Odorant-induced brain activation as a function of normal aging and Alzheimer's disease: A preliminary study

Olfactory dysfunction consistently occurs in patients with Alzheimer's disease (AD), beyond the mild and gradual decline in olfactory ability found in normal aging. This dysfunction begins early in the disease course, typically before clinical diagnosis, and progresses with disease severity. While odor identification and detection deficits clearly differentiate AD from controls, there remains uncertainty as to whether these are determined by olfactory threshold. The purpose of the current preliminary fMRI study was to examine the neural correlates of olfactory processing in healthy young and old adults and compare them with AD patients. We also explored the interplay between age and disease-related psychophysical olfactory declines and odorant-induced brain activation. Results indicated AD patients had decreased odor detection task-related signal in all regions of the primary olfactory cortex, with activity in the entorhinal cortex best differentiating the groups. Moderated-mediation analyses on neuro-psychophysical relationships found that increased brain activation in the entorhinal cortex moderated the negative effect of disease-related threshold changes on olfactory detection. Therefore, even in the face of higher (worse) olfactory thresholds, older adults and AD patients compensated for this effect with increased brain activation in a primary olfactory brain region. This was the case for odor detection but not odor identification. fMRI activation induced by an olfactory detection task may eventually be useful in improving early discovery of AD and may, eventually, facilitate early treatment interventions in subjects at risk for AD.