Study objectives To examine if sleep symptomatology was associated with subjective cognitive concerns or objective cognitive performance in a dementia-free community-based sample. Methods A total of 1421 middle-aged participants (mean±standard deviation = 57±7; 77% female) from the Healthy Brain Project completed the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Epworth Sleepiness Scale (ESS) to measure sleep quality, insomnia symptom severity, and daytime sleepiness, respectively. Participants were classified as having no sleep symptomatology (normal scores on each sleep measure), moderate sleep symptomatology (abnormal scores on one sleep measure), or high sleep symptomatology (abnormal scores on at least two sleep measures), using established cut-off values. Analysis of covariance was used to compare objective cognitive function (Cogstate Brief Battery) and subjective cognitive concerns (Modified Cognitive Function Instrument) across groups. Results Following adjustments for age, sex, education, mood, and vascular risk factors, persons classified as having high sleep symptomatology, versus none, displayed more subjective cognitive concerns (d=0.24) but no differences in objective cognitive performance (d=0.00-0.18). Subjective cognitive concerns modified the association between sleep symptomatology and psychomotor function. The strength of the relationship between high sleep symptomatology (versus none) and psychomotor function was significantly greater in persons with high as compared with low cognitive concerns (β±SE =-0.37±0.16; p=0.02). Conclusions More severe sleep symptomatology was associated with greater subjective cognitive concerns. Persons reporting high levels of sleep symptomatology may be more likely to display poorer objective cognitive function in the presence of subjective cognitive concerns.

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Background Impairments in sleep and cognitive function have been observed in patients with substance abuse disorders and may be potential factors contributing to drug relapse. In addition, sleep disruption may itself contribute to cognitive deficits. In the present study we examined the impact of prolonged cocaine self-administration and abstinence on actigraphy-based measures of night-time activity in rhesus macaques as an inferential measure of sleep, and determined whether sleep-efficiency correlated with cognitive impairments in the same subjects on drug free days. Methods Actigraphy data was obtained from a group of rhesus macaques intravenously self-administering cocaine (n=6) and a control group (n=5). Periods were evaluated during which the mean cumulative doses of cocaine were 3.0+0.0 and 4.5+0.2 mg/kg/day for 4 days (Tuesday-Thursday) each week. Results Actigraphy-based sleep efficiency decreased during days of cocaine self-administration in a dose-dependent manner. Consistent with this observation, sleep became more fragmented. Activity-based sleep efficiency normalized during the weekend without cocaine prior to cognitive assessment on Monday. The magnitude of activity-based sleep disruption during self-administration did not correlate with the level of cognitive impairment on drug free days. With continued self-administration, the impact of cocaine on activity-based sleep efficiency declined indicating the development of tolerance. Conclusions Cocaine self-administration disrupted sleep efficiency in rhesus macaques as measured by actigraphy, but normalized quickly in the absence of cocaine. The cognitive impairment observed on drug free days was unlikely to be related to disruption of the nightly activity patterns on days of cocaine self-administration.

Background: Insomnia is one of the most common sleep disorders yet its relationship to the biology of Alzheimer’s disease remains equivocal. Objective: We investigated the cross-sectional relationship between insomnia symptom severity and cerebrospinal fluid (CSF) concentrations of Alzheimer’s disease biomarkers in a cognitively unimpaired middle-aged community sample. Methods: A total of 63 participants from the Healthy Brain Project (age = 59±7 years; 67% women) completed a lumbar puncture and two weeks of actigraphy to measure two of insomnia’s core features: difficulty initiating sleep (prolonged sleep onset latency) and difficulty maintaining sleep (wake after sleep onset [WASO] and number of awakenings). Additionally, the Insomnia Severity Index (ISI) was completed by 58 participants. Linear and Tobit regression were used to estimate the associations between each insomnia variable and CSF Aβ42, phosphorylated tau 181 (p-tau181), total-tau, and neurofilament light chain protein (NfL), adjusting for age, sex, and APOE ɛ4 genotype. Results: Higher ISI score was associated with greater average levels of CSF Aβ 42 (per point: 30.7 pg/mL, 95% CI: 4.17–57.3, p = 0.023), as was higher WASO (per 10 min: 136 pg/mL, 95% CI: 48–223, p = 0.002) and more awakenings (per 5:123 pg/mL, 95% CI = 55–192, p < 0.001). Difficulty initiating sleep was not associated with CSF Aβ 42, nor were insomnia features associated with p-tau181, total-tau, or NfL levels. Conclusion: Insomnia symptoms were associated with higher CSF Aβ 42 levels in this relatively young, cognitively unimpaired sample. These findings may reflect increased amyloid production due to acute sleep disruption.

BackgroundAmyloid production increases during wakefulness before being cleared during sleep. Insomnia is one of the commonest sleep disorders, yet its relationship to core markers of preclinical Alzheimer’s disease remains unknown. We investigated the cross‐sectional relationship between insomnia symptom severity, APOE e4 carriage, and cerebrospinal spinal fluid (CSF) concentrations of Alzheimer’s disease biomarkers in a non‐demented community‐sample aged 43‐67 years.Method66 participants from the Healthy Brain Project Biomarker Sub‐study (age = 58±6 years; MMSE = 29±7; 68% women) completed a lumbar puncture, two weeks of actigraphy to measure sleep and wake patterns, and the Insomnia Severity Index (ISI) to measure insomnia symptom severity over the past two weeks. The ISI was split into two groups (normal vs. high [>7]) based on established cut‐off values (42% of the sample were high). Two core insomnia features were captured: Difficulty initiating sleep (prolonged sleep onset latency) and difficulty maintaining sleep (high wake after sleep onset (WASO) duration and number of awakenings), with each variable classified as the top 25th percentile versus the remainder of the sample. Analysis of covariance was used to compare CSF amyloid‐beta 42 (Aβ42), phosphorylated tau 181 (p‐tau181), total‐tau, and neurofilament light chain protein (NfL) across each of the sleep groups, adjusting for age and sex.ResultPersons with high insomnia symptom severity had higher CSF Aβ42 levels (p=0.033, d=0.58). Difficulty maintaining sleep (both high WASO and number of awakenings) was also associated with higher Aβ42 levels (p=0.023, d=0.77 for WASO; p=0.013, d=0.92 for awakenings), whereas difficulty initiating sleep was not (p= 0.776, d=0.08). The sleep variables were not associated with p‐tau181, total‐tau, or NfL levels (p>0.05). APOE e4 modified the association between WASO and Aβ42. The strength of the relationship between higher WASO (versus normal) and Aβ42 was stronger in e4 carriers, compared to non‐carriers (F(df) = 6.94 (1, 44), p=0.012).ConclusionIn this relatively young sample, symptoms and features of insomnia were associated with higher CSF Aβ42 levels. These findings may reflect increased amyloid production due to acute sleep disruption. Longitudinal studies are needed to determine whether sustained sleep disruption associates with amyloid accumulation over time.