Olfaction in Patients With Mild Cognitive Impairment and AD

Neurobiology of Aging 29 (2008) 693–706 Olfaction in patients with mild cognitive impairment and Alzheimer’s disease Jelena Djordjevic a,∗ , Marilyn Jones-Gotman a , Kathy De Sousa b , Howard Chertkow b a Montreal Neurological Institute, 3801 University Street, Department of Neurology and Neurosurgery, McGill University, Montreal, H3A 2B4, Qu´ ebec, Canada b Bloomfield Centre for Research in Aging, Lady Davis Institute, Department of Clinical Neurosciences, Sir Mortimer B. Davis - Jewish General Hospital, Department of Neurology and Neurosurgery, McGill University, Montreal, H3T 1E2, Canada Received 31 July 2006; received in revised form 10 November 2006; accepted 19 November 2006 Av ailable online 17 January 2007 Abstract Understanding of olfactory dysfunction in Alzheimer’s disease (AD) remains limited. In particular, it is not known how early in the course of the disease olfactory deficits occur, and whether they are restricted to identification or involve other aspects of olfaction. We studied olfactory (odor detection thresholds, quality discrimination, and identification) and cognitive (attention, reasoning, memory, naming and fluency) functioning in patients with AD, with mild cognitive impairment (MCI), and in normal elderly control (NEC) participants. MCI patients were impaired in olfactory sensitivity and identification, while a discrimination deficit was accounted for by abnormal thresholds. AD patients were impaired in all three domains, and were worse than the MCI group. Odor discrimination (OD) and identification performance correlated more prominently than detection thresholds with performance on neuropsychological tests. We concluded that deficits in olfactory detection thresholds and identification occur early in AD, before clinical symptoms are fully developed, and decline further over the course of the disease. High detection thresholds, together with impaired identification, may be useful as an early indicator of AD. © 2006 Elsevier Inc. All rights reserved. Keywords: Olfaction; Olfactory dysfunction; Mild cognitiv e impairment; Alzheimer’ s disease 1. Introductio n Decrease in olfactory function with advancing age has been well documented. Trends for such decline have been demonstrated with a variety of functions, including olfactory sensitivity, perceived intensity of suprathreshold odorants, odor quality discrimination, and identification ( Hummel et al., 2002). It is also wel l establ ish ed that pat ien ts wit h Alzh eimer ’s disease (AD) exhi bit olfac tory deficits that mar ked ly exceed those seen in normal agi ng. Studies of ∗ Correspondin g author. Tel.: +1 514 398 6644x00248; fax: +1 514 398 1338. E-mail addresses: [email protected](J. Djordjevic), [email protected](M. Jones-Gotman), [email protected] (K. De Sousa), [email protected] (H. Chertkow). olfaction in AD have shown several olfactory deficits in this population, such as in detection sensitivity, discrimination, identification, and memory (Doty, 2003; Mesholam et al., 1998). Olfa ctory deficit s are so promi nent in AD that some authors have proposed that olfactory dysfunction could be used as an early marker for Alzheimer’s disease, and that det ect ion of early Alz hei mer’s diseas e may be improved wit h inclusion of a criterion for olfactory decline (Morgan et al., 1995; Serby et al., 1991). One of the main questions that remains unresolved is the time course of olfactory deficits in AD. It is unclear whether these deficits occur before, simultaneously with, or after the occurrence of other clinical manifestations of the disease. This is not only a theoretical issue: if we could establish that specific olfactory deficits occur before other clinical manifestations of the disease, this finding could significantly 0197-4580/$ – see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.neurobiolaging.2006.11.014

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Olfaction in Patients With Mild Cognitive Impairment and AD