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. 2010 Oct 21:1357:184-94.
doi: 10.1016/j.brainres.2010.08.018. Epub 2010 Aug 13.

Olfactory deficit detected by fMRI in early Alzheimer's disease

Jianli Wang  1 , Paul J Eslinger, Richard L Doty, Erin K Zimmerman, Robert Grunfeld, Xiaoyu Sun, Mark D Meadowcroft, James R Connor, Joseph L Price, Michael B Smith, Qing X Yang
Affiliations

Olfactory deficit detected by fMRI in early Alzheimer's disease

Jianli Wang et al. Brain Res. .

Abstract

Alzheimer's disease (AD) is accompanied by smell dysfunction, as measured by psychophysical tests. Currently, it is unknown whether AD-related alterations in central olfactory system neural activity, as measured by functional magnetic resonance imaging (fMRI), are detectable beyond those observed in healthy elderly. Moreover, it is not known whether such changes are correlated with indices of odor perception and dementia. To investigate these issues, 12 early stage AD patients and 13 nondemented controls underwent fMRI while being exposed to each of three concentrations of lavender oil odorant. All participants were administered the University of Pennsylvania Smell Identification Test (UPSIT), the Mini-Mental State Examination (MMSE), the Mattis Dementia Rating Scale-2 (DRS-2), and the Clinical Dementia Rating Scale (CDR). The blood oxygen level-dependent (BOLD) signal at primary olfactory cortex (POC) was weaker in AD than in HC subjects. At the lowest odorant concentration, the BOLD signals within POC, hippocampus, and insula were significantly correlated with UPSIT, MMSE, DRS-2, and CDR scores. The BOLD signal intensity and activation volume within the POC increased significantly as a function of odorant concentration in the AD group, but not in the control group. These findings demonstrate that olfactory fMRI is sensitive to the AD-related olfactory and cognitive functional decline.

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Figures

Figure 1
Figure 1
3-D representation of average brain activation maps in response to the odor lavender. (A) healthy control group (one-sample t-test, voxel-wise threshold p < 0.005, uncorrected with extent threshold = 6) at lowest and first exposed odorant concentration (0.10%); (B) early AD group at same statistical threshold (one-sample t-test, voxel-wise threshold p < 0.005, uncorrected with extent threshold = 6) and at highest odorant concentration exposure (1.0%); (C) AD group with more relaxed statistical threshold (one-sample t-test, voxel-wise threshold p < 0.01, uncorrected with extent threshold = 0) and at highest odorant concentration exposure (1.0%).
Figure 2
Figure 2
fMRI activation differences between healthy control (n = 13) and early AD groups (n = 12) for odorant lavender at 0.10% concentration (two-sample t-test, voxel-wise threshold p < 0.005, uncorrected with extent threshold = 6). The HC group had significantly stronger activation in areas including the POC, hippocampus, insula, thalamus, and hypothalamus.
Figure 3
Figure 3
The BOLD signal intensity at POC responding to different odorant concentrations. There was no significant difference of BOLD signal intensity between the three odorant concentrations. However, the BOLD signal was significant stronger responding to the high odorant concentration than responding to the two lower odorant concentrations (two-sample t-test, p = 0.029 and 0.029). The BOLD signal in the HC group responding to the low odorant concentration is greater than that in the AD group (two-sample t-test, p = 0.020). Vertical bars represent standard error of the mean.
Figure 4
Figure 4
Correlation between fMRI brain response to the low concentration of lavender odorant (0.10%) and UPSIT score. The fMRI brain response was represented by the normalized β values calculated from SPM estimation using: Y = β·X+ε, where Y is the fMRI BOLD signal, X is the fMRI stimulation model, and ε is the estimation error. A: left POC; B: left hippocampus; and C: left insula. Open shapes represent early AD group and closed shapes represent healthy control group; dark line represents linear regression. Significant positive linear correlations between brain response and UPSIT score were observed (A: r = 0.671, p < 0.001; B: r = 0.695, p < 0.001; C: r = 0.628, p = 0.001).
Figure 5
Figure 5
Illustration of POC (yellow) and amygdala (green) in a standard MNI brain on coronal slices. y coordinate = −5 to 10 mm.
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