Long-term associations between objective sleep quality and quantity and verbal memory performance in normal cognition and mild cognitive impairment.

Introduction: Although the link between sleep and memory function is well established, associations between sleep macrostructure and memory function in normal cognition and Mild Cognitive Impairment remain unclear. We aimed to investigate the longitudinal associations of baseline objectively assessed sleep quality and duration, as well as time in bed, with verbal memory capacity over a 7-9 year period. Participants are a well-characterized subsample of 148 persons (mean age at baseline: 72.8 ± 6.7 years) from the Cretan Aging Cohort. Based on comprehensive neuropsychiatric and neuropsychological evaluation at baseline, participants were diagnosed with Mild Cognitive Impairment (MCI; n = 79) or found to be cognitively unimpaired (CNI; n = 69). Sleep quality/quantity was estimated from a 3-day consecutive actigraphy recording, whereas verbal memory capacity was examined using the Rey Auditory Verbal Learning Test (RAVLT) and the Greek Passage Memory Test at baseline and follow-up. Panel models were applied to the data using AMOS including several sociodemographic and clinical covariates. Results: Sleep efficiency at baseline directly predicted subsequent memory performance in the total group (immediate passage recall: ß = 0.266, p = 0.001; immediate word list recall: ß = 0.172, p = 0.01; delayed passage retrieval: ß = 0.214, p = 0.002) with the effects in Passage Memory reaching significance in both clinical groups. Wake after sleep onset time directly predicted follow-up immediate passage recall in the total sample (ß = -0.211, p = 0.001) and in the MCI group (ß = -0.235, p = 0.02). In the total sample, longer 24-h sleep duration was associated with reduced memory performance indirectly through increased sleep duration at follow-up (immediate passage recall: ß = -0.045, p = 0.01; passage retention index: ß = -0.051, p = 0.01; RAVLT-delayed recall: ß = -0.048, p = 0.009; RAVLT-retention index:ß = -0.066, p = 0.004). Similar indirect effects were found for baseline 24-h time in bed. Indirect effects of sleep duration/time in bed were found predominantly in the MCI group. Discussion: Findings corroborate and expand previous work suggesting that poor sleep quality and long sleep duration predict worse memory function in elderly. Timely interventions to improve sleep could help prevent or delay age-related memory decline among non-demented elderly.

IL-6 Enhances the Negative Impact of Cortisol on Cognition among Community-Dwelling Older People without Dementia.

There is growing evidence that high basal cortisol levels and systemic inflammation independently contribute to cognitive decline among older people without dementia. The present cross-sectional study examined (a) the potential synergistic effect of cortisol levels and systemic inflammation on executive function and (b) whether this effect is more prominent among older people with mild cognitive impairment (MCI). A sub-sample of 99 patients with MCI and 84 older people without cognitive impairment (CNI) (aged 73.8 ± 7.0 years) were recruited from a large population-based cohort in Crete, Greece, and underwent comprehensive neuropsychiatric and neuropsychological evaluation and a single morning measurement of cortisol and IL-6 plasma levels. Using moderated regression models, we found that the relation between cortisol and executive function in the total sample was moderated by IL-6 levels (b = -0.994, p = 0.044) and diagnostic group separately (b = -0.632, p < 0.001). Moreover, the interaction between cortisol and IL-6 levels was significant only among persons with MCI (b = -0.562, p < 0.001). The synergistic effect of stress hormones and systemic inflammation on cognitive status appears to be stronger among older people who already display signs of cognitive decline. Targeting hypercortisolemia and inflammation may be a promising strategy toward improving the course of cognitive decline.

Apolipoprotein E ɛ4 (APOE ɛ4) Allele is Associated with Long Sleep Duration Among Elderly with Cognitive Impairment.

BACKGROUND: Apolipoprotein E gene (APOE) ɛ4 allele increases the risk for Alzheimer's disease (AD). Furthermore, among patients with cognitive impairment, longer sleep duration is associated with worse cognitive performance. To date, literature examining the associations between APOE ɛ4 allele and objective sleep duration is limited. OBJECTIVE: Our aim was to assess the association between APOE ɛ4 and objective sleep duration, among patients with mild cognitive impairment (MCI) and AD. A sub-sample of 89 patients with AD (n = 49) and MCI (n = 40) were recruited from a large, population-based cohort of 3,140 elders (>60 years) residing on Crete, Greece. METHODS: All participants underwent medical history/physical examination, extensive neuropsychiatric and neuropsychological evaluation, 3-day 24 h actigraphy and APOE ɛ4 allele genotyping. Comparisons of sleep duration variables between APOE ɛ4 allele carriers and non-carriers were assessed using ANCOVA, controlling for confounders. RESULTS: The sample included 18 APOE ɛ4 carriers and 71 non-carriers, aged 78.6±6.6 and 78.2±6.5 years, respectively. Comparisons between the APOE ɛ4 carriers and non-carriers revealed no significant differences in terms of demographic and clinical variables. In terms of objective sleep duration across the two groups, APOE ɛ4 carriers compared to non-carriers had significantly longer nighttime Total Sleep Time (nTST) (7.7±1.4 versus 7.2±1.3  h, respectively, p = 0.011), as well as 24 h TST (8.5±1.6 versus 7.8±1.5  h, respectively, p = 0.012). CONCLUSION: Among patients with MCI and AD, APOE ɛ4 carriers have longer objective nighttime and 24 h sleep duration compared to non-carriers. These findings further support that objective long sleep duration is a genetically-driven pre-clinical marker associated with worse prognosis in elderly with cognitive impairment.

Objective Daytime Napping is Associated with Disease Severity and Inflammation in Patients with Mild to Moderate Dementia1.

BACKGROUND: Patients with dementia report excessive daytime sleep/sleepiness, which is associated with worse cognitive performance. Inflammatory markers may be elevated in patients with dementia and have been proposed as mediators of sleep/sleepiness. OBJECTIVE: To examine the association of objective daytime napping with cognitive performance and peripheral markers of inflammation in patients with dementia as compared to not cognitively impaired (NCI) controls. METHODS: A sub-sample of 46 patients with mild-to-moderate dementia and 85 NCI controls, were recruited from a large, population-based cohort of 3,140 elders (≥60 years) in Crete, Greece. All participants underwent medical history/physical examination, extensive neuropsychiatric and neuropsychological evaluation, 3-day 24 h actigraphy and a single morning measure of IL-6 and TNFα plasma levels. Comparisons of sleep parameters and inflammation markers between diagnostic groups, and between nappers and non-nappers within each diagnostic group, were conducted using ANCOVA controlling for demographics/related clinical factors. Associations between inflammatory markers, sleep variables, and neuropsychological performance were assessed within each group using partial correlation analysis controlling for confounders. RESULTS: Patients with dementia slept 15 minutes longer during the day than NCI. Within dementia patients, nappers had significantly worse performance on autobiographic memory (p = 0.002), working memory (p = 0.007), episodic memory (p = 0.010), and assessment of daily function (p = 0.012) than non-nappers. Finally, IL-6 levels were significantly associated with nap duration within dementia patients who napped (r = 0.500, p = 0.01). CONCLUSIONS: Daytime napping in patients with dementia is associated with worse cognitive performance and increased IL-6 levels. In dementia, objective daytime napping, may be a marker of the severity of the disease.

Associations between sleep duration and cognitive impairment in mild cognitive impairment.

The prevalence of mild cognitive impairment (MCI) increases among elderly people and is associated with a high risk of dementia. Identifying factors that may contribute to the progress of MCI to dementia is critical. The objective of this study was to examine the association of objective sleep with cognitive performance in MCI patients. A subsample of 271 participants with a diagnosis of probable Alzheimer's disease (AD; N = 50) or mild cognitive impairment (MCI; N = 121) and 100 persons who were not cognitively impaired (NI) were recruited from a large population-based cohort in the island of Crete, Greece (3140 older adults aged >60 years). All participants underwent extensive neuropsychiatric/neuropsychological evaluation and a 3-day 24-hr actigraphy. Objective sleep variables and their association with neuropsychological performance were examined across the three groups, controlling for demographics, body mass index, depression, sleep apnea symptoms and psychotropic medications. Patients with AD had significantly longer 24-hr total sleep time (TST) compared to the MCI and NI groups. Long 24-hr TST was associated with reduced performance on tasks that placed significant demands on attention and processing speed in the MCI group and the AD group. Elderly patients with MCI have similar objective sleep duration to normal controls, whereas AD patients sleep longer. Long sleep duration in patients with multidomain subtypes of MCI is associated with critical non-memory cognitive domains. It appears that within the MCI group those that sleep longer have more severe cognitive impairment.

Association between insomnia symptoms and cognitive impairment in the Cretan Aging Cohort.

PURPOSE: Population aging, characteristic of modern Western societies, is associated with various forms of cognitive decline. Insomnia/insomnia-type symptoms have been reported as modifiable risk factors for cognitive decline. The objective of this study was to examine, in a comprehensive way (a) the prevalence and the risk factors associated with insomnia-type symptoms and (b) the association of insomnia-type symptoms with cognitive impairment in a large, homogeneous, community-dwelling population in the island of Crete, Greece. METHODS: Our sample consisted of 3066 community-dwelling elders aged 60-100 years participating in the Cretan Aging Cohort. All participants were interviewed with a structured questionnaire assessing demographics, physical and mental health, sleep, lifestyle habits and cognitive function using the Mini Mental State Examination (MMSE). Furthermore, insomnia-type symptom prevalence was estimated in the presence of one or more sleep complaints. Linear and logistic regression analyses examined (a) the association between insomnia-type symptoms and demographics, physical/mental health and lifestyle and (b) the association between cognition and insomnia-type symptoms. RESULTS: Prevalence of one or more insomnia-type symptoms was 64.6%. Multivariate analyses showed that female gender, widowhood, benzodiazepine use and physical ailments were significantly associated with insomnia-type symptoms. Multivariate models also showed that insomnia-type symptoms were associated with increased odds of cognitive impairment (p < 0.0001). CONCLUSIONS: In a large population of older people in Crete, Greece, insomnia-type symptoms are very prevalent and associated with increased risk for cognitive impairment. Future studies should assess whether treatment of sleep problems improves or delays the deterioration of cognitive function in older adults.