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. 2024 Oct 11;47(10):zsae145.
doi: 10.1093/sleep/zsae145.

The interplay between insomnia symptoms and Alzheimer's disease across three main brain networks

Jorik D Elberse  1   2   3 , Amin Saberi  1   2   4 , Reihaneh Ahmadi  1   5 , Monir Changizi  6 , Hanwen Bi  1   2 , Felix Hoffstaedter  1   2 , Bryce A Mander  7 , Simon B Eickhoff  1   2 , Masoud Tahmasian  1   2   8 , Alzheimer's Disease Neuroimaging Initiative
Affiliations

The interplay between insomnia symptoms and Alzheimer's disease across three main brain networks

Jorik D Elberse et al. Sleep. .

Abstract

Study objectives: Insomnia symptoms are prevalent along the trajectory of Alzheimer's disease (AD), but the neurobiological underpinning of their interaction is poorly understood. Here, we assessed structural and functional brain measures within and between the default mode network (DMN), salience network, and central executive network (CEN).

Methods: We selected 320 participants from the ADNI database and divided them by their diagnosis: cognitively normal (CN), Mild Cognitive Impairment (MCI), and AD, with and without self-reported insomnia symptoms. We measured the gray matter volume (GMV), structural covariance (SC), degrees centrality (DC), and functional connectivity (FC), testing the effect and interaction of insomnia symptoms and diagnosis on each index. Subsequently, we performed a within-group linear regression across each network and ROI. Finally, we correlated observed abnormalities with changes in cognitive and affective scores.

Results: Insomnia symptoms were associated with FC alterations across all groups. The AD group also demonstrated an interaction between insomnia and diagnosis. Within-group analyses revealed that in CN and MCI, insomnia symptoms were characterized by within-network hyperconnectivity, while in AD, within- and between-network hypoconnectivity was ubiquitous. SC and GMV alterations were nonsignificant in the presence of insomnia symptoms, and DC indices only showed network-level alterations in the CEN of AD individuals. Abnormal FC within and between DMN and CEN hubs was additionally associated with reduced cognitive function across all groups, and increased depressive symptoms in AD.

Conclusions: We conclude that patients with clinical AD present with a unique pattern of insomnia-related functional alterations, highlighting the profound interaction between both conditions.

Keywords: Alzheimer’s disease; central executive network; default mode network; insomnia; mild cognitive impairment; salience network.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Flowchart of participant selection. Inclusion and exclusion procedures before and after participant matching are depicted. GDS, Geriatric Depression Scale; MMSE, Mini-Mental State Exam; NPI, Neuropsychiatric Inventory.
Figure 2.
Figure 2.
Three network functional connectivity changes in the presence of insomnia symptoms. (A) Network- and (B) ROI-level alterations in three network connectivity associated with insomnia symptoms in the CN, MCI, and AD groups. CEN, Central Executive Network; Cing, cingulate; DMN, Default Mode Network; Fr, frontal; Ins, insula; Med, medial; Occ, occipital; Oper, operculum; Par, parietal; PCC, posterior cingulate cortex; pCun, precuneus; PFC, prefrontal cortex; PFCd, dorsal prefrontal cortex; PFCl, lateral prefrontal cortex; PFCm, medial prefrontal cortex; PFCmp, medial posterior prefrontal cortex; PFCv, ventral prefrontal cortex; SN, Salience Network; Temp, temporal. *p < .05, **p < .01, ***p < .001, ****p < .0001. ß, estimate.
Figure 3.
Figure 3.
Abnormal inter-ROI connectivity and MMSE score in MCI. ROI-level edges in MCI +insomnia that predict significant changes in MMSE score. (1) ROI-level edges affected by the +insomnia condition. (2) Change in FC for selected edges across the +insomnia condition. (3) Overall correlation of ROI-level edge FC scores and MMSE scores. Hyperconnective intra-DMN edges are overwhelmingly associated with decreased cognitive functioning in MCI +insomnia. DMN, Default Mode Network; FC, functional connectivity; PCC, posterior cingulate cortex; pCun, precuneus; PFC, prefrontal cortex; PFCd, dorsal prefrontal cortex; PFCm, medial prefrontal cortex. *p < .05, **p < .01, ***p < .001, ****p < .0001. ß, estimate.
Figure 4.
Figure 4.
Abnormal inter-ROI connectivity and MMSE score in AD. ROI-level edges in AD +insomnia that predict significant changes in MMSE score. (1) ROI-level edges affected by the +insomnia condition. (2) Change in FC for selected edges across the +insomnia condition. (3) Overall correlation of ROI-level edge FC scores and MMSE scores. Certain hypoconnective intra-DMN, inter-SN-DMN, and inter-SN-CEN edges predicted decreased cognitive functioning in AD +insomnia. One hypoconnective inter-SN-CEN edge predicted increased cognitive functioning in AD +insomnia. CEN, Central Executive Network; DMN, Default Mode Network; FC, functional connectivity; Fr, frontal; Ins, insula; Med, medial; Occ, occipital; Oper, operculum; Par, parietal; PFC, prefrontal cortex; PFCl, lateral prefrontal cortex; SN, Salience Network; Temp, temporal. *p < .05, **p < .01, ***p < .001, ****p < .0001. ß, estimate.
Figure 5.
Figure 5.
Summary of main findings. Summary of network alterations associated with insomnia symptoms along the trajectory of AD. Within- and between-network FC alterations were the only significant marker of insomnia across the (A) Cognitively normal (B) Mild cognitive impairment, and (C) Alzheimer’s disease groups. Arrow width represents relative strength of FC alterations. FC, functional connectivity. Created with BioRender.com.
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