The influence of n-3 polyunsaturated fatty acids on cognitive function in individuals without dementia: a systematic review and dose-response meta-analysis.

BACKGROUND: Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been suggested as a cognitive enhancing agent, though their effect is doubtful. We aimed to examine the effect of n-3 PUFA on the cognitive function of middle-aged or older adults without dementia. METHODS: We reviewed randomized controlled trials of individuals aged 40 years or older. We systematically searched PubMed/MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Library databases. We used the restricted cubic splines model for non-linear dose-response meta-analysis in terms of the standardized mean difference with 95% confidence intervals. RESULTS: The current meta-analysis on 24 studies (n 9660; follow-up 3 to 36 months) found that the beneficial effect on executive function demonstrates an upward trend within the initial 12 months of intervention. This effect is prominently observed with a daily intake surpassing 500 mg of n-3 PUFA and up to 420 mg of eicosapentaenoic acid (EPA). Furthermore, these trends exhibit heightened significance in regions where the levels of blood docosahexaenoic acid (DHA) + EPA are not very low. CONCLUSIONS: Supplementation of n-3 PUFA may confer potential benefits to executive function among the middle-aged and elderly demographic, particularly in individuals whose dietary DHA + EPA level is not substantially diminished.

Effects of sleep quality on diurnal variation of brain volume in older adults: A retrospective cross-sectional study.

AIM: Brain volume is influenced by several factors that can change throughout the day. In addition, most of these factors are influenced by sleep quality. This study investigated diurnal variation in brain volume and its relation to overnight sleep quality. METHODS: We enrolled 1,003 healthy Koreans without any psychiatric disorders aged 60 years or older. We assessed sleep quality and average wake time using the Pittsburgh Sleep Quality Index, and divided sleep quality into good, moderate, and poor groups. We estimated the whole and regional brain volumes from three-dimensional T1-weighted brain MRI scans. We divided the interval between average wake-up time and MRI acquisition time (INT) into tertile groups: short (INT1), medium (INT2), and long (INT3). RESULTS: Whole and regional brain volumes showed no significance with respect to INT. However, the `interaction between INT and sleep quality showed significance for whole brain, cerebral gray matter, and cerebrospinal fluid volumes (p < .05). The INT2 group showed significantly lower volumes of whole brain, whole gray matter, cerebral gray matter, cortical gray matter, subcortical gray matter, and cerebrospinal fluid than the INT1 and INT3 groups only in the individuals with good sleep quality. CONCLUSION: Human brain volume changes significantly within a day associated with overnight sleep in the individuals with good sleep quality.

What is the impact of one's chronic illness on his or her spouse's future chronic illness: a community-based prospective cohort study.

BACKGROUND: Integrating a joint approach to chronic disease management within the context of a couple has immense potential as a valuable strategy for both prevention and treatment. Although spousal concordance has been reported in specific chronic illnesses, the impact they cumulatively exert on a spouse in a longitudinal setting has not been investigated. We aimed to determine whether one's cumulative illness burden has a longitudinal impact on that of their spouse. METHODS: Data was acquired from a community-based prospective cohort that included Koreans aged 60 years and over, randomly sampled from 13 districts nationwide. Data from the baseline assessment (conducted from November 2010 to October 2012) up to the 8-year follow-up assessment was analyzed from October 2021 to November 2022. At the last assessment, partners of the index participants were invited, and we included 814 couples in the analysis after excluding 51 with incomplete variables. Chronic illness burden of the participants was measured by the Cumulative Illness Rating Scale (CIRS). Multivariable linear regression and causal mediation analysis were used to examine the longitudinal effects of index chronic illness burden at baseline and its change during follow-up on future index and spouse CIRS scores. RESULTS: Index participants were divided based on baseline CIRS scores (CIRS < 6 points, n = 555, mean [SD] age 66.3 [4.79] years, 43% women; CIRS ≥ 6 points, n = 259, mean [SD] age 67.7 [4.76] years, 36% women). The baseline index CIRS scores and change in index CIRS scores during follow-up were associated with the spouse CIRS scores (ß = 0.154 [SE: 0.039], p < 0.001 for baseline index CIRS; ß = 0.126 [SE: 0.041], p = 0.002 for change in index CIRS) at the 8-year follow-up assessment. Subgroup analysis found similar results only in the high CIRS group. The baseline index CIRS scores and change in index CIRS scores during follow-up had both direct and indirect effects on the spouse CIRS scores at the 8-year follow-up assessment. CONCLUSIONS: The severity and course of one's chronic illnesses had a significant effect on their spouse's future chronic illness particularly when it was severe. Management strategies for chronic diseases that are centered on couples may be more effective.

The impact of the COVID-19 pandemic on depression in community-dwelling older adults: a prospective cohort study.

BACKGROUND: There are growing concerns about the impact of the COVID-19 pandemic on the mental health of older adults. We examined the effect of the pandemic on the risk of depression in older adults. METHODS: We analyzed data from the prospective cohort study of Korean older adults, which has been followed every 2 years. Among the 2308 participants who completed both the third and the fourth follow-up assessments, 58.4% completed their fourth follow-up before the outbreak of COVID-19 and the rest completed it during the pandemic. We conducted face-to-face diagnostic interviews using Mini International Neuropsychiatric Interview and used Geriatric Depression Scale. We performed generalized estimating equations and logistic regression analyses. RESULTS: The COVID-19 pandemic was associated with increased depressive symptoms in older adults [b (standard error) = 0.42 (0.20), p = 0.040] and a doubling of the risk for incident depressive disorder even in euthymic older adults without a history of depression (odds ratio = 2.44, 95% confidence interval 1.18-5.02, p = 0.016). Less social activities, which was associated with the risk of depressive disorder before the pandemic, was not associated with the risk of depressive disorder during the pandemic. However, less family gatherings, which was not associated with the risk of depressive disorder before the pandemic, was associated with the doubled risk of depressive disorder during the pandemic. CONCLUSIONS: The COVID-19 pandemic significantly influences the risk of late-life depression in the community. Older adults with a lack of family gatherings may be particularly vulnerable.

Altered resting state brain metabolic connectivity in dementia with Lewy bodies.

Although dementia with Lewy bodies (DLB) have Parkinsonism in common with Parkinson's disease (PD) or PD dementia (PDD), they have different neuropathologies that underlie Parkinsonism. Altered brain functional connectivity that may correspond to neuropathology has been reported in PD while never been studied in DLB. To identify the characteristic brain connectivity of Parkinsonism in DLB, we compared the resting state metabolic connectivity in striato-thalamo-cortical (STC) circuit, nigrostriatal pathway, and cerebello-thalamo-cortical motor (CTC) circuit in 27 patients with drug-naïve DLB and 27 age- and sex-matched normal controls using 18F-fluoro-2-deoxyglucose PET. We derived 118 regions of interest using the Automated Anatomical Labeling templates and the Wake Forest University Pick-Atlas. We applied the sparse inverse covariance estimation method to construct the metabolic connectivity matrix. Patients with DLB, with or without Parkinsonism, showed lower inter-regional connectivity between the areas included in the STC circuit (motor cortex-striatum, midbrain-striatum, striatum-globus pallidus, and globus pallidus-thalamus) than the controls. DLB patients with Parkinsonism showed less reduced inter-regional connectivity between the midbrain and the striatum than those without Parkinsonism, and higher inter-regional connectivity between the areas included in the CTC circuit (motor cortex-pons, pons-cerebellum, and cerebellum-thalamus) than those without Parkinsonism and the controls. The resting state metabolic connectivity in the STC circuit may be reduced in DLB. In DLB with Parkinsonism, the CTC circuit and the nigrostriatal pathway may be activated to mitigate Parkinsonism. This difference in the brain connectivity may be a candidate biomarker for differentiating DLB from PD or PDD.

Clinical Approaches to Late-Onset Psychosis.

Psychosis can include schizophrenia, mood disorders with psychotic features, delusional disorder, active delirium, and neurodegenerative disorders accompanied by various psychotic symptoms. Late-onset psychosis requires careful intervention due to the greater associated risks of secondary psychosis; higher morbidity and mortality rates than early-onset psychosis; and complicated treatment considerations due to the higher incidence of adverse effects, even with the black box warning against antipsychotics. Pharmacological treatment, including antipsychotics, should be carefully initiated with the lowest dosage for short-term efficacy and monitoring of adverse side effects. Further research involving larger samples, more trials with different countries working in consortia, and unified operational definitions for diagnosis will help elaborate the clinical characteristics of late-onset psychosis and lead to the development of treatment approaches.

Mood disorders increase mortality mainly through dementia: A community-based prospective cohort study.

OBJECTIVE: The effects of mood disorders on mortality may be mediated by their effects on the risk of dementia, and interventions to reduce the occurrence of dementia may reduce their overall mortality. This study aimed to investigate the direct effects of depressive and bipolar disorders on the 6-year risk of mortality and also their indirect effects on mortality due to their effect on the risk of dementia. METHODS: A total of 5101 Koreans were selected from a community-based prospective cohort study, and 6-year risks of mortality and dementia in participants with depressive and bipolar disorders were estimated by Cox proportional hazard analysis. The direct and indirect effects of depressive and bipolar disorders on the risk of mortality were estimated using structural equation modeling. RESULTS: The depressive and bipolar disorder groups showed 51% and 85% higher 6-year mortality, and 82% and 127% higher risk of dementia, respectively, compared to euthymic controls. The effects of depressive and bipolar disorders on mortality were mainly mediated by their effects on the risk of dementia in a structural equation model. The direct effects of each mood disorder on mortality were not significant. CONCLUSION: Both depressive and bipolar disorders increased the risks of mortality and dementia, and the effects of mood disorders on mortality were mainly mediated through dementia. As dementia occurs later in life than mood disorders, measures to prevent it may effectively reduce mortality in individuals with a history of mood disorders, as well as being more feasible than attempting to control other causes of death.

Optimal flickering light stimulation for entraining gamma waves in the human brain.

Although light flickering at 40 Hz reduced Alzheimer's disease (AD) pathologies in mice by entraining gamma waves, it failed to reduce cerebral amyloid burden in a study on six patients with AD or mild cognitive impairment. We investigated the optimal color, intensity, and frequency of the flickering light stimulus for entraining gamma waves in young adults. We compared the event-related synchronization (ERS) values of entrained gamma waves between four different light colors (white, red, green, and blue) in the first experiment and four different luminance intensities in the second experiment. In both experiments, we compared the ERS values of entrained gamma waves between 10 different flickering frequencies from 32 to 50 Hz. We also examined the severity of six adverse effects in both experiments. We compared the propagation of gamma waves in the visual cortex to other brain regions between different luminance intensities and flickering frequencies. We found that red light entrained gamma waves most effectively, followed by white light. Lights of higher luminance intensities (700 and 400 cd/m2) entrained stronger gamma waves than those of lower luminance intensities (100 and 10 cd/m2). Lights flickering at 34-38 Hz entrained stronger and more widely spread beyond the visual cortex than those flickering at 40-50 Hz. Light of 700 cd/m2 resulted in more moderate-to-severe adverse effects than those of other luminance intensities. In humans, 400 cd/m2 white light flickering at 34-38 Hz was most optimal for gamma entrainment.

Disease Burdens of Alzheimer's Disease, Vascular Dementia, and Mild Cognitive Impairment.

OBJECTIVES: Understanding disability-adjusted life-years (DALYs) based on dementia subtypes and mild cognitive impairment (MCI) is essential for optimal resource allocation. This study aimed to investigate disease burdens of various dementias and MCI in a representative South Korean population. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: 6481 Korean older adults. METHODS: We estimated the disease-specific DALYs. RESULTS: DALYs due to MCI and all-cause dementia are estimated to increase from 1295 per 100,000 in 2016 to 9501 per 100,000 in 2065. In 2016, DALYs attributed to Alzheimer's dementia, vascular dementia, and MCI accounted for 33% (423 per 100,000), 20% (316 per 100,000), and 24% (123 per 100,000), respectively, of the total DALYs due to MCI and all-cause dementia. In 2065, DALYs due to Alzheimer's dementia, vascular dementia, and MCI will account for 38% (3654 per 100,000), 17% (1654 per 100,000), and 27% (2585 per 100,000) of total DALYs due to MCI and all-cause dementia, respectively. The years of life lived with disability (YLDs) due to MCI and all-cause dementia are estimated to rise from 479 per 100,000 in 2016 to 2807 per 100,000 in 2065. In 2016, YLDs due to Alzheimer's dementia, vascular dementia, and MCI composed 37% (177 per 100,000), 18% (85 per 100,000), and 15% (70 per 100,000), respectively, of the total YLDs due to MCI and all-cause dementia. In 2065, YLDs due to Alzheimer's dementia, vascular dementia, and MCI will account for 48% (1358 per 100,000), 15% (410 per 100,000), and 10% (290 per 100,000), respectively, of total YLDs due to MCI and all-cause dementia. CONCLUSIONS AND IMPLICATIONS: Considering the rapidly growing disease burden, resources should be allocated to continuously monitor and manage the MCI and dementia burden. Particular attention to Alzheimer's dementia is required considering its significant contribution to current and future disease burden, especially to YLD.

Association of the Irregular 3-Dimensional Shape of White Matter Hyperintensities with Cognitive Function.

INTRODUCTION: The irregular shapes of white matter hyperintensities (WMHs) are associated with poor cognitive function, diabetes, or lacunes. However, the association between the WMH shape and dementia remains understudied. We investigated the association between the calculated shape index of WMH and the diagnosis of dementia and cognitive function. METHODS: The inverse sphericity index (ISIWMH) and volume of WMHs (VOLWMH) were compared among 82 participants with normal cognition, 82 with Alzheimer's dementia (AD), and 82 with subcortical vascular dementia (SVD). We examined the associations of ISIWMH and VOLWMH with the modified Hachinski Ischemic Score (mHIS), diagnosis of AD and SVD, and cognitive test scores, using linear, multinomial, or hierarchical linear regression models. RESULTS: The mHIS was associated with both ISIWMH (ß = 0.326, p < 0.001) and VOLWMH (ß = 0.299, p < 0.001). Both ISIWMH and VOLWMH were associated with the SVD diagnosis (odds ratio [OR] = 2.685, p = 0.002, ISIWMH; OR = 2.597, p = 0.005, VOLWMH), but not with AD. The SVD diagnosis was better explained when the multinomial regression model included both ISIWMH and VOLWMH instead of VOLWMH alone (χ2 = 20.768, df = 2, p < 0.001). The Trail Making Test-D (TMT-D) scores of the SVD patients were associated with both ISIWMH (ß = 0.308) and VOLWMH (ß = 0.293). CONCLUSION: An irregular WMH shape may be associated with the high cerebrovascular component of cognitive impairment and the diagnosis and low cognitive flexibility of SVD, which may improve the prediction of SVD diagnosis when used in combination with WMH volume.

Screening major depressive disorder using vocal acoustic features in the elderly by sex.

BACKGROUND: Vocal acoustic features are potential biomarkers of elderly depression. Previous automated diagnostic tests for depression have employed unstandardized speech samples, and few studies have considered differences in voice reactivity. We aimed to develop a voice-based screening test for depression measuring vocal acoustic features of elderly Koreans while they read a series of mood-inducing sentences (MIS). METHODS: In this case-control study, we recruited 61 individuals with major depressive disorder and 143 healthy controls (mean age [SD]: 72 [6]; female, 70%) from the community-dwelling elderly population. Participants were asked to read MIS and their variation pattern of acoustic features represented by the correlation distance between two MIS were analyzed as input features using the univariate feature selection technique and subsequently classified by AdaBoost. RESULTS: Acoustic features showing significant discriminatory performances were spectral and energy-related features for males (sensitivity 0.95, specificity 0.88, and accuracy 0.86) and prosody-related features for females (sensitivity 0.73, specificity 0.86, and accuracy 0.77). The correlation distance between negative and positive MIS was significantly shorter in the depressed group than in the healthy control (F = 18.574, P < 0.001). LIMITATIONS: Small sample size and relatively homogenous clinical profile of depression could limit the generalizability. CONCLUSIONS: While reading MIS, spectral and energy-related acoustic features for males and prosody-related features for females are good discriminators for major depressive disorder. These features may be used as biomarkers of depression in the elderly.

A 9-Year Comparison of Dementia Prevalence in Korea: Results of NaSDEK 2008 and 2017.

BACKGROUND: In many high-income Western countries, the prevalence of dementia had been reduced over the past decades. OBJECTIVE: We investigated whether the prevalence of all-cause dementia, Alzheimer's disease, vascular dementia, and mild cognitive impairment (MCI) had changed in Korea from 2008 to 2017. METHODS: Nationwide Survey on Dementia Epidemiology of Korea (NaSDEK) in 2008 and 2017 was conducted on representative elderly populations that were randomly sampled across South Korea. Both surveys employed a two-stage design (screening and diagnostic phases) and diagnosed dementia and MCI according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders and the consensus criteria from the International Working Group, respectively. The numbers of participants aged 65 years or older in the screening and diagnostic phases were 6,141 and 1,673 in the NaSDEK 2008 and 2,972 and 474 in the NaSDEK 2017, respectively. RESULTS: The age- and sex-standardized prevalence of all-cause dementia and Alzheimer's disease showed nonsignificant decrease (12.3% to 9.8%, odds ratio [OR] = 0.89, 95% confidence interval [CI] = 0.54-1.48 for all-cause dementia; 7.6% to 6.8%, OR [95% CI] = 0.91 [0.58-1.42] for Alzheimer's disease). Vascular dementia decreased in the young-old population aged less than 75 years (2.7% to 0.001%, OR [95% CI] = 0.04 [0.01-0.15]) and in women (1.9% to 0.5%, OR [95% CI] = 0.27 [0.10-0.72]) while MCI remained stable (25.3% to 26.2%, OR [95% CI] = 1.08 [0.67-1.73]). CONCLUSION: We found that the prevalence of dementia in Korea showed a nonsignificant decrease between 2008 and 2017.

Construction and validation of a cerebral white matter hyperintensity probability map of older Koreans.

BACKGROUND AND PURPOSE: Although two white matter hyperintensity (WMH) probability maps of healthy older adults already exist, they have several limitations in representing the distribution of WMH in healthy older adults, especially Asian older adults. We constructed and validated a WMH probability map (WPM) of healthy older Koreans and examined the age-associated differences of WMH. METHODS: We constructed WPM using development dataset that consisted of high-resolution 3D fluid-attenuated inversion recovery images of 5 age groups (60-64 years, 65-69 years, 70-74 years, 75-79 years, and 80+ years). Each age group included 30 age-matched men and women each. We tested the validity of the WPM by comparing WMH ages estimated by the WPM and the chronological ages of 30 healthy controls, 30 hypertension patients, and 30 S patients. RESULTS: Older age groups showed a higher volume of WMH in both hemispheres (p < 0.001). About 90% of the WMH were periventricular in all age groups. With advancing age, the peak of the distance histogram from the ventricular wall of the periventricular WMH shifted away from the ventricular wall, while that of deep WMH shifted toward the ventricular wall. The estimated WMH ages were comparable to the chronological ages in the healthy controls, while being higher than the chronological ages in hypertension and stroke patients. CONCLUSIONS: This WPM may serve as a standard atlas in research on WMH of older adults, especially Asians.

Estimating prevalence of subjective cognitive decline in and across international cohort studies of aging: a COSMIC study.

BACKGROUND: Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer's disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts. METHODS: We combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence. RESULTS: The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI = 23.3-24.4%) and IRT (25.6%, 95%CI = 25.1-26.1%); however, prevalence estimates varied largely between studies (QH 6.1%, 95%CI = 5.1-7.0%, to 52.7%, 95%CI = 47.4-58.0%; IRT: 7.8%, 95%CI = 6.8-8.9%, to 52.7%, 95%CI = 47.4-58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, in Asian and Black African people compared to White people, in lower- and middle-income countries compared to high-income countries, and in studies conducted in later decades. CONCLUSIONS: SCD is frequent in old age. Having a quarter of older individuals with SCD warrants further investigation of its significance, as a risk stage for AD and other dementias, and of ways to help individuals with SCD who seek medical advice. Moreover, a standardized instrument to measure SCD is needed to overcome the measurement variability currently dominant in the field.

Sex differences in subjective age-associated changes in sleep: a prospective elderly cohort study.

Subjective age-associated changes in sleep (AACS) and sex differences in AACS have never been prospectively investigated in elderly populations. We compared the AACS every 2 years over a total of 6 years between 4,686 community-dwelling healthy men and women aged 60 years or older who participated in the Korean Longitudinal Study on Cognitive Aging and Dementia. Sleep parameters including sleep duration, latency, and efficiency, mid-sleep time, daytime dysfunction, and overall subjective sleep quality were measured using the Pittsburgh Sleep Quality Index at baseline and at each follow-up. The effects of time and sex on subjective sleep parameters were analyzed using linear mixed-effects models. During the 6 years of follow-up, we observed that overall, sleep latency increased, while daytime dysfunction and sleep quality worsened. Significant sex differences in AACS was found, with women showing shortened sleep duration, delayed mid-sleep time, and decreased sleep efficiency over 6 years. Sleep quality worsened in both groups but a more pronounced change was observed in women. Clinicians should be cautious in determining when to treat declared sleep disturbances in this population.

Smaller pineal gland is associated with rapid eye movement sleep behavior disorder in Alzheimer's disease.

BACKGROUND: To investigate the association between pineal gland volume and symptoms of rapid eye movement (REM) sleep behavior disorder (RBD) in Alzheimer's disease (AD) patients without any feature of dementia with Lewy bodies. METHODS: We enrolled 296 community-dwelling probable AD patients who did not meet the diagnostic criteria for possible or probable dementia with Lewy bodies. Among them, 93 were amyloid beta (Aß) positive on 18F-florbetaben amyloid brain positron emission tomography. We measured RBD symptoms using the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) and defined probable RBD (pRBD) as the RBDSQ of 5 or higher. We manually segmented pineal gland on 3T structural T1-weighted brain magnetic resonance imaging. RESULTS: The participants with pRBD had smaller pineal parenchyma volume (VPP) than those without pRBD (p <  0.001). The smaller the VPP, the more severe the RBD symptoms (p <  0.001). VPP was inversely associated with risk of prevalent pRBD (odds ratio = 0.909, 95% confidence interval [CI] = 0.878-0.942, p <  0.001). Area under the receiver operator characteristic curve for pRBD of VPP was 0.80 (95% CI = 0.750-0.844, p <  0.0001). These results were not changed when we analyzed the 93 participants with Aß-positive AD separately. CONCLUSIONS: In AD patients, reduced pineal gland volume may be associated with RBD.

A cross-national study of depression in preclinical dementia: A COSMIC collaboration study.

INTRODUCTION: Depression commonly accompanies Alzheimer's disease, but the nature of this association remains uncertain. METHODS: Longitudinal data from the COSMIC consortium were harmonized for eight population-based cohorts from four continents. Incident dementia was diagnosed in 646 participants, with a median follow-up time of 5.6 years to diagnosis. The association between years to dementia diagnosis and successive depressive states was assessed using a mixed effect logistic regression model. A generic inverse variance method was used to group study results, construct forest plots, and generate heterogeneity statistics. RESULTS: A common trajectory was observed showing an increase in the incidence of depression as the time to dementia diagnosis decreased despite cross-national variability in depression rates. DISCUSSION: The results support the hypothesis that depression occurring in the preclinical phases of dementia is more likely to be attributable to dementia-related brain changes than environment or reverse causality.

Education and the moderating roles of age, sex, ethnicity and apolipoprotein epsilon 4 on the risk of cognitive impairment.

BACKGROUND: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4). METHODS: Participants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School. RESULTS: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers. CONCLUSION: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study.

Erythrocyte Characteristics and the Risk of Depression in Late Life: A Population-Based Prospective Study.

OBJECTIVES: Inflammation and vascular dysregulation may contribute to the development of depression and impose a burden on erythropoiesis. This study aimed to identify the association of erythrocyte indices with the severity of depressive symptoms and risk of developing depressive disorders in the older people. DESIGN: A prospective cohort study on a randomly sampled Korean older population; the baseline assessment from 2010 to 2012, the first follow-up assessment from 2012 to 2014, and the second follow-up assessment from 2014 to 2016 (mean follow-up duration = 3.4 years). SETTING: A nationwide and community-based cohort. PARTICIPANTS: A total of 4451 Koreans aged 60 years or older. METHODS: We examined the associations of the values and changes in mean corpuscular volume, mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) with the risk of prevalent and incident depression using logistic regression analyses. RESULTS: High MCH and MCHC in female participants and high MCHC in male participants were associated with high geriatric depression scale scores and risk of prevalent depression. In female participants, high- and middle-MCH tertile groups showed a 2.68- and 2.34-fold higher risk of incident depression than did the low tertile group. In male participants, the high-MCH tertile group showed a 1.79-fold higher risk of incident depression than did the low tertile group. In both sexes, the participants whose MCV changed to the high or middle tertile or remained in the high or middle tertile during the follow-up period, and whose MCH increased to the high tertile or remained in the high tertile, were at a higher risk of incident depression. CONCLUSIONS AND IMPLICATIONS: Changes in erythrocyte may be associated with the risk of depression in older adults. This prospective study proposes a new perspective of the old hematologic parameters for understanding the pathophysiology of late-life depression.

Driving-Related Adverse Events in the Elderly Men: A Population-Based Prospective Cohort Study.

OBJECTIVE: This study estimated the incidence of driving-related adverse events and examined the association of cognitive function with the risk of future driving-related adverse events in the elderly Korean male population. METHODS: We analyzed 1,172 male drivers aged 60 years or older in the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD). Using the data from Korean National Police Agency, we classified the participants into three groups: safe driving (drove for 2 years after baseline without a traffic accident or repeated violations), driving cessation (stopped driving), and risky driving (one or more traffic accidents or repeated violations). We estimated the incidences of driving cessation and risky driving, and examined the effect of cognitive function on their risks. RESULTS: The incidence of driving cessation and risky driving in the Korean male drivers aged 60 years or older was 19.3 and 69.9 per 1,000 person-years respectively and increased in the late 80s. Drivers with better baseline Word List Memory Test scores showed less risky driving (OR=0.94, p=0.039). CONCLUSION: Driving-related adverse events increased in late 80s, and better memory function was protective against these events.