Objective short sleep duration increases the risk of all-cause mortality associated with possible vascular cognitive impairment

Introduction: Short sleep duration has been associated with increased risk of cardiovascular and cerebrovascular disease (CVD), cognitive impairment (CI) and mortality. However, the role of sleep duration in predicting mortality in the context of CVD and CI is still not well-understood. Hypothesis: Short sleep duration is a key effect modifier of the relationship between CI associated with CVD and all-cause mortality. Methods: We addressed this hypothesis in the Penn State Adult Cohort, a random, general population sample of 1,741 middle-aged adults who were studied in the sleep lab and followed-up for 15y. An in-lab, 8-hour polysomnography was performed to ascertain sleep duration. CI associated with CVD was defined by the presence of hypertension, diabetes, heart disease and/or stroke with impaired higher-order, executive cognitive functioning, including slow processing speed. We tested the interaction between sleep duration and CI associated with CVD on all-cause mortality with multiple logistic regression while adjusting for sex, age, race, obesity, smoking, cholesterol, depression, insomnia, dementia, and sleep apnea. Results: The odds of mortality associated with CI-alone, CVD-alone, and CI associated with CVD were 1.3 (95% CI: 0.7-2.4), 1.7 (95% CI: 1.1-2.8), and 4.6 (95% CI: 2.8-7.7), respectively. As shown in Figure 1, the interaction between CI associated with CVD and sleep duration was significant (p < .01), indicating that the probability of mortality increased significantly as a function of shorter sleep duration in individuals with CI associated with CVD. Conclusion: We found that objective sleep duration modifies the relationship between CI associated with CVD and all-cause mortality in a dose-response manner. Short sleep duration in individuals with probable vascular cognitive impairment (VCI) may serve as a biomarker of the severity of central autonomic dysfunction. Future studies should examine whether improving sleep reduces the odds of mortality in individuals with VCI.

Download Full-text

Abstract MP23: Interplay of Cognitive Impairment and Short Sleep Duration on Cardiovascular and Cerebrovascular Mortality

Circulation ◽

10.1161/circ.141.suppl_1.mp23 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

Julio Fernandez-Mendoza ◽

Fan He ◽

Susan L Calhoun ◽

Duanping Liao ◽

Alexandros N Vgontzas ◽

...

Keyword(s):

Cognitive Impairment ◽

Sleep Duration ◽

Mental Health Problems ◽

Middle Age ◽

Experimental Studies ◽

Health Problems ◽

Short Sleep Duration ◽

Short Sleep ◽

Increased Risk ◽

All Cause Mortality

Introduction: Epidemiological and experimental studies have shown that short sleep duration is associated with cognitive impairment as well as cardiovascular (CVD) and cerebrovascular (CBV) diseases. However, its role in predicting CVD/CBV mortality is still not well-established, particularly using objective sleep measures. Hypothesis: Polysomnography (PSG)-measured short sleep duration modifies the increased risk of CVD/CBV mortality associated with cognitive impairment in middle-age. Methods: We addressed this hypothesis in the Penn State Adult Cohort, a random, population-based sample studied in the sleep laboratory (N=1,524, 48.9±13.4y, 54% women) and followed-up after 20.5 ± 5.7 years to ascertain their cause of death. Cognitive impairment (n=155) was ascertained using a comprehensive neuropsychological battery including Mini-Mental State Examination, Symbol Digit Modalities Test, Trail Making Test parts A and B, Benton Visual Retention Test and Thurstone Word Fluency Test. PSG total sleep time classified subjects as normal (≥6 h) and short (<6 h) sleepers. Out of the 563 subjects who were deceased as of December 31, 2018, 244 died of CVD/CBV. Cox proportional hazards regression controlling for age, sex, race, education, obesity, sleep apnea, mental health problems and physical health problems, including hypertension, diabetes, heart disease and stroke at baseline, was used to assess the association between cognitive impairment and mortality. Results: Cognitive impairment was associated with an increased risk of all-cause mortality [(HR: 1.72 (1.35-2.06)], which was significantly modified by objective sleep duration (p-interaction=0.01). The association between cognitive impairment and all-cause mortality was significantly stronger among subjects who slept < 6 hours [HR: 2.00 (1.54-2.59)] than among those who slept ≥ 6 hours [HR: 1.00 (0.59-1.67)]. Despite the smaller sample size, we observed a similar pattern (p-interaction=0.18) that the association between cognitive impairment and CVD/CBV mortality was stronger among subjects who slept < 6 hours [HR: 2.09 (1.43-3.05)] than among those who slept ≥ 6 hours [HR: 1.24 (0.60-2.57)]. Conclusions: The risk of mortality associated with cognitive impairment in middle-age is significantly increased in adults with objective short sleep duration. Middle-aged adults who sleep objectively short may be more vulnerable to the effect of clinical and subclinical cerebrovascular morbidity on cognitive impairment and, thus, early death from CVD/CBV.

Download Full-text

Insomnia with objective short sleep duration is associated with cognitive impairment: a first look at cardiometabolic contributors to brain health

SLEEP ◽

10.1093/sleep/zsaa150 ◽

2020 ◽

Author(s):

Julio Fernandez-Mendoza ◽

Fan He ◽

Kristina Puzino ◽

Gregory Amatrudo ◽

Susan Calhoun ◽

...

Keyword(s):

Cognitive Impairment ◽

Sleep Duration ◽

Vascular Cognitive Impairment ◽

Chronic Insomnia ◽

Cardiometabolic Health ◽

Apnea Hypopnea Index ◽

Poor Sleep ◽

Short Sleep Duration ◽

Sleep Difficulty ◽

Short Sleep

Abstract Study Objectives Insomnia with objective short sleep duration has been previously associated with adverse cardiometabolic health outcomes as well as poorer cognitive performance in otherwise noncognitively impaired adults. However, studies demonstrating an increased prevalence of cognitive impairment (CI) in this insomnia phenotype are lacking. Methods We analyzed data from Penn State Adult Cohort (N = 1,524; 48.9 ± 13.4 years; 53.4% women). Self-reported sleep difficulty was defined as normal sleep (n = 899), poor sleep (n = 453), and chronic insomnia (n = 172). Objective short sleep duration was defined as less than 6-h of sleep, based on in-lab, 8-h polysomnography. CI (n = 155) and possible vascular cognitive impairment (pVCI, n = 122) were ascertained using a comprehensive neuropsychological battery. Analyses adjusted for age, sex, race, education, body mass index, apnea/hypopnea index, smoking, alcohol, psychoactive medication, and mental and physical health problems. Results Participants who reported poor sleep or chronic insomnia and slept objectively less than 6 hours were associated with a 2-fold increased odds of CI (OR = 2.06, 95% confidence limits [CL] = 1.15–3.66 and OR = 2.18, 95% CL = 1.07–4.47, respectively) and of pVCI (OR = 1.94, 95% CL = 1.01–3.75 and OR = 2.33, 95% CL = 1.07–5.06, respectively). Participants who reported poor sleep or chronic insomnia and slept objectively more than 6 hours were not associated with increased odds of either CI (OR = 0.72, 95% CL = 0.30–1.76 and OR = 0.75, 95% CL = 0.21–2.71, respectively) or pVCI (OR = 1.08, 95% CL = 0.42–2.74 and OR = 0.76, 95% CL = 0.16–3.57, respectively). Conclusions Insomnia with objective short sleep duration is associated with an increased prevalence of CI, particularly as it relates to cardiometabolic health (i.e. pVCI). These data further support that this insomnia phenotype may be a more biologically severe form of the disorder associated with cardiovascular, cerebrovascular, and neurocognitive morbidity.

Download Full-text

0355 Insomnia with Objective Short Sleep Duration is Associated with Cognitive Impairment: A Closer Look at Cardiometabolic Brain Health

SLEEP ◽

10.1093/sleep/zsz067.354 ◽

2019 ◽

Vol 42 (Supplement_1) ◽

pp. A145-A145

Author(s):

Julio Fernandez-Mendoza ◽

Fan He ◽

Alexandros N Vgontzas ◽

Susan L Calhoun ◽

Duanping Liao ◽

...

Keyword(s):

Cognitive Impairment ◽

Sleep Duration ◽

Brain Health ◽

Short Sleep Duration ◽

Short Sleep

Download Full-text

0313 INSOMNIA WITH OBJECTIVE SHORT SLEEP DURATION AND ALL-CAUSE MORTALITY: SLEEP HEART HEALTH STUDY

SLEEP ◽

10.1093/sleepj/zsx050.312 ◽

2017 ◽

Vol 40 (suppl_1) ◽

pp. A116-A116

Author(s):

S Bertisch ◽

B Pollock ◽

MA Mittleman ◽

LA Bazzano ◽

DJ Buysse ◽

...

Keyword(s):

Sleep Duration ◽

Health Study ◽

Heart Health ◽

Short Sleep Duration ◽

Short Sleep ◽

All Cause Mortality

Download Full-text

1130 Insomnia Short Sleep Phenotype is Associated With Frailty in Patients With Mild Cognitive Impairment (MCI)

SLEEP ◽

10.1093/sleep/zsaa056.1124 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A430-A430

Author(s):

M Basta ◽

A Vgontzas ◽

E Koutentaki ◽

I Zaganas ◽

J Fernandez-Mendoza ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Sleep Duration ◽

Large Population ◽

Geriatric Depression Scale ◽

Depression Scale ◽

Sleep Time ◽

Physical And Mental Health ◽

Short Sleep Duration ◽

Short Sleep

Abstract Introduction Insomnia short sleep phenotype is associated with cardiometabolic morbidity and mortality and neuropsychological impairment. In elderly untreated insomnia is associated with worse cognitive performance. The goal of the study was to examine the association between insomnia, objective sleep duration and physical and mental health in elderly patients with Mild Cognitive Impairment (MCI). Methods A sub-sample of 105 patients with MCI (mean age: 75.9 years, males 36%) were recruited from a large population-based cohort (Cretan Aging Cohort) in the island of Crete, Greece of 3,140 elders (≥ 60yrs). All participants underwent a complete medical history/ physical examination, extensive neuropsychiatric and neuropsychological evaluation and 3-day 24hr actigraphy. Insomnia was defined based on a question “do you have insomnia for more than a year”. Frailty was assessed with the Simple “Frail” Questionnaire Screening Tool. Comparisons between patients with insomnia and without insomnia were made using ANOVA controlling for age, gender and BMI. Results MCI patients with insomnia (n=23) compared to those without insomnia (n=82), had significantly shorter objective total sleep time (TST: 377 vs. 410 min, p=0.05) and significantly higher scores on the Geriatric Depression Scale and the Hospital Anxiety Scale (both p <0.001). Furthermore, total frailty score, as well as scores in individual items, were significantly lower in MCI patients with insomnia (p<0.01). This association remained significant after controlling for demographics, depression and anxiety. Finally, there was a statistical trend of association between insomnia and hypertension (p= 0.1). Conclusion In MCI patients, insomnia is associated with objective short sleep duration, and frailty. Improving insomnia and lengthening sleep duration may decrease frailty, a major problem associated with morbidity, disability and mortality in elders with cognitive decline. Support National Strategic Reference Framework (ESPA) 2007-2013, Program: THALES, University of Crete, title: “A multi-disciplinary network for the study of Alzheimer’s Disease” (Grant: MIS 377299).

Download Full-text

Abstract MP085: Cognitive Impairment Mediates the Impact of Short Sleep Duration on Mortality in Individuals with Cardiovascular or Cerebrovascular Disease

Circulation ◽

10.1161/circ.135.suppl_1.mp085 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Julio Fernandez-Mendoza ◽

Fan He ◽

Alexandros N Vgontzas ◽

Duanping Liao ◽

Edward O Bixler

Keyword(s):

Cognitive Impairment ◽

Sleep Duration ◽

Processing Speed ◽

Short Term Memory ◽

Executive Attention ◽

Short Term ◽

Short Sleep Duration ◽

Short Sleep ◽

History Of ◽

The Impact

Background: Cardiovascular disease (CVD) and cerebrovascular disease (CBV) have been associated with short sleep duration and mortality. Furthermore, short sleep duration has been associated with impaired cognition. Most studies have been limited by using self-report measures and treating sleep duration as a sole, independent predictor, thus, its role in predicting mortality is still not well-established. Hypothesis: We hypothesized that 1) short sleep duration increases the impact of CVD and CBV on mortality and 2) cognitive impairment mediates the association of short sleep duration with mortality in those with CVD or CBV. Methods: We addressed this question in the Penn State Adult Cohort, a random, general population sample of 1,741 men and women (48.7 ± 13.5 years) who were studied in the sleep laboratory and followed-up for 16.7 ± 4.6 years. CVD was defined by a history of heart disease, including hypertension or diabetes, and CBV by a history of stroke. Polysomnographic (PSG) total sleep time was classified as normal (≥ 6 hours) and short (< 6 hours) sleep duration based on the median of the cohort. All individuals underwent a comprehensive neuropsychological evaluation, including Symbol Digit Modalities Test, Trail Making Test, Benton Visual Retention Test, Thurstone Word Fluency Test, and Mini-Mental State Examination. We tested the interaction between CVD, CBV and PSG sleep duration on mortality using Cox proportional hazard models controlling for multiple potential confounders. Results: The hazard ratios (95%CI) of mortality associated with CVD and CBV were 0.9 (0.6-1.3) and 1.3 (0.5-3.1) for individuals with normal sleep duration and 1.8 (1.3-2.5) and 2.4 (1.3-4.4) for individuals with short sleep duration (P-interaction < .05). In individuals with CVD or CBV, short sleep duration was associated with impaired processing speed, executive attention, and short-term memory (all Ps < .05). Cognitive impairment significantly mediated the impact of short sleep duration on mortality in those with CVD or CBV [proportion of mediation effects were 6.5% (1.4%-18.6%), 4.5% (0.4%-14.2%), and 6.2% (1.0%-18.4%) for processing speed, executive attention and short-term memory, respectively]. Conclusions: The risk of mortality associated with CVD and CBV is significantly increased in those with short sleep duration. Although cognitive impairment significantly mediated this association, its modest effect suggests that future studies should examine other underlying mechanisms linking short sleep duration with mortality in individuals with CVD or CBV.

Download Full-text

Insomnia with objective short sleep duration and risk of incident cardiovascular disease and all-cause mortality: Sleep Heart Health Study

SLEEP ◽

10.1093/sleep/zsy047 ◽

2018 ◽

Vol 41 (6) ◽

Cited By ~ 53

Author(s):

Suzanne M Bertisch ◽

Benjamin D Pollock ◽

Murray A Mittleman ◽

Daniel J Buysse ◽

Lydia A Bazzano ◽

...

Keyword(s):

Cardiovascular Disease ◽

Sleep Duration ◽

Health Study ◽

Heart Health ◽

Short Sleep Duration ◽

Short Sleep ◽

All Cause Mortality ◽

Incident Cardiovascular Disease

Download Full-text

369 Insomnia with objective short sleep duration is associated with increased cortisol in patients with Mild Cognitive Impairment

SLEEP ◽

10.1093/sleep/zsab072.368 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A147-A147

Author(s):

Alexandros Vgontzas ◽

Maria Basta ◽

Yun Li ◽

Julio Fernandez-Mendoza ◽

Ioannis Zaganas ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Sleep Duration ◽

Plasma Cortisol ◽

Neuropsychological Testing ◽

Short Sleep Duration ◽

Blood Draw ◽

Short Sleep ◽

Amnestic Mci ◽

Cortisol Levels

Abstract Introduction Mild cognitive impairment (MCI) is frequent in the elderly and is in a continuum with dementia in a significant amount of people. Both insomnia and increased cortisol levels have been suggested as risk factors for MCI. The goal of this study was to examine whether activation of the hypothalamic-pituitary-adrenal (HPA) axis, as measured by plasma cortisol levels, is associated with the insomnia with short sleep duration (ISS) phenotype, as measured by actigraphy, in elderly with MCI. Methods A sub-sample of 109 subjects with MCI and 92 cognitively non-impaired controls 60 years or older (75.37±6.54y) was recruited from a population-based cohort residing on Crete, Greece. Subjects underwent medical history, physical examination, neuropsychiatric evaluation, neuropsychological testing, 3-day 24-h actigraphy, assessment of subjective insomnia symptoms (i.e., difficulties initiating and/or maintaining sleep), and a morning blood draw to assay for plasma cortisol levels. The ISS phenotype was defined by the presence of at least one insomnia symptom and an actigraphy-measured sleep efficiency below the median of the entire sample (i.e., ≤81%). Group differences in plasma cortisol levels between MCI subjects with and without the ISS phenotype were tested using ANCOVA adjusting for age, gender, BMI and depression. Results Subjects with MCI had higher cortisol levels compared to controls (105.34±9.34 vs. 70.3±10.02 nmol/L, p<0.05). Subjects with MCI and the ISS phenotype (138.38±16.57 nmol/L) had significantly higher cortisol levels compared to those without insomnia (97.74±19.68 nmol/L) or those with insomnia and normal sleep duration (INS; 79.97±16.02 nmol/L, p=0.044). The association between the ISS phenotype and cortisol levels was modified by amnestic symptoms (p-interaction=0.079); commensurate, the ISS phenotype was associated with higher cortisol levels among the amnestic MCI subgroup (INS: 79.12±21.93 vs. ISS: 155.55±20.40 nmol/L, p=0.040), but not among the non-amnestic MCI subgroup (INS: 64.06±23.62 vs. ISS: 89.33±29.00 nmol/L, p=0.559). Conclusion The ISS phenotype is associated with increased cortisol levels in elderly with MCI, particularly those with amnestic type. Improving sleep quality, decreasing cortisol levels and lengthening sleep duration may slow down the progression of these individuals into dementia. Support (if any) National Strategic Reference Framework(NSRF), Program: THALES entitled “UOC-Multidisciplinary network for the study of Alzheimer’s Disease” Grant Cod:MIS 377299

Download Full-text

The relationship between sleep duration and all-cause mortality in the older people: an updated and dose-response meta-analysis

10.21203/rs.2.22427/v2 ◽

2020 ◽

Author(s):

Mengyang He ◽

Xiangling Deng ◽

Yuqing Zhu ◽

Luyao Huan ◽

Wenquan Niu

Keyword(s):

Older People ◽

Sleep Duration ◽

Dose Response ◽

Data Extraction ◽

Meta Analysis ◽

Short Sleep Duration ◽

Short Sleep ◽

Increased Risk ◽

Long Sleep ◽

All Cause Mortality

Abstract Background: Short or long sleep duration is proposed as a potential risk factor for all-cause mortality in the older people, yet the results of published studies are not often reproducible. Objectives: We aimed to investigate whether short or long sleep duration was associated with an increased risk of all-cause mortality in the older people via a comprehensive meta-analysis. Methods: Literature retrieval, study selection and data extraction were completed independently and in duplicate. Effect-size estimates are expressed as relative risk (RR) and its 95% confidence interval (CI). Results: Summary data from 35 articles, involving a total of 106990 older people, were meta-analyzed. Overall analyses revealed a significant association between long sleep duration and all-cause mortality (RR=1.27, 95% CI: 1.19-1.35, P <.001), whereas marginal significance was observed for short sleep duration (RR=1.05; 95% CI: 1.00-1.09; P =.045). There was a low probability of publication bias as indicated by Egger’s test for the association between sleep duration and all-cause mortality. In subgroup analyses, the association between long sleep duration and all-cause mortality was relatively strong in women (RR=1.48, 95% CI: 1.18-1.85, P =.002) relative to men (RR=1.30, 95% CI: 1.10-1.50, P =.001) (Two-sample Z test P = .219). Further dose-response regression analyses showed that trend estimation was not obvious for short sleep duration ( P = .016) compared with long sleep duration ( P < .001), indicating a J-shaped relationship between sleep duration and all-cause mortality. Conclusions: Our findings indicate a J-shaped relationship between sleep duration and all-cause mortality in the older people, with long sleep duration significantly associating with all-cause mortality, especially in women.

Download Full-text