2-(4--(methylamino)phenyl)-6-hydroxybenzothiazole and Sleep-Wake-Disorders

Independent evidence associates β-amyloid pathology with both non-rapid eye movement (NREM) sleep disruption and memory impairment in older adults. However, whether the influence of β-amyloid pathology on hippocampus-dependent memory is, in part, driven by impairments of NREM slow wave activity (SWA) and associated overnight memory consolidation is unknown. Here we show that β-amyloid burden in medial prefrontal cortex (mPFC) correlates significantly with the severity of impairment in NREM SWA generation. Moreover, reduced NREM SWA generation was further associated with impaired overnight memory consolidation and impoverished hippocampal-neocortical memory transformation. Furthermore, structural equation models revealed that the association between mPFC β-amyloid pathology and impaired hippocampus-dependent memory consolidation was not direct, but instead statistically depended on the intermediary factor of diminished NREM SWA. By linking β-amyloid pathology with impaired NREM SWA, these data implicate sleep disruption as a mechanistic pathway through which β-amyloid pathology may contribute to hippocampus-dependent cognitive decline in the elderly.

Topics: Aged; Aged, 80 and over; Amyloid beta-Peptides; Aniline Compounds; Brain Waves; Female; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Memory Disorders; Memory, Episodic; Polysomnography; Positron-Emission Tomography; Prefrontal Cortex; Recognition, Psychology; Sleep Stages; Sleep Wake Disorders; Thiazoles

Midlife may be an ideal window for intervention in Alzheimer's disease (AD). To determine whether sleep is associated with early signs of AD neuropathology (amyloid deposition) in late midlife, we imaged brain amyloid deposits using positron emission tomography with [C-11]Pittsburgh Compound B (PiB), and assessed sleep with the Epworth Sleepiness Scale and the Medical Outcomes Study Sleep Scale in 98 cognitively healthy adults (aged 62.4 ± 5.7 years) from the Wisconsin Registry for Alzheimer's Prevention. We used multiple regressions to test the extent to which sleep scores predicted regional amyloid burden. Participants reporting less adequate sleep, more sleep problems, and greater somnolence on the Medical Outcomes Study had greater amyloid burden in AD-sensitive brain regions (angular gyrus, frontal medial orbital cortex, cingulate gyrus, and precuneus). Amyloid was not associated with reported sleep amount, symptoms of sleep-disordered breathing, trouble falling asleep, or Epworth Sleepiness Scale. Poor sleep may be a risk factor for AD and a potential early marker of AD or target for preventative interventions in midlife.

Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Apolipoproteins E; Cerebral Cortex; Cohort Studies; Disease Progression; Female; Humans; Magnetic Resonance Imaging; Male; Mental Status Schedule; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography; Radiography; Self Report; Sleep Wake Disorders; Statistics as Topic; Thiazoles

Older adults commonly report disturbed sleep, and recent studies in humans and animals suggest links between sleep and Alzheimer disease biomarkers. Studies are needed that evaluate whether sleep variables are associated with neuroimaging evidence of β-amyloid (Aβ) deposition. OBJECTIVE To determine the association between self-reported sleep variables and Aβ deposition in community-dwelling older adults.. Cross-sectional study of 70 adults (mean age, 76 [range, 53-91] years) from the neuroimaging substudy of the Baltimore Longitudinal Study of Aging, a normative aging study. EXPOSURE Self-reported sleep variables. MAIN OUTCOMES AND MEASURES β-Amyloid burden, measured by carbon 11-labeled Pittsburgh compound B positron emission tomography distribution volume ratios (DVRs).. After adjustment for potential confounders, reports of shorter sleep duration were associated with greater Aβ burden, measured by mean cortical DVR (B = 0.08 [95% CI, 0.03-0.14]; P = .005) and precuneus DVR (B = 0.11 [0.03-0.18]; P = .007). Reports of lower sleep quality were associated with greater Aβ burden measured by precuneus DVR (B = 0.08 [0.01-0.15]; P = .03).. Among community-dwelling older adults, reports of shorter sleep duration and poorer sleep quality are associated with greater Aβ burden. Additional studies with objective sleep measures are needed to determine whether sleep disturbance causes or accelerates Alzheimer disease.

Topics: Aged; Aged, 80 and over; Aging; Amyloid beta-Peptides; Aniline Compounds; Brain; Cross-Sectional Studies; Female; Geriatric Assessment; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography; Residence Characteristics; Self Report; Sleep Wake Disorders; Thiazoles