title: Dopamine differently modulates central cholinergic circuits in patients with Alzheimer disease and CADASIL.
abstract: Short-latency afferent inhibition (SAI) technique gives the opportunity to non-invasively test an inhibitory circuit in the human cerebral motor cortex that depends mainly on central cholinergic activity. Important SAI abnormalities have been reported in both patients with Alzheimer disease (AD) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a model of "pure" vascular dementia (VD). Interestingly, a normalization of SAI was observed in AD after levo-dopa (L-dopa) administration. We aimed to determine whether the pharmacological manipulation of the dopaminergic system can also interfere with SAI test in CADASIL patients, compared with AD patients and healthy controls. SAI was found to be significantly reduced in both patient groups. L-Dopa significantly increased SAI in the AD patients, while it failed to restore SAI abnormality in CADASIL patients. Therefore, L-dopa-mediated changes on SAI in AD patients seem to be a specific effect. The present study supports the notion that relationship between acetylcholine and dopamine systems may be specifically abnormal in AD. L-Dopa challenge may thus be able to differentiate the patients with AD or a mixed form of dementia from those with "pure" VD.
authors.affiliation: Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University and Center for Cognitive Neuroscience, Salzburg, Austria, raffaele.nardone@asbmeran-o.it.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Nardone
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Höller
authors.forename: Aljosha
authors.initials: A
authors.lastname: Thomschewski
authors.forename: Alexander Baden
authors.initials: AB
authors.lastname: Kunz
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Lochner
authors.forename: Stefan
authors.initials: S
authors.lastname: Golaszewski
authors.forename: Eugen
authors.initials: E
authors.lastname: Trinka
authors.forename: Francesco
authors.initials: F
authors.lastname: Brigo
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000344:Afferent Pathways / Q000187:drug effects / Q000503:physiopathology; D000368:Aged; D000544:Alzheimer Disease / Q000503:physiopathology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D046589:CADASIL / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D050781:Transcranial Magnetic Stimulation
chemical_list: D015259:Dopamine Agents; D007980:Levodopa; D000109:Acetylcholine; D004298:Dopamine