005;  40 279-285
• 13 Hornung OP, Regen F, Danker-Hopfe H. et al . The relationship between REM sleep and memory consolidation in old age and effects of cholinergic medication.  Biol Psychiatry. 2007;  61 750-757
• 14 Huber R, Ghilardi MF, Massimini M. et al . Local sleep and learning.  Nature. 2004;  430 78-81
• 15 Moraes W, Poyares DR, Guilleminault C. et al . The effect of donepezil on sleep and REM sleep EEG in patients with Alzheimer disease: a double-blind placebo-controlled study.  Sleep. 2006;  29 199-205
• 16 Nissen C, Power AE, Nofzinger EA. et al . M1 muscarinic acetylcholine receptor agonism alters sleep without affecting memory consolidation.  J Cogn Neurosci. 2006;  18 1799-1807
• 17 Pace-Schott EF, Hobson JA. The neurobiology of sleep: genetics, cellular physiology and subcortical networks.  Nat Rev Neurosci. 2002;  3 591-605
• 18 Power AE. Slow-wave sleep, acetylcholine, and memory consolidation.  Proc Natl Acad Sci USA. 2004;  101 1795-1796
• 19 Riekkinen P, Aaltonen M, Riekkinen P. Tetrahydroaminoacridine inhibits high voltage spindle activity in aged rats after acute and chronic treatment.  Psychopharmacology. 1991;  103 265-267
• 20 Schabus M, Gruber G, Parapatics S. et al . Sleep spindles and their significance for declarative memory consolidation.  Sleep. 2004;  27 1479-1485
• 21 Schliebs R, Arendt T. The significance of the cholinergic system in the brain during aging and in Alzheimer's disease.  J Neural Transm. 2006;  113 1625-1644
• 22 Schredl M, Hornung O, Regen F. et al . The effect of donepezil on sleep in elderly, healthy persons: a double-blind placebo-controlled study.  Pharmacopsychiatry. 2006;  39 205-208
• 23 Terry AV, Buccafusco JJ. The cholinergic hypothesis of age and Alzheimer's disease-related cognitive deficits: recent challenges and their implications for novel drug development.  J Pharmacol Exp Ther. 2003;  306 821-827
• 24 Zizzari P, Bassant MH, Poindessous-Jazat F. et al . Donepezil restores GH secretion in old rats without affecting the sleep/wake cycle.  Neurobiol Aging. 2006;  27 784.e1-784.e5

Correspondence