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.
Highlights
Parkinson’s disease (PD) is a neurodegenerative illness characterized by degeneration of the dopamine-producing cells of the substantia nigra (SN) [1]
We report the analyses on the data for the Rey Auditory Verbal Learning Test (RAVLT) and Aggie Figures Learning Test (AFLT), contrasting measures that we intended to index encoding versus to stress retrieval
Raw scores were converted to Z-scores to avoid differences in the scale of performance across the RAVLT and AFLT
Summary
Parkinson’s disease (PD) is a neurodegenerative illness characterized by degeneration of the dopamine-producing cells of the substantia nigra (SN) [1]. The resulting dopamine depletion of the dorsal striatum in PD produces tremor, bradykinesia, and rigidity Dopaminergic medications such as L-3,4-dihydroxyphenylalanine (L-Dopa) or dopamine receptor agonists improve these motor symptoms that typify PD [2]. Contradictory findings in PD possibly result from comparing studies in which PD patients are tested off relative to on dopaminergic medication. Few studies have investigated the effect of dopamine replacement on memory in PD [10,24] and none have systematically examined the effect of medication on encoding and retrieval processes separately. A comprehensive study, where the same group of PD patients is investigated, on and off dopaminergic therapy, with both verbal and non-verbal materials, using tests in which encoding and retrieval can be relatively controlled and distinguished is needed
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