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29 Smoking as a Risk Factor: Altered Brain Activity in Areas Associated with Preclinical Alzheimer's Disease
- Jenna R Lewis, Conner Frank, Aaron Jacobson, Abigail Albertazzi, Claire Murphy
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 239-240
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Objective:
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.
Participants and Methods: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.
Results: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.
Conclusions: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.
3 Olfactory Dysfunction as a Preclinical Biomarker of AD: Psychophysical Olfactory Performance Reflects Hippocampal Integrity in Non-Demented Older Adults
- Abigail S Albertazzi, Conner Frank, Claire Murphy
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 215-216
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- Article
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Objective:
One of the greatest challenges of the Alzheimer’s disease (AD) epidemic is identifying the disease prior to substantial neurological compromise. The established biomarkers of AD, such as measures of cognitive impairment, hippocampal atrophy, and CSF measures of beta amyloid and tau, used in research and drug trials are less indicative of AD pathology in preclinical, non-demented, populations. Olfactory dysfunction, a well-established sensory impairment of AD found to correlate strongly with tau burden and hippocampal volume measures, has shown to be a promising preclinical biomarker for AD progression. Several studies have found either impaired odor identification or odor memory at baseline to predict 5-year follow-up cognitive decline and conversion from MCI to AD, but less is known about how olfactory performance reflects the integrity of associated brain regions such as the hippocampus. The present analysis aims to explore the value of psychophysical olfactory assessment as biomarker measure in preclinical AD studies and drug trials by investigating its relationships with structural measures of the hippocampus.
Participants and Methods:A sample consisted of non-demented older adults (age >75), recruited from the UCSD Alzheimer’s Disease Research Center as part of a ongoing olfactory biomarker study. Participants completed the AD Assessment Scale-Cognitive Subscale-13 (ADAS-Cog-13), San Diego Odor Identification Test (SDOIT), tests of odor recognition memory (ORMem) and odor associative memory (OAM), and MRI derived hippocampal volumes and average hippocampal occupancy (Avg HOC). Left and right hippocampal volumes were adjusted for each participant’s estimated intracranial volume. Bivariate correlations were calculated for ADAS-Cog-13 and SDOIT total scores, performance scores for odor recognition and odor associative memory tests, and the three hippocampal measures (bilateral volumes and average occupancy).
Results:ADAS-Cog-13 score did not show significant correlations with either hippocampal measure at the .05 level. SDOIT scores were significantly correlated with the measure of Avg HOC (p<.05). ORMem false positive responses were significantly correlated with Avg HOC (p<.01) and right hippocampal volume (p<.05). ORMem miss responses and OAM errors were both correlated with left (p<.05) and right (p<.01) hippocampal volumes.
Conclusions:These results demonstrate that psychophysical assessments of odor identification and odor memory can better reflect the integrity of the hippocampus in nondemented older adults, compared to the neuropsychological ADAS-Cog-13. This is congruent with olfactory dysfunction preceding cognitive-memory decline in AD cases and provides support for the utility of psychophysical olfactory assessment along with other established AD biomarkers in research and drug trials in preclinical populations.
Acknowledgements:Supported by NIH grant # R01AG062006-04 from the National Institute on Aging to CM. Special thank you to the staff and participants of the UCSD ADRC, especially Christina Gigliotti, and Aaron Jacobson at the UCSD Center for fMRI.