Cognitive Signatures of Parkinson’s Disease and Glucocerebrosidase (GBA) Mutation (P2.026)

OBJECTIVE: To determine whether the pattern of working (short-term) memory deficit associated with glucocerebrosidase (GBA) mutation is the same as that in Parkinson9s disease (PD) or whether the two conditions have different signatures of memory deficit. BACKGROUND: Individuals with mutations in the gene for the lysosomal enzyme GBA are at significantly higher risk of developing PD with cognitive deficit. We examined whether working memory impairments, long associated with PD, are also impaired in GBA+ve individuals, with and without PD. DESIGN/METHODS: Visual working memory was measured using a new serial order task in GBA+ve PD (N=15), GBA-ve PD (N=15), GBA+ve non-PD (N=20) cases and healthy controls (N=17). Crucially this allowed us to measure the precision of recall as well as analyse the sources of error in memory. Three tasks using the same stimuli controlled for perceptual, motor and temporal decay factors. RESULTS: There was a significant deficit of memory precision in GBA+ve individuals, with or without PD, as well as GBA-ve PD patients compared to healthy controls. Worst recall was observed in GBA+ve PD cases. The deficit observed in GBA+ve individuals, regardless of whether they had PD, was explained by systematic increase in interference from features of other items maintained in memory - so-called misbinding errors. In contrast, working memory deficits in PD patients, regardless of GBA status, was due to an increase in random responses which might, for example, be associated with fluctuations in attention. CONCLUSIONS: Although all groups were impaired in visual working memory, there was a double dissociation between sources of error associated with GBA mutation and PD. Individuals who were GBA+ve and also had PD suffered from both types of error and consequently demonstrated the worst performance in WM. Identifying GBA+ve people who show the pattern of deficit associated with PD might indicate those at greater risk of developing PD. Study Supported by: The Wellcome Trust, Medical Research Council, The Kattan Trust and Parkinson’s UK. Disclosure: Dr. Husain has received personal compensation in an editorial capacity for the Journal of Neuropsychology. Dr. Zokaei has nothing to disclose. Dr. McNeil has nothing to disclose. Dr. Proukakis has nothing to disclose. Dr. Beavan has nothing to disclose. Dr. Jarman has nothing to disclose. Dr. Korlipara has nothing to disclose. Dr. Hughes has received personal compensation for activities with Genzyme Corp., Sanofi-Aventis Pharmaceuticals Inc., and Shire HGT. Dr. Hughes has received research support from Genzyme Corp., Sanofi-Aventis Pharmaceuticals Inc., and Shire HGT. Dr. Mehta has received personal compensation for activities with Shire Pharmaceuticals Group, Actelion Pharmaceuticals, Genzyme Inc., and Amicus Therapeutics. Dr. Hu has nothing to disclose. Dr. Schapira has received personal compensation for activities with Merck Serono, Novartis, GlaxoSmithKline Inc., BI, UCB Pharma, Teva-Lundbeck. Dr. Schapira has received personal compensation in an editorial capacity for the European Journal of Neurology.