Author(s): Keith A Wesnes*,David J Burn
Background: Destruction of dopaminergic neurones decreases hippocampal Dentate Gyrus (DG) neurogenesis in rodents and primates. Post-mortem work in Parkinson’s Disease (PD) patients identified evidence of compromised hippocampal neurogenesis. In both animals and man, difficult discriminations in tests which require discrimination between previously seen objects and closely similar ones (object pattern separation tasks) reflect DG activity and thus potentially neurogenesis. The object of this study was to use such a task in PD patients to seek evidence of compromised DG activity.
Methods: The CDR System picture recognition task has been validated as an object pattern separation task. In the task pictures of objects and scenes are presented which later must be discriminated from closely similar pictures. fMRI work in man has identified that difficult discriminations in object pattern separation tasks (i.e deciding whether or not a closely similar object was previously presented) to selectively result in increased DG activity. Data from this task in 72 patients with Parkinson’s disease were compared with 62 age and gender matched controls.
Results: The PD patients showed selective, marked and highly significant deficits to the DG-sensitive measure which was unrelated to dopaminergic medication. Such a pattern was not seen on a word recognition paradigm, which is consistent with fMRI work showing verbal tasks are not related to DG activation.
Conclusions: This is the first behavioural demonstration of compromised OPS in Parkinson’s patients, supporting work with rats and primates. This finding is consistent with impairment to DG function and thus potentially compromised neurogenesis. Implications for current and novel PD therapies will be discussed, in relation to compounds such as rasagiline which promote neurogenesis.
