Functional Connectivity Between the Posterior Default Mode Network and Parahippocampal Gyrus Is Disrupted in Older Adults with Subjective Cognitive Decline and Correlates with Subjective Memory Ability

Article type: Research Article

Authors: Sharma, Namita^a | Murari, Geetanjali^a | Vandermorris, Susan^b | Verhoeff, Nicolaas Paul L.G.^{b; d} | Herrmann, Nathan^{c; d} | Chen, J. Jean^{a; e} | Mah, Linda^{a; d; *}

Affiliations: [a] Rotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada | [b] Baycrest Health Sciences, Toronto, Ontario, Canada | [c] Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada | [d] Department of Psychiatry, Geriatric Psychiatry Division, University of Toronto, Toronto, ON, Canada | [e] Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

Correspondence: [*] Correspondence to: Linda Mah, MD, MHS, FRCPC, Associate Professor, Department of Psychiatry, Division of Geriatric Psychiatry, University of Toronto Faculty of Medicine, KFB 732, 3560 Bathurst St. Toronto, Ontario M6A 2E1, Canada. Tel.: +1 416 785 2500/Ext. 3365; E-mail: [email protected].

Abstract: Background:Subjective cognitive decline (SCD) is associated with increased risk of developing Alzheimer’s disease (AD). However, the underlying mechanisms for this association remain unclear. Neuroimaging studies suggest the earliest AD-related changes are large-scale network disruptions, beginning in the posterior default mode (pDMN) network. Objective:To examine the association between SCD and pDMN network connectivity with medial temporal lobe (MTL) regions using resting-state functional magnetic resonance imaging. Methods:Forty-nine participants with either SCD (n = 23, 12 females; mean age: 70.7 (5.5)) or who were cognitively unimpaired (CU; n = 26, 16 females, mean age: 71.42 (7.3)) completed the Memory Functioning Questionnaire, a measure of subjective memory, and underwent resting state functional MRI at 3 Tesla. Functional connectivity between the posterior cingulate cortex (PCC), as the key pDMN node, and MTL regions were compared between SCD and CU groups. Further, the association between pDMN-MTL connectivity and the Frequency of Forgetting subscale of the Memory Functioning Questionnaire was examined. Results:Connectivity between the PCC-MTL was observed in the CU group but was absent in SCD (t(47) = 2.69, p = 0.01). Across all participants, self-perception of frequency of forgetting, but not objective memory, was strongly correlated with connectivity between the PCC-left parahippocampal gyrus (r = 0.43, p = 0.002). Conclusion:These findings support the hypothesis that increased AD risk in SCD may be mediated by disrupted pDMN-parahippocampal connectivity. In addition, these findings suggest that frequency of forgetting may serve as a potential biomarker of SCD due to incipient AD.

Keywords: Alzheimer’s disease, default mode network, depression, functional connectivity, memory functioning questionnaire, parahippocampal gyrus, posterior cingulate cortex, resting state functional magnetic resonance imaging, subjective cognitive decline, subjective memory

DOI: 10.3233/JAD-201579

Journal: Journal of Alzheimer's Disease, vol. 82, no. 1, pp. 435-445, 2021