Effect of Integrated Cognitive Intervention Therapy in Patients with Mild to Moderate Alzheimer's Disease

Background and purpose: The effect of the integrated program comprising cognitive training, art therapy, and music therapy has not been extensively studied in patients with Alzheimer's disease (AD). The present study investigated the effect of integrated cognitive intervention therapy on cognition, and activity of daily life (ADL), and mood in patients with mild to moderate AD. Methods: In this study, the data of 59 patients who met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer disease and Related Disorders Association (NINCDS-ADRDS) criteria of probable AD among those who registered at the Centenarian's Good Memory Program in Goyang from September 2014 to August 2019 were collected. We statistically analyzed the scores of Korean version of a Mini-Mental Status Examination (K-MMSE), Korean Dementia Screening Questionnaire-Cognition (KDSQ-C), Geriatric Depression Scale (GDS), Beck Anxiety Inventory (BAI), and Seoul-Instrumental Activities of Daily Living (S-IADL) of the same patients before and after the use of integrated cognitive intervention therapy. Results: K-MMSE slightly increased from 18.7±4.5 to 19.7±5.0 (p<0.001) and KDSQ-C improved from 14.5±7.6 before therapy to 12.6±7.2 after therapy (p=0.001). Mean S-IADL score improved from 17.6±7.6 before therapy to 15.7±9.5 after therapy (p<0.001). Additionally, mean GDS score before the therapy was 5.6±3.5 that improved to 4.2±3.0 after the therapy (p<0.001). Mean BAI score decreased from 8.4±10.3 before therapy to 5.9±8.4 after therapy (p=0.001). Conclusions: In conclusion, this study demonstrated the possibility that the use of an integrated cognitive therapy improved cognition, ADL, and mood (depression and anxiety) in patients with mild to moderate ADs.ope

Cox Proportional Hazard Regression Versus a Deep Learning Algorithm in the Prediction of Dementia: An Analysis Based on Periodic Health Examination

BACKGROUND: With the increase in the world's aging population, there is a growing need to prevent and predict dementia among the general population. The availability of national time-series health examination data in South Korea provides an opportunity to use deep learning algorithm, an artificial intelligence technology, to expedite the analysis of mass and sequential data. OBJECTIVE: This study aimed to compare the discriminative accuracy between a time-series deep learning algorithm and conventional statistical methods to predict all-cause dementia and Alzheimer dementia using periodic health examination data. METHODS: Diagnostic codes in medical claims data from a South Korean national health examination cohort were used to identify individuals who developed dementia or Alzheimer dementia over a 10-year period. As a result, 479,845 and 465,081 individuals, who were aged 40 to 79 years and without all-cause dementia and Alzheimer dementia, respectively, were identified at baseline. The performance of the following 3 models was compared with predictions of which individuals would develop either type of dementia: Cox proportional hazards model using only baseline data (HR-B), Cox proportional hazards model using repeated measurements (HR-R), and deep learning model using repeated measurements (DL-R). RESULTS: The discrimination indices (95% CI) for the HR-B, HR-R, and DL-R models to predict all-cause dementia were 0.84 (0.83-0.85), 0.87 (0.86-0.88), and 0.90 (0.90-0.90), respectively, and those to predict Alzheimer dementia were 0.87 (0.86-0.88), 0.90 (0.88-0.91), and 0.91 (0.91-0.91), respectively. The DL-R model showed the best performance, followed by the HR-R model, in predicting both types of dementia. The DL-R model was superior to the HR-R model in all validation groups tested. CONCLUSIONS: A deep learning algorithm using time-series data can be an accurate and cost-effective method to predict dementia. A combination of deep learning and proportional hazards models might help to enhance prevention strategies for dementia.ope

Lethality-Associated Factors in Deliberate Self-Poisoning

Objectives: Deliberate self-poisoning (DSP) is the most common suicide method and can be life-threatening. The purpose of this study was to investigate the factors related to the lethality of DSP and the characteristics of the adolescent group. Methods: A retrospective study was conducted on patients who had visited an academic hospital's regional emergency medical center between 2015 and 2018. The data reviewed through their medical records included sociodemographic factors, clinical variables, and psychiatric treatment. Four groups (Q1-Q4) were categorized by descriptive analysis using the risk-rescue rating scale. Results: A total of 491 patients were enrolled in this study. This study showed that high lethality had statistically significant associa-tions with male sex, older age, admitting suicidal intentions, and the use of herbicides for suicide. Logistic regression analyses showed a significant association between high-lethality and female [odds ratio (OR)=0.50, 95% confidence interval (CI)=0.30-0.81, p=0.01], non-psychiatric drugs (over-the-counter drug: OR=2.49, 95% CI=1.08-5.74, p=0.03; herbicide: OR=8.65, 95% CI=3.91-19.13, p<0.01), and denial of suicide intent (OR=0.28, 95% CI=0.15-0.55, p<0.01). Conclusion: This study showed the clinical factors associated with the high lethality of DSP and suggested that efforts were needed to care for and thoroughly examine patients with DSP.ope

Risk of mortality associated with concomitant antidepressant and benzodiazepine therapy among patients with depression: a population-based cohort study

Background: With antidepressants (ADs) having minimal therapeutic effects during the initial weeks of treatment, benzodiazepines (BZDs) are concomitantly used to alleviate depressive symptoms of insomnia or anxiety. However, with mortality risks associated with this concomitant use yet to be examined, it remains unclear as to whether this concomitant therapy offers any benefits in treating depression. Methods: We conducted a population-based cohort study using South Korea's nationwide healthcare database from 2002 to 2017. Of 2.6 million patients with depression, we identified 612,729 patients with incident depression and newly prescribed ADs or BZDs, by excluding those with a record of diagnosis or prescription within the 2 years prior to their incident diagnosis. We classified our study cohort into two discrete groups depending on the type of AD treatment received within 6 months of incident diagnosis-AD monotherapy and AD plus BZD (AD+BZD) therapy. We matched our study cohort in a 1:1 ratio using propensity scores to balance baseline characteristics and obtain comparability among groups. The primary outcome was all-cause mortality, and patients were followed until the earliest of outcome occurrence or end of the study period. We conducted multivariable Cox proportional hazards regression analysis to estimate adjusted hazards ratios (HRs) with 95% confidence intervals (CIs) for the risk of mortality associated with AD+BZD therapy versus AD monotherapy. Results: The propensity score-matched cohort had 519,780 patients with 259,890 patients in each group, where all baseline characteristics were well-balanced between the two groups. Compared to AD monotherapy, AD+BZD therapy was associated with an increased risk of all-cause mortality (adjusted HR, 1.04; 95% CI, 1.02 to 1.06). Conclusions: Concomitantly initiating BZDs with ADs was associated with a moderately increased risk of mortality. Clinicians should therefore exercise caution when deciding to co-prescribe BZDs with ADs in treating depression, as associated risks were observed.ope

The Behavioral Effects of Combination Therapy of Memantine and Acetylcholinesterase Inhibitors Compared with Acetylcholinesterase Inhibitors Alone in Patients with Moderate Alzheimer's Dementia: A Double-Blind Randomized Placebo-Controlled Trial

Objective: This study aimed to investigate treatment effects of combination therapy of memantine and acetylcholinesterase inhibitors (AchEIs) compared with AchEIs alone on behavioral and psychological symptoms of dementia (BPSD) in patients with moderate Alzheimer's dementia (AD). Methods: This was a 12-week, double-blind, randomized, placebo-controlled trial. A total of 148 patients with moderate AD participated in this study. Mini-Mental State Examination, Neuropsychiatric Inventory (NPI), Clinician's Interview-Based Impression of Change plus caregiver input, Gottfries-Bråne-Steen Scale, and Zarit Burden Interview were used as assessment scales. Results: There were no significant differences in age, sex, or education between AChEIs alone and combination groups. The combination group showed significantly more improvement of NPI-disinhibition score (0.76±2.15) than the AChEIs alone group (-0.14±1.71) after 12 weeks. Conclusion: Our findings suggest that the combination therapy of memantine and AchEIs might be a beneficial option for reducing disinhibition symptoms of patients with moderate AD compared with AchEIs alone. We believe that clinicians need to consider additional memantine treatment when patients with moderate AD complain disinhibition symptom. A larger clinical trial is needed to further determine the efficacy and advantages of such combination therapy of memantine and AchEIs for treating BPSD of patients with moderate AD.ope

Effectiveness of Nootropics in Combination with Cholinesterase Inhibitors on Cognitive Function in Mild-to-Moderate Dementia: A Study Using Real-World Data

The clinical benefits of nootropics in the treatment of cognitive decline has been either limited or controversial. This study aimed to observe the effectiveness of cholinesterase inhibitor (ChEI) and nootropics combination in the treatment of cognitive impairment in dementia. Data were based on electronic medical records in a university health system. Patients with mild-to-moderate dementia and no history of prior cognitive enhancer use were included (n = 583). The subjects were categorized into the ChEI only group and the ChEI and nootropics combination group. The primary outcome measure was the change in cognitive function, as assessed by the mini-mental state examination (MMSE) from baseline to 300-400 days after the first ChEI prescription. Subsequent analyses were conducted in consideration of the dementia type, medical adherence, and type of nootropics. The changes in MMSE scores from baseline to endpoint were not significantly different between the two groups. In Alzheimer's dementia, the combination group showed significantly less deterioration in MMSE language subscale scores compared to the ChEI only group (F = 6.86, p = 0.009), and the difference was consistent in the highly adherent subjects (F = 10.16, p = 0.002). The choline alfoscerate and the ginkgo biloba extract subgroups in Alzheimer's dementia showed more significant improvements in the MMSE language subscale scores compared to the other nootropics subgroup (F = 7.04, p = 0.001). The present study showed that the effectiveness of ChEI and nootropics combination on cognition may appear differently according to the dementia type. This emphasizes the need for well-controlled studies to generalize the effectiveness of nootropics across various clinical settings.ope

Sleep disturbance-related depressive symptom and brain volume reduction in shift-working nurses

Disturbed sleep is the most common effect of shift work. A large corpus of research indicates an association between sleep disturbance and depressive symptom in shift workers. In this study, we proposed the mediating role of grey matter (GM) structure in the relationship between sleep disturbance and depressive symptom. We collected structural MRI (sMRI) data as well as assessing the level of sleep disturbance and depressive symptom with the Pittsburgh Sleep disturbance Index and Zung Self-Rating Depression Scale, respectively, in 20 shift-working nurses and 19 day-working nurses. The shift-working nurses reported greater severity of sleep disturbance and depressive symptom, and furthermore, they exhibited reduced GM volume in the left postcentral gyrus (PostCG), right PostCG, right paracentral lobule, and left superior temporal gyrus (STG), compared to the day-working nurses. For each of the four brain regions, we formulated a mediation hypothesis by developing a mediation model that represents a causal chain between GM volume, sleep disturbance, and depressive symptom. Tests of the hypothesis on the mediation of GM volume revealed that inter-individual variations in left PostCG volume and left STG volume accounted for the influence of sleep disturbance on depressive symptom. These results suggest that structural alterations in PostCG and STG play an intervening role in the development of depressive symptom following sleep disturbance. We propose the need of considering neuroanatomical abnormalities in explaining and understanding symptomatic changes induced by sleep disturbance.ope

Benzodiazepine-Related Cognitive Impairment or Dementia: A Signal Detection Study Using a Case/Non-Case Approach

Objective: The association between benzodiazepine use and the risk of cognitive impairment or dementia has been controversial. Our study aims to detect this association through a case/non-case method using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD) between 2007 and 2016. Methods: Cases were adverse event (AE)-pairs with suspected cognitive impairment or dementia. 10 non-cases were matched to each case on age and sex. Exposure was defined as use of benzodiazepines, including long-, intermediate-, and short-acting benzodiazepine. We conducted multivariable logistic regression analyses to estimate reporting odds ratios (ROR) and 95% confidence intervals (CI). Results: Of the 1,086,584 AE-pairs, 887 cases were suspected AE-pairs of cognitive impairment or dementia, and 775,444 non-cases were selected. Benzodiazepine use was associated with increased AE-pairs of cognitive impairment or dementia when assessed using those with certain, probable, and/or possible in causality assessments (ROR=2.69, 95% CI=1.66-4.38). Higher ROR estimates were shown in female (2.33, 1.48-3.67) and in those with polypharmacy (2.20, 1.35-3.57). Dementia safety profiles were inconsistent across individual benzodiazepine components. Conclusion: These results suggest the potentially increased association between benzodiazepine use and cognitive impairment or dementia in female and those with polypharmacy. Inconsistent safety profiles of benzodiazepine components should be further investigated.ope

Clinical Characteristics of HIV-Infected Patients With Sleep Disturbance

Objective This study aims to examine clinical characteristics and to identify possible risk factors of sleep disturbances in people living with HIV (PLWH). Methods All research data of patients who were first diagnosed with HIV/AIDS from January 1, 2012 to December 31, 2021 and complained of sleep disturbance at least once were retrospectively reviewed by the Severance Clinical Research Analysis Portal (SCRAP) service of Severance hospital. The presence of sleep disturbance was evaluated based on whether insomnia disorder diagnosis code was included or whether insomnia medication was prescribed. The patients were divided into either the group with sleep disturbance within 3 months (SDW3) and the group with after 3 months (SDA3). All data were reported using descriptive statistics. Results Of the 674 patients diagnosed with HIV during the period, 56 patients experienced sleep disturbances at least once and approximately 50% of patients have experienced sleep disturbance in the first 3 months after HIV diagnosis. CD4+ cell count at the time of first onset of sleep disturbance was significantly lower (p=0.03) and HIV viral load at the time of first onset of sleep disturbance was significantly higher (p<0.001) in SDW3 group. SDW3 patients showed higher rates of opportunistic infections compared to SDA3 patients. Conclusion The current study suggests that further investigation of the underlying pathophysiology of sleep disturbance and association with immunological changes for early diagnosis and treatment of sleep disturbance in PLWH.ope

Frailty and Insomnia in Older Adults

Frailty is a geriatric syndrome with increased risk for poor health outcomes, including falls, cognitive impairment, hospitalization, and mortality. In previous studies, associations between frailty and sleep-related factors or sleep disorders have been investigated. We examined the relationship between frailty and insomnia, which are both common condition in older adults. Hormonal changes with aging and/or lifestyle changes all affect sleep physiology, which are vulnerable to the risk of insomnia. As the severity of frailty decreases the quality of sleep, and the long/short sleep duration is related to the risk of frailty, it can be assumed that frailty and sleep are reciprocally related. The association between frailty and insomnia has been variously proven in epidemiological studies conducted around the world. A close evaluation of insomnia and frailty in older adults provides a basis for improving the health of people in the aged society. There are few related studies in Korea, and in the future, not only basic epidemiological studies but also studies explaining the psychoneuroendocrinological mechanism of the relationship between insomnia and frailty should be performed together.ope