Those at genetic risk for Alzheimer's Disease (AD) because of the ApoE ε4 allele show differences in activation during olfactory information processing and memory in areas such as MTL structures, entorhinal cortex, posterior cingulate, precuneus, and inferior parietal lobule, suggesting preclinical AD neuropathology and olfactory impairment as a biomarker for predicting later AD onset (Murphy, 2019). The effects of smoking on AD have varied, with early studies suggesting either no effect or protective effects, and recent studies suggesting smoking as a risk factor for AD but with the need for further investigation in preclinical stages. Therefore, this study focused on olfaction and smoking as risk factors for preclinical AD neuropathology by studying differences in fMRI BOLD signal changes in smokers and nonsmokers during olfactory tasks.

Archival data from 25 non-demented older adults recruited from the UCSD Alzheimer's Disease Research Center who completed an Assessment Scale-Cognitive Subscale (ADAS-Cog) and functional MRI scans at 3T, acquired during performance of an odor identification task. Odor Identification (OI) measured correct (hits) or incorrect (misses) identification of odors presented by an olfactometer to deliver the odor stimuli in short, controlled durations during fMRI scanning.

fMRI data were preprocessed using fMRIprep, smoothed at 4mm, scaled, and first level analyses were conducted using 3dDeconvolve in AFNI with time points corresponding to hits and misses as regressors. Differences between smokers and nonsmokers revealed smokers show a larger difference in BOLD signal change from hits minus misses at five significant clusters (p = 0.01 with the minimum cluster size [voxels] at 42). Peak areas of significant clusters included the right precuneus, right calcarine gyrus, left inferior parietal lobule, left superior parietal lobule, and left middle occipital gyrus. Analyses suggested a greater difference in activity between hits and misses in smokers compared to nonsmokers, with more activity during hits.

Differences in activation between smokers and nonsmokers during an olfactory identification task, with greater activity in smokers during hits, suggests greater effort to correctly identify an odor. These findings of hyperactivation in areas (such as the precuneus and inferior parietal lobule) are similar to findings of hyperactivation during odor memory observed in studies of ε4 carriers during preclinical stages. Results provide further insight into smoking as a risk factor for AD. Moreover, results suggest the risk of smoking could potentially be reflected in altered activity in olfactory information processing networks in preclinical stages of AD. The study highlights the need for research to further understand the role smoking plays in the development of AD and the use of olfaction as a biomarker to aid in disease detection, prevention, and stage-associated treatments.