Modulation of memory and visuospatial processes by biperiden and rivastigmine in elderly healthy subjects
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The central cholinergic system is implicated in cognitive functioning. The dysfunction of this system is expressed in many diseases like Alzheimer's disease, dementia of Lewy body, Parkinson's disease and vascular dementia. In recent animal studies, it was found that selective cholinergic modulation affects visuospatial processes even more than memory function.
In the current study, we tried to replicate those findings. In order to investigate the acute effects of cholinergic drugs on memory and visuospatial functions, a selective anticholinergic drug, biperiden, was compared to a selective acetylcholinesterase-inhibiting drug, rivastigmine, in healthy elderly subjects.
A double-blind, placebo-controlled, randomised, cross-over study was performed in 16 healthy, elderly volunteers (eight men, eight women; mean age 66.1, SD 4.46 years). All subjects received biperiden (2 mg), rivastigmine (3 mg) and placebo with an interval of 7 days between them. Testing took place 1 h after drug intake (which was around T max for both drugs). Subjects were presented with tests for episodic memory (wordlist and picture memory), working memory tasks (N-back, symbol recall) and motor learning (maze task, pursuit rotor). Visuospatial abilities were assessed by tests with high visual scanning components (tangled lines and Symbol Digit Substitution Test).
Episodic memory was impaired by biperiden. Rivastigmine impaired recognition parts of the episodic memory performance. Working memory was non-significantly impaired by biperiden and not affected by rivastigmine. Motor learning as well as visuospatial processes were impaired by biperiden and improved by rivastigmine.
These results implicate acetylcholine as a modulator not only of memory but also of visuospatial abilities.
KeywordsBiperiden Rivastigmine Anticholinergic Acetylcholinesterase inhibitor Memory Visuospatial processes Healthy elderly volunteers
Funding was provided by NV Organon. We would like to thank them for their financial and technical support to perform this study.
We would also like to thank Jan Leijtens and Drs. Sevla Cinar for their helpful assistance in data collection and analysis.
This experiment complies with the current laws of the Netherlands.
- Atri A, Sherman S, Norman KA, Kirchhoff BA, Nicolas MM, Greicius MD, Cramer SC, Breiter HC, Hasselmo ME, Stern CE (2004) Blockade of central cholinergic receptors impairs new learning and increases proactive interference in a word paired-associate memory task. Behav Neurosci 118:223–236CrossRefPubMedGoogle Scholar
- Birks J, Grimley Evans J, Iakovidou V, Tsolaki M (2003) Rivastigmine for Alzheimer's disease (Cochrane Review). In: The Cochrane Library, Issue 3Google Scholar
- Bond A, Lader M (1974) Use of analog scales in rating subjective feelings. Br J Med Psychol 47:211–218Google Scholar
- Bouma A, Mulder J, Lindeboom J (1998) Neuropsychologische diagnostiek, handboek. Zwets & Zeitlinger, LisseGoogle Scholar
- Bridgeman B (2000) Interactions between vision for perception and vision for behavior. In: Rossetti Y, Revonsuo A (eds) Beyond dissociation: interaction between dissociated implicit and explicit processing. John Benjamins, Amsterdam, pp 17–40Google Scholar
- de Jong WP, Hulstijn W, Jogems-Kosterman BJM, Smits-Engelsman BCM (1996) OASIS software and its application in experimental handwriting research. In: Simmers ML, Leedham CG, Thomassen AJWM (eds) Handwriting and drawing research: basic and applied issues. IOS, AmsterdamGoogle Scholar
- Ekstrom RB, French JW, Harmon H, Dermen D (1976) Manual for the kit of factor referenced cognitive tests. Educational Testing Service, Princeton, NYGoogle Scholar
- French JW (1954) Manual for kit of selected tests for reference aptitude and achievement factors. Educational Testing Service, Princeton, NYGoogle Scholar
- Kaplan E, Fein D, Morris R, Delis D (1991) Wais-R as a neuropsychological instrument. The Psychological Corporation, San Antonio, TXGoogle Scholar
- Lezak MD (1995) Neuropsychological assessment, 3rd edn. Oxford University Press, New YorkGoogle Scholar
- Poirier J (2002) Evidence that the clinical effects of cholinesterase inhibitors are related to potency and targeting of action. Int J Clin Pract 127:6–19Google Scholar
- Robbins TW, Semple J, Kumar R, Truman MI, Shorter J, Ferraro A, Fox B, Mckay G, Matthews K (1997b) Effects of scopolamine on delayed-matching-to-sample and paired associates tests of visual memory and learning in human subjects: comparison with diazepam and implications for dementia. Psychopharmacology 134:95–106CrossRefPubMedGoogle Scholar
- Sharma T, Hughes C, Aasen I, Kumari V (2004) A placebo-controlled double-blind investigation of cognitive effects of rivastigmine in schizophrenia. Biol Psychiatry 55:27SGoogle Scholar
- Ungerleider LG, Mishkin M (1982) Two cortical visual systems. In: Engle DJ, Goodale MA, Mansfield RJ (eds) Analysis of visual behavior. MIT Press, Cambridge, pp 549–586Google Scholar
- Wild R, Petit T (2004) Cholinesterase inhibitors for dementia with Lewy bodies (Cochrane Review). In: The Cochrane LibraryGoogle Scholar