Differences in resting state functional connectivity underlie visuomotor performance declines in older adults with a genetic risk (APOE ε4) for Alzheimer's disease

Alica Rogojin; Diana J Gorbet; Kara M Hawkins; Lauren E Sergio

doi:10.3389/fnagi.2022.1054523

Differences in resting state functional connectivity underlie visuomotor performance declines in older adults with a genetic risk (APOE ε4) for Alzheimer's disease

Front Aging Neurosci. 2022 Dec 1:14:1054523. doi: 10.3389/fnagi.2022.1054523. eCollection 2022.

Authors

Alica Rogojin^{1

2

3}, Diana J Gorbet^{1

2}, Kara M Hawkins¹, Lauren E Sergio^{1

2}

Affiliations

¹ School of Kinesiology and Health Science, York University, Toronto, ON, Canada.
² Centre for Vision Research, York University, Toronto, ON, Canada.
³ Vision Science to Applications (VISTA) Program, York University, Toronto, ON, Canada.

Abstract

Introduction: Non-standard visuomotor integration requires the interaction of large networks in the brain. Previous findings have shown that non-standard visuomotor performance is impaired in individuals with specific dementia risk factors (family history of dementia and presence of the APOE ε4 allele) in advance of any cognitive impairments. These findings suggest that visuomotor impairments are associated with early dementia-related brain changes. The current study examined the underlying resting state functional connectivity (RSFC) associated with impaired non-standard visuomotor performance, as well as the impacts of dementia family history, sex, and APOE status.

Methods: Cognitively healthy older adults (n = 48) were tested on four visuomotor tasks where reach and gaze were increasingly spatially dissociated. Participants who had a family history of dementia or the APOE ε4 allele were considered to be at an increased risk for AD. To quantify RSFC within networks of interest, an EPI sequence sensitive to BOLD contrast was collected. The networks of interest were the default mode network (DMN), somatomotor network (SMN), dorsal attention network (DAN), ventral attention network (VAN), and frontoparietal control network (FPN).

Results: Individuals with the ε4 allele showed abnormalities in RSFC between posterior DMN nodes that predicted poorer non-standard visuomotor performance. Specifically, multiple linear regression analyses revealed lower RSFC between the precuneus/posterior cingulate cortex and the left inferior parietal lobule as well as the left parahippocampal cortex. Presence of the APOE ε4 allele also modified the relationship between mean DAN RSFC and visuomotor control, where lower mean RSFC in the DAN predicted worse non-standard visuomotor performance only in APOE ε4 carriers. There were otherwise no effects of family history, APOE ε4 status, or sex on the relationship between RSFC and visuomotor performance for any of the other resting networks.

Conclusion: The preliminary findings provide insight into the impact of APOE ε4-related genetic risk on neural networks underlying complex visuomotor transformations, and demonstrate that the non-standard visuomotor task paradigm discussed in this study may be used as a non-invasive, easily accessible assessment tool for dementia risk.

Keywords: Alzheimer’s disease; apolipoprotein E4 (APOE ε4); default mode network; dorsal attention network; early detection; resting state functional connectivity; visuomotor integration.