The olfactory functional network in the Alzheimer's Disease continuum: a resting state fMRI study

Daniela Ballotta¹Claudia Casadio¹Manuela Tondelli^1*Vanessa Zanelli¹Francesco Ricci¹Omar Carpentiero¹Fausta Lui¹Nicola Filippini²Annalisa Chiari³Maria Angela Molinari⁴Francesca Benuzzi¹

• ¹Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
• ²IRCCS Ospedale San Camillo, Venice, Italy
• ³Neurology Unit, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
• ⁴Azienda Ospedaliero-Universitaria di Modena, Modena, Italy

Olfactory dysfunction is common in the Alzheimer's Disease continuum, and olfaction may be altered before clinical syndrome onset. The present study aimed at investigating the functional connectivity of the olfactory cortex and its correlation with olfaction performance in a group of thirty patients with Mild Cognitive Impairment who subsequently converted or not converted to Alzheimer's Disease dementia. At baseline, they were evaluated with the Sniffin' Sticks (threshold, discrimination, and identification) to evaluate olfactory capacities, and they were followed up over time to identify converter and stable patients. Resting-state fMRI data acquired at baseline were analyzed to assess functional connectivity of left and right olfactory cortex. Beta values were extracted from the stable versus converter contrasts and correlated with olfactory scores. Functional connectivity of the olfactory cortex was significantly increased with the posterior cingulate cortex, and significantly decreased with middle cingulate cortex, supplementary motor area, and left pre-and postcentral gyri, in converter compared to stable patients. Reduced negative functional connectivity between olfactory cortex and left angular gyrus emerged in converter patients, and a negative correlation was found between angular gyrus and discrimination scores. Our findings indicate alterations of functional connectivity of the olfactory cortex in subjects with Mild Cognitive Impairment at risk of conversion to Alzheimer's Disease dementia, even at the early stages of the disease. Additionally, the negative correlation between olfactory ability and the angular gyrus functional connectivity, a cerebral region known to be involved in multisensory integration processing, may be considered as a marker of disease progression.