Differential effects of Parkinson's disease and dopamine replacement on memory encoding and retrieval.

Authors

Alex A MacDonald, The Brain and Mind Institute, University of Western Ontario, London, Ontario, Canada
Ken N Seergobin, The Brain and Mind Institute, University of Western Ontario, London, Ontario, Canada
Adrian M Owen, The Brain and Mind Institute, University of Western Ontario, London, Ontario, Canada & Department of Psychology, University of Western Ontario, London, Ontario, Canada
Ruzbeh Tamjeedi, Faculty of Law, University of Ottawa, Ottawa, Ontario, Canada
Oury Monchi, Functional Neuroimaging Unit, Centre de Recherche, Institut Universitaire de Ge´ riatrie de Montre´ al, Montreal, Quebec, Canada & Department of Radiology, University of Montreal, Montreal, Quebec, Canada
Hooman Ganjavi, Department of Psychiatry, University of Western Ontario, London, Ontario, Canada
Penny A MacDonald, The Brain and Mind Institute, University of Western Ontario, London, Ontario, Canada & Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada

Document Type

Article

Publication Date

1-1-2013

Journal

PLoS One

Volume

8

Issue

9

First Page

74044

Last Page

74044

URL with Digital Object Identifier

10.1371/journal.pone.0074044

Abstract

Increasingly memory deficits are recognized in Parkinson's disease (PD). In PD, the dopamine-producing cells of the substantia nigra (SN) are significantly degenerated whereas those in the ventral tegmental area (VTA) are relatively spared. Dopamine-replacement medication improves cognitive processes that implicate the SN-innervated dorsal striatum but is thought to impair those that depend upon the VTA-supplied ventral striatum, limbic and prefrontal cortices. Our aim was to examine memory encoding and retrieval in PD and how they are affected by dopamine replacement. Twenty-nine PD patients performed the Rey Auditory Verbal Learning Test (RAVLT) and a non-verbal analogue, the Aggie Figures Learning Test (AFLT), both on and off dopaminergic medications. Twenty-seven, age-matched controls also performed these memory tests twice and their data were analyzed to correspond to the ON-OFF order of the PD patients to whom they were matched. We contrasted measures that emphasized with those that accentuated retrieval and investigated the effect of PD and dopamine-replacement on these processes separately. For PD patients relative to controls, encoding performance was normal in the off state and was impaired on dopaminergic medication. Retrieval was impaired off medication and improved by dopamine repletion. This pattern of findings suggests that VTA-innervated brain regions such as ventral striatum, limbic and prefrontal cortices are implicated in encoding, whereas the SN-supplied dorsal striatum mediates retrieval. Understanding this pattern of spared functions and deficits in PD, and the effect of dopamine replacement on these distinct memory processes, should prompt closer scrutiny of patients' cognitive complaints to inform titration of dopamine replacement dosages along with motor symptoms.