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Objectives:  To compare gray matter microstructural characteristics of higher-order olfactory regions among older adults with and without hyposmia.   Methods:  Data from the Brief Smell Identification Test (BSIT) were obtained in 1998–99 for 265 dementia-free adults from the Health, Aging, and Body Composition study (age at BSIT: 74.9 ± 2.7; 62% White; 43% male) who received 3T diffusion tensor imaging in 2006–08 [Interval of time: mean (SD): 8.01 years (0.50)], Apolipoprotein (ApoEε4) genotypes, and repeated 3MS assessments until 2011–12. Cognitive status (mild cognitive impairment, dementia, normal cognition) was adjudicated in 2011–12. Hyposmia was defined as BSIT ≤ 8. Microstructural integrity was quantified by mean diffusivity (MD) in regions of the primary olfactory cortex amygdala, orbitofrontal cortex (including olfactory cortex, gyrus rectus, the orbital parts of the superior, middle, and inferior frontal gyri, medial orbital part of the superior frontal gyrus), and hippocampus. Multivariable regression models were adjusted for total brain atrophy, demographics, cognitive status, and ApoEε4 genotype.   Results:  Hyposmia in 1998–99 ( n  = 57, 21.59%) was significantly associated with greater MD in 2006–08, specifically in the orbital part of the middle frontal gyrus, and amygdala, on the right [adjusted beta (p value): 0.414 ( 0.01 ); 0.527 ( 0.01 ); respectively].   Conclusion:  Older adults with higher mean diffusivity in regions important for olfaction are more likely to have hyposmia up to ten years prior. Future studies should address whether hyposmia can serve as an early biomarker of brain microstructural abnormalities for older adults with a range of cognitive functions, including those with normal cognition.

Diffusion Tensor Imaging of the Olfactory System in Older Adults With and Without Hyposmia