Implications of helplessness in depression: diagnosing mild cognitive impairment and analyzing its effects on cognitive decline in older adults

BackgroundThis study focuses on how elements of depression correlate with mild cognitive impairment (MCI) in older adults and the diagnostic efficacy of combining these components with the Mini-Mental State Examination (MMSE). The study also investigated the connection between individual depression components and overall cognitive function, as measured by the total score (TS) of the consortium to establish a registry for Alzheimer’s disease (AD) assessment battery.MethodsThe study included 196 nondemented adults aged 65 to 90 years at a university hospital and community. Comprehensive clinical assessments including the 30-item Geriatric Depression Scale (GDS) to measure components of depressive symptoms, TS, and blood nutritional biomarkers.ResultsOur stepwise logistic regression analysis highlighted the ‘helplessness item’ (odds ratio = 4.531, 95% CI = 2.218 to 9.258, p < 0.001) as a significant predictor for MCI diagnosis. Further, models incorporating ‘helplessness item + MMSE’ demonstrated markedly enhanced accuracy in diagnosing MCI, surpassing the performance of the MMSE used independently. Notably, the group characterized by helplessness showed a significant reduction in TS (B = −5.300, SE = 1.899, β = −0.162, p = 0.006), with this trend being particularly pronounced in individuals exhibiting lower levels of physical activity. Interestingly, this correlation did not manifest in participants with higher physical activity levels.ConclusionOur findings suggest that helplessness is highly effective in diagnosing MCI and is linked to a decrease in cognitive function. Therefore, when addressing MCI and AD-related cognitive decline, clinicians should consider helplessness

Association between physical activity and episodic memory and the moderating effects of the apolipoprotein E ε4 allele and age

BackgroundAn abundance of evidence indicates that physical activity may protect against Alzheimer’s disease (AD) and related cognitive decline. However, little is known about the association between physical activity and AD-related cognitive decline according to age and the apolipoprotein E (APOE) ε4 allele (APOE4) as major risk factors. Therefore, we examined whether age and APOE4 status modulate the effects of physical activity on episodic memory as AD-related cognition in non-demented older adults.MethodsWe enrolled 196 adults aged between 65 and 90 years, with no dementia. All participants underwent comprehensive clinical assessments including physical activity evaluation and APOE genotyping. The AD-related cognitive domain was assessed by the episodic memory, as the earliest cognitive change in AD, and non-memory cognition for comparative purposes. Overall cognition was assessed by the total score (TS) of the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery.ResultsWe found significant physical activity × age and physical activity × APOE4 interaction effects on episodic memory. Subgroup analyses indicated that an association between physical activity and increased episodic memory was apparent only in subjects aged > 70 years, and in APOE4-positive subjects.ConclusionOur findings suggest that physical activity has beneficial effects on episodic memory, as an AD-related cognitive domain, in individuals aged > 70 years and in APOE4-positive individuals. Physicians should take age and APOE4 status account into when recommending physical activity to prevent AD-related cognitive decline

Ginseng intake and Alzheimer disease-specific cognition in older adults according to apolipoprotein ε4 allele status

BackgroundThe probable association among ginseng intake, Alzheimer’s disease (AD)-specific cognition, and apolipoprotein ε4 (APOE4) remains poorly investigated. Hence, we examined the association between ginseng intake and AD-specific cognition in older adults under the moderating effect of APOE4 status.MethodsThis study enrolled 160 adults aged 65–90 years without dementia. All participants underwent comprehensive dietary and clinical assessments including ginseng intake, AD-related cognition (i.e., delayed episodic memory, as the earliest cognitive change in AD), and non-memory cognition for comparative purposes.ResultsGinseng intake was associated with higher delayed episodic memory, but not non-memory cognition, compared to no ginseng intake. The interaction between ginseng intake and APOE4 status had a significant effect on delayed episodic memory. Subgroup analyses showed that ginseng intake was associated with higher delayed episodic memory in the APOE4-negative but not the APOE4-positive subgroup. The benefits of ginseng intake on delayed episodic memory were prominent in the high duration (≥5 years) and midlife onset (<65 years) groups.ConclusionOur study of older adults with no dementia suggests that ginseng intake (with high duration and midlife onset) had a beneficial effect on AD-specific cognitive decline, i.e., the delayed episodic memory. In addition, APOE4 status moderates the association between ginseng intake status and AD-specific cognitive decline

High-intensity walking in midlife is associated with improved memory in physically capable older adults

Background Little is known about the associations of midlife- and late life-initiated walking with Alzheimers disease (AD)-related cognitive decline in humans. We aimed to investigate whether high-intensity, prolonged, midlife-initiated walking is associated with changes in AD-related cognitive decline in physically capable older adults. Methods We studied 188 physically capable participants aged 65–90 years without dementia who underwent comprehensive clinical assessment, including of their walking modality (i.e., intensity, duration, midlife- or late life-onset), memory- or non-memory and total cognitive performance, and blood or nutritional biomarkers. Results The walking group showed better episodic memory (B = 2.852, SE = 1.214, β = 0.144, p = 0.020), but not non-memory cognition, than the non-walking group. High-intensity walking starting in midlife was significantly associated with better episodic memory (B = 9.360, SE = 3.314, β = 0.446, p = 0.005) compared to the non-walking group. In contrast, there were no differences in cognition according to walking duration, regardless of the onset time. The walking group also showed a similar association with overall cognition. Conclusions Among physically capable older adults without dementia, walking, particularly at high intensity and starting in midlife, is associated with improved episodic memory, an AD-related cognitive domain. Further attention should be paid to the role of walking in terms of AD prevention.This study was supported by grants from the Hallym University Research Fund (grant no. HURF-2020–56 and HURF-2022–13) and the Ministry of Science and ICT, Republic of Korea (grant no. NRF-2020R1G1A1099652). This study was also supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (grant no. RS-2023-00210820). The funding sources had no role in the study design, data collection, data analysis, data interpretation, writing of the manuscript, or decision to submit it for publication

Epigenetic Changes of Serotonin Transporter in the Patients with Alcohol Dependence: Methylation of an Serotonin Transporter Promoter CpG Island

ObjectiveaaPsychiatric disorders such as depression, anxiety and alcohol dependence are associated with serotonin metabolism. We assessed the methylation level of the serotonin transporter (5-HTT) promoter region in control and alcohol dependent patients. MethodsaaTwenty seven male patients who met the Diagnostic and Statistical Manual of Mental Disorder IV (DSM-IV) criteria for alcohol dependence were compared with fifteen controls. Polymerase chain reaction (PCR) assays of bisulfate-modified DNA were designed to amplify a part of the CpG island in the 5HTT gene. Pyrosequencing was performed and the methylation level at seven CpG island sites was measured. ResultsaaWe found no differences in the methylation patterns of the serotonin transporter linked promoter region (5-HTTLPR) between alcohol-dependent and control subjects. ConclusionaaOur negative finding may be because 5-HTT epigenetic variation may not affect the expression for 5-HTT or there may be other methylation site critical for its expression. To find out more conclusive result, repeating the study in more methylation sites with a larger number of samples in a well-controlled setting is needed. Psychiatry Investig 2011;8:130-13

Increased Transforming Growth Factor-beta1 in Alcohol Dependence

Ethanol and its metabolite acetaldehyde increase transforming growth factor beta1 (TGF-β1) expression in animal studies. TGF-β1 is related with the hepatic stellate cell (the key element of hepatic fibrogenesis) and the radial glia (the key element of neuronal migration). Blood samples were collected from 41 patients with alcohol dependence, TGF-β1 levels measured by ELISA were compared with 41 normal subjects. Plasma TGF-β1 levels in the patients with alcohol dependence (1,653.11±532.45 pg/mL) were significantly higher than those of healthy subjects (669.87±366.53 pg/mL) (P=0.000). Patients with or without liver pathology showed no difference in TGF-β1 (P=0.36). Increased TGF-β1 may mediate deleterious effect of alcohol such as hepatic fibrosis and suppressed neuronal developments in alcohol dependence patients

Incidence of Severe Chronic Neutropenia in South Korea and Related Clinical Manifestations: A National Health Insurance Database Study

Background and objectives: Severe chronic neutropenia (SCN) is a condition in which absolute neutrophil counts remain at a low level (under 500/µL) over months or years. Because of the rare onset of SCN, its epidemiology, prognosis, and clinical manifestations have not yet been fully understood. In particular, large-cohort studies in Asian countries are still insufficient. Therefore, in this study, national health insurance data was used to investigate the epidemiologic features and prognosis of SCN in South Korea. Materials and Methods: The data from the Health Insurance Review and Assessment database recorded between 1 January 2011 and 31 December 2015 were explored. SCN was defined based on the ICD-10 code, registry of benefit extension policy, and inclusion criteria of the study. After identifying patients with SCN, annual incidence and their co-morbidities were analyzed. Results: Among the initially identified patients with severe neutropenia (N = 2145), a total of 367 patients had SCN and were enrolled. The annual incidence rate of SCN ranged from 0.12 to 0.17 per 100,000 person-year (PY) during the study period. The highest incidence was observed in pediatric patients aged between 0 to 9 years (N = 156), followed by women in their fifties (N = 43). The total incidence rate was 0.17 in females and 0.12 in males (Relative risk (RR): 1.43, 95%, CI: 1.16–1.76). The most common accompanying condition was mild respiratory infection, but about 3.2% of patients progressed to hematologic malignancy after an average of 2.4 years. Conclusions: This nationwide population-based epidemiological study showed that incidence of SCN is higher in pediatrics and middle-aged women. As progression to hematologic malignancy was significantly higher in the age of in 45–49 year olds, careful follow-up is necessary in this group. However, since this study lacks the molecular information, these finding need to be interpreted with great caution

The neural substrates of affective processing toward positive and negative affective pictures in patients with major depressive disorder

Previous studies examining neural responses to emotional stimuli in individuals with major depressive disorder (MDD) have indicated increased responses within the left amygdala to sad faces, and increased activity within the visual cortex and striatum to expressions of happiness. Using functional magnetic resonance imaging (fMRI), the current study measured neural responses to neutral, positive and negative pictures of the International Affective Picture System in 15 healthy individuals and 15 patients with MDD. Depressed individuals demonstrated lower activity in the right hippocampus and the right insula to negative affective pictures, whereas they showed lower activity in the right anterior cingulate cortex and the left insula to positive pictures. However, within the MDD group, the severity of depression correlated with the activity of the left amygdala, bilateral inferior orbitofrontal areas, and the left insula to negative pictures, whereas there were no clear indications of association between specific cerebral regions and positive pictures. Our findings indicate that preferential decreases in the left amygdala in response to negative pictures might be involved in the processing of emotional stimuli in depressed individuals. Also, these findings suggest that the bilateral inferior orbitofrontal cortices and left amygdala may be preferentially recruited in MDD patients, but not in healthy individuals

Effects of Paliperidone Palmitate on Healthcare Utilization and Costs for Patients with Schizophrenia: A Claim-based Mirror-image Study in South Korea

Objective: Long-acting injectable (LAI) antipsychotics, such as paliperidone palmitate (PP), are known to improve treatment adherence in patients with schizophrenia, which can lead to reductions in relapse and hospitalization rates. However, relatively few studies have demonstrated the economic impact of LAIs, especially in Asian populations. Methods: We conducted a claim-based mirror-image study to explore changes in healthcare utilization and associated costs, among 1,272 South Korean patients with schizophrenia (ICD-10-CM code F20), between the 1-year periods before and after the initiation of PP treatment. Results: Patients accessed outpatient services more frequently after versus before starting PP treatment, with the number of prescription days increasing by 133.45 (p < 0.0001) and the associated costs increasing by USD 1,497.15 (p < 0.0001). The number of admission days was reduced by 11.33 after starting PP treatment (p < 0.0001) and the associated costs were reduced by USD 1,220.75 (p < 0.0001). However, admission cost savings were different according to patients' oral drug compliance. The daily dosages for benztropine, procyclidine, and propranolol decreased, showing that there were fewer side-effects after PP-treatment (p < 0.0001). Conclusion: Although the high acquisition cost of PP has been regarded as an obstacle to its clinical use, our results imply that the high prescription costs for PP may be counterbalanced by the reduced admission costs associated with its use. Economic outcomes for patients treated with LAIs should be investigated further to help healthcare decision-makers and providers to determine the value of LAIs relative to other treatment medications.N