Lifestyle and incident dementia: A COSMIC individual participant data meta­analysis.

INTRODUCTION: The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS: We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis. RESULTS: A one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSION: Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. HIGHLIGHTS: A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.

Association of Depression With the Progression of Multimorbidity in Older Adults: A Population-Based Cohort Study.

BACKGROUND: The relationship between depression and the risk of multimorbidity progression has rarely been studied in older adults. This study was aimed to determine whether depression is associated with progression in the severity and complexity of multimorbidity, considering the influence of depression's severity and subtype. METHODS: As a part of the Korean Longitudinal Study on Cognitive Aging and Dementia, this population-based cohort study followed a random sample of community-dwelling Koreans aged 60 and older for 8 years at 2-year intervals starting in 2010. Participants included those who completed mood and multimorbidity assessments and did not exhibit complex multimorbidity at the study's outset. Depression was assessed using the Geriatric Depression Scale, while multimorbidity was evaluated using the Cumulative Illness Rating Scale. The study quantified multimorbidity complexity by counting affected body systems and measured multimorbidity severity by averaging scores across 14 body systems. FINDINGS: The 2,486 participants (age = 69.1 ± 6.5 years, 57.6% women) were followed for 5.9 ± 2.4 years. Linear mixed models revealed that participants with depression had a faster increase in multimorbidity complexity score (ß = .065, SE = 0.019, p = 0.001) than those without depression, but a comparable increase in multimorbidity severity score (ß = .001, SE = .009, p = 0.870) to those without depression. Cox proportional hazard models revealed that depression was associated with the risk of developing highly complex multimorbidity affecting five or more body systems, particularly in severe or anhedonic depression. INTERPRETATION: Depression was associated with the worsening of multimorbidity in Korean older adults, particularly when severe or anhedonic. Early screening and management of depression may help to reduce the burden of multimorbidity in older adults.

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.

Textural and Volumetric Changes of the Temporal Lobes in Semantic Variant Primary Progressive Aphasia and Alzheimer's Disease.

BACKGROUND: Texture analysis may capture subtle changes in the gray matter more sensitively than volumetric analysis. We aimed to investigate the patterns of neurodegeneration in semantic variant primary progressive aphasia (svPPA) and Alzheimer's disease (AD) by comparing the temporal gray matter texture and volume between cognitively normal controls and older adults with svPPA and AD. METHODS: We enrolled all participants from three university hospitals in Korea. We obtained T1-weighted magnetic resonance images and compared the gray matter texture and volume of regions of interest (ROIs) between the groups using analysis of variance with Bonferroni posthoc comparisons. We also developed models for classifying svPPA, AD and control groups using logistic regression analyses, and validated the models using receiver operator characteristics analysis. RESULTS: Compared to the AD group, the svPPA group showed lower volumes in five ROIs (bilateral temporal poles, and the left inferior, middle, and superior temporal cortices) and higher texture in these five ROIs and two additional ROIs (right inferior temporal and left entorhinal cortices). The performances of both texture- and volume-based models were good and comparable in classifying svPPA from normal cognition (mean area under the curve [AUC] = 0.914 for texture; mean AUC = 0.894 for volume). However, only the texture-based model achieved a good level of performance in classifying svPPA and AD (mean AUC = 0.775 for texture; mean AUC = 0.658 for volume). CONCLUSION: Texture may be a useful neuroimaging marker for early detection of svPPA in older adults and its differentiation from AD.

Examining the links between burnout and suicidal ideation in diverse occupations.

Introduction: It is uncertain whether burnout is associated with suicidal ideation among workers not in health care services. The aim of this study was to identify how burnout and suicidal ideation are linked among employees in various occupations and whether depression affects this link. Methods: This cross-sectional study collected data from 12,083 participants aged 19-65 years from 25 companies and public institutions who underwent workplace mental health screening. Burnout and depression were assessed using both the Oldenburg Burnout Inventory and the Center for Epidemiologic Studies Depression Scale. Suicidal ideation was assessed by a self-rated questionnaire from the Korea National Health and Nutrition Examination Survey. Results: Exhaustion but not the cynicism dimension of burnout was associated with increased odds of suicidal ideation after adjustment for depression and other covariates (odds ratio [OR] = 1.47, 95% CI = 1.26-1.72). The association of exhaustion with suicidal ideation was significant in both depressed (OR = 1.36, 95% CI = 1.14-1.61) and not depressed (OR = 1.77, 95% CI = 1.13-2.76) participants. In exhausted participants, insufficient job control, an unfavorable occupational climate, low educational level, and depression were associated with increased odds of suicidal ideation. Conclusion: Exhaustion is linked with risk of suicidal ideation in employees not in health care service, regardless of depression status. Exhausted employees, particularly those having poor job resources, should be recognized as an at-risk group.

Use of Antihypertensives, Blood Pressure, and Estimated Risk of Dementia in Late Life: An Individual Participant Data Meta-Analysis.

Importance: The utility of antihypertensives and ideal blood pressure (BP) for dementia prevention in late life remains unclear and highly contested. Objectives: To assess the associations of hypertension history, antihypertensive use, and baseline measured BP in late life (age >60 years) with dementia and the moderating factors of age, sex, and racial group. Data Source and Study Selection: Longitudinal, population-based studies of aging participating in the Cohort Studies of Memory in an International Consortium (COSMIC) group were included. Participants were individuals without dementia at baseline aged 60 to 110 years and were based in 15 different countries (US, Brazil, Australia, China, Korea, Singapore, Central African Republic, Republic of Congo, Nigeria, Germany, Spain, Italy, France, Sweden, and Greece). Data Extraction and Synthesis: Participants were grouped in 3 categories based on previous diagnosis of hypertension and baseline antihypertensive use: healthy controls, treated hypertension, and untreated hypertension. Baseline systolic BP (SBP) and diastolic BP (DBP) were treated as continuous variables. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data reporting guidelines. Main Outcomes and Measures: The key outcome was all-cause dementia. Mixed-effects Cox proportional hazards models were used to assess the associations between the exposures and the key outcome variable. The association between dementia and baseline BP was modeled using nonlinear natural splines. The main analysis was a partially adjusted Cox proportional hazards model controlling for age, age squared, sex, education, racial group, and a random effect for study. Sensitivity analyses included a fully adjusted analysis, a restricted analysis of those individuals with more than 5 years of follow-up data, and models examining the moderating factors of age, sex, and racial group. Results: The analysis included 17 studies with 34 519 community dwelling older adults (20 160 [58.4%] female) with a mean (SD) age of 72.5 (7.5) years and a mean (SD) follow-up of 4.3 (4.3) years. In the main, partially adjusted analysis including 14 studies, individuals with untreated hypertension had a 42% increased risk of dementia compared with healthy controls (hazard ratio [HR], 1.42; 95% CI 1.15-1.76; P = .001) and 26% increased risk compared with individuals with treated hypertension (HR, 1.26; 95% CI, 1.03-1.53; P = .02). Individuals with treated hypertension had no significant increased dementia risk compared with healthy controls (HR, 1.13; 95% CI, 0.99-1.28; P = .07). The association of antihypertensive use or hypertension status with dementia did not vary with baseline BP. There was no significant association of baseline SBP or DBP with dementia risk in any of the analyses. There were no significant interactions with age, sex, or racial group for any of the analyses. Conclusions and Relevance: This individual patient data meta-analysis of longitudinal cohort studies found that antihypertensive use was associated with decreased dementia risk compared with individuals with untreated hypertension through all ages in late life. Individuals with treated hypertension had no increased risk of dementia compared with healthy controls.

Evaluation of Efficacy and Safety Using Low Dose Radiation Therapy with Alzheimer's Disease: A Protocol for Multicenter Phase II Clinical Trial.

BACKGROUND: Alzheimer's disease (AD), the most common cause of dementia, is a neurodegenerative disease resulting from extracellular and intracellular deposits of amyloid-ß (Aß) and neurofibrillary tangles in the brain. Although many clinical studies evaluating pharmacological approaches have been conducted, most have shown disappointing results; thus, innovative strategies other than drugs have been actively attempted. OBJECTIVE: This study aims to explore low-dose radiation therapy (LDRT) for the treatment of patients with AD based on preclinical evidence, case reports, and a small pilot trial in humans. METHODS: This study is a phase II, multicenter, prospective, single-blinded, randomized controlled trial that will evaluate the efficacy and safety of LDRT to the whole brain using a linear accelerator in patients with mild AD. Sixty participants will be randomly assigned to three groups: experimental I (24 cGy/6 fractions), experimental II (300 cGy/6 fractions), or sham RT group (0 cGy/6 fractions). During LDRT and follow-up visits after LDRT, possible adverse events will be assessed by the physician's interview and neurological examinations. Furthermore, the effectiveness of LDRT will be measured using neurocognitive function tests and imaging tools at 6 and 12 months after LDRT. We will also monitor the alterations in cytokines, Aß42/Aß40 ratio, and tau levels in plasma. Our primary endpoint is the change in cognitive function test scores estimated by the Alzheimer's Disease Assessment Scale-Korea compared to baseline after 6 months of LDRT. CONCLUSIONS: This study is registered at ClinicalTrials.gov [NCT05635968] and is currently recruiting patients. This study will provide evidence that LDRT is a new treatment strategy for AD.

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.

Parental history of dementia and the risk of dementia: A cross-sectional analysis of a global collaborative study.

BACKGROUND: Parental history of dementia appears to increase the risk of dementia, but there have been inconsistent results. We aimed to investigate whether the association between parental history of dementia and the risk of dementia are different by dementia subtypes and sex of parent and offspring. METHODS: For this cross-sectional study, we harmonized and pooled data for 17,194 older adults from nine population-based cohorts of eight countries. These studies conducted face-to-face diagnostic interviews, physical and neurological examinations, and neuropsychological assessments to diagnose dementia. We investigated the associations of maternal and paternal history of dementia with the risk of dementia and its subtypes in offspring. RESULTS: The mean age of the participants was 72.8 ± 7.9 years and 59.2% were female. Parental history of dementia was associated with higher risk of dementia (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.15-1.86) and Alzheimer's disease (AD) (OR = 1.72, 95% CI = 1.31-2.26), but not with the risk of non-AD. This was largely driven by maternal history of dementia, which was associated with the risk of dementia (OR = 1.51, 95% CI = 1.15-1.97) and AD (OR = 1.80, 95% CI = 1.33-2.43) whereas paternal history of dementia was not. These results remained significant when males and females were analyzed separately (OR = 2.14, 95% CI = 1.28-3.55 in males; OR = 1.68, 95% CI = 1.16-2.44 for females). CONCLUSIONS: Maternal history of dementia was associated with the risk of dementia and AD in both males and females. Maternal history of dementia may be a useful marker for identifying individuals at higher risk of AD and stratifying the risk for AD in clinical trials.

Erratum: A Comparison Between the Performances of Verbal and Nonverbal Fluency Tests in Discriminating Between Mild Cognitive Impairments and Alzheimer's Disease Patients and Their Brain Morphological Correlates.

[This corrects the article on p. 17 in vol. 21, PMID: 35154337.].

Risk Factors for Various Cognitive Function Decline Trajectories in Adults Over 40 Years of Age: A Retrospective Cohort Study.

OBJECTIVE: The aims of our study were to identify distinct trajectories of cognitive function using the group-based trajectory model. We also investigate which demographic factors act as risk factors for cognitive decline in each group. METHODS: The data from the Seoul National University Hospital Healthcare System Gangnam Center, from 2005 to 2019. The number of study subjects was 637. We used a group-based model to identify cognitive function trajectories. Multinomial logistic regression was employed to define risk factors for cognitive function decline. RESULTS: The cognitive function trajectories among adults over 40 years of age were heterogeneous. We identified four trajectories: high (27.3%), medium (41.0%), low (22.7%), and rapid decline (9.1%). Older age, male, low educational level, bad dietary habits, diabetes mellitus, technical worker, and lower income increased the likelihood of a cognitive function decline. CONCLUSION: A younger age, a higher educational level, professional worker, good dietary habits, no diabetes mellitus, and no obesity improved cognitive function. A combination of these factors can improve "cognitive reserve" and delay cognitive decline. Interventions to prevent cognitive decline are needed after identification of high-risk groups for cognitive decline.

Shared Risk Factors for Depressive Disorder Among Older Adult Couples in Korea.

Importance: Although couples may share many risk factors for depressive disorders in their lifetime, whether these factors mediate the shared risk of depressive disorders has rarely been investigated. Objectives: To identify the shared risk factors for depressive disorder in couples and investigate their mediating roles in the shared risk of depressive disorders among older adult couples. Design, Setting, and Participants: This nationwide, multicenter, community-based cohort study assessed 956 older adults from the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) and a cohort of their spouses (KLOSCAD-S) between January 1, 2019, to February 28, 2021. Exposures: Depressive disorders of the KLOSCAD participants. Main Outcomes and Measures: The mediating roles of shared factors in couples on the association between one spouse's depressive disorder and the other's risk of depressive disorders was examined using structural equation modeling. Results: A total of 956 KLOSCAD participants (385 women [40.3%] and 571 men [59.7%]; mean [SD] age, 75.1 [5.0] years) and their spouses (571 women [59.7%] and 385 men [40.3%]; mean [SD] age, 73.9 [6.1] years) were included. The depressive disorders of the KLOSCAD participants were associated with an almost 4-fold higher risk of depressive disorders in their spouses in the KLOSCAD-S cohort (odds ratio, 3.89; 95% CI, 2.06-7.19; P < .001). Social-emotional support mediated the association between depressive disorders in the KLOSCAD participants and their spouses' risk of depressive disorders by itself (ß = 0.012; 95% CI, 0.001-0.024; P = .04; mediation proportion [MP] = 6.1%) and through chronic illness burden (ß = 0.003; 95% CI, 0.000-0.006; P = .04; MP = 1.5%). Chronic medical illness burden (ß = 0.025; 95% CI, 0.001-0.050; P = .04; MP = 12.6%) and presence of a cognitive disorder (ß = 0.027; 95% CI, 0.003-0.051; P = .03; MP = 13.6%) mediated the association. Conclusions and Relevance: The risk factors shared by older adult couples may mediate approximately one-third of the spousal risk of depressive disorders. Identification of and intervention in the shared risk factors of depression among older adult couples may reduce the risk of depressive disorders in the spouses of older adults with depression.

Correlates of Gait Speed Among Older Adults From 6 Countries: Findings From the COSMIC Collaboration.

BACKGROUND: Few studies have compared gait speed and its correlates among different ethnogeographic regions. The goals of this study were to describe usual and rapid gait speed, and identify their correlates across Australian, Asian, and African countries. METHODS: We used data from 6 population-based cohorts of adults aged 65+ from 6 countries and 3 continents (N = 6 472), with samples ranging from 231 to 1 913. All cohorts are members of the Cohort Studies of Memory in an International Consortium collaboration. We investigated whether clinical (body mass index [BMI], hypertension, stroke, apolipoprotein status), psychological (cognition, mood, general health), and behavioral factors (smoking, drinking, physical activity) correlated with usual (N = 4 cohorts) and rapid gait speed (N = 3 cohorts) similarly across cohorts. Regression models were controlled for age, sex, and education, and were sex-stratified. RESULTS: Age- and sex-standardized usual gait speed means ranged from 0.61 to 1.06 m/s and rapid gait speed means ranged from 1.16 to 1.64 m/s. Lower BMI and better cognitive function consistently correlated with faster gait speed in all cohorts. Less consistently, not having hypertension and greater physical activity engagement were associated with faster gait speed. Associations with mood, smoking, and drinking were largely nonsignificant. These patterns were not attenuated by demographics. There was limited evidence that the associations differed by sex, except physical activity, where the greater intensity was associated with usual gait among men but not women. CONCLUSIONS: This study is among the first to describe the usual and rapid gait speeds across older adults in Africa, Asia, and Australia.

Lower cognitive function attenuates the convergence between self-ratings and observer ratings of depressive symptoms in late-life cognitive impairment.

OBJECTIVES: Assessment of depressive symptoms in older adults is challenging especially in the presence of risks in cognitive impairment. We aimed to examine whether the convergence between two measures of depressive symptoms (self-report and observer ratings) is affected by varying levels of cognitive function in older adults. METHODS: Self-reported scale of depression, informant-based rating of affective symptoms, and global cognitive function were assessed in 2533 older adults with no impairment, mild cognitive impairment, and Alzheimer's disease. The strength of rank-order correlation between the Geriatric Depression Scale (GDS) and behavioral ratings of the Neuropsychiatric Inventory (NPI) was examined as the metric of convergent validity. RESULTS: The results showed that the strength of convergence between the two measurements gradually decreased as a function of lowered cognitive function. Overall tendency showed that diagnoses of cognitive impairment and lower levels of cognitive function were associated with lower correspondence between the two depression measurements. The loss of convergent validity is especially evident in the behavioral symptom of apathy. CONCLUSIONS: Utilizing self-report scales of depression in older adults requires a cautious approach even with minimal or mild levels of cognitive impairment.

Association of Low Emotional and Tangible Support With Risk of Dementia Among Adults 60 Years and Older in South Korea.

Importance: The association between social support and dementia risk has been debated. Most previous prospective studies have not differentiated the subtypes of social support. Objective: To examine whether the association between social support and risk of dementia differs by subtype of social support and by sex. Design, Setting, and Participants: This nationwide prospective cohort study included randomly sampled South Korean adults 60 years or older. The study was launched November 1, 2010, with follow-up every 2 years until November 30, 2020. The 5852 participants who completed the assessment for social support and were not diagnosed as having dementia, severe psychiatric disorders including major depressive disorder, or major neurological disorders at the baseline assessment were included in the analysis. Exposures: Geriatric psychiatrists administered the structured diagnostic interviews and physical examinations to every participant based on the Korean version of the Consortium to Establish a Registry for Alzheimer Disease (CERAD-K) Assessment Packet Clinical Assessment Battery. Main Outcomes and Measures: Baseline levels of emotional and tangible support using the Medical Outcomes Survey Social Support Survey. Results: Among the 5852 participants (mean [SD] age, 69.8 [6.6] years; 3315 women [56.6%]; mean [SD] follow-up duration, 5.9 [2.4] years), 237 (4.0%) had incident all-cause dementia and 160 (2.7%) had incident Alzheimer disease (AD) subtype of dementia. Compared with women who reported having emotional support, those with low emotional support had almost a 2-fold higher incidence of all-cause dementia (18.4 [95% CI, 13.6-23.2] vs 10.7 [95% CI, 9.0-12.5] per 1000 person-years) and AD (14.4 [95% CI, 10.2-18.6] vs 7.8 [95% CI, 6.3-9.3] per 1000 person-years). Adjusted Cox proportional hazard analysis revealed that low emotional support was associated with increased risk of all-cause dementia (hazard ratio, 1.61 [95% CI, 1.10-2.36]; P = .02) and AD (hazard ratio, 1.66 [95% CI, 1.07-2.57]; P = .02) only in women. Low tangible support was not associated with a risk of all-cause dementia or AD regardless of sex. Conclusions and Relevance: The findings of this cohort study suggest that older women with low emotional support constitute a population at risk for dementia. The level of emotional support should be included in risk assessments of dementia.

Clinical and biological subtypes of late-life depression.

BACKGROUND: Late-life depression (LDD) results from multiple psychosocial and neurobiological changes occurring in later life. The current study investigated how patterns of clinical symptoms and brain structural features are classified into LDD subtypes. METHOD: Self-report scale of depression, behavioral rating of affective symptoms, and brain structural imaging of white matter change and cortical thickness were assessed in 541 older adults with no cognitive impairment or mild cognitive impairment. Latent profile analysis was used to identify distinct subtypes of depression. RESULTS: The latent profile analysis identified four classes with mild to severe depressive symptoms and two classes with minimal symptoms. While the classes primarily differed in the overall severity, the combinatory patterns of clinical symptoms and neuropathological signature distinguished the classes with similar severity. The classes were distinguished in terms of whether or not neurodegenerative risk accompanied the corresponding depressive symptoms. The presence of the negative self-scheme and cortical thinning pattern notably characterized the subtypes of LDD. LIMITATIONS: The underlying etiologies of the biological subtypes are still speculative, and the current study lacks clinical history that differentiates late- and early-onset depression. CONCLUSIONS: Our finding provides insight in identifying heterogeneities of depressive disorder in later life and suggests that self-report and behavioral symptom profile in combination with white matter lesion and cortical thickness effectively characterizes distinct subtypes of LDD.

Association between serum free hemoglobin level and cerebral white matter hyperintensity volume in older adults.

The association between serum free hemoglobin (sfHb) level and white matter hyperintensity (WMH) volume is controversial. This study is to examine this association considering nonlinearity, sex dimorphism, and WMH type. We enrolled 704 older adults among the participants of the Korean Longitudinal Study on Cognitive Aging and Dementia and visitors to the Dementia Clinic of Seoul National University Bundang Hospital. We measured sfHb level in the venous blood and WMH volume (VWMH) using fluid-attenuated inversion recovery magnetic resonance images. The association between sfHb level and periventricular VWMH was linear in men (linear regression; ß = - 0.18, p = 0.006) and U-shaped in women (restricted cubic spline; F = 6.82, p < 0.001). sfHb level was not associated with deep VWMH in either sex. These findings were also observed in participants without anemia. To conclude, sfHb level is associated with periventricular VWMH in older adults of both sexes. Maintaining an optimal sfHb level may contribute to the prevention of WMH.

A Comparison Between the Performances of Verbal and Nonverbal Fluency Tests in Discriminating Between Mild Cognitive Impairments and Alzheimer's Disease Patients and Their Brain Morphological Correlates.

BACKGROUND AND PURPOSE: Verbal and nonverbal fluency tests are the conventional methods for examining executive function in the elderly population. However, differences in impairments result in fluency tests in patients with mild cognitive impairments (MCIs) and Alzheimer's disease (AD) and in neural correlates underlying the tests still necessitate concrete evidence. METHODS: We compared the test performances in 27 normal controls, 28 patients with MCI, and 20 with AD, and investigated morphological changes in association with the test performances using structural magnetic imaging. RESULTS: Patients with AD performed poorly across all the fluency tests, and a receiver operating characteristics curve analysis revealed that only category fluency test discriminated all the 3 groups. Association, category, and design fluency tests involved temporal and frontal regions, while letter fluency involved the cerebellum and caudate. CONCLUSIONS: Category fluency is a reliable measure for screening patients with AD and MCI, and this efficacy might be related to morphological correlates that underlie semantic and executive processing.

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.