Abstract Details

To investigate the association between olfactory brain structures and olfactory function across the adult human lifespan, and to examine to what extent olfactory bulb volume (OBV) mediates the association between central olfactory structures and olfactory function.

Impaired olfactory function is among the earliest signs of many neurodegenerative disorders and often precedes formal diagnosis by many years. It is therefore important to elucidate its neuroanatomical basis as this could provide insights into its underlying causes and facilitate identification of individuals at an increased risk of developing neurodegenerative conditions later in life.

We used baseline data from the first 2000 participants of the Rhineland Study. Performance on the 12-item “Sniffin’ Sticks” odor identification test (SIT-12) was used as a proxy for olfactory function. Volumetric measures were derived from 3 Tesla MRI T1-weighted brain scans using FreeSurfer. OBV was manually segmented on T2-weighted images.

SIT-12 were available for 1915 participants (56.6% women, mean [SD] age 54.5 [14.0] years), with complete data on MRI-derived measures in a subset of 541 individuals. Worse olfactory function was associated with increasing age, male sex and nasal congestion, but not with smoking status. Volumes of the amygdala, hippocampus and insular and medial orbitofrontal cortex were positively associated with OBV. Across all age groups, larger OBV was related to better olfactory function. Larger volumes of amygdala, parahippocampal cortex and hippocampus were also related to better olfactory function but only in older age groups. The age-moderated association between volumes of central olfactory structures and olfactory function was largely mediated through OBV.

OBV is robustly associated with SIT-12 and largely explains the relation between volumes of central olfactory structures and olfactory function. Thus, neurodegeneration-associated olfactory dysfunction may primarily originate from pathology of the olfactory bulb or more distal structures, while OBV may serve as a preclinical quantitative marker for neurodegenerative diseases.