IC‐P‐149: Olfactory identification correlates with cerebral blood flow in cognitively normal adults at risk of Alzheimer's dementia

Cerebral perfusion decreases in normal individual at risk of Alzheimer's disease who eventually progress to AD (Johnson, 2000). Similarly perfusion is known to be reduced in AD and, to a lesser extent, in MCI. This phenomenon is most evident in precuneus and bilateral parietal cortices as regions of interest (ROI) (Binnewijzend, 2013). Such hypoperfusion may reflect reduced metabolic demand in regions undergoing neuronal loss. Neurodegeneration may also be revealed by deficits in olfactory identification, especially in AD where olfactory loss correlates with neuropathology and severity of clinical symptoms. If olfactory impairments reflect reduced neural mass and AD pathology, they should be related to cerebral blood-flow (CBF). Hence, we hypothesized that olfactory identification would be associated with CBF in a cohort at risk of pre-symptomatic AD. Cognitively normal subjects with a parental history of AD were scanned using MPRAGE T1 and pCASL sequences. Their odor identification performance was assessed with the 40-item University of Pennsylvania Smell Identification Test. Neurolens software was used for ASL analysis. After pre-processing (motion-correction, subtraction of tagged images from the control images and spatial smoothing of 6 mm, a GLM was fitted to the flow series and CBF was computed. Individual grey matter (GM) probability masks were created from the T1 scan using CIVET automatic segmentation algorithms. Anterior and posterior cingulate cortices (ACC, PCC) and precuneus were defined as ROIs using the AAL template and multiplied by the GM mask. Resulting ROI masks were registered to the ASL space and used for average CBF extraction. Due to noise, we were unable to investigate hippocampal, and entorhinal perfusion. In age adjusted robust-fit regression analyses, olfactory identification correlated with global average CBF in GM (fig.1a), precuneus (fig.1b) and PCC (fig.1c), but not in ACC (fig.1d). Olfactory circuitry parallels major arteries in the medial brain and may be associated with cardiovascular health, as we also found a correlation between olfaction and systolic blood pressure (fig.2). Scatterplot graphs of partial regression analysis for smell identifucation and perfusion for GM, precuneus, PCC,ACC. Scatter plot graph of correlation between smell identifaction and systolic blood pressure. Impaired olfactory identification is associated with reduced CBF in the overall GM and in key ROIs vulnerable to early changes in AD (Iturria-Medina, 2014). Olfactory identification deficits therefore hold interest as potential markers of pre-symptomatic AD.

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