Recent neuroimaging studies have demonstrated that the heterogeneous antidepressant responsiveness in patients with major depressive disorder (MDD) is associated with diverse resting-state functional brain network (rsFBN) topology; however, only limited studies have explored the rsFBN using electroencephalography (EEG). In this study, we aimed to identify EEG-derived rsFBN-based biomarkers to predict pharmacotherapeutic responsiveness.

The resting-state EEG signals were acquired for demography-matched three groups: 98 patients with treatment-refractory MDD (trMDD), 269 those with good-responding MDD (grMDD), and 131 healthy controls (HCs). The source-level rsFBN was constructed using 31 sources as nodes and beta-band power envelope correlation (PEC) as edges. The degree centrality (DC) and clustering coefficients (CCs) were calculated for various sparsity levels. Network-based statistic and one-way analysis of variance models were employed for comparing PECs and network indices, respectively. The multiple comparisons were controlled by the false discovery rate.

Patients with trMDD were characterized by the altered dorsal attention network and salience network. Specifically, they exhibited hypoconnection between eye fields and right parietal regions (p = 0.0088), decreased DC in the right supramarginal gyrus (q = 0.0057), and decreased CC in the reward circuit (qs < 0.05). On the other hand, both MDD groups shared increased DC but decreased CC in the posterior cingulate cortex.

We confirmed that network topology was more severely deteriorated in patients with trMDD, particularly for the attention-regulatory networks. Our findings suggested that the altered rsFBN topologies could serve as potential pathologically interpretable biomarkers for predicting antidepressant responsiveness.

Physical activities are widely implemented for non-pharmacological intervention to alleviate depressive symptoms. However, there is little evidence supporting their genotype-specific effectiveness in reducing the risk of self-harm in patients with depression.

To assess the associations between physical activity and self-harm behaviour and determine the recommended level of physical activity across the genotypes.

We developed the bidirectional analytical model to investigate the genotype-specific effectiveness on UK Biobank. After the genetic stratification of the depression phenotype cohort using hierarchical clustering, multivariable logistic regression models and Cox proportional hazards models were built to investigate the associations between physical activity and the risk of self-harm behaviour.

A total of 28 923 subjects with depression phenotypes were included in the study. In retrospective cohort analysis, the moderate and highly active groups were at lower risk of self-harm behaviour. In the followed prospective cohort analysis, light-intensity physical activity was associated with a lower risk of hospitalisations due to self-harm behaviour in one genetic cluster (adjusted hazard ratio, 0.28 [95% CI, 0.08–0.96]), which was distinguished by three genetic variants: rs1432639, rs4543289 and rs11209948. Compliance with the guideline-level moderate-to-vigorous physical activities was not significantly related to the risk of self-harm behaviour.

A genotype-specific dose of light-intensity physical activity reduces the risk of self-harm by around a fourth in depressive patients.

The present study aimed to develop neuropsychological norms for older Asian Americans with English as a primary or secondary language, using data from the National Alzheimer’s Coordinating Center (NACC).

A normative sample of Asian American participants was derived from the NACC database using robust criteria: participants were cognitively unimpaired at baseline (i.e., no MCI or dementia) and remained cognitively unimpaired at 1-year follow-up. Clinical and demographic characteristics were compared between Primary and Secondary English speakers using analyses of variance for continuous measures and chi-square tests for categorical variables. Linear regression models compared neuropsychological performance between the groups, adjusting for demographics (age, sex, and education). Regression models were developed for clinical application to compute demographically adjusted z-scores.

Secondary English speakers were younger than Primary English speakers (p < .001). There were significant differences between the groups on measures of mental status (Mini-Mental State Examination, p = .002), attention (Trail Making Test A, Digit Span Forward Total Score, p <.001), language (Boston Naming Test, Animal Fluency, Vegetable Fluency, p < .001), and executive function (Trail Making Test B, p = .02).

Separate normative data are needed for Primary vs. Secondary English speakers from Asian American backgrounds. We provide normative data on older Asian Americans to enable clinicians to account for English use in the interpretation of neuropsychological assessment scores.

Aggregation of phosphorylated tau (pTau) is a hallmark feature of Alzheimer’s disease (AD). Novel assays now allow pTau to be measured in plasma. Elevated plasma pTau predicts subsequent development of AD, cortical atrophy and AD-related pathologies in the brain. We aimed to determine whether elevated pTau is associated with cognitive functioning in older adults prior to the development of dementia.

Independently living older adults (N = 48, mean age = 70.0 years; SD = 7.7; age range 55-88 years; 35.4% male) free of dementia or clinical stroke were recruited from the community and underwent blood draw and neuropsychological assessment. Plasma was assayed using the Quanterix Simoa® pTau-181 V2 Advantage Kit to quantify pTau-181 levels and APOE genotyping was conducted on the blood cell pellet fraction obtained from plasma separation. Global cognition was assessed using the Dementia Rating Scale-2 (DRS-2) and executive function was assessed using the Stroop, D-KEFS-2 Fluency, and Trails Making Test. Diagnosis of mild cognitive impairment (MCI) was determined based on overall neuropsychological performance. Participants were diagnosed as MCI if they scored >1 SD below norm-referenced values on 2 or more tests within a domain (language, executive, memory) or on 3 tests across domains.

Multiple linear regression analysis revealed a significant negative association between plasma pTau-181 levels and DRS-2 (B = -2.57, 95% CI (-3.68, -1.47), p <.001), Stroop Color-Word score (B = -2.64, 95% CI (-4.56, - 0.71), p = .009) and Fruits and Vegetables Fluency (B = -1.67, 95% CI (-2.84, -0.49), p = .007), adjusting for age, sex, education and APOE4 status. MCI diagnosis was determined for 43 participants, of which 8 (18.6%) met criteria. Logistic regression analysis revealed that pTau-181 levels are associated with increased odds of MCI diagnosis (OR = 2.18, 95% CI (1.01, 4.68), p = .046), after accounting for age, sex, education and APOE4 status.

Elevated plasma pTau-181 is associated with worse cognition, particularly executive function, and predicts MCI diagnosis in older adults. Higher plasma pTau-181 was associated with increased odds of MCI diagnosis. Detection of pTau-181 in plasma allows a novel, non-invasive method to detect burden of one form of AD pathology. These findings lend support to the use of plasma pTau-181 as a valuable marker in detecting even early cognitive changes prior to the development of AD. Additional longitudinal studies are warranted to explore the prognostic value of plasma pTau-181 over time.

The locus coeruleus (LC) innervates the cerebrovasculature and plays a crucial role in optimal regulation of cerebral blood flow. However, no human studies to date have examined links between these systems with widely available neuroimaging methods. We quantified associations between LC structural integrity and regional cortical perfusion and probed whether varying levels of plasma Alzheimer’s disease (AD) biomarkers (Aß42/40 ratio and ptau181) moderated these relationships.

64 dementia-free community-dwelling older adults (ages 55-87) recruited across two studies underwent structural and functional neuroimaging on the same MRI scanner. 3D-pCASL MRI measured regional cerebral blood flow in limbic and frontal cortical regions, while T1-FSE MRI quantified rostral LC-MRI contrast, a well-established proxy measure of LC structural integrity. A subset of participants underwent fasting blood draw to measure plasma AD biomarker concentrations (Aß42/40 ratio and ptau181). Multiple linear regression models examined associations between perfusion and LC integrity, with rostral LC-MRI contrast as predictor, regional CBF as outcome, and age and study as covariates. Moderation analyses included additional terms for plasma AD biomarker concentration and plasma x LC interaction.

Greater rostral LC-MRI contrast was linked to lower regional perfusion in limbic regions, such as the amygdala (ß = -0.25, p = 0.049) and entorhinal cortex (ß = -0.20, p = 0.042), but was linked to higher regional perfusion in frontal cortical regions, such as the lateral (ß = 0.28, p = 0.003) and medial (ß = 0.24, p = 0.05) orbitofrontal (OFC) cortices. Plasma amyloid levels moderated the relationship between rostral LC and amygdala CBF (Aß42/40 ratio x rostral LC interaction term ß = -0.31, p = 0.021), such that as plasma Aß42/40 ratio decreased (i.e., greater pathology), the strength of the negative relationship between rostral LC integrity and amygdala perfusion decreased. Plasma ptau181levels moderated the relationship between rostral LC and entorhinal CBF (ptau181 x rostral LC interaction term ß = 0.64, p = 0.001), such that as ptau181 increased (i.e., greater pathology), the strength of the negative relationship between rostral LC integrity and entorhinal perfusion decreased. For frontal cortical regions, ptau181 levels moderated the relationship between rostral LC and lateral OFC perfusion (ptau181 x rostral LC interaction term ß = -0.54, p = .004), as well as between rostral LC and medial OFC perfusion (ptau181 x rostral LC interaction term ß = -0.53, p = .005), such that as ptau181 increased (i.e., greater pathology), the strength of the positive relationship between rostral LC integrity and frontal perfusion decreased.

LC integrity is linked to regional cortical perfusion in non-demented older adults, and these relationships are moderated by plasma AD biomarker concentrations. Variable directionality of the associations between the LC and frontal versus limbic perfusion, as well as the differential moderating effects of plasma AD biomarkers, may signify a compensatory mechanism and a shifting pattern of hyperemia in the presence of aggregating AD pathology. Linking LC integrity and cerebrovascular regulation may represent an important understudied pathway of dementia risk and may help to bridge competing theories of dementia progression in preclinical AD studies.

Blood pressure variability (BPV), independent of traditionally targeted average blood pressure levels, is an emerging vascular risk factor for stroke, cerebrovascular disease, and dementia, possibly through links with vascular-endothelial injury. Recent evidence suggests visit-to-visit (e.g., over months, years) BPV is associated with cerebrovascular disease severity, but less is known about relationships with short-term (e.g., < 24 hours) fluctuations in blood pressure. Additionally, it is unclear how BPV may be related to angiogenic growth factors that play a role in cerebral arterial health.

We investigated relationships between short-term BPV, white matter hyperintensities on MRI, and levels of plasma vascular endothelial growth factor (VEGF) in a sample of community-dwelling older adults (n = 57, ages 55-88) without history of dementia or stroke. Blood pressure was collected continuously during a 5-minute resting period. BPV was calculated as variability independent of mean, a commonly used index of BPV uncorrelated with average blood pressure levels. Participants underwent T2-FLAIR MRI to determine severity of white matter lesion burden. Severity of lesions was classified as Fazekas scores (0-3). Participants also underwent venipuncture to determine levels of plasma VEGF. Ordinal logistic regression examined the association between BPV and Fazekas scores. Multiple linear regression explored relationships between BPV and VEGF. Models controlled for age, sex, and average blood pressure.

Elevated BPV was related to greater white matter lesion burden (i.e., Fazekas score) (systolic: OR = 1.17 [95% CI 1.01, 1.37]; p = .04; diastolic: OR = 2.47 [95% CI 1.09, 5.90]; p = .03) and increased levels of plasma VEGF (systolic: ß = .39 [95% CI .11, .67]; adjusted R2 = .16; p = .007; diastolic: ß = .48 [95% CI .18, .78]; adjusted R2 = .18; p = .003).

Findings suggest short-term BPV may be related to cerebrovascular disease burden and angiogenic growth factors relevant to cerebral arterial health, independent of average blood pressure. Understanding the role of BPV in cerebrovascular disease and vascular-endothelial health may help elucidate the increased risk for stroke and dementia associated with elevated BPV.

Population ageing is a global phenomenon that necessitates consideration of health-related quality of life (HRQoL) in older adults. Previous studies have investigated related factors including mobility, social support and living situations.

This study aimed to provide a network perspective on factors related to HRQoL.

Cross-sectional nationwide data were obtained from the Korean National Health and Nutrition Examination Survey conducted from 2018 to 2020 for network analyses. Data for participants aged 65 years or above were analysed, resulting in a total of 4317 eligible cases. The variables included were EQ-5D (a measure of HRQoL), household income, education, living situation, subjective perceived health, Charlson Comorbidity Index (a measure of medical comorbidities), stress, exercise per week, alcohol consumption and smoking. Three networks were produced: (a) EQ-5D dimensions network, (2) EQ-5D dimensions, lifestyle and psychosocial factors network, and (3) overall EQ-5D index, lifestyle and psychosocial factors network. Node centralities, bridge centralities and edges of the networks were examined.

The most central EQ-5D dimension was the ability to carry out usual activities. In the second network, subjective health, stress and anxiety/depression were revealed as nodes with high bridge centralities. Subjective health, exercise, and Charlson Comorbidity Index were nodes closely linked to the overall EQ-5D index.

The results emphasise the importance of enhancing functional independence and subjective health cognition, increasing routine exercise and reducing stress as targets for interventions to improve HRQoL in older adults.

Some incidents require early deployment of emergency department personnel not designated as disaster medical assistance team (DMAT). Although not as trained as DMAT members, they should be aware of basic disaster response concepts and knowledge. Educating disaster readiness to every healthcare staff in emergency departments would be ideal but it is very costly in both time and expense. To overcome this problem, we tried to evaluate the effectiveness of teaching basic concept and knowledge to non-designated personnel in a short-session and measure the effect.

This study is a before-and-after comparison study. From July 2020 to July 2022, a two-hour education was given to volunteers among doctors, nurses, paramedics and administrative staff working in emergency departments across four hospitals in Korea. Educational sessions consisted of basic disaster concept, pre-deployment DMAT preparations, initial actions required on incident site, key elements of incident response (command, control, safety, communication), and triage. Attendees were given a pretest before the session and another test after the session. Chi-square test and Wilcoxon rank test were used to compare the results.

Total of 105 volunteers participated in the study. Participants were mostly nurses (62.9%) followed by paramedics (23.8%). Overall knowledge level reported to be increased, including knowledge regarding DMAT deployment (29.5% to 93.3%, p<0.001), DMAT personnel (26.7% to 94.3%, p<0.001), DMAT-designated equipment (23.8% to 60.0%, p<0.001), initial response (27.6% to 69.5%, p<0.001) and patient transport priority (74.3% to 94.3%, p<0.001). Questions testing triage and rate of participants answering every question showed improvement with post-test median score of 67% and rate of 1.0% to post-test median score of 100% and rate of 35.2%, respectively (both p<0.001).

Educating non-DMAT personnel in emergency departments with a short session showed significant improvement in basic knowledge of disaster response. It may help institutions with limited resources.

There are growing concerns about the impact of the COVID-19 pandemic on the mental health of older adults. We examined the effect of the pandemic on the risk of depression in older adults.

We analyzed data from the prospective cohort study of Korean older adults, which has been followed every 2 years. Among the 2308 participants who completed both the third and the fourth follow-up assessments, 58.4% completed their fourth follow-up before the outbreak of COVID-19 and the rest completed it during the pandemic. We conducted face-to-face diagnostic interviews using Mini International Neuropsychiatric Interview and used Geriatric Depression Scale. We performed generalized estimating equations and logistic regression analyses.

The COVID-19 pandemic was associated with increased depressive symptoms in older adults [b (standard error) = 0.42 (0.20), p = 0.040] and a doubling of the risk for incident depressive disorder even in euthymic older adults without a history of depression (odds ratio = 2.44, 95% confidence interval 1.18–5.02, p = 0.016). Less social activities, which was associated with the risk of depressive disorder before the pandemic, was not associated with the risk of depressive disorder during the pandemic. However, less family gatherings, which was not associated with the risk of depressive disorder before the pandemic, was associated with the doubled risk of depressive disorder during the pandemic.

The COVID-19 pandemic significantly influences the risk of late-life depression in the community. Older adults with a lack of family gatherings may be particularly vulnerable.