Risk Score for Predicting Mortality in People With Dementia: A Nationwide, Population-Based Cohort Study in Taiwan With 11 Years of Follow-Up.

OBJECTIVE: Many researchers and physicians attempt to determine the prognosis and short- and long-term mortality risks of dementia for formulating suitable care plans for patients and their families. However, the published prediction models have been insufficient for this purpose and have worked only in certain specific populations. For medical autonomy and end-of-life decisions, an informative tool to predict 6-month, 1-year, 2-year, 3-year, and 5-year mortality rates for dementia patients merits further investigation. METHODS: Patients aged ≥ 65 years who received ICD-9-CM diagnoses of dementia between 2002 and 2009 were identified from Taiwan's National Health Insurance Research Database and followed until the end of 2013. Patient characteristics and comorbidities that were considered potential risk factors for mortality were assessed. Mortality-predicting risk scores were developed using a regression coefficient-based scoring approach. In total, 6,556 patients were identified and then randomly divided into a derivation cohort (n = 4,371) and validation cohort (n = 2,185). RESULTS: By the end of the study, 1,693 of the 4,371 dementia patients (38.7%) in the derivation cohort were deceased. Mean duration of follow-up was 6.26 years. Eleven acute and chronic factors were identified for building the predictive score model, which produced scores from 0 to 24 points (higher scores indicated higher mortality). The score model exhibited good predictive power for various life expectancies (area under receiver operating characteristic curve: 6-month = 0.852, 1-year = 0.779, 2-year = 0.725, 3-year = 0.721, 5-year = 0.703) and good calibration in the validation cohort (Hosmer-Lemeshow test, χ² = 4.709, P = .788). CONCLUSIONS: The developed predictive score model may be the first tool that uses the same clinical factors to determine both short- and long-term mortality risks in patients with dementia.

Caregiver active participation in psychoeducational intervention improved caregiving skills and competency.

AIM: To determine whether giving dementia caregivers active psychoeducational intervention is more efficacious than passive intervention for improving their caregiving skills and reducing their caregiving burden. METHODS: This study was a prospective, single-blinded, controlled trial with 43 caregiver/person-with-dementia dyads. The dyads were randomly assigned to the active psychoeducational intervention (AP) group, which used role-play, discussion, and development of problem-solving capacity to build up their caregiving skills and competence, or the passive psychoeducational intervention (PP) group, which gave caregivers educational materials on common caregiving strategies. Primary outcomes were the levels of caregiver competence (Care Skill Inventory [CSI]), burden (Chinese Zarit Burden Inventory [CZBI]), and distress caused by the behavioral and psychological symptoms of dementia (Neuropsychiatric Inventory-Questionnaire [NPI-Q]). Outcomes were assessed pre-test, post-test and after 3 months. Repeated measures one-way analysis of variance was used to compare mean-change scores between time-points, and generalized estimating equations (GEE) were used to compare groups. RESULTS: Post-test or 3-month (or both) Care Skill Inventory, Chinese Zarit Burden Inventory and Neuropsychiatric Inventory-Questionnaire distress levels were significantly (p < 0.05) better in the AP but not in the PP group. The generalized estimating equation intergroup comparison, adjusted for potential confounders, showed that Care Skill Inventory in the AP group was more significantly improved than in the PP group, and that Chinese Zarit Burden Inventory nearly reached significance. CONCLUSIONS: Active rather than passive psychoeducation, even in a short (3 months) intervention of six visits, was more efficacious for improving caregiving competence. Future studies will require larger samples. Geriatr Gerontol Int 2018; 18: 750-757.

The epidemiology and burden of Alzheimer's disease in Taiwan utilizing data from the National Health Insurance Research Database.

PURPOSE: The objectives of this study were to estimate the incidence, cumulative incidence, and economic burden of Alzheimer's disease (AD) in Taiwan, using data from the National Health Insurance Research Database (NHIRD). MATERIALS AND METHODS: This was a retrospective, longitudinal, observational study using data from the Longitudinal Health Insurance Database of the NHIRD. Patients were included in this study if they were 50 years of age or older and their records included a primary or secondary diagnosis of AD. New patients who met inclusion criteria were followed up longitudinally from 2005 to 2010. Costs were calculated for the first year following the diagnosis of AD. RESULTS: Overall, a higher percentage of women than men were diagnosed with AD (54% vs 46%, respectively). The first AD diagnosis occurred most frequently in the age of 75-84 years. The person-year incidence rate increased from 5.63/1,000 persons (95% CI, 5.32-5.94) in 2005 to 8.17/1,000 persons (95% CI, 7.78-8.57) in 2010. The cumulative incidence rate was 33.54/1,000 persons (95% CI, 32.76-34.33) in 2005-2010. The total mean inflated annual costs per patient in new Taiwan dollars (NT$) in the first year of diagnosis ranged from NT$205,413 (2009) to NT$227,110 (2005), with hospitalization representing the largest component. CONCLUSION: AD represents a substantial burden in Taiwan, and based on the observed increase in incidence rate over time, it is likely that this burden will continue to increase. The findings reported here are consistent with previous research. The NHIRD contains extensive real-world information that can be used to conduct research, allowing us to expand our understanding of the incidence, prevalence, and burden of disease in Taiwan.

Depression of Family Caregivers Is Associated with Disagreements on Life-Sustaining Preferences for Treating Patients with Dementia.

BACKGROUND: Family caregivers may not agree with patients with dementia regarding attitudes toward end-of-life preferences, and the effects of this type of disagreement are not well understood. This study sought to identify such a disagreement and its predictors. METHODS: A cross-sectional sample of 84 family caregivers and patients with dementia was recruited from memory clinics. We used the Mini-Mental State Examination, Neuropsychiatric Inventory, Clinical Dementia Rating, and Katz index of independence in activities of daily living to assess patient symptoms, functions, and severity of dementia. Caregivers completed questionnaires on perceived patient end-of-life care preferences, caregiver end-of-life care preferences for patients, Zarit Burden Interview (ZBI), Center for Epidemiological Studies-Depression Scale (CES-D), and knowledge of clinical complications of advanced dementia. RESULTS: The self-disclosure rates of patient preferences were 34.5% for tube feeding, 39.3% for cardiopulmonary resuscitation, and 45.2% for mechanical ventilation. For patients who had disclosed preferences, the disagreement rate between them and their caregivers was 48.3% for tube feeding, 48.5% for cardiopulmonary resuscitation, and 60.3% for mechanical ventilation. Caregiver depression (i.e., CES-D ≥16) was associated with disagreements on cardiopulmonary resuscitation (adjusted odds ratio (aOR) = 6.6, 95% CI = 1.4-31.1, P = 0.01) and mechanical ventilation (aOR = 14, 95% CI = 2.2-87.2, P = 0.005) preferences. CONCLUSION: The preferences of end-of-life issues differed greatly between dementia patients and their caregivers. Depression in caregivers is associated with such discrepancy.

Effect of the BDNF Val66Met polymorphism on regional gray matter volumes and cognitive function in the Chinese population.

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is common and influences the activity-dependent secretion of BDNF, which is critical for neuronal plasticity and survival. This study investigated the genetic effect of the BDNF Val66Met polymorphism on cognitive function and regional gray matter (GM) volume in a healthy Chinese population (n = 330). Voxel-based morphometry (VBM)-optimized analysis was used. There was no significant difference in the neuropsychological performances among the three BDNF genotypic groups. VBM analyses demonstrated that Met homozygotes had greater GM volumes than Val homozygotes in the left medial frontal gyrus, the left middle temporal gyrus, the left cerebellum, and the right middle temporal gyrus, and had larger GM volumes than Val/Met heterozygotes in the left middle temporal gyrus, the left inferior temporal gyrus, and the right superior frontal gyrus. Our findings suggest that the presence of two Met alleles has a protective effect on regional GM volumes in the Chinese population.

Daytime sleepiness: a risk factor for poor social engagement among the elderly.

BACKGROUND: The aim of this study was to investigate the relationship between social engagement and daytime sleepiness among aged residents of a veterans' housing facility in Taiwan. METHODS: A total of 597 men were enrolled in this cross-sectional study. Each subject was assessed with the Resident Assessment Instrument-Minimum Data Set, Geriatric Depression Scale, Pittsburgh Sleep Quality Index, and Mini-Mental State Examination. Social engagement was measured with the Index of Social Engagement (ISE), and daytime sleepiness was defined according to the relevant Pittsburgh Sleep Quality Index subcomponent. Subjects were divided into two groups according to their ISE levels. A multivariate logistic regression model was used to examine the association between ISE and other variables. RESULTS: The sample's mean age was 80.8 ± 5.0 years (range: 65-99 years). Mean ISE score was 1.5 ± 1.3 (range 0-5), with 52% of participants reporting poor social engagement (ISE = 0-1). Mean Pittsburgh Sleep Quality Index global score was 5.6 ± 3.6 (range: 0-18), and 31% of participants reported daytime sleepiness. The analysis was adjusted for level of depression, cognitive impairment, dependence in activities of daily life, unsettled relationships, and illiteracy. After adjustment, daytime sleepiness was found to be independently associated with subjects' level of social engagement (odds ratio: 2.5; 95% confidence interval: 1.7-3.8; P < 0.001). CONCLUSIONS: Daytime sleepiness and poor social engagement are common among aged residents of a veterans' housing facility. Subjects experiencing daytime sleepiness but not poor general sleep quality were at increased risk of poor social engagement. The clinical care of older residents must focus on improving daytime sleepiness to enhance their social engagement.

Cognitive and neuropsychiatric correlates of EEG dynamic complexity in patients with Alzheimer's disease.

This study assessed the utility of multiscale entropy (MSE), a complexity analysis of biological signals, to identify changes in dynamics of surface electroencephalogram (EEG) in patients with Alzheimer's disease (AD) that was correlated to cognitive and behavioral dysfunction. A total of 108 AD patients were recruited and their digital EEG recordings were analyzed using MSE methods. We investigate the appropriate parameters and time scale factors for MSE calculation from EEG signals. We then assessed the within-subject consistency of MSE measures in different EEG epochs and correlations of MSE measures to cognitive and neuropsychiatric symptoms of AD patients. Increased severity of AD was associated with decreased MSE complexity as measured by short-time scales, and with increased MSE complexity as measured by long-time scales. MSE complexity in EEGs of the temporal and occipitoparietal electrodes correlated significantly with cognitive function. MSE complexity of EEGs in various brain areas was also correlated to subdomains of neuropsychiatric symptoms. MSE analysis revealed abnormal EEG complexity across short- and long-time scales that were correlated to cognitive and neuropsychiatric assessments. The MSE-based EEG complexity analysis may provide a simple and cost-effective method to quantify the severity of cognitive and neuropsychiatric symptoms in AD patients.

Effect of Bcl-2 rs956572 SNP on regional gray matter volumes and cognitive function in elderly males without dementia.

The Bcl-2 gene is a major regulator of neural plasticity and cellular resilience. A single-nucleotide polymorphism (SNP) in the Bcl-2 gene, Bcl-2 rs956572, significantly modulates the expression of Bcl-2 protein and cellular vulnerability to apoptosis. This study investigated the association between the Bcl-2 rs956572 SNP and brain structural abnormalities in non-demented elders, and to test the relationship between neuropsychological performance and regional gray matter (GM) volumes. Our sample comprised 97 non-demented elderly men with a mean age of 80.6 ± 5.6 years (range, 65 to 92 years). Cognitive test results, magnetic resonance imaging, and genotyping of Bcl-2 rs956572 were examined for each subject. The differences in regional GM volumes between G homozygotes and A-allele carriers were tested using optimized voxel-based morphometry. Subjects with G homozygotes exhibited significantly worse performance in the language domain of the Cognitive Abilities Screening Instrument (CASI; p = 0.009). They also showed significantly smaller GM volumes in the right middle temporal gyrus (MTG) (BA 21), but larger GM volumes in the left precuneus (BA 31), right lingual gyrus (BA 18), and left superior occipital gyrus (BA 19) relative to A-allele carriers (p < 0.001). A trend toward a positive correlation between right MTG GM volumes and the language domain of CASI was also evident (r = 0.181; p = 0.081). The findings suggest that Bcl-2 rs956572 SNP may modulate cognitive function and regional GM volume in non-demented elderly men, and that this polymorphism may affect language performance through its effect on the right MTG.

Association of MTHFR C677T polymorphism with loneliness but not depression in cognitively normal elderly males.

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is involved in folate and homocysteine metabolism, and has been associated with geriatric disorders, including dementia and late-life depression. The present work aimed to investigate the effect of MTHFR C677T polymorphism on the presence of depression and loneliness in cognitively normal male subjects. A total of 323 cognitively normal male subjects were included in this study (mean age=80.6; SD=5.3). Depression was assessed by the Geriatric Depression Scale-Short Form (GDS-SF) and loneliness by UCLA loneliness scales. Analysis of variance (ANOVA) was used to test the between MTHFR genotype difference in depression and loneliness. Multiple regression was used to test the effect of MTHFR polymorphism on the loneliness, controlling for age, education, cognitive function, and depression. ANOVA showed a significant between-genotype difference in loneliness scores (P=0.015), and post hoc comparisons showed that subjects with C/C genotype had significantly higher loneliness ratings, compared to those with C/T or T/T genotype. Regression analysis indicated that the effect of MTHFR polymorphism on loneliness was independent of age, education, cognitive function, and depression. Our findings suggest that MTHFR C677T polymorphism may be linked more to loneliness than depression in the cognitively normal elderly males, and may be implicated in the pathophysiology of late-life depression in relation to MTHFR genes.

Heterozygote advantage of the MTHFR C677T polymorphism on specific cognitive performance in elderly Chinese males without dementia.

AIMS: Aging is associated with cognitive deterioration, and genetic factors are implicated in individual cognitive differences in the aged. The C677T mutation in the 5,10-methylenetetrahydrofolate reductase gene (MTHFR) yields a common thermolabile variant (T) with reduced enzyme activity and consequent elevation of serum homocysteine concentrations. We designed the present study to investigate whether this functional polymorphism may affect global and specific cognitive functions in older Chinese males without dementia. METHODS: The subjects included 356 elderly males without major psychiatric disorders or dementia, who were assessed by the Cognitive Abilities Screening Instruments (CASI) and the Wechsler Digit Span Task tests. RESULTS: A significant association was found between the MTHFR C677T polymorphism and total CASI scores (p = 0.012), particularly in short-term memory (p = 0.002) and concentration/mental manipulation (p = 0.007). Post hoc tests indicated that the C/T heterozygotes achieved better cognitive function test results than C/C or T/T carriers. No association was found between the MTHFR genotype and the Wechsler Digit Span Task tests. CONCLUSION: These results suggest that a heterozygote advantage exists for the MTHFR C677T polymorphism in specific cognitive functions in elderly Chinese males without dementia.

Cortical and subcortical abnormalities in late-onset depression with history of suicide attempts investigated with MRI and voxel-based morphometry.

Late-onset major depression is thought to have a biological (vascular) basis, which could be a result of brain structure change. Vascular lesions can affect both the gray matter (GM) and white matter (WM), while most previous studies addressed WM abnormality. This study explored the disease- and symptom (history of suicide attempt) -related GM morphometry in elderly male patients with late-onset depression. A total of 70 patients with depression admitted to our geriatric psychiatric ward were investigated, and 26 age-matched males were recruited as controls. We used T1-weighted magnetic resonance imaging (MRI) to obtain cerebral structural information and adopted voxel-based morphometry (VBM) to investigate brain volume change related to disease (depression vs control) and symptom (depression with history of suicide attempt vs depression without history of suicide attempt). Late-onset depression was associated with smaller volumes in several regions of GM (insula and the posterior cingulate region) and WM (subcallosal cingulate cortex, floor of lateral ventricles, parahippocampal region, insula, and the cerebellum). Compared with nonsuicidal counterpart, suicidal depression was associated with decreased GM and WM volume in the frontal, parietal, and temporal regions, and the insula, lentiform nucleus, midbrain, and the cerebellum. Marked regional volume reduction was noticed at dorsal medial prefrontal cortex. Our results demonstrate that the development of suicidal behaviors in major depression is related to widespread but discrete volume reduction in several cortical and subcortical structures, fitting with the hypothesis that decreased cerebral volume in certain regions renders biological susceptibility to attempt suicide during depressive states.

Gene-gene interactions of the brain-derived neurotrophic-factor and neurotrophic tyrosine kinase receptor 2 genes in geriatric depression.

Brain-derived neurotrophic-factor (BDNF) and its receptor neurotrophic tyrosine kinase receptor 2 (NTRK2) have been implicated in both major depression and cognitive function. This study examines the main effects of single loci and multilocus interactions to test the hypothesis that the BDNF and NTRK2 genes may contribute to the etiology of geriatric depression independently and/or through complex interactions. We genotyped the BDNF gene Val66Met (rs6265) polymorphism and four single-nucleotide polymorphisms (SNPs) (including rs1187323, rs1187329, rs1778929, and rs1545285) in the NTRK2 gene in 155 elderly inpatients diagnosed with major depression and 195 age- and sex-similar control subjects. All patients were assessed with the Hamilton Rating Scale for Depression (HAM-D) for depression severity and the Mini-Mental Status Examination (MMSE) for cognitive function after admission. The genotype distributions of all five SNPs tested were significantly different between depressed patients and control subjects. BDNF rs6265, NTRK2 rs1187323, and NTRK2 rs1778929 (p = 0.0031, 0.002, and 0.0014, respectively) also displayed statistically significant differences in the genotypic tests after Bonferroni correction (p < 0.05/5 = 0.01). In addition, the 2-marker haplotype derived from the rs1187323 and rs1187329 polymorphisms demonstrated a significant difference between geriatric depression and control groups according to haplotype distribution (global p = 0.003). Furthermore, BDNF and NTRK2 interactions were found in the significant 2-locus, 3-locus, 4-locus, and 5-locus gene-gene interaction models (p = 0.014, <0.001, 0.007, and 0.032, respectively) using a generalized multifactor dimensionality reduction (GMDR) method. Analyses using logistic regression models confirmed the gene-gene interactions. The results suggest that the BDNF and NTRK2 genes may contribute to the risk of geriatric depression independently and in an interactive manner.

Interleukin-1 beta -511C/T genetic polymorphism is associated with age of onset of geriatric depression.

The pro-inflammatory cytokine interleukin-1 beta has been implicated in the pathogenesis of major depressive disorder and in cognitive function decline in the elderly. This study tests the hypothesis that a biallelic functional polymorphism in the promoter region of the interleukin-1 beta gene (IL1B -511C/T) affects vulnerability to geriatric depression and its manifestations, including age of onset, depression severity, and cognitive function. We genotyped the IL1B -511C/T polymorphism in 125 elderly inpatients diagnosed with major depression and 282 normal elderly controls. The depressed patients were evaluated at baseline after admission using the Hamilton Rating Scale for Depression (HAM-D) for depression severity and the Mini-Mental Status Examination (MMSE) for cognitive function; depression age of onset was evaluated by interview and medical records. We found no association between IL1B -511C/T genotypes and geriatric depression susceptibility (P = 0.213), depression severity (HAM-D scores; P = 0.766) or cognitive function (MMSE scores; P = 0.827); however, compared with depressed subjects carrying the -511C allele, depressed subjects who were -511T homozygotes showed a significantly later depression age of onset of 7 years (P = 0.021). Our findings suggest that the IL1B -511C/T polymorphism may be related to age at manifestation among individuals vulnerable to depression, but they do not affect the basic vulnerability to or severity of depression in elderly Chinese adults. Further study is warranted to confirm this finding and to assess its generalization to other ethnic groups.

Chinese demented inpatients admitted following a suicide attempt: a case series.

OBJECTIVE: Suicide attempt is rarely reported in dementia. This study explores the clinical and phenomenological aspects as well as the treatment of Chinese demented patients who have attempted suicide. METHODS: During a 1-year period, demented patients admitted to a geropsychiatric unit as a result of suicide attempt were investigated for factors related to suicide attempt, such as motives and method. RESULTS: In this 1-year survey, seven demented patients (11.7% of all demented patients) were admitted immediately following a suicide attempt. All seven patients had mild or moderate dementia. Three had significant clinical depression symptoms on admission. In all patients, delusions were the primary cause of suicide attempt. Their suicidal ideations were improved with antipsychotic and antidepressant treatment. CONCLUSION: These cases, taken together, suggest that suicide attempt can occur in patients with dementia. It is important for clinicians to be aware of the risk of suicide in patients with dementia, especially those associated with delusions, even if they have no major depression or suicide attempt history. Antidepressants and antipsychotics may play a critical role in the treatment of suicide attempt in dementia.

Association of APOE genetic polymorphism with cognitive function and suicide history in geriatric depression.

Apolipoprotein E (APOE) has been associated with a variety of late-life neuropsychiatric disorders, including geriatric depression. This study determined whether APOE genotypes affect vulnerability to geriatric depression. We also tested the effect of the presence of the APOE epsilon4 (APOE4) allele on age of onset, suicide attempt history and cognitive function in geriatric depressed patients. We genotyped APOE in 111 elderly inpatients diagnosed as having major depression and 144 normal controls. The depressed patients were evaluated at baseline using the Hamilton Rating Scale for Depression and the Mini-Mental State Examination (MMSE) after admission. Age of onset of depression and suicide attempt history in the depressed group were evaluated by interview and medical record. We found no association between APOE genotypes and geriatric depression (p = 0.342) or APOE4 status and age of onset of depression (p = 0.281). However, compared with depressed subjects lacking the APOE epsilon4 allele, depressed subjects who were also APOE4 carriers showed significantly lower MMSE scores (p = 0.021) and an increased suicide attempt history (p = 0.012). The APOE genotype may contribute to cognitive performance and suicidality in geriatric depression, rather than being a specific risk factor for the disorder.

The Val66Met polymorphism of the brain-derived neurotrophic-factor gene is associated with geriatric depression.

Brain-derived neurotrophic-factor (BDNF), the most abundant of the neurotrophins in the brain, has been implicated in both major depression and cognitive function. This study examines the association between the BDNF-gene Val66Met polymorphism and depression susceptibility and severity, age-of-onset, cognitive function and suicidal attempt history in an elderly Chinese sample population. We genotyped the BDNF-gene Val66Met polymorphism in 110 elderly inpatients diagnosed with major depression and 171 age- and sex-similar control subjects. All patients were assessed with the Hamilton Rating Scale for Depression (HAM-D) for depression severity and the Mini-Mental Status Examination (MMSE) for cognitive function after admission. Suicide attempt history and age-of-onset of depression were evaluated by interview and medical record. The BDNF Val66Met genotype distribution was significantly different between depressed patients and control subjects (P=0.003) and there was a significant excess of Met allele in the depressed patients compared to the control group (P=0.001). The BDNF polymorphism did not affect age-of-onset, depression severity, cognitive function or suicidal attempt history. The results suggest that the BDNF Val66Met polymorphism is a relevant risk factor for geriatric depression.

The efficacy and safety of quetiapine for treatment of geriatric psychosis.

Quetiapine, an atypical antipsychotic, is effective for psychosis in younger patients, with limited adverse effects reported. This open-label naturalistic study was conducted to assess the 4-week efficacy and safety of quetiapine for treatment of geriatric psychosis. Clinical efficacy was evaluated using the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Improvement (CGI-I) instruments before and after 4 weeks of quetiapine treatment. The sample population consisted of 100 geropsychiatric inpatients with psychosis, with the therapeutic evaluation completed by 91. Eighty-one of these 91 patients (89.0%) experienced mild-to-substantial improvement, as determined from the CGI-I. Further, a mean reduction in BPRS score of 39.5% (from baseline) was also determined. The mean daily dose of quetiapine for the fourth week was 276.1 177.2mg/day (range 50-800). Higher quetiapine dosages were administered for patients with functional psychoses compared to an analogous group with organic mental disorders. The most common adverse effects were somnolence (30.0%), lower-limb weakness (28.0%) and dizziness (27.0%). Body weight and fasting triglyceride were significantly elevated after quetiapine treatment (2.2% and 8.9% from baseline, respectively). Based on the results of this study, it appears that quetiapine is an efficacious and safe treatment for geriatric inpatients with psychosis, however, there is a wide dosing range and optimal dosage is diagnosis-dependent.