title: Dopaminergic basis for deficits in working memory but not attentional set-shifting in Parkinson's disease.
abstract: Although Parkinson's disease is a common neurodegenerative disorder characterised by its motoric symptoms, there is an increasing recognition of accompanying impairments in cognition that have a profound impact on the quality of life of these patients. These deficits predominantly affect executive function and impairments of working memory have been frequently reported. However, the underlying neurochemical and pathological basis for these deficits are not well understood. In this study, 20 patients were tested 'on' and 'off' levodopa (L-dopa) medication on a task that allowed different aspects of working memory function such as maintenance, retrieval and manipulation to be tested within the same general paradigm as well as on an unrelated test of attentional set-shifting, which is known to be sensitive to deficits in early Parkinson's disease. Compared to healthy volunteers, PD patients were impaired at manipulation more than maintenance or retrieval of information within working memory. The patients were also impaired at the attentional set-shifting task. However, whereas L-dopa ameliorated the working memory deficit in manipulation (improving both accuracy and cognitive response time), it had no effect on the attentional set-shifting impairment. These results confirm that working memory deficits in PD are both psychologically specific and related to dopamine depletion. It is anticipated that greater understanding of these mechanisms will lead to future therapeutic improvements.
authors.affiliation: Cambridge Centre for Brain Repair, Forvie Site, Addenbrooke's Hospital, Cambridge CB2 2PY, UK. sjgl2@wbic.cam.ac.uk
authors.forename: Simon J G
authors.initials: SJ
authors.lastname: Lewis
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Slabosz
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Robbins
authors.forename: Roger A
authors.initials: RA
authors.lastname: Barker
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Owen
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D001288:Attention / Q000187:drug effects / Q000502:physiology*; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007980:Levodopa / Q000494:pharmacology / Q000627:therapeutic use; D016555:Matched-Pair Analysis; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology*; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012016:Reference Values; D012718:Set, Psychology
chemical_list: D015259:Dopamine Agents; D007980:Levodopa; D004298:Dopamine