Novel psychophysical and electrophysiological tools to assess human olfactory function and evaluation of their potential for an early diagnosis of Alzheimer’s disease

The main aims of this thesis were (1) to develop new electrophysiological signal-processing methods to improve the signal-to-noise ratio of CSERPs and (2) to evaluate whether psychophysical and electrophysiological olfactory testing can be useful for the early diagnosis of AD. First, because of the poor signal-to-noise ratio of CSERPs, we developed new electrophysiological signal-processing methods to characterize the EEG responses elicited by chemosensory stimulation in humans, based on (1) spatio-temporal signal-denoising using an independent component analysis and (2) time-frequency analysis of non phase-locked EEG responses using a continuous wavelet transform. We then validated this technique in a group of healthy controls and evaluated its feasibility and clinical usefulness to assess olfactory function in patients suffering from smell disorders (postinfectious and posttraumatic). We then investigated whether psychophysical and electrophysiological olfactory testing can be useful for the early differential diagnosis of MCI. Olfactory dysfunction in AD patients has been widely investigated. However, as reported before, studies investigating olfaction in AD present several drawbacks, which we have attempted to overcome. First, in contrast with several studies, we did not only investigate odor identification performance but also odor detection threshold and odor discrimination, using the validated Sniffin’ Sticks test. Second, we aimed to improve our understanding of the relationship between olfaction and AD, and disentangle the contribution of pure perceptual impairment and semantic memory impairment. For this purpose, we developed a specific psychophysical test relying on picture-based olfactory identification test and a control picture-based auditory identification test. Third, data was acquired in homogenous and well-characterized populations. Only MCI patients with a positive Amyloid-β PET were included in the MCI group. This group was compared to an age-matched group of healthy controls. Both groups were characterized using detailed neuropsychological testing, Amyloid-β PET ([F18]-Flutemetamol PET), [F18]-FDG-PET, apolipoprotein E genotyping and volumetric brain MRI. Fourth, we performed a unirhinal psychophysical and electrophysiological assessment of olfactory function in order to evaluate if an asymmetry in olfactory function could be predictive of MCI. Another point that deserved to be raised was that olfactory dysfunction is frequent among the general population but only a minority of these patients will evolve towards AD. It is generally admitted that patients at risk for developing neurodegenerative disease are those with idiopathic olfactory loss. In contrast, it is assumed that patients suffering from postinfectious or posttraumatic olfactory loss do not have an increased risk of developing AD. Thus, we included patients suffering from postinfectious olfactory loss as a supplementary control group, in order to evaluate and compare the olfactory dysfunction observed in MCI and idiopathic olfactory loss.