Examining functional connectivity in metabolic syndrome and small vessel disease: A novel approach to understanding olfactory dysfunction and Alzheimer's disease.

INTRODUCTION

The prevalence of Alzheimer's Disease (AD) is projected to triple by 2050, highlighting the need to identify early markers and underlying mechanisms associated with its progression. Olfactory dysfunction has emerged as an early indicator of AD, with its neural basis linked to changes in the medial temporal lobe and associated networks. Cardiovascular risk factors, including metabolic syndrome (MetS) and cerebral small vessel disease (SVD), have been implicated in neurodegenerative processes, yet their impact on olfactory network connectivity remains underexplored. This study aimed to investigate task-based functional connectivity in the olfactory network, medial temporal lobe, and default mode network among cognitively unimpaired individuals with MetS or SVD.

METHOD: Participants were grouped based on MetS and SVD status. Using fMRI, functional connectivity patterns during olfactory processing were analyzed for group differences.

RESULTS

Functional connectivity revealed hypoconnectivity between the right angular gyrus and secondary olfactory cortex between MetS groups and altered connectivity between the hippocampus and frontoparietal control network between SVD groups. Both conditions demonstrated increased within-network cerebellar connectivity compared to controls.

DISCUSSION: These findings highlight distinct neural alterations in olfactory and cognitive control networks associated with cardiovascular risk factors, providing novel insights into early brain changes linked to cardiovascular risk factors for dementia.