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Olfactory deficits are present in early AD and MCI (1-4). It is critical, however, to determine whether these deficits are due to degeneration of the central or peripheral olfactory system. We investigated involvement of the central olfactory system in AD and MCI with an implicit olfactory associative learning paradigm.
Sixty-three subjects (15 AD, 21 MCI and 27 age-matched CN) were studied with cognitive tests, the University of Pennsylvania Smell Identification Test (UPSIT) and fMRI. The olfactory associative learning paradigm (Fig. 1) consisted of visual cues paired with lavender odor (visual+odor) followed by the same visual cue without an odor (visual-only).
Visual-only cue activated in the primary olfactory cortex (POC) and hippocampus as did the preceded visual+odor cue for each group (p<0.05), suggesting a rapid implicit olfactory associative learning under this paradigm (Fig. 2). The CN subjects had greater activated volume in hippocampus and POC during both visual+odor and visual-only conditions than either the MCI or AD subjects (P < 0.05). Both conditions correlated with the cognitive and olfactory tests.
The activation by visual-only cue in POC and hippocampus is likely a result of implicit learning/memory since it occurs only when preceded by the visual cue paired with odor. The significant decline in brain activation under this condition suggests that the central olfactory processing contributed the olfactory dysfunction in AD and MCI patients, which could lead a sensitive functional imaging marker for AD.