. Increased Alzheimer pathology in Parkinson's disease related to antimuscarinic drugs. Ann Neurol. 2003 Aug;54(2):235-8. PubMed.

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  1. An important paper. It would be good to have an exhaustive list of anticholinergics listed in order of their atropine equivalent effect.

    View all comments by Paul Chabun
  2. This is an important finding that adds to the human evidence pointing to a cholinergic-amyloid connection. Our group has contributed by showing that both muscarinic agonists and acetylcholinesterase inhibitors lower CSF and cortical ABeta levels in normal animals and both classes of drug also prevent the ABeta deposition induced experimentally by nucleus basalis lesion. It appears likely that the cortical cholinergic deficit associated with normal aging may be at least partially responsible for age-associated Abeta deposition and that cholinergic agents may be effective at preventing this. It is time for primary prevention trials of cholinergic agents for AD.

    References:

    . Cholinergic deafferentation of the rabbit cortex: a new animal model of Abeta deposition. Neurosci Lett. 2000 Mar 31;283(1):9-12. PubMed.

    . The cholinergic deficit coincides with Abeta deposition at the earliest histopathologic stages of Alzheimer disease. J Neuropathol Exp Neurol. 2000 Apr;59(4):308-13. PubMed.

    . Reduction of cerebrospinal fluid amyloid beta after systemic administration of M1 muscarinic agonists. Brain Res. 2001 Jun 29;905(1-2):220-3. PubMed.

    . Reduction of cortical amyloid beta levels in guinea pig brain after systemic administration of physostigmine. Neurosci Lett. 2001 Sep 7;310(1):21-4. PubMed.

    . Anti-Amyloidogenic Activity of Cholinergic Agents. Drug Dev. Res. 56 (2002) 242-247.

    . Muscarinic agonists as preventative therapy for Alzheimer's disease. Curr Opin Investig Drugs. 2002 Nov;3(11):1633-6. PubMed.

    . Immunotoxin lesion of the cholinergic nucleus basalis causes Abeta deposition: towards a physiologic animal model of Alzheimer's disease. Curr Med Chem 3:57-75, 2003.

    View all comments by Thomas Beach