Long sleep duration is associated with lower cognitive function among middle-age adults – the Doetinchem Cohort Study

ObjectivesIn older adults, both short and long sleep duration are associated with lower cognitive function, suggesting an inverted U-shaped association between sleep duration and cognitive outcomes. This study examined whether sleep duration is associated with (changes in) cognitive function in a middle-aged population.MethodsIn the Doetinchem Cohort Study, the cognitive function of 2970 men and women aged 41–75 years at baseline (1995–2007) was examined 2–3 times, with 5-year time intervals. Global cognitive function and the domains memory, information processing speed, and cognitive flexibility were assessed. In multivariable linear regression models, (change in) self-reported sleep duration was studied in association with the level and change in cognitive function. In a subsample of the population (n = 2587), the association of sleep duration and feeling rested with cognitive function was studied.ResultsSleep duration of 9 h and more was statistically significantly associated with lower global cognitive function (p < 0.01), memory (p = 0.02), and flexibility (p = 0.03), compared to a sleep duration of 7 or 8 h. Among adults feeling frequently not well rested, both short and long sleep duration were associated with a lower speed of cognitive function. An inverted U-shaped association between sleep duration and cognitive function was observed for speed, flexibility, and global cognitive function. Sleep duration was not associated with change in cognitive function.ConclusionsMiddle-age adults with long sleep duration had a lower cognitive function.     

Rate of progression from mild cognitive impairment to dementia in an essential tremor cohort: A prospective,longitudinal study

BackgroundEssential tremor (ET), among the most common neurological diseases, is associated with cognitive dysfunction. Yet, nearly all knowledge of ET-related cognitive impairment is static and cross-sectional (e.g., prevalence), with virtually no dynamic information (i.e., course and progression, conversion rates, and clinical outcomes).ObjectivesTo quantify the rate of progression from mild cognitive impairment (MCI) to dementia in a cohort of elderly ET cases.Methods167 ET cases, enrolled in a prospective, longitudinal, clinical-pathological study, underwent an extensive neuropsychological testing battery at baseline (T1), 1.5 years (T2), and 3 years (T3). Results of these assessments informed clinical diagnoses of normal cognition (ET-NC), MCI (ET-MCI), and dementia (ET-D).ResultsAt baseline, 26 cases (82.7 ± 7.7 years) were diagnosed with ET-MCI and were available for follow-up at T2. At T2, three of 26 (11.5%) had converted to ET-D. At the start of T2, 23 cases (83.6 ± 7.7 years) were diagnosed with ET-MCI and were available for follow-up at T3. At T3, six of 23 (26.1%) converted to ET-D. The average annual conversion rate from ET-MCI to ET-D was 12.5%.ConclusionsThe study of cognitive impairment in ET is a nascent field, with limited data. We show that the conversion rate from ET-MCI to ET-dementia was 12.5%. Available studies on historical controls have reported conversion rates of 2.6–6.3%. Data such as these systematically fill gaps in knowledge, creating a scientifically-derived knowledge base to guide physicians and patients in clinical settings.     

Associations of accelerometer-based sleep duration and self-reported sleep difficulties with cognitive function in late mid-life: the Finnish Retirement and Aging Study

ObjectivesPrior evidence suggests that sleep duration and sleep difficulties may be associated with cognitive function in old age, but little is known about the sleep–cognition association in late mid-life. Our aim was to examine the associations of accelerometer-based sleep duration as well as subjective sleep difficulties with different domains of cognitive function among aging workers.MethodsThe study population consisted of 289 participants (mean age 62.4 years, SD 1.02; 83% women) from the Finnish Retirement and Aging Study (FIREA). Sleep difficulties were measured using Jenkins Sleep Problem Scale (difficulties falling asleep, difficulties maintaining sleep, waking up too early in the morning, and nonrestorative sleep). Sleep duration was measured with wrist-worn accelerometer and self-report, and participants were divided into short (<7 h/night), mid-range (7–9 h/night) and long (≥9 h/night) sleepers. Participants underwent extensive cognitive testing covering three domains: (1) memory, (2) executive function, and (3) attention and information processing.ResultsGreater difficulties in waking up too early in the morning were associated with poorer executive function measured with Spatial Working Memory (SWM) test (p = 0.005). Additionally, nonrestorative sleep was associated with poorer executive function measured with Trail Making Test, B–A, (p = 0.036) and borderline significantly with lower SWM (p = 0.056). Compared to mid-range sleepers, long sleepers tended to have poorer cognitive function (all memory function tests and SWM), but the associations were not statistically significant due to small number of long sleepers.ConclusionsSubjective sleep difficulties may be linked to poorer executive function in a relatively healthy population of older workers in their 60 s. Thus, promoting good sleep quality may translate into better cognitive health in late mid-life.     

Quantitative gait,cognitive decline,and incident dementia: The Rotterdam Study

IntroductionPoor gait has recently emerged as a potential prodromal feature of cognitive decline and dementia. We assessed to what extent various aspects of poor gait are independently associated with cognitive decline and incident dementia.MethodsWe leveraged detailed quantitative gait (GAITRite™) and cognitive assessments in 4258 dementia-free participants (median age 67 years, 55% women) of the population-based Rotterdam Study (baseline 2009–2013). We summarized 30 gait parameters into seven mutually independent gait domains and a Global Gait score. Participants underwent follow-up cognitive assessments between 2014 and 2016 and were followed up for incident dementia until 2016 (median 4 years).ResultsThree independent gait domains (Base of Support, Pace, and Rhythm) and Global Gait were associated with cognitive decline. Two independent gait domains (Pace and Variability) and Global Gait were associated with incident dementia. Associations of gait with cognitive decline and incident dementia were only present in individuals who had been cognitively unimpaired at baseline.DiscussionPoor performance on several independent gait domains precedes cognitive decline and incident dementia.     

Cognitive ability in young adulthood and risk of dementia in a cohort of Danish men,brothers, and twins

IntroductionWe examined the association between cognitive ability in young adulthood and dementia in Danish men, brothers, and male twins.MethodsIn total, 666,986 men born between 1939 and 1959 were identified for dementia diagnosis in national registries from 1969 to 2016. The association between cognitive ability from draft board examination and dementia was examined using Cox regression.ResultsDuring a 44-year follow-up, 6416 (0.96%) men developed dementia, 1760 (0.26%) and 970 (0.15%) of which were classified as Alzheimer's and vascular dementia, respectively. Low cognitive ability was associated with increased risk of dementia (hazard ratio [HR]_{per SD decrease} 1.33 [95% confidence interval {CI} = 1.30–1.35]) with the strongest associations for vascular dementia (HR_{per SD decrease} 1.47 [95% CI = 1.31–1.56]) and a weaker for Alzheimer's disease (HR_{per SD decrease} 1.07 [95% CI = 1.03–1.13]). The intrabrother and twin analyses (taking shared family factors into account) showed attenuated risk estimates but with wide CIs.DiscussionLow early-life cognitive ability increases the risk of dementia before the age of 78 years. The association is partly explained by shared family factors.     

The association between 25-hydroxyvitamin D levels and children's sleep-wake patterns: a prospective cohort study

ObjectiveTo explore the association between vitamin D in cord blood or in venous blood and children's sleep-wake patterns at two years of age.MethodsData were from 209 children in a birth cohort, Shanghai Sleep Birth Cohort Study (SSBC). 25-Hydroxyvitamin D (25(OH)D) was assessed in cord blood and venous blood samples at two years of age by electrochemiluminescence immunoassay. Children's sleep-wake patterns were measured with the Brief Infant Sleep Questionnaire (BISQ) and Acti-Watch at two years of age.ResultsThe prevalence of vitamin D deficiency (defined as <50 nmol/L) was 50.4% in cord blood and 28% at two years of age. The cord blood 25(OH)D level was not significantly associated with children's sleep at two years of age. Children with 25(OH)D deficiency at two years old had shorter reported and actigraphic night sleep duration (NSD) and total sleep duration (TSD) than those with normal 25(OH)D concentration. 25(OH)D level at two years old was positively associated with night and total sleep duration (β_reported-NSD = 0.6, p = 0.011; β_reported-TSD = 0.6, p = 0.029; β_{actigraphic-NSD} = 0.82, p = 0.003; β_{actigraphic-TSD} = 0.78, p = 0.006), but was not associated with daytime sleep duration. There was no significant association between 25(OH)D level with night waking duration and midpoint of sleep either measured subjectively or objectively.ConclusionWe found that not cord blood 25(OH)D level but two-year-old 25(OH)D level was associated with children's sleep-wake patterns at two years of age. These findings suggest more attention should be paid to the assessment of 25(OH)D levels in children with short sleep duration.     

Urate and risk of Alzheimer's disease and vascular dementia: A population-based study

IntroductionLow serum urate (sU) has been suggested to increase the risk of dementia since a reduction might impair antioxidant capacity. On the other hand, high sU is associated with increased cardiovascular risk which might increase the risk of dementia, especially for vascular dementia.MethodsIn 1968–1969, a population-based sample of 1462 women aged 38 to 60 years was examined and were followed up over 44 years (mean 33.1 years). We examined whether sU (determined in 1968–1969 and 1992–1994) is associated with risk of late-life dementia.ResultsDuring 44 years of follow-up, a higher sU (per standard deviation of 76.5 μmol/L) was associated with lower risk for dementia (n = 320; hazard ratio [HR] 0.81; confidence interval [CI] 0.72–0.91), Alzheimer's disease (n = 152; HR 0.78; CI 0.66–0.91), and vascular dementia (n = 52; HR 0.66; CI 0.47–0.94).DiscussionOur findings support the hypothesis that sU has a protective role in the development of dementia, regardless of dementia subtype. This may have important implications in the treatment of dementia and treatment goals for hyperuricemia in patients with gout.     

Hippocampal volume and white matter disease in the prediction of dementia in Parkinson's disease

BackgroundLongitudinal neuroimaging studies could provide insights into pathophysiology of cognitive impairment in PD. We examined the role of hippocampal atrophy and cerebral white matter disease as risk factors for mild cognitive impairment and dementia in PD.MethodsProspective longitudinal study of patients with mild PD in a tertiary neurology center. All subjects underwent baseline MRI brain and had baseline and 6 monthly cognitive evaluations. Cognitive impairment was diagnosed based on the Movement Disorder Society Criteria. The predictive role of hippocampal volume and white matter hyperintensity at baseline on progression of cognitive impairment was studied.Results97 subjects with mean age 65.3 years, mean education of 10.3 years and mean Hoehn & Yahr of 1.9 were studied. Over 2 years, 16 subjects developed mild cognitive impairment and 8 subjects with mild cognitive impairment progressed to dementia. After adjusting for age and vascular risk factors, hippocampal volume was a significant predictor for mild cognitive impairment (OR 7.05, CI 1.5–34.1; p = 0.015) and dementia (OR 7.03, CI 2.39–25.2; p = 0.001). With Cox regression, hippocampal volume was a significant predictor for “time to cognitive impairment” (HR 7.67; CI 3.47–16.95, p < 0.001). Difference between survival curves based on volume of white matter hyperintensity in predicting “time to mild cognitive impairment” was significant (p = 0.0295).ConclusionsHippocampal volume is a major factor predicting the development of mild cognitive impairment and dementia in PD. White matter hyperintensity also contributes to the longitudinal cognitive status in PD.     

Sleep duration and obesity in children and adolescents: evidence from an updated and dose–response meta-analysis

Background and objectivesThe association between sleep duration and obesity in children and adolescents has been widely evaluated, whereas the current findings are mixed and prospective studies are limited. To shed more light on this issue and explore the dose–response relationship, we performed the present updated meta-analysis by synthesizing the results of prospective cohorts.MethodsLiterature retrieval, study selection and data extraction were completed independently and in duplicate. Effect-size estimates are expressed as relative risk (RR) with 95% confidence interval (CI) or standardized regression coefficient (β) with standard error.ResultsData from 33 articles, involving 57,848 children and adolescents, were meta-analyzed. Overall analyses revealed statistically significant associations of short (adjusted RR = 1.57, 95% CI: 1.36 to 1.81, P < 0.001) and long sleep duration (0.83, 0.75 to 0.93, 0.001) with obesity. Short sleep duration was also associated with significant changes in body mass index z-score (mean difference = −0.06; 95% CI: −0.09 to −0.04; P < 0.001). By contrast, long sleep duration was identified as a protective factor for childhood obesity. In dose–response analyses, short sleep duration was significantly associated with obesity in toddlers (1–2 years) (adjusted RR = 1.20, 95% CI: 1.07 to 1.34, P = 0.001), preschool-aged (3–5 years) children (1.58, 1.36 to 1.83, <0.001), and school-aged (6–13 years) children (1.82, 1.51 to 2.21, <0.001). In subgroup analyses, geographic region, sleep duration assessment, age, and follow-up interval were possible sources of heterogeneity.ConclusionsOur findings indicate that short sleep duration can increase the risk of obesity in children and adolescents, especially within 3–13 years of age, and long sleep duration seemed beneficial in preventing obesity.     

18F-FDG PET,the early phases and the delivery rate of 18F-AV45 PET as proxies of cerebral blood flow in Alzheimer's disease: Validation against 15O-H2O PET

IntroductionDual-biomarker positron emission tomography (PET), providing complementary information on cerebral blood flow and amyloid-β deposition, is of clinical interest for Alzheimer's disease (AD). The purpose of this study was to validate the perfusion components of early-phase ¹⁸F-florbetapir (eAV45), the ¹⁸F-AV45 delivery rate (R1), and ¹⁸F-FDG against ¹⁵O-H₂O PET and assess how they change with disease severity.MethodsThis study included ten controls, 19 amnestic mild cognitive impairment, and 10 AD dementia subjects. Within-subject regional correlations between modalities, between-group regional and voxel-wise analyses of covariance per modality, and receiver operating characteristic analyses for discrimination between groups were performed.ResultsFDG standardized uptake value ratio, eAV45 (0–2 min) standardized uptake value ratio, and AV45-R1 were significantly associated with H₂O PET (regional Pearson r = 0.54–0.82, 0.70–0.94, and 0.65–0.92, respectively; P < .001). All modalities confirmed reduced cerebral blood flow in the posterior cingulate of patients with amnestic mild cognitive impairment and AD dementia, which was associated with lower cognition (r = 0.36–0.65, P < .025) and could discriminate between patient and control groups (area under the curve > 0.80). However, eAV45 was less sensitive to reflect the disease severity than AV45-R1 or FDG.DiscussionR1 is preferable over eAV45 for accurate representation of brain perfusion in dual-biomarker PET for AD.     

Suboptimal sleep and incident cardiovascular disease among African Americans in the Jackson Heart Study (JHS)

BackgroundSuboptimal sleep, including insufficient/long sleep duration and poor sleep quality, is a risk factor for cardiovascular disease (CVD) common but there is little information among African Americans, a group with a disproportionate CVD burden. The current study examined the association between suboptimal sleep and incident CVD among African Americans.MethodsThis study included 4,522 African Americans without CVD at baseline (2000–2004) of the Jackson Heart Study (JHS). Self-reported sleep duration was defined as very short (<6 h/night), short (6 h/night), recommended (7–8 h/night), and long (≥9 h/night). Participants’ self-reported sleep quality was defined as “high” and “low” quality. Suboptimal sleep was defined by low quality sleep and/or insufficient/long sleep duration. Incident CVD was a composite of incident coronary heart disease and stroke. Associations between suboptimal sleep and incident CVD were examined using Cox proportional hazards models over 15 follow-up years with adjustment for predictors of CVD risk and obstructive sleep apnea.ResultsSample mean age was 54 years (SD = 13), 64% female and 66% reported suboptimal sleep. Suboptimal sleep was not associated with incident CVD after covariate adjustment [HR(95% CI) = 1.18(0.97–1.46)]. Long [HR(95%CI) = 1.32(1.02–1.70)] and very short [HR(95% CI) = 1.56(1.06–2.30)] sleep duration were associated with incident CVD relative to recommended sleep duration. Low quality sleep was not associated with incident CVD (p = 0.413).ConclusionsLong and very short self-reported sleep duration but not self-reported sleep quality were associated with increased hazard of incident CVD.     

Sleep duration on workdays or nonworkdays and cardiac–cerebral vascular diseases in Southern China

ObjectivesThis study aimed to assess the relationship between sleep duration on work or nonworkdays and myocardial infarction (MI) and stroke in Southern China.MethodsA cross-sectional survey was conducted among 15,364 participants of age ≥15 years in Southern China from November 2013 to August 2014. Data on self-reported duration of sleep on workdays or nonworkdays as well as history of MI and stroke were collected in the questionnaire. The subjects were examined for weight, height, waist circumference, and blood pressure. Multivariate logistic regression analyses were performed to evaluate the association of sleep duration with MI and stroke.ResultOverall, compared with a sleep duration of 6–8 h, individuals who slept <6 h on workdays and nonworkdays were associated with increased risk for MI (odds ratio [OR] = 3.17, 2.04). Furthermore, individuals who slept >8 h on workdays and nonworkdays were associated with an increased risk for stroke (OR = 1.86, 1.54). Although this association persisted in men and subjects aged <65 years, we also observed that long sleep duration on workdays was associated with MI, especially among women, and short sleep duration on nonworkdays was associated with stroke among those aged 65 years or older. Participants with abnormal sleep duration and hypertension had higher risk of MI and stroke. Sleep debt was independently associated with MI risk, but not stroke (OR = 1.40; 95% confidence interval [CI]: 1.06–1.86), specifically among men aged <65 years.ConclusionsCompared with a sleep duration of 6–8 h, both short and long sleep duration were associated with the prevalence of MI and stroke and these associations were more pronounced among hypertensive persons, and tended to vary by age and sex. Moreover, sleep debt was linked to greater MI risk among men aged <65 years. These findings suggest that we should develop a healthy biological clock.     

Sleep and cognitive performance: cross-sectional associations in the UK Biobank

ObjectiveThe relationship between insomnia symptoms and cognitive performance is unclear, particularly at the population level. We conducted the largest examination of this association to date through analysis of the UK Biobank, a large population-based sample of adults aged 40–69 years. We also sought to determine associations between cognitive performance and self-reported chronotype, sleep medication use and sleep duration.MethodsThis cross-sectional, population-based study involved 477,529 participants, comprising 133,314 patients with frequent insomnia symptoms (age: 57.4 ± 7.7 years; 62.1% female) and 344,215 controls without insomnia symptoms (age: 56.1 ± 8.2 years; 52.0% female). Cognitive performance was assessed by a touchscreen test battery probing reasoning, basic reaction time, numeric memory, visual memory, and prospective memory. Adjusted models included relevant demographic, clinical, and sleep variables.ResultsFrequent insomnia symptoms were associated with cognitive impairment in unadjusted models; however, these effects were reversed after full adjustment, leaving those with frequent insomnia symptoms showing statistically better cognitive performance over those without. Relative to intermediate chronotype, evening chronotype was associated with superior task performance, while morning chronotype was associated with the poorest performance. Sleep medication use and both long (>9 h) and short (<7 h) sleep durations were associated with impaired performance.ConclusionsOur results suggest that after adjustment for potential confounding variables, frequent insomnia symptoms may be associated with a small statistical advantage, which is unlikely to be clinically meaningful, on simple neurocognitive tasks. Further work is required to examine the mechanistic underpinnings of an apparent evening chronotype advantage in cognitive performance and the impairment associated with morning chronotype, sleep medication use, and sleep duration extremes.     

Duration of preclinical,prodromal, and dementia stages of Alzheimer's disease in relation to age,sex, and APOE genotype

IntroductionWe estimated the age-specific duration of the preclinical, prodromal, and dementia stages of Alzheimer's disease (AD) and the influence of sex, setting, apolipoprotein E (APOE) genotype, and cerebrospinal fluid tau on disease duration.MethodsWe performed multistate modeling in a combined sample of 6 cohorts (n = 3268) with death as the end stage and estimated the preclinical, prodromal, and dementia stage duration.ResultsThe overall AD duration varied between 24 years (age 60) and 15 years (age 80). For individuals presenting with preclinical AD, age 70, the estimated preclinical AD duration was 10 years, prodromal AD 4 years, and dementia 6 years. Male sex, clinical setting, APOE ε4 allele carriership, and abnormal cerebrospinal fluid tau were associated with a shorter duration, and these effects depended on disease stage.DiscussionEstimates of AD disease duration become more accurate if age, sex, setting, APOE, and cerebrospinal fluid tau are taken into account. This will be relevant for clinical practice and trial design.     

Swallowing disturbances in Parkinson's disease: A multivariate analysis of contributing factors

BackgroundSwallowing disturbances are an important issue in Parkinson's disease (PD) as several studies have shown that they are associated with increased risk of aspiration pneumonia and mortality. Information about factors related to swallowing disturbances, such as disease duration, age at assessment and concomitant dementia, is limited and would be useful for their management.MethodsAll consecutive PD out-patients evaluated at a movement disorders clinic over a 7-year period (2007–2014), were included in the present retrospective study. Presence of symptomatic swallowing disturbances was assessed using the specific item of the Non Motor Symptom Questionnaire.ResultsIn the whole PD population (N = 6462), prevalence of symptomatic swallowing disturbances was 11.7% (95%CI, 10.9–12.5). Multivariable logistic regression analysis (adjusted for education) disclosed a significant interaction between disease duration and gender (P = 0.009). In both gender strata, swallowing disturbances were significantly associated with longer disease duration and dementia (P < 0.001 for all). A significant effect for age at assessment was also found in male patients. In non-demented patients, swallowing disturbances were associated with male gender, age and disease duration (P < 0.02 for all). In demented patients an association was found only with male gender (P = 0.018) and disease duration (P < 0.001).ConclusionsGender, age, disease duration and dementia all seem to contribute to the occurrence of swallowing disturbances independently. However, the role played by these factors in sub-groups of patients stratified by gender and concomitant dementia suggests that swallowing disturbances are likely related to different neuro-degenerative patterns within the brain. The underlying mechanisms deserve further investigation.     

Mild cognitive impairment and abnormal brain metabolic expression in idiopathic REM sleep behavior disorder

BackgroundMild cognitive impairment (MCI) is a common feature of isolated rapid-eye-movement sleep behavior disorder (iRBD). Here, we assessed cognitive functions and MCI in a prospective iRBD cohort and investigated their association with disease-specific brain metabolic patterns.MethodsForty-four patients with polysomnography-confirmed iRBD performed a standardized battery of neuropsychological examinations every two years. We used previously established spatial covariance patterns from de novo drug-naïve Parkinson's disease with concomitant RBD (_denovoPDRBD-RP) and iRBD (iRBD-RP) using ¹⁸F-fluorodeoxyglucose PET scan. We compared those expressions between iRBD with normal cognition (iRBD-NC) and with mild cognitive impairment (iRBD-MCI), and evaluated whether they predict progressive cognitive deterioration.ResultsTwenty iRBD patients (45 %) had MCI at baseline and 12 patients (27 %, about 7 % per year) had clinically significant cognitive deterioration after 4 years. The iRBD-MCI and iRBD-NC groups showed similar rates of cognitive change, but iRBD-MCI consistently performed worse in the domains of verbal memory and executive function. Elevated _denovoPDRBD-RP expression predicted cognitive deterioration (hazard ratio = 5.98 [1.70–21.06]), whereas iRBD-RP did not.ConclusionsIncreased disease-specific brain metabolic patterns are associated with iRBD-MCI and impending cognitive deterioration with the risk of progression to Lewy body dementia.     

Potential biochemical pathways for the relationship between sleep duration and mortality

ObjectiveThe objective of this study was to elucidate new evidence on the presence of a relationship among sleep duration, cardiovascular mortality and total mortality, and to investigate sleep duration-related multiple biochemical changes.MethodsThe longitudinal study is based on the SAKUCESS study of 12,489 residents of Japan aged 20–79 years at baseline.ResultsIn the study, compared to respondents who reported 7 h of sleep, long sleep duration (⩾9 h) was associated with an increased risk of cardiovascular disease mortality and total mortality in men, hazard ratios (HRs) were 1.70 (95% confidence interval [CI] = 1.07–2.70) and 2.73 (95% CI = 1.22–6.11) and an increased risk of total mortality in women, HR was 1.85 (95% CI = 1.09–3.13). Sleep duration was significantly associated with changes in blood biochemical levels. The results of the logistic regression analysis showed that the levels of multiple biochemical parameters are associated with increased risk of total mortality.ConclusionsThis is the first large longitudinal study to indicate that sleep duration was associated with changes in multiple biochemical levels in the blood and total mortality.     

Associations of sleep duration and quality with incident cardiovascular disease,cancer, and mortality: a prospective cohort study of 407,500 UK biobank participants

ObjectiveFew studies have investigated the associations of sleep duration and sleep quality with incident cardiovascular diseases (CVDs), cancer, and mortality in the same large population. This study aimed at estimating the independent risk factors of long or short sleep durations and several typical characteristics of poor sleep quality for incident CVDs, cancer, and mortality.MethodsIn this prospective cohort study, 407 500 individuals were enrolled. Cox proportional hazards models were used to calculate the adjusted hazard ratios and 95% confidence intervals (HR, 95%CI) of associations of sleep duration and quality with incident CVDs, cancer, and mortality.ResultsCompared with the sleep duration of 7 h, sleep duration of ≤5 h and ≥9 h were both associated with higher risk of all-cause mortality (HR = 1.25, 95% CI: 1.16–1.34 and HR = 1.30, 95% CI: 1.22–1.38, respectively), CVD mortality (HR = 1.27, 95% CI: 1.09–1.49 and HR = 1.32, 95% CI: 1.16–1.50, respectively), and CVD incidence (HR = 1.23, 95% CI: 1.16–1.31 and HR = 1.08, 95% CI: 1.02–1.15, respectively). Additionally, long sleep duration (≥9 h) was associated with a higher risk of cancer mortality (HR = 1.19, 95% CI: 1.10–1.30) and cancer incidence (HR = 1.08, 95% CI: 1.04–1.12). Moreover, CVD incidence was significantly associated with snoring, insomnia and narcolepsy, increasing the risk by 7%, 26%, and 20%, respectively.ConclusionLong sleep durations may substantially increase the risk of mortality and morbidity. Snoring, insomnia, and narcolepsy were independent risk factors for incident CVD.     

Cognitive changes in people with temporal lobe epilepsy over a 13-year period

ObjectivesThe aims of our study were to evaluate cognitive decline in people with temporal lobe epilepsy over a period of 13 years and to determine what clinical and treatment characteristics may have been associated with these.Materials and methodsThirty-three individuals with temporal lobe epilepsy underwent the same neuropsychological assessment of verbal and nonverbal memory, attention, and executive functions using the same cognitive test battery as one used 13 years ago. Long-term verbal and nonverbal memory was tested four weeks later. Results were compared with those carried out 13 years earlier.ResultsThere was no significant change in verbal and verbal–logical memory tests; however, nonverbal memory worsened significantly. Long-term verbal memory declined for 21.9% of participants, long-term verbal–logical memory for 34.4%, and long-term nonverbal memory for 56.3%. Worsening of working verbal and verbal–logical memory was associated with longer epilepsy duration and lower levels of patients' education; worsening of verbal delayed recall and long-term verbal–logical memory was associated with higher seizure frequency. Decline in long-term nonverbal memory had significant association with a longer duration of epilepsy. The worsening of reaction and attention inversely correlated with the symptoms of depression.ConclusionOver a 13-year period, cognitive functions did not change significantly. Good seizure control and reduced symptoms of depression in this sample of people with temporal lobe epilepsy were associated with better cognitive functioning. The predictors of change of cognitive functions could be complex and require further study.     

Cognitive impairment in Parkinson's disease is associated with Default Mode Network subsystem connectivity and cerebrospinal fluid Aβ

IntroductionTo identify clinically implementable biomarkers of cognitive impairment in Parkinson's Disease (PD) derived from resting state-functional MRI (rs-fMRI) and CSF protein analysis.MethodsIn this single-center longitudinal cohort study, we analyzed rs-fMRI and CSF biomarkers from 50 PD patients (23 cognitively normal, 18 mild cognitive impairment, 9 dementia) and 19 controls, who completed comprehensive neuropsychological testing. A subgroup of participants returned for follow-up cognitive assessments three years later. From rs-fMRI, we studied the connectivity within two distinct Default Mode Network subsystems: left-to-right hippocampus (LHC-RHC) and medial prefrontal cortex-to-posterior cingulate cortex (mPFC-PCC). We used regression analyses to determine whether imaging (LHC-RHC, mPFC-PCC), clinical (CSF Aβ-42:40, disease duration), and demographic (age, sex, education) variables were associated with global and domain-specific cognitive impairments.ResultsLHC-RHC (F_3,67 = 3.41,p=0.023) and CSF Aβ-42:40 (χ²(3) = 8.77,p = 0.033) were reduced across more cognitively impaired PD groups. Notably, LHC-RHC connectivity was significantly associated with all global and domain-specific cognitive impairments (attention/executive, episodic memory, visuospatial, and language) at the baseline visit. In an exploratory longitudinal analysis, mPFC-PCC was associated with future global and episodic memory impairment.ConclusionWe used biomarker techniques that are readily available in clinical and research facilities to shed light on the pathophysiologic basis of cognitive impairment in PD. Our findings suggest that there is a functionally distinct role of the hippocampal subsystem within the DMN resting state network, and that intrinsic connectivity between the hippocampi is critically related to a broad range of cognitive functions in PD.