Effects of sexual orientation-based prejudice and discrimination in family of origin on depressive symptoms and life satisfaction in a Chinese sample: Reciprocal and authoritarian filial piety as moderators.

Experiencing prejudice and discrimination from family has been found to be positively associated with mental health problems among sexual minorities. Emerging evidence also shows the value of contextualizing the internalization of minority stress by considering individual cultural factors, such as filial piety. We examined whether authoritarian filial piety (AFP) and reciprocal filial piety (RFP) moderated the link between distal stressors in one's family and mental health outcomes. A total of 362 (56.9% male; age: M = 24.55, SD = 6.60) Chinese lesbian, gay, bisexual, queer/questioning, and other non-heterosexual (LGBQ+) individuals participated in this study. They provided demographic information and completed a battery of measures for AFP and RFP, sexual orientation-based prejudice and discrimination in family of origin (SOPDF), depressive symptoms, and life satisfaction. Structural equation modeling results showed that SOPDF had a positive and negative link with depressive symptoms and life satisfaction, respectively. In addition, we identified AFP and RFP as significant moderators for the association between SOPDF and depressive symptoms, and the association between SOPDF and life satisfaction, respectively. Specifically, the positive effect of SOPDF on depressive symptoms was greater for participants with higher levels of AFP; the negative effect of SOPDF on life satisfaction was greater for participants who endorsed higher levels of RFP. Our findings corroborated past studies' conclusion about the detrimental impact of familial sexual stigma on LGBQ+ people's mental health. Furthermore, such impact on negative and positive mental health outcomes are respectively conditioned by the degree to which LGBQ+ individuals endorse AFP and RFP. These findings underscore the importance for therapists who endorse family therapy to help LGBQ+ clients navigate familial sexual stigma and consider the role of filial piety beliefs in shaping the impact of familial sexual stigma on these clients' mental health.

Unsupervised multimodal modeling of cognitive and brain health trajectories for early dementia prediction.

Predicting the course of neurodegenerative disorders early has potential to greatly improve clinical management and patient outcomes. A key challenge for early prediction in real-world clinical settings is the lack of labeled data (i.e., clinical diagnosis). In contrast to supervised classification approaches that require labeled data, we propose an unsupervised multimodal trajectory modeling (MTM) approach based on a mixture of state space models that captures changes in longitudinal data (i.e., trajectories) and stratifies individuals without using clinical diagnosis for model training. MTM learns the relationship between states comprising expensive, invasive biomarkers (ß-amyloid, grey matter density) and readily obtainable cognitive observations. MTM training on trajectories stratifies individuals into clinically meaningful clusters more reliably than MTM training on baseline data alone and is robust to missing data (i.e., cognitive data alone or single assessments). Extracting an individualized cognitive health index (i.e., MTM-derived cluster membership index) allows us to predict progression to AD more precisely than standard clinical assessments (i.e., cognitive tests or MRI scans alone). Importantly, MTM generalizes successfully from research cohort to real-world clinical data from memory clinic patients with missing data, enhancing the clinical utility of our approach. Thus, our multimodal trajectory modeling approach provides a cost-effective and non-invasive tool for early dementia prediction without labeled data (i.e., clinical diagnosis) with strong potential for translation to clinical practice.

Mentorship for young gay men in Hong Kong: A pilot mixed-methods randomized controlled trial.

This study examined whether mentorship could promote young gay men's identities and well-being, and whether a mentor's sexual orientation matters. A randomized control trial compared outcomes across three conditions: Arm A (a mentee matched with a sexual minority mentor), Arm B (a mentee matched with a heterosexual mentor), and a control arm receiving psychoeducation only. A community sample of 60 mentees aged 18-25 years was randomly allocated to the three arms and completed questionnaires at baseline, 3 months into the intervention, and at the end of the 6-month program. Fifteen mentees recounted their mentoring experiences through in-depth interviews. Linear mixed effects models showed that for both intervention and control conditions, internalized homonegativity declined while resilience, loneliness, and body acceptance improved over time. No time and group interactions were found. Meanwhile, a mentor's sexual orientation did not drive differential quality and outcomes of mentorship. Interviewees cited various benefits of mentorship, including providing companionship, enriching connection with lesbian, gay, bisexual (LGB) communities, and adding knowledge and perspectives of LGB lives and identities. Although quantitative data did not support any exclusive benefits of mentorship, most mentees recognized mentorship as a vital source of affirmation and companionship. Implications for research and mentoring programs are discussed.

The Mental Health Costs of Online Heterosexism Among LGBTQ+ Individuals: Development and Initial Validation of the Perceived Online Heterosexism Scale.

Experiences of heterosexism are rampant online, where bias and harassment against LGBTQ+ individuals spread conveniently and widely. Yet, research has been limited in understanding the exposure to online heterosexism among LGBTQ+ individuals partly due to the lack of a quantitative measure to advance this research. Thus, the current study developed and examined the psychometric properties of the Perceived Online Heterosexism Scale (POHS). Items were developed via a literature review, a survey of social media platforms, and an expert review. Exploratory (N = 288) and confirmatory (N = 653) factor analyses yielded a 4-factor structure and produced a 20-item scale with the following subscales: (1) Heterosexist Cyberaggression (4 items), (2) Online Heterosexist Stereotyping (4 items), (3) Online Exposure to Systemic Heterosexism (8 items), and (4) Heterosexist Online Media (four items). Internal consistency estimates ranged from .91 to .96, and the POHS accounted for 65.9% of the variance. Examination of a second-order model suggested that a total scale score can also be used. Initial construct validity was evidenced as POHS scores were associated with an existing heterosexism measure, anxiety and depressive symptoms, internalized heterosexism, and LGBTQ+ community connectedness in line with theory and empirical evidence. Implications for research practice are discussed.

Longitudinal associations between ß-amyloid and cortical thickness in mild cognitive impairment.

How beta-amyloid accumulation influences brain atrophy in Alzheimer's disease remains contentious with conflicting findings. We aimed to elucidate the correlations of regional longitudinal atrophy with cross-sectional regional and global amyloid in individuals with mild cognitive impairment and no cognitive impairment. We hypothesized that greater cortical thinning over time correlated with greater amyloid deposition, particularly within Alzheimer's disease characteristic regions in mild cognitive impairment, and weaker or no correlations in those with no cognitive impairment. 45 patients with mild cognitive impairment and 12 controls underwent a cross-sectional [11C]-Pittsburgh Compound B PET and two retrospective longitudinal structural imaging (follow-up: 23.65 ± 2.04 months) to assess global/regional amyloid and regional cortical thickness, respectively. Separate linear mixed models were constructed to evaluate relationships of either global or regional amyloid with regional cortical thinning longitudinally. In patients with mild cognitive impairment, regional amyloid in the right banks of the superior temporal sulcus was associated with longitudinal cortical thinning in the right medial orbitofrontal cortex (P = 0.04 after False Discovery Rate correction). In the mild cognitive impairment group, greater right banks amyloid burden and less cortical thickness in the right medial orbitofrontal cortex showed greater visual and verbal memory decline over time, which was not observed in controls. Global amyloid was not associated with longitudinal cortical thinning in any locations in either group. Our findings indicate an increasing influence of amyloid on neurodegeneration and memory along the preclinical to prodromal spectrum. Future multimodal studies that include additional biomarkers will be well-suited to delineate the interplay between various pathological processes and amyloid and memory decline, as well as clarify their additive or independent effects along the disease deterioration.

A curvilinear association between therapists' use of discourse particles and therapist empathy in psychotherapy.

This study investigates the relationships between therapists' use of discourse particles and therapist empathy. Discourse particles, commonly found in non-English languages, are verbal elements that constitute metacommunication by encoding speakers' emotions and attitudes, which are typically expressed by nonverbal behaviors (e.g., intonation, tone, facial expression, nodding). We hypothesize an inverted U-shaped curvilinear relationship between therapists' use of discourse particles and therapist empathy, given the notion that an optimal level of therapists' emotion in psychotherapy can facilitate clients' inner experiencing and self-expression. Four psychotherapy sessions each from 39 therapist-client dyads were analyzed. After each session, therapist empathy was rated by trained observers using the Therapist Empathy Scale (TES) and by clients using the Barrett-Lennard Relationship Inventory (BLRI). Multilevel modeling shows that both the person-level negative quadratic term and positive linear term for therapists' usage of discourse particles are significant in predicting mean TES with large effect sizes. The same predictors do not yield significant results in predicting mean BLRI but they trend in similar directions of associations with medium effect sizes. Our results suggest the optimal usage of discourse particles by therapists is around 20.3% (out of all utterances). The nonsignificant results in BLRI may be attributed to the relatively small sample size of our data and the noncommunication orientation of the client-rated measure. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Examining the protective role of self-compassion in the links between daily sexual orientation salient experiences and affect.

Research has shown that minority stress is linked to poorer mental health across a variety of stigmatized populations, including lesbian, gay, bisexual, and queer (LGBQ) people. It is therefore essential to understand factors that can counteract minority stress. To date, most research on LGBQ people's resilience relied on retrospective reports of stressful identity-salient experiences. This limits the understanding about resilience factors that enable LGBQ people to thrive in the face of minority stressors as they occur on a day-to-day basis. The present study addressed this gap by using a daily diary design to test whether self-compassion protects LGBQ people's affective well-being from daily stressful sexual orientation-salient experiences (SOSEs). A sample of 235 LGBQ adults completed a baseline survey that assessed self-compassion, as well as brief online surveys twice daily for a maximum of 17 days that assessed SOSEs and affect, providing a total of 3,310 days of data. As anticipated, results of multilevel modeling showed that negative and positive SOSEs were linked to negative and positive evening affect, respectively, at both the daily and person levels. Self-compassion moderated the link between daily negative SOSEs and positive evening affect, such that daily negative SOSEs were linked to lower positive affect only among those with lower self-compassion. Moderation effect was not observed for negative evening affect as an outcome. Exploratory analysis suggested that the buffering effect of self-compassion could be impacted by contextual factors. Our study showed the importance of self-compassion and access to positive SOSEs for LGBQ people's well-being. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Short-term Trajectories of Poststroke Cognitive Function: A STROKOG Collaboration Study.

BACKGROUND AND OBJECTIVES: Past studies on poststroke cognitive function have focused on the average performance or change over time, but few have investigated patterns of cognitive trajectories after stroke. This project used latent class growth analysis (LCGA) to identify clusters of patients with similar patterns of cognition scores over the first-year poststroke and the extent to which long-term cognitive outcome is predicted by the clusters ("trajectory groups"). METHODS: Data were sought from the Stroke and Cognition consortium. LCGA was used to identify clusters of trajectories based on standardized global cognition scores at baseline (T1) and at the 1-year follow-up (T2). One-step individual participant data meta-analysis was used to examine risk factors for trajectory groups and association of trajectory groups with cognition at the long-term follow-up (T3). RESULTS: Nine hospital-based stroke cohorts with 1,149 patients (63% male; mean age 66.4 years [SD 11.0]) were included. The median time assessed at T1 was 3.6 months poststroke, 1.0 year at T2, and 3.2 years at T3. LCGA identified 3 trajectory groups, which were characterized by different mean levels of cognition scores at T1 (low-performance, -3.27 SD [0.94], 17%; medium-performance, -1.23 SD [0.68], 48%; and high-performance, 0.71 SD [0.77], 35%). There was significant improvement in cognition for the high-performance group (0.22 SD per year, 95% CI 0.07-0.36), but changes for the low-performance and medium-performance groups were not significant (-0.10 SD per year, 95% CI -0.33 to 0.13; 0.11 SD per year, 95% CI -0.08 to 0.24, respectively). Factors associated with the low- (vs high-) performance group include age (relative risk ratio [RRR] 1.18, 95% CI 1.14-1.23), years of education (RRR 0.61, 95% CI 0.56-0.67), diabetes (RRR 3.78, 95% CI 2.08-6.88), large artery vs small vessel strokes (RRR 2.77, 95% CI 1.32-5.83), and moderate/severe strokes (RRR 3.17, 95% CI 1.42-7.08). Trajectory groups were predictive of global cognition at T3, but its predictive power was comparable with scores at T1. DISCUSSION: The trajectory of cognitive function over the first-year poststroke is heterogenous. Baseline cognitive function ∼3.6 months poststroke is a good predictor of long-term cognitive outcome. Older age, lower levels of education, diabetes, large artery strokes, and greater stroke severity are risk factors for lower cognitive performance over the first year.

Prevalence, risk, and protective factors of self-stigma for people living with depression: A systematic review and meta-analysis.

BACKGROUND: People living with depression are subjected to widespread stigmatization worldwide. Self-stigma may negatively affect patients' treatment, recovery, and psychological well-being. This review aims to summarize and synthesize the evidence on the prevalence, risk, and protective factors of depression self-stigma. METHODS: Four online databases, PubMed, PsycINFO, Web of Science, and Embase, were searched to identify eligible studies. Fifty-six studies involving a total of 11,549 samples were included in the final analysis. Four reviewers independently screened the literature, extracted data, and assessed the risk of bias in eligible studies. Pearson's r was chosen as the effect size metric of risk and protective factors. RESULTS: The results showed that the global prevalence of depression self-stigma was 29 %. Levels of self-stigma varied across regions, but this difference was not significant. Two demographic factors were identified: ethnicity (r = 0.10, p < 0.05) and having a partner/married (r = -0.22, p < 0.001). Five risk factors were identified: depression severity (r = 0.33, p < 0.01), public stigma (r = 0.44, p < 0.001), treatment stigma (r = 0.46, p < 0.001), perceived stigma (r = 0.37, p < 0.001), and enacted stigma (r = 0.71, p < 0.001). Five protective factors were identified: quality of life (r = -0.38, p < 0.001), social relationship (r = -0.26, p < 0.05), self-esteem (r = -0.46, p < 0.001), extroversion (r = -0.32, p < 0.001), and social functioning (r = -0.49, p < 0.001). LIMITATIONS: Heterogeneity was observed in some of the results. Causality cannot be inferred due to the predominance of cross-sectional designs among the included literature. CONCLUSIONS: Risk and protective factors of depression self-stigma exist across many dimensions. Future research should examine the inner mechanisms and effectiveness of interventions to reduce stigma.

LGBQ affirmative practice and psychological well-being in China.

Research has consistently shown the importance of affirmative practice when therapists work with lesbian, gay, bisexual, queer/questioning (LGBQ) clients. However, less is known about factors that may influence the extent to which clients benefit from affirmative practice. The present study intends to address this gap by examining whether LGBQ affirmative practice would be positively associated with psychological well-being, and whether individuals factors including internalized homophobia (IH), reciprocal filial piety (RFP; providing care and support for parents based on affective bonding), and authoritarian filial piety (AFP; showing unconditional obedience to parents based on parental authority) would moderate this relationship. A total of 128 Chinese LGBQ clients (50% male, 38.3% female, and 11.7% nonbinary/gender queer; age: M = 25.26 years, SD = 5.46) from 21 provinces and regions completed the online survey. Results revealed that LGBQ affirmative practice was positively associated with psychological well-being after controlling for LGBQ clients' pretherapy distress and therapists' credibility. Such association was greater for LGBQ clients who had higher levels of IH and AFP, whereas such effect did not vary with RFP. This study provides preliminary empirical evidence for the effectiveness of LGBQ affirmative practice in psychological health among Chinese LGBQ clients. Moreover, LGBQ affirmative practice might be more helpful for LGBQ clients with higher IH and AFP. These findings implicate that Chinese counselors and therapists should engage in LGBQ affirmative practice when they work with LGBQ clients, especially for those who have high levels of IH and AFP. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Association of Interleukin-6 and Interleukin-8 with Cognitive Decline in an Asian Memory Clinic Population.

BACKGROUND: Neuroinflammation has been postulated to play an important role in cognitive impairment, cognitive decline, and dementia. Inflammatory biomarkers such as interleukin-6 (IL-6) and IL-8 are found to be associated with the neuro-inflammatory process and worse cognitive function. However, it is unknown whether these interleukins are associated with long-term cognitive function. OBJECTIVE: To investigate the association of baseline IL-6 and IL-8 with cognitive function at baseline as well as its association with cognitive decline over five-year follow-up. METHODS: 387 patients were recruited from an ongoing memory clinic-based study who underwent comprehensive physical, medical, neuropsychological and blood assessments together with brain MRI. IL-6 and IL-8 were measured using LUMINEX assays. The National Institute of Neurological Disorders and Stroke-Canadian Stroke Network neuropsychological battery was used to assess cognitive decline across multiple domains. RESULTS: Among the 387 (mean age = 72.9 years and 53.7% males) participants, 322 had at least two follow-up assessments and were included in the longitudinal analysis. Negative linear trend associations were found between tertiles of IL-8 with baseline global cognition (p-trend< 0.001), attention (p-trend = 0.005), executive function (p-trend< 0.001), and visuospatial function (p-trend = 0.002) domains. No association was found between baseline IL-8 and cognitive decline. IL-6 was not associated with both baseline and follow-up cognition. CONCLUSION: IL-8 was associated with worse cognition especially in attention, executive function, and visuospatial function, suggesting the role of neuroinflammation in cognitive impairment. Hence, blood inflammatory biomarkers may be useful indicators in identifying patients at risk of cognitive impairment and warrant consideration for inclusion in treatment trials.

On the Link Between Reciprocal/Authoritarian Filial Piety and Internalized Homonegativity: Perceived Pressure to Get Married in a Heterosexual Marriage as a Mediator.

Previous research has revealed that filial piety belief plays a critical role in self-acceptance of sexual orientation, but studies have rarely examined whether and how reciprocal (i.e., providing care and support based on affective bonding) and authoritarian (i.e., showing unconditional obedience to parents because of parental authority) filial piety contribute to internalized homonegativity. A total of 477 Chinese lesbian, gay, bisexual, questioning/queer, or other non-heterosexual (LGBQ +) adults participated in this study. These participants completed a battery of measures for reciprocal and authoritarian filial piety, perceived internalized, social, and parental pressure to get married in a heterosexual marriage, internalized heteronormativity, socially oriented identity (i.e., negative beliefs about how others in society would negatively treat them because of their sexual orientation), and family-oriented identity (e.g., guilt related to filial piety and worries about present and future life). The results indicated that higher reciprocal filial piety was directly associated with higher internalized heteronormativity. Higher authoritarian filial piety had a direct link with higher family-oriented identity. In addition, authoritarian filial piety was positively associated with internalized heteronormativity through internalized pressure to get married; authoritarian filial piety had a positive link with socially oriented identity through perceived social pressure to get married; authoritarian filial piety was positively related to family-oriented identity through perceived parental pressure to get married. Conclusions: Authoritarian filial piety is a risk factor for internalized homonegativity, and perceived pressure to get married in a heterosexual marriage might be the underlying mechanism for the relationship between authoritarian filial piety and internalized homonegativity.

Validation of the Informant Quick Dementia Rating System (QDRS) among Older Adults in Singapore.

BACKGROUND: The Quick Dementia Rating System (QDRS) is a brief and rapid tool that can be administered by an informant without the need for a trained assessor. OBJECTIVE: Our objective was to examine the validity, reliability, and cost-effectiveness of the informant QDRS in a Singapore memory clinic sample. METHODS: We assessed a total of 177 older adults, among whom, 32 had no cognitive impairment (NCI), 61 had mild cognitive impairment (MCI), and 84 had dementia. Elderly underwent 1) the informant QDRS, 2) the Clinical Dementia Rating (CDR) as the gold standard diagnosis, 3) the Mini-Mental State Examination (MMSE), and 4) the Ascertain Dementia 8 (AD8) as comparisons to the QDRS. The extent to which the QDRS may reduce the recruitment cost (time) of clinical trials was also calculated. RESULTS: The QDRS had excellent internal consistency (Cronbach alpha = 0.939). It correlated highly with the CDR-global (R = 0.897), CDR Sum-of-Boxes (R = 0.915), MMSE (R = -0.848), and the AD8 (R = 0.747), showing good concurrent validity. With an optimal cut-off of 1.5 for MCI (sensitivity 85.2%, specificity 96.3%) and 6 for dementia (sensitivity 90.1%, specificity 89.2%), the QDRS achieved a higher overall accuracy of 85.0%, as compared to MMSE (71.2%) and AD8 (73.4%). A simulated clinical trial recruitment scenario demonstrated that pre-screening with the QDRS followed by a confirmatory CDR would reduce the time needed to identify NCI subjects by 23.3% and MCI subjects by 75.3%. CONCLUSION: The QDRS is a reliable cognitive impairment screening tool which is suitable for informant-administration, especially for identification of MCI.

Long-Term Cognitive Decline After Stroke: An Individual Participant Data Meta-Analysis.

BACKGROUND: Poststroke cognitive impairment is common, but the trajectory and magnitude of cognitive decline after stroke is unclear. We examined the course and determinants of cognitive change after stroke using individual participant data from the Stroke and Cognition Consortium. METHODS: Nine longitudinal hospital-based cohorts from 7 countries were included. Neuropsychological test scores and normative data were used to calculate standardized scores for global cognition and 5 cognitive domains. One-step individual participant data meta-analysis was used to examine the rate of change in cognitive function and risk factors for cognitive decline after stroke. Stroke-free controls were included to examine rate differences. Based on the literature and our own data that showed short-term improvement in cognitive function after stroke, key analyses were restricted to the period beginning 1-year poststroke to focus on its long-term effects. RESULTS: A total of 1488 patients (mean age, 66.3 years; SD, 11.1; 98% ischemic stroke) were followed for a median of 2.68 years (25th-75th percentile: 1.21-4.14 years). After an initial period of improvement through up to 1-year poststroke, decline was seen in global cognition and all domains except executive function after adjusting for age, sex, education, vascular risk factors, and stroke characteristics (-0.053 SD/year [95% CI, -0.073 to -0.033]; P<0.001 for global cognition). Recurrent stroke and older age were associated with faster decline. Decline was significantly faster in patients with stroke compared with controls (difference=-0.078 SD/year [95% CI, -0.11 to -0.045]; P<0.001 for global cognition in a subgroup analysis). CONCLUSIONS: Patients with stroke experience cognitive decline that is faster than that of stroke-free controls from 1 to 3 years after onset. An increased rate of decline is associated with older age and recurrent stroke.

Cerebral Microbleeds and White Matter Hyperintensities are Associated with Cognitive Decline in an Asian Memory Clinic Study.

BACKGROUND: Cerebral Small Vessel Disease (SVD); lacunes, Cerebral Microbleeds (CMBs), and White Matter Hyperintensities (WMH) have a vital role in cognitive impairment and dementia. SVD in lobar location is related to cerebral amyloid angiopathy, whereas SVD in a deep location with hypertensive arteriopathy. It remains unclear how different locations of SVD affect long-term cognitive decline. The present study aimed to analyse the association between different locations and severity of SVD with global and domain-specific cognitive decline over the follow-up interval of 3 years. METHODS: We studied 428 participants who had performed MRI scans at baseline and at least 3 neuropsychological assessments. Locations of lacunes and CMBs were categorized into strictly lobar, strictly deep and mixed-location, WMH volume into anterior and posterior. The National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Harmonization Neuropsychological Battery was used to assess cognitive function. To analyse the association between baseline location and severity of SVD with cognitive decline, linear regression models with generalized estimated equations were constructed to calculate the mean difference, 95% confidence interval and two-way interaction factor between time and SVD. RESULTS: Increased numbers of baseline CMBs were associated with a decline in global cognition as well as a decline in executive function and memory domains. Location-specific analysis showed similar results with strictly lobar CMBs. There was no association with strictly deep and mixed-location CMBs with cognitive decline. Baseline WMH volume was associated with a decline in global cognition, executive function and memory. Similar results were obtained with anterior and posterior WMH volumes. Lacunes and their locations were not associated with cognitive decline. CONCLUSION: Strictly lobar CMBs, as well as WMH volume in anterior and posterior regions, were associated with cognitive decline. Future research focuses are warranted to evaluate interventions that may prevent cognitive decline related to SVD.

Domain-Specific Cognitive Trajectories Among Patients with Minor Stroke or Transient Ischemic Attack in a 6-Year Prospective Asian Cohort: Serial Patterns and Indicators.

BACKGROUND: Long-term post-stroke cognitive impairment (PSCI) has often been overlooked, especially among patients with minor stroke or transient ischemic attack (TIA). OBJECTIVE: To assess 6-year domain-specific cognitive trajectories among survivors of minor stroke or TIA and to identify possible indicators associated with cognitive trajectories, as well as long-term and incident PSCI. METHODS: Eligible participants completed cognitive and clinical assessments at baseline (2 weeks after stroke) and up to 5 follow-up visits in 6 years. Mixed linear models and generalized estimating equations were adopted to analyze longitudinal data and survival analysis to explore incident PSCI, controlling for demographic, clinical, and vascular indicators. RESULTS: The prevalence of PSCI and mortality rate ranged from 34.6% to 53.7%, and 0 to 7.7% respectively, among 244 patients. Incidence of PSCI was 21.9%. While visual memory demonstrated a significant improvement (p < 0.05), other cognitive domains showed a fluctuating yet stable pattern across visits (all ps > 0.05). Besides age, baseline IQCODE (attention: -0.218 SD/y, executive function: -0.238 SD/y, visual memory: -0.266 SD/y), and MoCA improvement within 1 year (visuoconstruction: 0.007 SD/y, verbal memory: 0.012 SD/y) were associated with longitudinal cognitive changes. Baseline MoCA (OR = 0.66, 95% CI = [0.59-0.74]), MoCA improvement within 3-6 months (OR = 0.79, 95% CI = [0.71-0.89], and within 1 year (OR = 0.86, 95% CI = [0.76-0.96]) were associated with long-term PSCI, while baseline MoCA (OR = 0.76, 95% CI = [0.61-0.96]) was also associated with incident PSCI. CONCLUSION: While most domains remained stable across-time, visual memory demonstrated an overall improvement. Short-term cognitive improvement could be an early indicator of long-term cognitive trajectory to identify individuals who may be resilient to PSCI.

NEURoaid II (MLC901) in cognitively Impaired not demenTEd patientS (NEURITES): A pilot double blind, placebo-controlled randomized trial.

OBJECTIVE: To investigate the efficacy and safety of MLC901 in vascular cognitive impairment no dementia (VCIND) patients. DESIGN: This was a multi-center, double-blind, randomized, placebo-controlled pilot study. SETTING AND PARTICIPANT: VCIND patients from hospitals in Singapore (67), Vietnam (19), and the Philippines (17) were recruited and followed-up from March 2013 to April 2018. METHODS: The primary outcome was executive function as measured by the Verbal Fluency (VF) and 2-part Color Trails Test (CTT). The mean difference in the scores between baseline and week 12, and baseline and week 24, was compared between MLC901 and placebo using a two-sample t-test. RESULTS: The trial randomized 103 subjects: MLC901 (n = 57) and placebo (n = 46). The mean age of participants was 68.3 ± 8.4 years and 38.8% were female. Improvement in executive function with MLC901 was not significantly better than placebo at week 12 (CTT1 mean difference [md] 3.8 seconds, 95% confidence interval [CI]: -9.0 to 16.5, CTT2 md 10.9 seconds, 95% CI: -0.2 to 22.0), and at week 24 (CTT1 md 2.8 seconds, 95% CI: -8.4 to 14.0, CTT2 md = 4.4 seconds, 95% CI: -8.2 to 16.9). Improvement in VF from baseline was not significantly different between MLC901 and placebo at weeks 12 and 24. There were no significant differences in adverse events (43.5% vs. 56.1%) or serious adverse events (13% vs. 22.8%) in placebo versus MLC901 groups. In post hoc exploratory analysis, the treatment effect of MLC901 on cognitive function appears more apparent in subjects with existing impairment in executive function: CTT2 (md 14.4 seconds [P = .05] and 9.9 seconds [P = .3] at week 12 and week 24, respectively). CONCLUSIONS: Whilst MLC901 appears to be safe, there was no significant cognitive benefit from MLC901 in the study population. Post hoc hypotheses generating analyses suggest that VCIND patients with existing impairment in executive function may show benefit.

Vision, vision-specific functioning and mobility, and their relationship with clinically assessed cognitive impairment.

BACKGROUND: The relationship between self-reported visual disability and cognitive impairment in older individuals is unclear. OBJECTIVE: To determine the relationship of vision-specific functioning (VSF), vision-specific mobility (VSM) and visual acuity (VA) with clinically assessed cognitive impairment in the Epidemiology of Dementia in Singapore study. DESIGN: Cross-sectional. SETTING: Population-based. SUBJECTS: Eight hundred and seventy-four adults aged ≥60 years at higher risk of possible cognitive impairment by the Abbreviated Mental Test and progressive forgetfulness question. METHODS: VSF and VSM were measured using Rasch-transformed continuous scores of two Impact of Vision Impairment questionnaire domains. Cognitive impairment was objectively determined using detailed neuropsychological testing and defined as no cognitive impairment (NCI), mild cognitive impairment-no dementia (CIND), moderate CIND only and moderate CIND or dementia. Associations were assessed using multinomial logistic regression models. RESULTS: Of the 874 participants (49.0% males, mean age (SD) 65.5 (7.0) years), 277, 281 and 316 had NCI, mild CIND and moderate CIND or dementia, respectively. Compared to NCI, the odds of moderate CIND, and moderate CIND or dementia increased for every SD worsening in VSF (OR: 1.44, 95% CI 1.14-1.82, and OR: 1.52, 95%CI 1.19-1.94, respectively) and VSM (OR: 1.42, 95%CI 1.11-1.81, and OR: 1.50, 95%CI 1.15-1.95). Similarly, the odds of mild CIND (OR: 1.62, 95%CI 1.19-2.22), moderate CIND (OR: 1.93, 95%CI 1.45-2.58), and moderate CIND or dementia (OR: 2.25, 95%CI 1.62-3.11) increased significantly with every SD worsening of VA. CONCLUSIONS: Our results emphasise the importance of interventions to prevent vision loss and improve quality of life to reduce likelihood of age-related cognitive decline.

The Impact of Strategic White Matter Hyperintensity Lesion Location on Language.

OBJECTIVE: The impact of white matter hyperintensities (WMH) on language possibly depends on lesion location through disturbance of strategic white matter tracts. We examined the impact of WMH location on language in elderly Asians. DESIGN: Cross-sectional. SETTING: Population-based. PARTICIPANTS: Eight-hundred nineteen residents of Singapore, ages (≥65 years). MEASUREMENTS: Clinical, cognitive and 3T magnetic resonance imaging assessments were performed on all participants. Language was assessed using the Modified Boston Naming Test (MBNT) and Verbal Fluency (VF). Hypothesis-free region-of-interest-based (ROI) analyses based on major white matter tracts were used to determine the association between WMH location and language. Conditional dependencies between the regional WMH volumes and language were examined using Bayesian-network analysis. RESULTS: ROI-based analyses showed that WMH located within the anterior thalamic radiation (mean difference: -0.12, 95% confidence interval [CI]: -0.22; -0.02, p = 0.019) and uncinate fasciculus (mean difference: -0.09, 95% CI: -0.18; -0.01, p = 0.022) in the left hemisphere were significantly associated with worse VF but did not survive multiple testing. Conversely, WMH volume in the left cingulum of cingulate gyrus was significantly associated with MBNT performance (mean difference: -0.09, 95% CI: -0.17; -0.02, p = 0.016). Bayesian-network analyses confirmed the left cingulum of cingulate gyrus as a direct determinant of MBNT performance. CONCLUSION: Our findings identify the left cingulum of cingulate gyrus as a strategic white matter tract for MBNT, suggesting that language - is sensitive to subcortical ischemic damage. Future studies on the role of sporadic ischemic lesions and vascular cognitive impairment should not only focus on total WMH volume but should also take WMH lesion location into account when addressing language.

Cerebral microinfarcts affect brain structural network topology in cognitively impaired patients.

Cerebral microinfarcts (CMIs), a novel cerebrovascular marker, are prevalent in Alzheimer's disease (AD) and associated with cognitive impairment. Nonetheless, the underlying mechanism of how CMIs influence cognition remains uncertain. We hypothesized that cortical-CMIs disrupted structural connectivity in the higher-order cognitive networks, leading to cognitive impairment. We analyzed diffusion-MRI data of 92 AD (26 with cortical-CMIs) and 110 cognitive impairment no dementia patients (CIND, 28 with cortical-CMIs). We compared structural network topology between groups with and without cortical-CMIs in AD/CIND, and tested whether structural connectivity mediated the association between cortical-CMIs and cognition. Cortical-CMIs correlated with impaired structural network topology (i.e. lower efficiency/degree centrality in the executive control/dorsal attention networks in CIND, and lower clustering coefficient in the default mode/dorsal attention networks in AD), which mediated the association of cortical-CMIs with visuoconstruction dysfunction. Our findings provide the first in vivo human evidence that cortical-CMIs impair cognition in elderly via disrupting structural connectivity.