Olfactory identification in subjective cognitive decline and mild cognitive impairment: Association with tau but not amyloid positron emission tomography

Abstract

Introduction: We investigated the association between olfactory identification and Alzheimer's disease biomarkers, including amyloid, tau, and neurodegeneration.

Methods: Thirty-four older adults, including 19 cognitively normal (CN), 10 subjective cognitive decline (SCD), and 5 mild cognitive impairment, underwent amyloid positron emission tomography, magnetic resonance imaging, and the University of Pennsylvania Smell Identification Test (UPSIT). Twenty-six also underwent tau positron emission tomography. Associations between the UPSIT and regionally sampled amyloid, tau, and temporal atrophy were evaluated. Voxel-wise regression models were also utilized. Analyses were conducted with the full sample and only CN/SCD.

Results: Lower UPSIT scores were associated with increased temporal and parietal tau burden in regional and voxel-wise analyses in the full sample and in CN and SCD only. Temporal lobe atrophy was associated with lower UPSIT score. Amyloid was not associated with the UPSIT.

Discussion: Impairment on the UPSIT may be a good marker for tau and neurodegeneration in preclinical or prodromal Alzheimer's disease.

Keywords: Alzheimer's disease; Neurodegeneration; Olfaction; Tau; [18F]Flortaucipir (AV-1451).

Fig. 1

Tau in the temporal lobe is associated with UPSIT performance in the pooled sample (CN, SCD, and MCI individuals). Increased tau deposition in the (A) entorhinal cortex (r = −0.48, P < .05 FDR), (B) fusiform (r = −0.66, P < .005 FDR), (C) inferior temporal gyri (r = −0.58, P < .005 FDR), (D) parahippocampal gyri (r = −0.58, P < .005 FDR), and (E) whole temporal lobe (r = −0.45, P < .05 FDR) is associated with reduced preadjusted UPSIT total score across CN, SCD, and MCI individuals (n = 26). A trend for an association between increased tau deposition in the (F) piriform cortex and UPSIT performance (r = −0.35, P < .1 FDR) was also observed. Abbreviations: CN, cognitively normal; FDR, false discovery rate; MCI, mild cognitive impairment; SCD, subjective cognitive decline; SUVR, standardized uptake value ratio; UPSIT, University of Pennsylvania Smell Identification Test.

Fig. 2

Tau in the temporal lobe is associated with UPSIT performance in CN individuals with and without cognitive concerns (CN/SCD subsample). Similar to the full sample, increased tau deposition in the (A) entorhinal cortex (r = −0.55, P < .05 FDR), (B) fusiform (r = −0.60, P < .01 FDR), (C) inferior temporal gyri (r = −0.63, P < .01 FDR), (D) parahippocampal gyri (r = −0.64, P < .01 FDR), and (E) whole temporal lobe (r = −0.61, P < .01 FDR) is associated with reduced preadjusted UPSIT total score in CN and SCD only (n = 21). In addition, a trend for an association between increased tau deposition in the (F) piriform cortex and UPSIT performance (r = −0.46, P < .1 FDR) was also observed. Abbreviations: CN, cognitively normal; FDR, false discovery rate; SCD, subjective cognitive decline; SUVR, standardized uptake value ratio; UPSIT, University of Pennsylvania Smell Identification Test.

Fig. 3

Temporal lobe atrophy is associated with UPSIT performance in the pooled sample. Atrophy in the (A) hippocampus (r = 0.53, P < .005 FDR), (B) entorhinal cortex (r = 0.45, P < .01 FDR), and (C) whole temporal lobe (r = 0.59, P < .005 FDR) is associated with reduced preadjusted UPSIT total score across CN, SCD, and MCI individuals (n = 34). No significant associations between atrophy and UPSIT performance were seen in CN and SCD only. Abbreviations: CN, cognitively normal; FDR, false discovery rate; GM, gray matter; MCI, mild cognitive impairment; SCD, subjective cognitive decline; UPSIT, University of Pennsylvania Smell Identification Test.

Fig. 4

Exploratory voxel-wise associations show widespread regions where increased tau deposition is associated with reduced UPSIT performance. (A) Across all individuals (CN, SCD, MCI; n = 26), reduced preadjusted UPSIT total score was associated with increased tau in widespread medial and lateral temporal lobe regions, as well as regions of the inferior parietal and occipital lobes. (B) In CN and SCD individuals only (n = 21), reduced preadjusted UPSIT total score was associated with increased tau in the medial and lateral temporal lobes, as well as throughout the inferior, middle, and superior frontal lobes. No associations were seen in the opposite direction (i.e., increased tau associated with better UPSIT score). Voxel-wise association are shown at a voxel-wise threshold of P < .01 (uncorrected for multiple comparisons) and minimum cluster size (k) = 100 voxels. Abbreviations: CN, cognitively normal; MCI, mild cognitive impairment; SCD, subjective cognitive decline; UPSIT, University of Pennsylvania Smell Identification Test.