Neural Correlates of Sleep Disturbance in Alzheimer’s Disease: Role of the Precuneus in Sleep Disturbance

Abstract

Background:Sleep disturbance may affect the development of Alzheimer’s disease (AD), but the neural correlates of sleep disturbance in AD have not been fully clarified.Objective:To examine the factors associated with sleep disturbance in AD.Methods:A retrospective study was performed in 63 patients with AD. None of the patients had been prescribed antidementia or psychoactive drugs, and all underwent brain magnetic resonance imaging (MRI) before medication. Sleep disturbance was defined as a score of at least 1 point on the sleep disturbance subscale of the Neuropsychiatric Inventory (NPI). Whole brain image analysis was performed using SPM8 and VBM8. A two-sample t-test was used to compare patients with AD with (n = 19) and without (n = 44) sleep disturbance, with age and gender included as covariates. The statistical thresholds were set to an uncorrected p-value of 0.001 at the voxel level and a corrected p-value of 0.05 at the cluster level. In addition, pineal gland volume (PGV) measured using MRI, and white matter hyperintensity (WMH) assessed with the modified Fazekas scale were compared between patients with AD with and without sleep disturbance using independent group t-tests.Results:In whole brain analysis, the precuneus volume in patients with AD with sleep disturbance was significantly smaller than those without sleep disturbance. There were no significant differences in PGV and WMH between the two groups.Conclusion:Sleep disturbance in AD was associated with reduction of precuneus volume. This suggests that the precuneus might be an important region in sleep disturbance in AD.

Prevalence of Mild Behavioral Impairment and Risk of Dementia in a Psychiatric Outpatient Clinic

“…Psychiatric symptoms, including sleep disturbance [2,3] and depression [4,5], are risk factors of dementia. Sleep disturbance might contribute to dysfunction of amyloid clearance, and then contribute to the development of Alzheimer's disease (AD) [6,7]. Affective neuropsychiatric symptoms including depressive symptoms are predictors of dementia even in those with normal cognition and subjective cognitive decline (SCD) [8].…”

Comparative transcriptome analysis of the hippocampus from sleep-deprived and Alzheimer’s disease mice

“…Recently, human and transgenic animal studies show that amyloid deposition and tau aggregation directly cause sleep impairment (Roh et al, 2012;Mander et al, 2015). Besides, dysfunction of neurotransmitter systems responsible for sleep including the cholinergic system, and physiological alterations in the suprachiasmatic nucleus (SCN) and pineal gland, as well as reduction of precuneus volume have been reported to be associated with sleep disturbance in patients with AD (Sarter and Bruno, 1997;Wu and Swaab, 2007;Matsuoka et al, 2018). Therefore, sleep deprivation is initially considered to be a biomarker of a subclinical neurodegenerative process, such as AD.…”

Pineal volume reduction in patients with mild cognitive impairment who converted to Alzheimer's disease

“…18 Reduction of pineal-derived melatonin also causes sleep disturbance, and might cause an AD pathology via a dysfunctional glymphatic pathway. 20,21 A reduction in CSF melatonin is seen in preclinical stages. 17 Higher production of melatonin in elderly people results in a lower prevalence of cognitive impairment, 27 and the melatonin secretory capacity is proportional to the PPV.…”

“…[17][18][19] Melatonin also affects circadian rhythm and sleep regulation 17 ; thus, reduction of melatonin causes sleep disturbance, and sleep disturbance is correlated with AD pathology via dysfunction of the glymphatic pathway. 20,21 Indeed, CSF melatonin levels decrease even in preclinical stages, and therefore, a reduction in CSF melatonin may be one of the early signs of AD. 17 Melatonin might thus play an important role in preventing progression to AD.…”