Association of Sleep Disturbances With Brain Amyloid and Tau Burden, Cortical Atrophy, and Cognitive Dysfunction Across the AD Continuum

Abstract

Background and ObjectivesPatients with Alzheimer’s disease (AD) frequently suffer from various sleep disturbances. However, how sleep disturbance is associated with AD and its progression remains poorly investigated. We investigated the association of total sleep time with brain amyloid and tau burden, cortical atrophy, cognitive dysfunction, and their longitudinal changes in the AD spectrum.MethodsIn this retrospective cohort study, we enrolled participants on the AD spectrum who were positive on18F-florbetaben (FBB) PET. All participants underwent the Pittsburgh Sleep Quality Index, brain MRI, FBB PET,18F-flortaucipir (FTP) PET, and detailed neuropsychological testing. In addition, a subset of participants completed follow-up assessments. We analyzed the association of total sleep time with the baseline and longitudinal FBB-standardized uptake value ratio (SUVR), FTP-SUVR, cortical thickness, and cognitive domain composite scores.ResultsWe examined 138 participants on the AD spectrum (15 with preclinical AD, 62 with prodromal AD, and 61 with AD dementia; mean age 73.4 ± 8.0 years; female 58.7%). Total sleep time was longer in the AD dementia group (7.4 ± 1.6 hours) compared to the preclinical (6.5 ± 1.4 hours;p= 0.026) and prodromal groups (6.6 ± 1.4 hours;p= 0.001), while other sleep parameters did not differ between groups. Longer total sleep time was not associated with amyloid accumulation but rather with tau accumulation, especially in the amygdala, hippocampus, basal forebrain, insular, cingulate, occipital, inferior temporal cortices, and precuneus. Longer total sleep time predicted faster tau accumulation in Braak regions V-VI (β = 0.016,p= 0.007) and disease progression to mild cognitive impairment or dementia (hazard ratio = 1.554,p= 0.024). Longer total sleep time was also associated with memory deficit (β = -0.19,p= 0.008).DiscussionProlonged total sleep time was associated with tau accumulation in sleep-related cortical and sub-cortical areas as well as memory dysfunction. It also predicted faster disease progression with tau accumulation. Our study highlights the clinical importance of assessing total sleep time as a marker for disease severity and prognosis in the AD spectrum.

Herbal medicines in Alzheimer’s disease and the involvement of gut microbiota

“…16S rRNA gene sequencing demonstrated that LB rectified the disturbed floras including Porphyromonadaceae, Lactobacillus and Escherichia at the genus level ( Si et al, 2022 ). From another perspective, previous studies have indicated the intensely adverse influence of insomnia on cognitive functions of AD patients ( Bubu et al, 2017 ; Pak et al, 2020 ; Yoon et al, 2023 ). Therefore, LB may ameliorate impaired cognitive functions of AD patients directly through maintaining the gut microbiota homeostasis or indirectly through alleviation of sleep problems.…”