Psychometric Properties of the Korean Version of THINC-integrated Tool (THINC-it-K): A Tool for Screening Assessment of Cognitive Function in Patients with Major Depressive Disorder.

Objective: : The present study was performed to investigate the validity and reliability of the Korean version of the THINC-it tool (THINC-it-K) in adult patients with major depressive disorder (MDD). Methods: : Subjects aged 19-65 years with recurrent MDD experiencing moderate to severe major depressive episode (n = 44) were evaluated and compared to age and sex matched healthy controls (n = 44). Subjects completed the THINC-it-K which includes variants of the Identification Task (IDN) using Choice Reaction Time, One-Back Test, Digit Symbol Substitution Test, Trail Making Test-Part B, and the Perceived Deficits Questionnaire for Depression-5-item (PDQ-5-D). Results: : A total of 75.0% of patients with MDD exhibited cognitive performance 1 standard deviation or below. The differences in Spotter (p = 0.001), Codebreaker (p = 0.001), PDQ-5-D (p ＜ 0.001) and objective THINC-it-K composite score (p = 0.002) were significant between the two groups. Concurrent validity of the THINC-it-K based on a calculated composite score was good (r = 0.856, p ＜ 0.001), and ranges for each component tests were from 0.076 (IDN) to 0.928 (PDQ-5-D). Conclusion: : The THINC-it-K exhibits good reliability and validity in adults with MDD. It could be a useful tool for the measurement of cognitive deficits in persons with MDD and should be implemented in clinical practice.

Changes in dementia treatment patterns associated with changes in the National Policy in South Korea among patients with newly diagnosed Alzheimer's disease between 2011 and 2017: results from the multicenter, retrospective CAPTAIN study.

BACKGROUND: The South Korean government has been actively involved in plans to combat dementia, implementing a series of national strategies and plans since 2008. In July 2014, eligibility for mandatory long-term care insurance (LTCI) was extended to people with dementia enabling access to appropriate long-term care including the cognitive function training program and home nursing service. This study aimed to investigate changes in treatment patterns for Alzheimer's disease (AD) between July 2011 and June 2017 which spanned the 2014 revision. METHODS: This multicenter, retrospective, observational study of patients with newly diagnosed AD analyzed electronic medical records from 17 general hospitals across South Korea. Based on their time of AD diagnosis, subjects were categorized into Cohort 1 (1 July 2011 to 30 June 2014) and Cohort 2 (1 July 2014 to 30 June 2017). RESULTS: Subjects (N=3,997) divided into Cohorts 1 (n=1,998) and 2 (n=1,999), were mostly female (66.4%) with a mean age of 84.4 years. Cohort 1 subjects were significantly older (P<0.0001) and had a lower number of comorbidities (P=0.002) compared with Cohort 2. Mean Mini-Mental State Examination (MMSE) scores in Cohorts 1 and 2 at the time of AD diagnosis or start of initial treatment were 16.9 and 17.1, respectively (P=0.2790). At 1 year, mean MMSE scores in Cohorts 1 and 2 increased to 17.9 and 17.4, respectively (P=0.1524). Donepezil was the most frequently administered medication overall (75.0%), with comparable rates between cohorts. Rates of medication persistence were ≥98% for acetylcholinesterase inhibitor or memantine therapy. Discontinuation and switch treatment rates were significantly lower (49.7% vs. 58.0%; P<0.0001), and mean duration of initial treatment significantly longer, in Cohort 2 vs. 1 (349.3 vs. 300.2 days; P<0.0001). CONCLUSIONS: Comparison of cohorts before and after revision of the national LTCI system for dementia patients found no significant difference in mean MMSE scores at the time of AD diagnosis or start of initial treatment. The reduction in the proportion of patients who discontinued or changed their initial treatment, and the significant increase in mean duration of treatment, were observed following revision of the LTCI policy which enabled increased patient access to long-term care.

A Brief Review of Paradigm Shifts in Prevention of Alzheimer's Disease: From Cognitive Reserve to Precision Medicine.

Alzheimer's disease (AD) and related dementias can be an enormous economic burden for taxpayers, patients, their families, medical systems, and society as a whole. Since disease-modifying treatments have failed, several studies have instead focused on a paradigm shift for preventing and treating AD. A higher cognitive reserve (e.g., greater education, occupational attainment, or more leisure activities) is associated with protection against disease-related cognitive decline. Precision medicine aims to optimize the effectiveness of disease prevention and treatment by considering specific biological components of individuals. We suggest that research into cognitive reserve and precision medicine could be a key to overcoming the limitations of traditional approaches to the prevention and treatment of AD.

An Exploration of the Oryza sativa L. Cyanidin-3-glucoside on the Cognitive Function in Older Adults with Subjective Memory Impairment.

OBJECTIVE: Cyanidin-3-glucoside (C3G), is a component of anthocyanin, have been considered to positively influence cognition and be beneficial for the prevention and treatment of dementia. We aimed to assess the safety and efficacy of cyanidin-3-glucoside-rich Oryza sativa L. (black rice) extract on cognitive function. METHODS: A 12-weeks double-blind randomized, placebo controlled trial assessed safety and cognitive outcomes in participants with subjective memory impairment (n=48) following consumption of 6 black rice extract capsules or a placebo. Cognitive function was assessed using the ADAS-cog and the CERAD-K. Subjective memory impairment also assessed. Safety was assessed by hematologic blood test, urine analysis, and participant reports of adverse events. RESULTS: There was significant improvement on subjective memory in intervention group. There was no statistically significant difference in objective cognitive outcomes following 12 weeks of consuming black rice extract. ADAS-cog scores, however, trended toward improvement in the intervention group compared to the placebo group. There was no adverse event. CONCLUSION: Although significant improvement in objective cognitive function was not proved, we found that C3G-rich Oryza sativa L. extract improves subjective memory in this study. Therefore the results may be informative of the possible effectiveness of the C3G-rich Oryza sativa L. on cognitive function.

Gender-Specific Association between Alcohol Consumption and Stress Perception, Depressed Mood, and Suicidal Ideation: The 2010-2015 KNHANES.

OBJECTIVE: Alcohol drinking can cause various psychiatric and medical diseases. Although women generally consume less alcohol than men, they may be at a greater risk for alcohol-related psychological distress. The aim of the current study is to evaluate whether the association between alcohol consumption and psychological distress, including stress, depressed mood, and suicidal ideation and the risks of psychological distress differ based on gender. METHODS: The cross-sectional study included 31,657 participants (17,915 women and 13,742 men) from the 2010-2013 and 2015 Korea National Health and Nutrition Examination Survey. Alcohol drinking and Alcohol Use Disorders Identification Test (AUDIT) levels were assessed for evaluating the amount of alcohol intake and alcohol-related problems. Self-perception of stress, depressed mood, and suicidal ideation were assessed for evaluating psychological distress. Odds ratio and 95% confidence intervals for psychological distress were calculated using multiple logistic regression models. RESULTS: The risks of psychological distress were not significantly associated with drinking level in both sexes. However, the risks of psychological distress were associated with an increase in AUDIT levels, and there were gender differences in the psychological consequences of alcohol-related problems. The association was more drastic in women, and women showed a significant association even though the severity of drinking problem was low with the exception of stress perception. CONCLUSION: The risks of psychological distress were associated with the severity of alcohol-related problems and women were more likely to be susceptible. Therefore, it is recommended that women even at low-risk for problematic drinking should be screened for psychological distress.

Corrigendum: A Brief Review of Paradigm Shifts in Prevention of Alzheimer's Disease: From Cognitive Reserve to Precision Medicine.

[This corrects the article DOI: 10.3389/fpsyt.2019.00786.].

Feasibility of Psychosocial Distress Screening and Management Program for Hospitalized Cancer Patients.

OBJECTIVE: Although the diagnosis and treatment of cancer is associated with psychosocial distress, routine distress screening is difficult in hospitalized oncology settings. We developed a consecutive screening program for psychosocial distress to promote psychiatric treatment of cancer patients and evaluated the feasibility of our program by Distress Thermometer (DT) and Hospital Anxiety and Depression Scale (HADS). METHODS: Among 777 cancer inpatients recruited from the Catholic Comprehensive Institute of Seoul St. Mary's Hospital, 499 agreed to complete primary distress screening through DT. We conducted secondary distress screening through HADS in 229 patients who had high scores of DT. RESULTS: Of the 499 participants, 270 patients with low scores of DT were included in the distress education program. 229 patients with high scores of DT received secondary distress screening through HADS. Among 115 patients with low scores of HADS, 111 patients received distress management. Among 114 patients with high scores in the secondary distress screening, 38 patients received psychiatric consultation service whereas 76 patients refused psychiatric consultation. CONCLUSION: Using consecutive screening for psychosocial distress appeared to be feasible in an inpatient oncology setting. Nevertheless, the low participation rate of psychiatric consultation service in cancer patients with high distress level should be improved.

Association between mental health status and bone mineral density: Analysis of the 2008-2010 Korea national health and nutrition examination survey.

The current study aimed to investigate the association between mental health status and bone mineral density (BMD) using data from the Korean National Health and Nutrition Examination Survey (KNHANES) 2008-2010. We enrolled 15,876 South Korean participants (4,010 postmenopausal females, 4,836 premenopausal females, and 7,016 males, all aged 20 years or older). BMD was measured using dual-energy radiography absorptiometry at the femoral neck (NK), lumbar spine (LSP), and total femur (TFM). Mental health status data were obtained from a self-report questionnaire that assessed psychological stress, depressed mood, and suicidal ideation. Psychological stress was negatively correlated with BMD in the LSP, NK, and TFM for the male group. Depressed mood was associated with lower BMD in the LSP, NK and TFM for the premenopausal female group, and in the LSP for the male group. Suicidal ideation was associated with lower BMD in the NK and TFM for the male group. Mental health problems were associated with lower BMD, especially in premenopausal females and males. Future investigations should focus on the shared pathophysiology between mental health problems and BMD, and the interrelationship between increased BMD and recovery from mental health problems.

Thalamic Shape and Cognitive Performance in Amnestic Mild Cognitive Impairment.

OBJECTIVE: This study aimed to investigate thalamic shape alterations and their relationships with various episodic memory impairments in subjects with amnestic mild cognitive impairment (aMCI). METHODS: We compared volumes and morphological alterations of the thalamus between aMCI subjects and healthy controls. In addition, we investigated the correlation between thalamic deformations and various memory impairments in aMCI subjects using a comprehensive neuropsychological battery. RESULTS: The normalized left thalamic volumes of the aMCI group were significantly smaller than those of the healthy control group (p<0.0001). aMCI subjects exhibited significant thalamic deformations in the left thalamic dorso-medial and antero-medial areas compared with healthy individuals. CERAD-K Word List Memory scores were significantly correlated with the left dorso-medial areas in aMCI subjects. There were no significant correlations between verbal fluency, Boston naming test, constructional praxis, Word List Recognition, and Visuospatial Recall scores and thalamic shape in aMCI subjects. Verbal delayed recall scores were also significantly correlated with the left dorso-medial areas in the aMCI group. CONCLUSION: Structural alterations in the thalamic deformations in the left dorso-medial and antero-medial areas might be core underlying neurobiological mechanisms of thalamic dysfunction related to Word List Memory and delayed verbal recall in individuals with aMCI.

Sub-regional volumes changes of the corpus callosum in the drug naive patients with late-onset depression.

Although sub-regional analysis methods of the corpus callosum (CC) have been developed, there has been no in vivo magnetic resonance imaging (MRI) study on a sub-regional volume analysis of the CC of late-onset depression (LOD). The aim of this study was to investigate the CC volume differences between LOD subjects and healthy elderly controls using a sub-regional analysis technique. Forty subjects with LOD and thirty nine group-matched healthy control subjects underwent 3T MRI scanning, and sub-regional volumes of the CC were measured and compared between the groups. The volumes of total (F=5.8, p=0.001), the anterior (F=5.2, p=0.001) and the posterior CC (F=5.1, p=0.001) were significantly reduced in the LOD group as compared to the control group. We measured cognitive functions in several different domains (language functions, verbal learning, visuospatial functions, delayed recall, memory consolidation, recognition memory, and executive functions) through the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease. The anterior CC volume in the LOD group showed significant positive correlation with the Verbal Fluency scores. The posterior CC volume in the LOD group was positively correlated significantly with the Word List Memory, the Word List Recall and the Constructional Praxis scores. This study is the first to elaborate the sub-regional volume differences of the CC between controls and LOD patients. These structural changes in the CC might be at the core of the underlying neurobiological mechanisms in LOD.

Is there a shared neurobiology between aggression and Internet addiction disorder?

PURPOSE: Evidences indicate that Internet addiction disorder (IAD) has a higher risk of developing aggression and violent behavior. A few correlation studies between IAD and aggression have implicated a common biological mechanism. However, neurobiological approaches to IAD and aggression have not yet been studied. METHODS: A literature search for studies for Internet addiction disorder or aggression was performed in the PubMed database and we selected articles about neurobiology of IAD or aggression. RESULTS: This review includes (a) common neural substrates such as the prefrontal cortex and the limbic system between aggression and IAD; (b) common neuromodulators such as dopamine, norepinephrine, serotonin, opiate and nicotine between aggression and IAD. CONCLUSIONS: Through reviewing the relevant literature, we suggested the possibility of common neurobiology between the two psychiatric phenomena and direction of research on aggression in IAD.

Neuroimaging findings in late-onset schizophrenia and bipolar disorder.

In recent years, there has been an increasing interest in late-onset mental disorders. Among them, geriatric schizophrenia and bipolar disorder are significant health care risks and major causes of disability. We discussed whether late-onset schizophrenia (LOS) and late-onset bipolar (LOB) disorder can be a separate entity from early-onset schizophrenia (EOS) and early-onset bipolar (EOB) disorder in a subset of late-life schizophrenia or late-life bipolar disorder through neuroimaging studies. A literature search for imaging studies of LOS or LOB was performed in the PubMed database. Search terms used were "(imaging OR MRI OR CT OR SPECT OR DTI OR PET OR fMRI) AND (schizophrenia or bipolar disorder) AND late onset." Articles that were published in English before October 2013 were included. There were a few neuroimaging studies assessing whether LOS and LOB had different disease-specific neural substrates compared with EOS and EOB. These researches mainly observed volumetric differences in specific brain regions, white matter hyperintensities, diffusion tensor imaging, or functional neuroimaging to explore the differences between LOS and LOB and EOS and EOB. The aim of this review was to highlight the neural substrates involved in LOS and LOB through neuroimaging studies. The exploration of neuroanatomical markers may be the key to the understanding of underlying neurobiology in LOS and LOB.

Development and validation of a smartphone addiction scale (SAS).

OBJECTIVE: The aim of this study was to develop a self-diagnostic scale that could distinguish smartphone addicts based on the Korean self-diagnostic program for Internet addiction (K-scale) and the smartphone's own features. In addition, the reliability and validity of the smartphone addiction scale (SAS) was demonstrated. METHODS: A total of 197 participants were selected from Nov. 2011 to Jan. 2012 to accomplish a set of questionnaires, including SAS, K-scale, modified Kimberly Young Internet addiction test (Y-scale), visual analogue scale (VAS), and substance dependence and abuse diagnosis of DSM-IV. There were 64 males and 133 females, with ages ranging from 18 to 53 years (M = 26.06; SD = 5.96). Factor analysis, internal-consistency test, t-test, ANOVA, and correlation analysis were conducted to verify the reliability and validity of SAS. RESULTS: Based on the factor analysis results, the subscale "disturbance of reality testing" was removed, and six factors were left. The internal consistency and concurrent validity of SAS were verified (Cronbach's alpha = 0.967). SAS and its subscales were significantly correlated with K-scale and Y-scale. The VAS of each factor also showed a significant correlation with each subscale. In addition, differences were found in the job (p<0.05), education (p<0.05), and self-reported smartphone addiction scores (p<0.001) in SAS. CONCLUSIONS: This study developed the first scale of the smartphone addiction aspect of the diagnostic manual. This scale was proven to be relatively reliable and valid.

Apathy and white matter integrity in Alzheimer's disease: a whole brain analysis with tract-based spatial statistics.

The aim of this study was to investigate the microstructural alterations of white matter (WM) in Alzheimer's disease (AD) patients with apathy and to observe the relationships with the severity of apathy. Sixty drug-naïve subjects took part in this study (30 apathetic and 30 nonapathetic subjects with AD). The loss of integrity in WM was compared in AD patients with and without apathy through measurement of fractional anisotropy (FA) using by tract-based spatial statistics (TBSS). In addition, we explored the correlation pattern between FA values and the severity of apathy in AD patients with apathy. The apathy group had significantly reduced FA values (p(corrected)<0.05) in the genu of the corpus callosum compared to the nonapathy group. The severity of apathy was negatively correlated with FA values of the left anterior and posterior cingulum, right superior longitudinal fasciculus, splenium, body and genu of the corpus callosum and bilateral uncinate fasciculusin the apathy group (p(corrected)<0.05). This study was the first to explore FA values in whole brain WM in AD patients with apathy. The findings of these microstructural alterations of WM may be the key to the understanding of underlying neurobiological mechanism and clinical significances of apathy in AD.

Reliability and validity of the korean version of the cornell scale for depression in dementia.

OBJECTIVE: The aim of this study was to explore the reliability and validity of the Korean version of the Cornell Scale for Depression in Dementia (CSDD-K), a scale for assessment of depression in dementia. METHODS: The original CSDD was translated into Korean and the content was verified through back-translation procedures. This study included 59 depressive patients with Alzheimer's disease (AD), 62 non-depressive patients with AD and 36 healthy elderly controls. The subjects were assessed using CSDD-K, the 17-item Hamilton Depression Rating Scale (HAM-D(17)), the 15-item Korean version of Geriatric Depression Scale (GDS(15)) and the Korean version of Mini-mental Status Examination (MMSE-K). RESULTS: In the reliability test, Cronbach's α coefficient and test-retest reliabilities were 0.92 and 0.91, respectively, indicating that the CSDD-K has good internal consistency. There were significant differences in CSDD-K total scores between AD patients with depression and AD patients without depression (p<0.001). In the analysis of the concurrent validity of the CSDD-K, there were significant correlations between the CSDD-K and HAM-D(17) (r=0.91, p<0.001) and between the CSDD-K and GDS(15) (r=0.75, p<0.001). ROC curve analysis identified a cut-off score of 7 for the CSDD-K, where the sensitivity was 87.5% and the specificity was 100%. Factor analysis resulted in a four-factor solution accounting for 63.8% of the common variance. CONCLUSION: The CSDD-K showed good reliability and validity for the assessment of depressive symptom severity in AD patients. The CSDD-K is a useful instrument for assessing AD patients with depressive symptoms in Korean ethnic population.

Automated hippocampal subfield segmentation in amnestic mild cognitive impairments.

Although a few automated hippocampal subfield segmentation methods have been developed, the effects of amnestic mild cognitive impairment (aMCI) on the hippocampal subfield volumes on magnetic resonance imaging (MRI) are not clear. The aim of this study was to investigate the hippocampal subfield volume changes and their relationships with various neuropsychological tests in aMCI using an automated hippocampal subfield segmentation technique. Forty-five subjects with aMCI and 49 group-matched healthy control subjects underwent 3-tesla MRI scanning, and hippocampal subfield volumes were measured and compared. Additionally, we explored the correlation pattern between hippocampal subfield volumes and the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K) neuropsychological test scores in aMCI subjects. Subjects with aMCI exhibited significant hippocampal volume reductions in the presubiculum, subiculum and cornu ammonis 2-3 areas compared with healthy subjects. In addition, we also found significant positive correlations between presubiculum and subicular area volumes and the CERAD-K verbal and visuospatial delayed recall scores in aMCI. This study was the first to explore the relationships between hippocampal subfield volumes and various types of cognitive performances in aMCI. These structural changes might be at the core of the underlying neurobiological mechanisms of hippocampal dysfunction in aMCI.

Automated hippocampal subfields segmentation in late life depression.

Although a few automated hippocampal subfields segmentation methods have been developed, there has been no in vivo Magnetic Resonance Imaging (MRI) study on the hippocampal subfields volumes of Late Life Depression (LLD). The aim of this study was to investigate the hippocampal subfields volume differences between LLD subjects and healthy elderly controls using an automated hippocampal subfields segmentation technique. Thirty subjects with LLD and 30 group-matched healthy control subjects underwent 3T MRI scanning, and hippocampal subfields volumes were measured and compared between the groups. Subjects with LLD exhibited significant hippocampal volume reductions in the total hippocampus, subiculum, and Cornu Ammonis (CA) 2-3 areas compared with healthy subjects (uncorrected, p<0.001). This study is the first to elaborate the subfields volume differences of both hippocampi between controls and LLD patients. These structural changes in the hippocampal presubiculum, subiculum, and CA2-3 areas might be at the core of the underlying neurobiological mechanisms of hippocampal dysfunction in LLD.

Relationships between hippocampal shape and cognitive performances in drug-naïve patients with Alzheimer's disease.

Previous studies provided hippocampal shape analysis of Alzheimer's disease (AD) patients using automated segmentation techniques. However, the relationships between the hippocampal deformations and various cognitive impairments were not clear. The aim of this study was to investigate hippocampal shape changes and their relationship to cognitive impairments. Fifty-one drug-naïve patients with AD and 50 group-matched healthy control subjects underwent 3T MRI scanning, and the hippocampal volumes and deformations were compared between the groups. Additionally, we explored the correlation pattern between the hippocampal deformations and the cognitive dysfunctions in AD using the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K). AD subjects exhibited significant hippocampal deformations in the cornu ammnonis (CA1) and subiculum areas compared to those in healthy subjects (p<0.05, false discovery rate (FDR) corrected). Significant correlations were observed between hippocampal deformations in CA1 and subiculum areas and verbal immediate recall, verbal delayed recall, verbal recognition memory, and constructional recall scores (p<0.05, FDR corrected). This study was the first to explore the relationships between hippocampal deformations and various cognitive impairments of drug-naïve patients with AD. These structural changes in hippocampal CA1 and subiculum areas might be the core of the underlying neurobiological mechanisms of hippocampal dysfunction and their relevance to the various cognitive dysfunctions in AD.

Hippocampal shape and cognitive performance in amnestic mild cognitive impairment.

Previous studies have carried out hippocampal shape analysis of amnestic mild cognitive impairment (aMCI) patients using automated segmentation techniques. However, the relationships between hippocampal deformations and various episodic memory impairments were not clear. The aim of this study was to investigate hippocampal shape changes and their relationships with various episodic memory impairments in aMCI. Hippocampal volumes and deformations were compared between the aMCI and the controls. In addition, we explored the correlation pattern between hippocampal deformations and cognitive dysfunctions in aMCI using a comprehensive neuropsychological battery. Patients with aMCI exhibited significant hippocampal deformations in the right cornu ammonis 1 (CA1) and subiculum areas compared with healthy individuals. Significant correlations were observed between constructional recall scores and the right CA1 and subiculum areas in aMCI. Verbal delayed recall scores were also significantly correlated with the left CA1 and subiculum areas in aMCI. This study was the first to explore the relationships between hippocampal deformations and various types of cognitive performances in aMCI. These structural changes in the hippocampal CA1 and subiculum areas might be at the core of underlying neurobiological mechanisms of hippocampal dysfunction and their relevance to verbal and visuospatial delayed recall in aMCI.

Regional cortical thickness and subcortical volume changes are associated with cognitive impairments in the drug-naive patients with late-onset depression.

Previous studies have shown an association between late-onset depression (LOD) and cognitive impairment in older adults. However, the neural correlates of this relationship are not yet clear. The aim of this study was to investigate the differences in both cortical thickness and subcortical volumes between drug-naive LOD patients and healthy controls and explore the relationship between LOD and cognitive impairments. A total of 48 elderly, drug-naive patients with LOD and 47 group-matched healthy control subjects underwent 3T MRI scanning, and the cortical thickness was compared between the groups in multiple locations, across the continuous cortical surface. The subcortical volumes were also compared on a structure-by-structure basis. Subjects with LOD exhibited significantly decreased cortical thickness in the rostral anterior cingulate cortex, the medial orbitofrontal cortex, dorsolateral prefrontal cortex, the superior and middle temporal cortex, and the posterior cingulate cortex when compared with healthy subjects (all p<0.05, false discovery rate corrected). Reduced volumes of the right hippocampus was also observed in LOD patients when compared with healthy controls (p<0.001). There were significant correlations between memory functions and cortical thickness of medial temporal, isthmus cingulate, and precuneus (p<0.001). This study was the first study to explore the relationships between the cortical thickness/subcortical volumes and cognitive impairments of drug-naive patients with LOD. These structural changes might explain the neurobiological mechanism of LOD as a risk factor of dementia.