Neuro-Navigated rTMS Improves Sleep and Cognitive Impairment via Regulating Sleep-Related Networks’ Spontaneous Activity in AD Spectrum Patients

STUDY OBJECTIVES: By examining spontaneous activity changes of sleep-related networks in patients with the Alzheimer’s disease (AD) spectrum with or without insomnia disorder (ID) over time via neuro-navigated repetitive transcranial magnetic stimulation (rTMS), we revealed the effect and mechanism of rTMS targeting the left-angular gyrus in improving the comorbidity symptoms of the AD spectrum with ID. METHODS: A total of 34 AD spectrum patients were recruited in this study, including 18 patients with ID and the remaining 16 patients without ID. All of them were measured for cognitive function and sleep by using the cognitive and sleep subscales of the neuropsychiatric inventory. The amplitude of low-frequency fluctuation changes in sleep-related networks was revealed before and after neuro-navigated rTMS treatment between these two groups, and the behavioral significance was further explored. RESULTS: Affective auditory processing and sensory-motor collaborative sleep-related networks with hypo-spontaneous activity were observed at baseline in the AD spectrum with ID group, while substantial increases in activity were evident at follow-up in these subjects. In addition, longitudinal affective auditory processing, sensory-motor and default mode collaborative sleep-related networks with hyper-spontaneous activity were also revealed at follow-up in the AD spectrum with ID group. In particular, longitudinal changes in sleep-related networks were associated with improvements in sleep quality and episodic memory scores in AD spectrum with ID patients. CONCLUSION: We speculated that left angular gyrus-navigated rTMS therapy may enhance the memory function of AD spectrum patients by regulating the spontaneous activity of sleep-related networks, and it was associated with memory consolidation in the hippocampus-cortical circuit during sleep. CLINICAL TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trial Registry, registration ID: ChiCTR2100050496, China.