Reply: Cognition and olfaction in Parkinson’s disease

Sir, We thank Drs Postuma and Gagnon for their interest in our study and for providing additional information regarding the association between cognition and performance on an odour identification task in Parkinson’s disease. We are pleased to see our findings of an association between memory and olfactory performance replicated. The findings of Postuma and Gagnon agree also with our results that scores on the University of Pennsylvania Smell Identification Test correlate best with measures of verbal learning but not significantly with executive functions or visuoconstructive abilities. It should be noted, however, that the study populations in our and in Postuma and Gagnon’s series did not suffer from severe cognitive impairment or dementia, as demonstrated by the average score on the Mini-Mental State Examination. It is possible that studies in a population of patients with more severe cognitive symptoms may demonstrate correlations with different cognitive domains. Longitudinal studies in normal elderly subjects at risk for mild cognitive impairment and pre-symptomatic Alzheimer’s disease demonstrated a significant association between performance on odour identification tasks and subsequent decline in episodic memory functions (Wilson et al., 2009). These results strengthen our inferences that decreased odour identification may be a marker of a limbic neurodegenerative process and that odour identification and verbal learning, at least in part, may share a common neural substrate. We agree with the concerns raised about correlation versus causation, though our imaging findings suggest a central cholinergic rather than a dopaminergic component (Bohnen et al., 2010). Furthermore, we found relative specific regional cerebral changes in acetylcholinesterase activity, which were most robust for the limbic, compared with neocortical, areas. A possible cholinergic contribution to odour identification functions is also supported by a recent pharmacological intervention study in patients with Alzheimer’s disease (Velayudhan and Lovestone, 2009). Pharmacological intervention studies and longitudinal assessments documenting changes in acetylcholinesterase innervation, smell and cognition in patients with Parkinson’s disease may clarify the nature of these relationships in the future. Changes in smell test performance may prove to be a simple biomarker to identify patients with Parkinson’s disease at risk for incident dementia and/or other neurobehavioural features. We support Postuma and Gagnon’s suggestions to further explore relationships among olfactory function findings, motor subtypes and visual, sleep, autonomic and psychiatric features of Parkinson’s disease in future analyses.

Funding

This work was supported by the Department of Veterans Affairs; the Michael J. Fox Foundation; and National Institutes of Health [grant number P01 NS015655].