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
Dr. O. P. Hornung
Department of Psychiatry and Psychotherapy
Charité – University Medicine Berlin
Campus Benjamin Franklin
Eschenallee 3
14050 Berlin
Germany
Phone: +49/30/8445/87 71
Fax: +49/30/8445/82 33
Email: orla.hornung@charite.de
