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.

Evidence of risky driving in Korean older adults: A longitudinal cohort.

OBJECTIVES: The aim of this study was to determine the differences in the risk factors for dangerous driving between older adults with normal cognition and those with cognitive impairment. DESIGN: The driving risk questionnaire (DRQ) that was applied to a community-dwelling older adult cohort and 2 years of accident/violation records from the National Police Agency were analyzed. We conducted regression analyses with the presence or absence of risky driving based on records (accidents + violations) 2 years before and after evaluation as a dependent variable and dichotomized scores of each risky driving factor as independent variables. RESULTS: According to four identified factors-crash history, safety concern, reduced mileage, and aggressive driving-significant associations were found between risky driving over the past 2 years and crash history and for aggressive driving in the normal cognition group. In the cognitive impairment group, only crash history was significantly associated, although safety concerns showed a trend toward significance. CONCLUSIONS: In this study, it was suggested that the factors of DRQ have a significant association with actual risky driving. Our results are expected to contribute to establishing the evidence for evaluating and predicting risky driving and advising whether to continue driving in clinics.

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.

Executive dysfunction and risk of suicide in older adults: a population-based prospective cohort study.

OBJECTIVE: It is uncertain what factors increases the risk of suicide in older adults without depression, and it is unknown whether executive dysfunction (ED) is one of those factors. We aimed to examine the effect of ED on the risk of suicide in non-demented older adults without depression. METHODS: In an ongoing population-based prospective cohort of Korean older adults, we identified suicide using the National Mortality Database and suicidal ideation or attempt (SIA) based on the Korean version of the Mini International Neuropsychiatric Interview. We defined ED as performing below -1.5 SD of age-adjusted, gender-adjusted and education-adjusted norms in any of following tests: Frontal Assessment Battery, Trail Making Test A, Digit Span Test or Verbal Fluency Test. RESULTS: The mean age of the 4791 participants at baseline was 69.7 (SD 6.4) years, and 57.1% of them were women (mean follow-up duration=4.9 years). ED at baseline increased the risk of suicide by about seven times (HR 7.20, 95% CI 1.84 to 28.12, p=0.005) but did not change the risk of SIA. However, cognitive impairment without ED did not change the risks of suicide and SIA. In participants with ED, being aged 75 years or above, living alone, and having a low socioeconomic status were associated with the risk of suicide. CONCLUSION: ED is a strong risk factor of late life suicide independent from depression, particularly in very old adults living in disadvantaged environments.

Chronic subsyndromal depression and risk of dementia in older adults.

OBJECTIVES: Subsyndromal depression is prevalent and associated with poor outcomes in late life, but its effect on the risk of dementia has barely been investigated. This study is aimed to investigate the effect of subsyndromal depression on dementia risk in cognitively normal older adults and patients with mild cognitive impairment. METHODS: Data were collected from a nationwide, population-based, prospective cohort study on a randomly sampled Korean elderly population aged 60 years or older, which has been followed every 2 years. Using 6-year follow-up data of 4456 non-demented elderly, the authors examined the risk of dementia associated with late-onset subsyndromal depression using multivariate Cox proportional hazard models. After standardized diagnostic interviews, subsyndromal depression and dementia were diagnosed by the operational diagnostic criteria and Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria, respectively. RESULTS: Subsyndromal depression tripled the risk of dementia in non-demented elderly individuals (hazard ratio = 3.02, 95% confidence interval = [1.56, 5.85], p < 0.001). In subgroup analyses, subsyndromal depression was associated with the risk of dementia in cognitively normal participants only (hazard ratio = 4.59, 95% confidence interval = [1.20, 17.54], p = 0.026); chronic/recurrent subsyndromal depression with increasing severity during the follow-up period was associated with the risk of dementia (hazard ratio = 15.34, 95% confidence interval = [4.19, 56.18], p < 0.001). CONCLUSION: Late-onset subsyndromal depression is a potential predictor of incident dementia when it is chronic or recurrent with increasing severity in cognitively normal older adults.

Does parity matter in women's risk of dementia? A COSMIC collaboration cohort study.

BACKGROUND: Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied. METHODS: We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries over 3 continents, including 14,792 women aged 60 years or older. We investigated the association between parity and the risk of dementia using logistic regression models that adjusted for age, educational level, hypertension, diabetes mellitus, and cohort, with additional analyses by region and dementia subtype. RESULTS: Across all cohorts, grand multiparous (5 or more childbirths) women had a 47% greater risk of dementia than primiparous (1 childbirth) women (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.10-1.94), while nulliparous (no childbirth) women and women with 2 to 4 childbirths showed a comparable dementia risk to primiparous women. However, there were differences associated with region and dementia subtype. Compared to women with 1 to 4 childbirths, grand multiparous women showed a higher risk of dementia in Europe (OR = 2.99, 95% CI = 1.38-6.47) and Latin America (OR = 1.49, 95% CI = 1.04-2.12), while nulliparous women showed a higher dementia risk in Asia (OR = 2.15, 95% CI = 1.33-3.47). Grand multiparity was associated with 6.9-fold higher risk of vascular dementia in Europe (OR = 6.86, 95% CI = 1.81-26.08), whereas nulliparity was associated with a higher risk of Alzheimer disease (OR = 1.91, 95% CI 1.07-3.39) and non-Alzheimer non-vascular dementia (OR = 3.47, 95% CI = 1.44-8.35) in Asia. CONCLUSION: Parity is associated with women's risk of dementia, though this is not uniform across regions and dementia subtypes.

Epidemiological characteristics of subsyndromal depression in late life.

OBJECTIVES: Subsyndromal depression is prevalent and associated with poor outcomes in late life, but its epidemiological characteristics have barely been investigated. The aim of this prospective cohort study is to compare the prevalence, incidence and risk factors of subsyndromal depression with those of syndromal depression including major and minor depressive disorders in community-dwelling elderly individuals. METHODS: In a nationwide community-based study of randomly sampled Korean elderly population aged 60 years or older (N = 6640), depression was assessed with standardized diagnostic interviews. At baseline and at 2-year and 4-year follow-ups, the authors diagnosed subsyndromal depression by the operational criteria and syndromal depression by the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) diagnostic criteria. Multivariate logistic regression analyses were conducted to identify the risk factors for incident depression. RESULTS: The age- and gender-adjusted prevalence rate of subsyndromal depression was 9.24% (95% confidence interval = [8.54, 9.93]), which was 2.4-fold higher than that of syndromal depression. The incidence rate of subsyndromal depression was 21.70 per 1000 person-years (95% confidence interval = [19.29, 24.12]), which was fivefold higher than that of syndromal depression. The prevalence to incidence ratio of subsyndromal depression was about half that of syndromal depression. The risk for subsyndromal depression was associated with female gender, low socioeconomic status, poor social support and poor sleep quality, while that of syndromal depression was associated with old age and less exercise. CONCLUSION: Subsyndromal depression should be validated as a clinical diagnostic entity, at least in late life, since it has epidemiological characteristics different from those of syndromal depression.

Sleep and cognitive decline: A prospective nondemented elderly cohort study.

OBJECTIVE: To investigate sleep disturbances that induce cognitive changes over 4 years in nondemented elderlies. METHODS: Data were acquired from a nationwide, population-based, prospective cohort of Korean elderlies (2,238 normal cognition [NC] and 655 mild cognitive impairment [MCI]). At baseline and 4-year follow-up assessments, sleep-related parameters (midsleep time, sleep duration, sleep latency, subjective sleep quality, sleep efficiency, and daytime dysfunction) and cognitive status were measured using the Pittsburgh Sleep Quality Index and Consortium to Establish a Registry for Alzheimer's Disease Assessment, respectively. We used logistic regression models adjusted for covariates including age, sex, education, apolipoprotein E genotype, Geriatric Depression Scale, Cumulative Illness Rating Scale, and physical activity. RESULTS: In participants with NC, long sleep latency (>30 minutes), long sleep duration (≥7.95 hours), and late midsleep time (after 3:00 am) at baseline were related to the risk of cognitive decline at 4-year follow-up assessment; odds ratio (OR) was 1.40 for long sleep latency, 1.67 for long sleep duration, and 0.61 for late midsleep time. These relationships remained significant when these variables maintained their status throughout the follow-up period. Newly developed long sleep latency also doubled the risk of cognitive decline. In those with MCI, however, only long sleep latency reduced the chance of reversion to NC (OR = 0.69). INTERPRETATION: As early markers of cognitive decline, long sleep latency can be used for elderlies with NC or MCI, whereas long sleep duration and relatively early sleep time might be used for cognitively normal elderlies only. Ann Neurol 2018;83:472-482.

Application of the European quality indicators for psychosocial dementia care in long-term care facilities in the Asia-Pacific region: a pilot study.

OBJECTIVES: An Asia-Pacific regional collaboration group conducted its first multi-country research project to determine whether or not European quality indicators (QIs) for psychosocial care in dementia could be implemented as a valid tool in residential aged care across seven Asia-Pacific sites (Australia, Hong Kong Special Administrative Region, Mainland China, Malaysia, Singapore, South Korea, and Thailand). METHOD: Following the European QI protocol, auditing and data extraction of medical records of consenting residents with dementia were conducted by trained auditors with relevant health care backgrounds. Detailed field notes by the auditors were also obtained to describe the characteristics of the participating care facilities, as well as key issues and challenges encountered, for each of the 12 QIs. RESULTS: Sixteen residential care facilities in the seven Asia-Pacific sites participated in this study. Data from 275 residents' records revealed each of the 12 Qis' endorsement varied widely within and between the study sites (0%-100%). Quality of the medical records, family and cultural differences, definitions and scoring of certain indicators, and time-consuming nature of the QI administration were main concerns for implementation. CONCLUSION: Several items in the European QIs in the current format were deemed problematic when used to measure the quality of psychosocial care in the residential aged care settings in participating Asia-Pacific countries. We propose refinements of the European QIs for the Asian-Pacific context, taking into account multiple factors identified in this study. Our findings provide crucial insights for future research and implementation of psychosocial dementia care QIs in this region.

Prevalence Rates of Dementia and Mild Cognitive Impairment Are Affected by the Diagnostic Parameter Changes for Neurocognitive Disorders in the DSM-5 in a Korean Population.

AIM: To examine the impact of the revised diagnostic criteria for neurocognitive disorders (NCDs) in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) on the prevalence of dementia and mild cognitive impairment (MCI). METHODS: A total of 755 participants aged 65 years or older in the Nationwide Survey on Dementia Epidemiology in Korea 2012 were rediagnosed according to the DSM-5 criteria. RESULTS: The estimated age-, gender-, education-, and urbanicity-standardized prevalence rates of major and mild NCDs were 8.35 and 11.10%, respectively, and those of dementia and MCI were 8.74 and 31.85%, respectively. Cohen's κ for dementia and major NCD was 0.988, and that for MCI and mild NCD was 0.273. CONCLUSION: Diagnostic discrepancies between major/mild NCDs and dementia/MCI might depend on the operationalization of neuropsychological performance criteria.

A normative study of total scores of the CERAD neuropsychological assessment battery in an educationally diverse elderly population.

BACKGROUND: This study aimed to investigate the influences of age, education, and gender on the two total scores (TS-I and TS-II) of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological assessment battery (CERAD-NP) and to provide normative information based on an analysis for a large number of elderly persons with a wide range of educational levels. METHODS: In the study, 1,987 community-dwelling healthy volunteers (620 males and 1,367 females; 50-90 years of age; and zero to 25 years of education) were included. People with serious neurological, medical, and psychiatric disorders (including dementia) were excluded. All participants underwent the CERAD-NP assessment. TS-I was generated by summing raw scores from the CERAD-NP subtests, excluding Mini-Mental State Examination and Constructional Praxis (CP) recall subtests. TS-II was calculated by adding CP recall score to TS-I. RESULTS: Both TS-I and TS-II were significantly influenced by demographic variables. Education accounted for the greatest proportion of score variance. Interaction effect between age and gender was found. Based on the results obtained, normative data of the CERAD-NP total scores were stratified by age (six overlapping tables), education (four strata), and gender. CONCLUSIONS: The normative information will be very useful for better interpretation of the CERAD-NP total scores in various clinical and research settings and for comparing individuals' performance of the battery across countries.

Improvement of dementia screening accuracy of mini-mental state examination by education-adjustment and supplementation of frontal assessment battery performance.

This study aimed to investigate whether the demographic variable-adjustment and supplementation of Frontal Assessment Battery (FAB) score can improve the screening ability of Mini-Mental State Examination (MMSE) for dementia and its subtypes. Five hundred forty-one non-demented comparison (NC) and 474 dementia (320 Alzheimer's disease [AD]; 139 non-Alzheimer's disease dementia [NAD]; and 15 mixed AD-NAD dementia) individuals living in the community were included. Education-adjusted MMSE (MMSE-edu) score showed significantly better screening accuracy for overall dementia, AD, and NAD than MMSE raw score. FAB-supplemented MMSE (MMSE-FAB) score had significantly better screening ability for NAD, but not for overall dementia and AD, than MMSE raw score alone. Additional supplementation of FAB to MMSE-edu further increased the ability for overall dementia or NAD screening, but not for AD screening. Further education adjustment of MMSE-FAB also improved its ability for overall dementia, AD, and NAD screening. These results strongly support the usefulness of education-adjustment and supplementation of frontal function assessment to improve screening performance of MMSE for dementia and its subtypes, NAD in particular.

A Preliminary Study on the Potential Protective Role of the Antioxidative Stress Markers of Cognitive Impairment: Glutathione and Glutathione Reductase.

Objective: : To investigate the relationship between reduced glutathione (GSH), a key molecule of the antioxidant defense system in the blood, and glutathione reductase (GR), which reduces oxidized glutathione (glutathione disulfide [GSSG]) to GSH and maintains the redox balance, with the prevalence of Alzheimer's dementia and cognitive decline. Methods: : In all, 20 participants with Alzheimer's dementia who completed the third follow-up clinical evaluation over 6 years were selected, and 20 participants with normal cognition were selected after age and sex matching. The GSH and GR concentrations were the independent variables. Clinical diagnosis and neurocognitive test scores were the dependent variables indicating cognitive status. Results: : The higher the level of GR, the greater the possibility of having normal cognition than of developing Alzheimer's dementia. Additionally, the higher the level of GR, the higher the neurocognitive test scores. However, this association was not significant for GSH. After 6 years, the conversion rate from normal cognition to cognitive impairment was significantly higher in the lower 50th percentile of the GR group than in the upper 50th percentile. Conclusion: : The higher the GR, the lower the prevalence of Alzheimer's dementia and incidence of cognitive impairment and the higher the cognitive test scores. Therefore, GR is a potential protective biomarker against Alzheimer's dementia and cognitive decline.

Choline acetyltransferase 2384G>a polymorphism and the risk of Alzheimer disease.

The potential association between choline acetyltransferase (CHAT) polymorphism and the risk of Alzheimer disease (AD) has been controversial. We examined the main effect of CHAT polymorphism and its interaction with apolipoprotein E (APOE) polymorphism in the development of AD in a well-powered elderly Korean sample. We analyzed CHAT 2384G>A polymorphism and APOE polymorphism among 736 Korean patients with probable AD and 1386 nondemented Korean controls. We tested the association between AD and CHAT genotype using a logistic regression model. In addition, we used generalized multifactor dimensionality reduction to investigate the interaction between CHAT and APOE with regard to the risk of AD. The CHAT A allele was associated with AD risk in a dose-dependent manner (odds ratio=1.40, 95% confidence interval=1.06-1.85, P=0.018 for heterozygotes; and odds ratio=3.92, 95% confidence interval=1.78-8.58, P=0.001 for homozygotes). The generalized multifactor dimensionality reduction approach identified a significant gene-gene interaction between CHAT and APOE (Balanced accuracy score=0.647, P=0.001). The CHAT A/A genotype was associated with earlier onset of AD (F=5.070, df=2, P=0.007). The CHAT A allele was associated with AD risk in a dose-dependent manner, and its interaction with the APOE ε4 allele was significant with regard to the development of AD. The CHAT A allele was also associated with earlier onset and possibly accelerated progression of AD.

Association Between Plasma Monocyte Trafficking-Related Molecules and Future Risk of Depression in Older Adults.

BACKGROUND: The recruitment of monocytes to the brain plays an important role in the development of depression. However, the association between plasma biomarkers of monocyte trafficking and depression is unclear. This study is aimed to examine the effects of plasma monocyte chemoattractant protein 1 (MCP-1), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) on the risk of depression. METHODS: Data were acquired from an ongoing prospective cohort study involving randomly sampled, community-dwelling Korean older adults, which has been followed every 2 years. We included 1539 euthymic older adults (age = 68.2 [5.6] years; 51.7% were women) without a history of major psychiatric disorders and dementia and neurological diseases. Geriatric psychiatrists diagnosed incident depression through a structured interview using the Korean version of the Mini-International Neuropsychiatric Interview. RESULTS: Depression had developed in 134 (8.7%) participants during the follow-up period of 5.7 (0.8) years. The high-plasma MCP-1 tertile group showed twofold higher risk of depression than the low-plasma MCP-1 tertile group (hazards ratio = 2.00, 95% confidence interval = 1.27-3.13, p = .003). The association between high levels of plasma MCP-1 and future risk of depression was significant in the middle-plasma ICAM-1 and VCAM-1 tertile groups; the high-plasma MCP-1 tertile group showed about fourfold higher risk of depression than the low-plasma MCP-1 tertile group. CONCLUSIONS: Molecules involved in monocyte trafficking may be good candidates as diagnostic biomarkers and/or therapeutic targets for late-life depression.

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.

Dual Sensory Impairment and Cognitive Impairment in the Korean Longitudinal Elderly Cohort.

OBJECTIVE: To investigate the effects of single sensory impairment (SSI; visual or auditory) or dual sensory impairment (DSI; visual and auditory) on dementia and longitudinal changes of neuropsychological test scores. METHODS: In this nationwide, prospective, community-based elderly cohort study, KLOSCAD (the Korean Longitudinal Study on Cognitive Aging and Dementia), 6,520 elderly individuals (58-101 years) representing the general population were included. We defined visual and auditory sensory impairment via self-report questionnaire: 932 had normal sensory function, 2,957 had an SSI, and 2,631 had a DSI. Demographic and clinical variables including cognitive outcomes were evaluated every 2 years over 6 years. Through logistic regression, Cox regression, and linear mixed model analysis, the relationship between SSI or DSI and dementia prevalence, dementia incidence, and change in neuropsychological scores were evaluated. RESULTS: At baseline, DSI was significantly associated with increased dementia prevalence compared to normal sensory function (odds ratio [OR] 2.17, 95% confidence interval [CI] 1.17-4.02), but SSI was not (OR 1.27, 95% CI 0.66-2.41). During the 6-year follow-up, the incidence of dementia was significantly higher in the DSI group than in the normal sensory function group (hazard ratio 1.9, 95% CI 1.04-3.46) and neuropsychological scores significantly decreased (ß -0.87, 95% CI [-1.17 to -0.58]). CONCLUSIONS: Our results suggest that coexisting visual and hearing impairments facilitate dementia prevalence, dementia incidence, and cognitive decline, but visual or hearing impairment alone do not. Visual and hearing impairment may lead to dementia or cognitive decline independent of Alzheimer pathology.

Hypohomocysteinemia may increases the risk of dementia and Alzheimer's disease: A nationwide population-based prospective cohort study.

BACKGROUND: Hyperhomocysteinemia has been repeatedly found to increase the risk of dementia. However, the effects of hypohomocysteinemia on the risk of dementia have been barely investigated. If hypohomocysteinemia, like hyperhomocysteinemia, increases the risk of dementia, misuse or overuse of homocysteine-lowing agents such as vitamin supplements may increase the risk of dementia. AIMS: To investigate whether hypohomocysteinemia, like hyperhomocysteinemia, could increase the risk of dementia and Alzheimer's disease (AD) in a large population-based cohort of older adults. METHODS: This prospective cohort study followed 2655 randomly sampled, community-dwelling, non-demented individuals aged 60 years or older from 2010 to 2018. We measured baseline serum total homocysteine (tHcy) levels and examined the effect of serum tHcy on the risks of dementia and AD using Cox proportional hazards models. RESULTS: During the follow-up period (mean = 5.4 years, SD = 0.9), dementia and AD developed in 85 and 64 participants, respectively. Not only the participants with high serum tHcy (≥10.6 µmol/L) but also those with low serum tHcy (≤8.9 µmol/L) were 4-5 times more likely to develop dementia and AD compared to those with serum tHcy levels between 9.0 and 10.5 µmol/L. With the increase in serum tHcy concentration, the use of vitamin supplements decreased, and 41.2% of the participants with low serum tHcy (≤8.9 µmol/L) were taking vitamin supplements. CONCLUSIONS: Not only hyperhomocysteinemia but also hypohomocysteinemia considerably increased the risk of dementia and AD in older adults. The risk of dementia that results from overuse or misuse of vitamin supplements should be acknowledged and homocysteine-lowering health policies should be tailored to consider dementia risks that are associated with hypohomocysteinemia.

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.

Discrimination of normal aging, MCI and AD with multimodal imaging measures on the medial temporal lobe.

This study aimed to compare the discrimination accuracy of hippocampal volume (HC-Vol), parahippocampal cingulum fractional anisotropy (PHC-FA), hippocampal glucose metabolism (HC-Glu), and any combination of the three measurements among normal control (NC), mild cognitive impairment (MCI), and Alzheimer's disease (AD). Three-dimensional MRI, diffusion tensor imaging, and FDG-PET were applied to age- and gender-matched 17 NC, 17 MCI, and 17 mild AD patients. Subjects also underwent a neuropsychological test battery including three verbal episodic memory tests. Logistic regression analyses were systematically conducted to select the best model for between-group discrimination. PHC-FA plus HC-Vol model, HC-Glu only model, and the model combining all three modalities were finally chosen for NC vs. MCI (discrimination accuracy: 79.4%), MCI vs. AD (73.5%), and NC vs. AD discrimination (94.1%), respectively. All the three imaging measures also showed significant correlation with all three episodic memory tests. These findings support that each imaging measure, respectively, and their combination have a stage-specific potential as a useful neuroimaging marker for detection and progression monitoring of early stage of AD.