Transcranial direct current stimulation (tDCS) is a promising treatment for major depressive disorder (MDD). This study evaluated its antidepressant and cognitive effects as a safe, effective, home-based therapy for MDD.

This double-blind, sham-controlled, randomized trial divided participants into low-intensity (1 mA, n = 47), high-intensity (2 mA, n = 49), and sham (n = 45) groups, receiving 42 daily tDCS sessions, including weekends and holidays, targeting the dorsolateral prefrontal cortex for 30 minutes. Assessments were conducted at baseline and weeks 2, 4, and 6. The primary outcome was cognitive improvement assessed by changes in total accuracy on the 2-back test from baseline to week 6. Secondary outcomes included changes in depressive symptoms (HAM-D), anxiety (HAM-A), and quality of life (QLES). Adverse events were monitored. This trial was registered with ClinicalTrials.gov (NCT04709952).

In the tDCS study, of 141 participants (102 [72.3%] women; mean age 35.7 years, standard deviation 12.7), 95 completed the trial. Mean changes in the total accuracy scores from baseline to week 6 were compared across the three groups using an F-test. Linear mixed-effects models examined the interaction of group and time. Results showed no significant differences among groups in cognitive or depressive outcomes at week 6. Active groups experienced more mild adverse events compared to sham but had similar rates of severe adverse events and dropout.

Home-based tDCS for MDD demonstrated no evidence of effectiveness but was safe and well-tolerated. Further research is needed to address the technical limitations, evaluate broader cognitive functions, and extend durations to evaluate its therapeutic potential.

Dry mouth is a subjective symptom of the feeling of dehydration inside of the mouth and is closely linked to reduced salivary secretion. The occurrence of dry mouth and GI disorders due to antidepressants greatly affects the course of the mental disorder and medication compliance, but it has barely ever been studied.

The purpose of this study was to identify the characteristics of dry mouth and gastrointestinal (GI) disorders in antidepressant patients.

The study included 103 antidepressant-taking patients. Antidepressants were classified according to their mode of action. The GI disorders were investigated using the medical records of the patients. The Patient Health Questionnaire-15 and a questionnaire for assessing dry mouth symptoms were used in this study. The questionnaire for the evaluation of dry mouth symptoms, a visual analog scale (VAS)–based instrument, developed and evaluated for reliability by Lee et al. was used to assess dry mouth. In the questionnaire, 6 VAS items were assessed for the extent of dry mouth (0-100 points) : 1) dry mouth at night or when waking up in the morning, 2) dry mouth during the day, 3) dry mouth when eating, 4) difficulty in swallowing, 5) subjective evaluation of the volume of saliva in the mouth, and 6) overall discomfort in daily life. Additionally, four items examined behaviors due to dry mouth (1-5points) : 1) frequency of waking up from sleep due to dry mouth, 2) frequency of preparing drinking water before going to bed, 3) frequency of drinking water when eating solid foods, and 4) frequency of eating hard candies or chewing gums to help dry mouth.

The score for “overall discomfort due to dry mouth in daily life” (31.72±33.82), “dry mouth at night or in the morning” (47.86±35.87), and “dry mouth during the day” (39.83±31.67) were slightly higher than “discomfort in chewing or swallowing foods”. According to somatization severity, the mean values were 116.36±113.34 in the mild, 213.18±136.98 in the moderate, and 277.59±201.44 in the severe, the between-group difference was significant (F=10.294, p<0.001). According to the class of antidepressants, the mean score was 180.00±147.5 for vortioxetine, 194.25±169.33 for selective serotonin reuptake inhibitors (SSRIs), 223.61±156.70 for serotonin and norepinephrine reuptake inhibitors (SNRIs), 75.00±57.00 for norepinephrine dopamine reuptake inhibitors (NDRIs), 201.67±174.66 for Nassau, and 116.67±132.03 for agomelatine. A total of 67 (65.0%) patients had at least one GI disorder.

The study findings are expected to help increase medication compliance in antidepressant patients by better controlling the side effects experienced by the patients.

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Gaming disorder has become a global concern and it could have a variety of health and social consequences. The trauma model has been applied to the understanding of different types of addictions as behavioral addictions can sometimes be conceptualized as self-soothing strategies to avoid trauma-related stressors or triggers. However, much less is known about the relationship between trauma exposure and gaming disorder.

To inform prevention and intervention strategies and to facilitate further research, we conducted the first scoping review to explore and summarize the literature on the relationship between trauma and gaming disorder.

A systematic search was conducted on the Web of Science, Scopus and ProQuest. We looked for original studies published in English that included a measure of trauma exposure and a measure of gaming disorder symptoms, as well as quantitative data regarding the relationship between trauma exposure and gaming disorder.

The initial search generated 412 articles, of which 15 met the inclusion criteria. All of them were cross-sectional studies, recruiting participants from both clinical and non-clinical populations. Twelve of them (80%) reported significant correlations between trauma exposure and the severity of gaming disorder symptoms (r = 0.18 to 0.46, p < 0.010). Several potential mediators, including depressive symptoms and dissociative experiences, have been identified. One study found that parental monitoring moderated the relationship between trauma and gaming disorder symptoms. No studies reported the prevalence of trauma or trauma-related symptoms among people with gaming disorder.

There is some evidence supporting the association between trauma and gaming disorder, at small to medium effect sizes. Future studies should investigate the mediators and moderators underlying the relationship between trauma and gaming disorder. The longitudinal relationship between trauma exposure and the development of gaming disorder should be clarified. A trauma-informed approach may be a helpful strategy to alleviate gaming disorder symptoms.

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People with mental illness often experience a concealable stigmatized identity that may be invisible to others. As a result, they are often faced with the dilemmas of whether to disclosure or conceal their diagnosis and their experience. However, in order to overcome the social stigma and self-stigma that hinder their recovery, they must establish a network and social support through identity disclosure.

This study investigates the effect of clinical characteristics (symptom and social function level), self-stigma and social support on the disclosure of people with mental illness.

The research was conducted with 236 respondents who are currently using community mental health services. (Male: 51.9%, Female: 48.1%; Mean age = 47.97±13.24; SPR: 66.8%, other diagnosis: 33.2%).

Most respondents disclosed their mental illness to health service providers and family, but they are least open about their identity toward neighbors and co-workers. A regression analysis of predictors of disclosure revealed that only social functioning level and social support had significant predictive power. It was discovered that individuals with better level of social function and social support disclosure more about their mental illness.

A program that increases social functions and support network can be recommended to improve disclosure efficacy.

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Maintenance electroconvulsive therapy (ECT) can be effective and necessary in the long-term for patients with severe and recurrent mood or psychotic disorders that are not amenable to any other forms of treatment. Patients with such treatment resistance affecting their ability to maintain minimal daily activities may eventually fall within the palliative psychiatric care domain in which advanced medical directives become an important beacon to direct care. There are Psychiatric Advance Directives which allow people with severe mental health conditions to consent to or refuse to consent to hospital admission and psychiatric treatment in the event they lose decision-making capacity and this can be especially important for a potentially controversial treatment such as ECT. However, the focus tends to be on enforcing involuntary treatment and less about a comprehensive long-term care plan. To our knowledge, there is no available framework to structure maintenance ECT as a patient-centred care plan.

Our aim is to share the process of development of a patient-centred care plan for patients requiring maintenance ECT. Our objectives are:

1. 1. Constant engagement with patients and family or caregivers

2. 2. Regular reviews of clinical and consent aspects of treatment

3. 3. Advocating for the welfare of patients and respect of values

4. 4. Focus on dignity especially for patients who require treatment well into old age

5. 5. Being prepared for termination of treatment if necessary

We reviewed our management of previous and existing patients on maintenance ECT and incorporated diligent consent-taking practices. Adopting good practices from known palliative approaches and involving the patient voice helped to form a framework for a patient-centred care plan.

Our patient-centred care plan features half-yearly discussions about the risks and benefits of treatment, as well as an assessment of the patient’s cognition and ability to consent which may change over time. Opportunities for them to share their values and expectations of care and engagement with their caregivers about their quality of life guide the continued treatment. A framework for discussing the disruption or eventual termination of ECT prepares for scenarios where older-aged patients may develop frailty or present with acute, prolonged or devastating medical concerns. This end-of-life care approach manages anticipated psychiatric-specific behavioural concerns and prepares for the possibility of death following the planned termination of ECT for patients who required long-term treatment throughout their life. Lastly, issues of grief amongst caregivers and ethical concerns from medical staff are addressed.

We hope that our patient-centred care plan provides a well-considered conversation and structure for the initiation, continuation and termination of maintenance ECT in the long-term.

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Home nursing and medical services have an established role in delivering chronic medical care to populations which face difficulty accessing physical clinics. Those with chronic medical conditions and reduced mobility face a higher likelihood of suffering from psychiatric co-morbidity. However, till date there has been limited research done on home-based psychiatric care in this population.

Since 2021, the Psychiatry department of Tan Tock Seng Hospital (TTSH) has been collaborating with TTSH Community Health Team (CHT) to manage potential psychiatric issues in community patients.

These patients would be discussed in a weekly multidisciplinary setting. If indicated, home visit by both teams for home-based assessment and treatment would be arranged, allowing for detection and treatment of psychiatric illness.

To demonstrate that the collaboration between the psychiatry team and CHT leads to diagnosis and treatment of psychiatric illness in a population that might otherwise have been unable to access psychiatric services.

We performed a retrospective study on all referrals from the CHT to the psychiatry team, within the 2-year period of August 2021 to August 2023. We collected demographic information, psychiatric history prior to referral, reason for referral, outcome of multidisciplinary discussion, and outcome of the home visits (including diagnoses made, and medications initiated).

A total of 92 patients were referred by the CHT to the psychiatry team. Most were elderly with multiple medical co-morbidities; of note, a history of stroke was present in 24 of the referred patients.

Common reasons for referral include suspected mental illness, risk assessment, and management of behavioural issues.

28 of the referred patients did not have a prior psychiatric history at the point of referral. Among these, home visits involving the psychiatric team were done for 16 patients. 11 (68%) of these home visits led to diagnosis of a new psychiatric illness. 9 of these patients were initiated on psychotropic medications in the home setting.

A significant proportion of patients (68% of home visits without prior psychiatric diagnosis) were newly diagnosed with psychiatric illness, allowing early psychiatric intervention to be delivered. This was achieved in a population with a high prevalence of multiple medical comorbidity and barriers to clinic-based psychiatric evaluation and treatment.

We propose future comparative studies into how the collaboration between the psychiatric team and community health team can improve the quality of life and caregiver experience of patients with chronic medical problems, as well as how the service had improved the confidence of the community health team in identifying and managing patients with possible psychiatric issues.

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Majority of international guidelines for bipolar disorders are based on evidences from clinical trials. In contrast, the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was developed to adopt an expert-consensus paradigm which was more practical and specific to the atmosphere in Korea.

In this study, preferred medication strategies for acute mania over six consecutively published KMAP-BP (2002, 2006, 2010, 2014, 2018, and 2022) were investigated.

A written survey using a nine-point scale was asked to Korean experts about the appropriateness of various treatment strategies and treatment agents. A written survey asked about the appropriateness of various treatment strategies and treatment agents commonly used by clinicians as the first-line.

The most preferred option for the initial treatment of mania was a combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP) in every edition. Preference for combined treatment for euphoric mania increased, peaked in KMAP-BP 2010, and declined slightly. Either MS or AAP monotherapy was also considered a first-line strategy for mania, but not for all types of episodes, including mixed/psychotic mania. Among MSs, lithium and valproate are almost equally preferred except in the mixed subtype where valproate is the most recommended MS. The preference of valproate showed reverse U-shaped curve. This preference change of valproate may indicate the concern about teratotoxicity in women. Quetiapine, aripiprazole, and olanzapine were the preferred AAP for acute mania since 2014. This change might depend on the recent evidences and safety profile. In cases of unsatisfactory response to initial medications, switching or adding another first-line agent was recommended. The most notable changes over time included the increasing preference for AAPs.

The Korean experts have been increasingly convinced of the effectiveness of a combination therapy for acute mania. There have been evident preference changes: increased for AAP and decreased for carbamazepine.

None Declared

Even though depression is a severe health issue among older adults, few studies have explored their knowledge of geriatric depression.

This study aimed to explore older adults’ knowledge of geriatric depression and its related factors.

A cross-sectional survey was conducted. Older adults were recruited by convenience from outpatient clinics of three hospitals in Taiwan.

A total of 327 older adults participated in this study. Their mean score of knowledge was 7.73 (SD=2.12, Range=2-12) on an 18-item knowledge scale, indicating poor knowledge of geriatric depression. Females had significantly higher geriatric depression knowledge scores than males (t=2.50, p=0.01). Junior and senior high school graduates had significantly higher geriatric depression knowledge scores than illiterate and primary school graduates (F=10.23, p<0.01). In addition, their geriatric depression knowledge scores also differed by religious belief (F=4.91, p<0.01), living status (F=8.64, p<0.01), and perceived health condition (F=8.81, p<0.01). Buddhists had significantly higher geriatric depression knowledge scores than Taoists. Living with partners and perceiving their health status as fair and good tended to have higher geriatric knowledge scores than their counterparts. However, their geriatric depression knowledge scores did not significantly correlate with their mean scores of social distance toward older adults with depression.

Older adults tended to have poor geriatric depression knowledge. Improving their knowledge shall be an urgent task. Our results may serve as references for developing further depression prevention.

None Declared

New prevalence and time trend data from various Asian countries show that Eating Disorders (ED) are increasingly common in Asia. (Youl-Ri Kim. Int J Eat Disord. Dec 2020). A recent study estimating the prevalence of ED in Singapore found an alarming 6.2% screened positive for a clinical ED diagnosis, 19.5% were screened to be at high risk, and estimated the point prevalence of Anorexia Nervosa (AN) to be 0.9%. (Chua SN et al. Int J Eat Disord. Jan 2021).

The ED unit in Singapore General Hospital (SGH) was set up in 2003 as a National Treatment Programme for patients with ED.

Two local studies have been published to date on the demographics and clinical profile of patients with AN. The first study examined 126 patients from 1994 – 2002 (HY Lee et al. Singapore Med J 2005; 46(6): 275-281). The second study reported on 271 cases from our SGH ED unit from 2003-2010 (Kuek et al. SIngapore Med J 2015; 56(6): 324-328). There have been no further studies in the last decade.

1. 1. Study the demographics and clinical profile of patients who presented with AN to our ED unit from 2011-2022

2. 2. Compare our data with the 2 previous studies and examine for any changes and trends in the past 30 years.

We conducted a review of the ED unit new case registry at SGH from 2011-2022. A total of 910 patients were diagnosed with AN at presentation. The data was analysed with approval from the hospital instituitional review board.

A total of 910 cases presented with AN over 12 years. Comparing with the 2 previous studies, the number of new cases each year has continued to increase from <15 in the 1990s to hit a peak of 109 per year in 2022. 94% were females, with a mean presenting age of 19. 79.2% were Chinese, 5.2% were Indians and 2.9% were of Malay ethnicity. The Malay population continue to be under-represented whereas other ethnic groups continue to be over-represented, increasing from 3.2% to 7% in the previous studies to 11.1%. Referrals were mainly from tertiary healthcare intuitions accounting for 41.4% of cases. Self-referrals have decreased over the last decade whereas referrals from primary care has increased. The mean presenting body mass index (BMI) was 15.9. Compared to a previous study, there was a significant increase in presenting BMI (15.9+/- 0.78 vs 14.4 +/- 1.77, p value 0.0074).

The number of new cases of AN has seen an almost 10-fold increase in the last 30years. The Malay ethnicity continues to be under-represented – more research is needed if they are somehow culturally protected or if they are not coming forth for treatment. Majority of referrals are from tertiary healthcare institutions but referrals from primary care have increased, reflecting a possible increase in awareness amongst primary care doctors. The mean presenting BMI has increased – hopefully reflecting an increase in ED awareness such that patients are coming forward earlier for treatment.

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In the United States, lesbian, gay, bisexual, transgender, queer, intersex, asexual and other sexually minoritized and gender expansive (LGBTQ+) young adults are at increased risk for experiencing mental health inequities, including anxiety, depression and psychological distress-related challenges associated with their sexual and gender identities. LGBTQ+ young adults may have unique experiences of sexual and gender minority-related vulnerability because of LGBTQ+-related minority stress and stressors, such as heterosexism, family rejection, identity concealment and internalized homophobia. Identifying and understanding specific LGBTQ+-related minority stress experiences and their complex roles in contributing to mental health burden among LGBTQ+ young adults could inform public health efforts to eliminate mental health inequities experienced by LGBTQ+ young adults. Therefore, this study sought to form empirically based risk profiles (i.e., latent classes) of LGBTQ+ young adults based on their experiences with familial heterosexist experiences, LGBTQ+-related family rejection, internalized LGBTQ+-phobia and LGBTQ+ identity concealment, and then identify associations of derived classes with psychological distress.

We recruited and enrolled participants using nonprobability, cross-sectional online survey data collected between May and August 2020 (N = 482). We used a three-step latent class analysis (LCA) approach to identify unique classes of response patterns to LGBTQ+-related minority stressor subscale items (i.e., familial heterosexist experiences, LGBTQ+-related family rejection, internalized LGBTQ+-phobia and LGBTQ+ identity concealment), and multinomial logistic regression to characterize the associations between the derived classes and psychological distress.

Five distinct latent classes emerged from the LCA: (1) low minority stress, (2) LGBTQ+ identity concealment, (3) family rejection, (4) moderate minority stress and (5) high minority stress. Participants who were classified in the high and moderate minority stress classes were more likely to suffer from moderate and severe psychological distress compared to those classified in the low minority stress class. Additionally, relative to those in the low minority stress class, participants who were classified in the LGBTQ+ identity concealment group were more likely to suffer from severe psychological distress.

Familial heterosexist experiences, LGBTQ+-related family rejection, internalized LGBTQ+-phobia and LGBTQ+ identity concealment are four constructs that have been extensively examined as predictors for mental health outcomes among LGBTQ+ persons, and our study is among the first to reveal nuanced gradients of these stressors. Additionally, we found that more severe endorsement of minority stress was associated with greater psychological distress. Given our study results and the previously established negative mental health impacts of minority stressors among LGBTQ+ young adults, findings from our study can inform research, practice, and policy reform and development that could prevent and reduce mental health inequities among LGBTQ+ young adults.

Population-wide restrictions during the COVID-19 pandemic may create barriers to mental health diagnosis. This study aims to examine changes in the number of incident cases and the incidence rates of mental health diagnoses during the COVID-19 pandemic.

By using electronic health records from France, Germany, Italy, South Korea and the UK and claims data from the US, this study conducted interrupted time-series analyses to compare the monthly incident cases and the incidence of depressive disorders, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, personality disorders and psychoses diagnoses before (January 2017 to February 2020) and after (April 2020 to the latest available date of each database [up to November 2021]) the introduction of COVID-related restrictions.

A total of 629,712,954 individuals were enrolled across nine databases. Following the introduction of restrictions, an immediate decline was observed in the number of incident cases of all mental health diagnoses in the US (rate ratios (RRs) ranged from 0.005 to 0.677) and in the incidence of all conditions in France, Germany, Italy and the US (RRs ranged from 0.002 to 0.422). In the UK, significant reductions were only observed in common mental illnesses. The number of incident cases and the incidence began to return to or exceed pre-pandemic levels in most countries from mid-2020 through 2021.

Healthcare providers should be prepared to deliver service adaptations to mitigate burdens directly or indirectly caused by delays in the diagnosis and treatment of mental health conditions.

Observer rating scales are necessary to evaluate the risk of suicide because individuals at risk for suicide are often unwilling to seek help on their own. Reliability and validity were evaluated for the newly developed Suicide Screening Questionnaire-Observer Rating (SSQ-OR).

Preliminary items were assessed by 251 experts online and 25 questions were selected. 328 individuals at high-risk and 661 controls from 12 Crisis Response Centers and 5 university counseling centers were recruited to complete SSQ-OR, Beck Scale for Suicide Ideation (BSSI) and Patient Health Questionnaire-9 (PHQ-9). In a 6 months follow-up, we reached out to 176 participants to ask whether they had experienced a suicidal thought, plan, or attempt since the baseline assessment. Cronbach's 慣, Mann-Whitney U test, Spearman's correlation, factor analyses, Receiver operating characteristic (ROC) analysis and logistic regression analysis were used to verify the SSQ-OR.

Structural validity was supported by a two-factor solution using exploratory and confirmatory factor analyses. Excellent model fit indices for the two-factor structure using exploratory factor analysis were confirmed (RMSEA = 0.033, TLI = 0.980, CFI = 0.983). The SSQ-OR demonstrated strong internal consistency. The concurrent validity based on the correlations with other self-reported indicators of suicidal potential-BSSI and PHQ-9- revealed substantial relationships. The high-risk group was effectively characterized by a cut-off point of 4, with a sensitivity of 0.73 and a specificity of 0.79. The SSQ-OR scores were significant predictors of suicidal thoughts and behaviors within 6 months.

The SSQ-OR exhibits sound psychometric properties, and could be used as a complement to a self-report or clinical-administered scale to screen suicide risk comprehensively.

Poor cardiovascular health occurs with age and is associated with increased dementia risk, yet its impact on frontotemporal lobar degeneration (FTLD) and autosomal dominant neurodegenerative disease has not been well established. Examining cardiovascular risk in a population with high genetic vulnerability provides an opportunity to assess the impact of lifestyle factors on brain health outcomes. In the current study, we examined whether systemic vascular burden associates with accelerated cognitive and brain aging outcomes in genetic FTLD.

166 adults with autosomal dominant FTLD (C9orf72 n= 97; GRN n= 34; MAPT n= 35; 54% female; Mage = 47.9; Meducation = 15.6 years) enrolled in the Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Longitudinal FTD study (ALLFTD) were included. Participants completed neuroimaging and were screened for cardiovascular risk and functional impairment during a comprehensive neurobehavioral and medical interview. A vascular burden score (VBS) was created by summing vascular risk factors (VRS) [diabetes, hypertension, hyperlipidemia, and sleep apnea] and vascular diseases (VDS) [cerebrovascular disease (e.g., TIA, CVA), cardiac arrhythmia (e.g., atrial fibrillation, pacemaker, defibrillator), coronary artery disease (e.g., myocardial infarction, cardiac bypass, stent), and congestive heart failure] following a previously developed composite (range 0 to 8). We examined the interaction between each vascular health metric (VBS, VDS, VRS) and age (vascular health*age) on clinical severity (CDR plus NACC FTLD-SB), and white matter hyperintensity (WMH) volume outcomes, adjusting for age and sex. Vascular risk, disease, and overall burden scores were examined in separate models.

There was a statistically significant interaction between total VBS and age on both clinical severity (ß=0.20, p=0.044) and WMH burden (ß=0.20, p=0.032). Mutation carriers with higher vascular burden evidenced worse clinical and WMH outcomes for their age. When breaking down the vascular burden score into (separate) vascular risk (VRS) and vascular disease (VDS) scores, the interaction between age and VRS remained significant only for WMH (ß=0.26, p=0.009), but not clinical severity (ß=0.04, p=0.685). On the other hand, the interaction between VDS and age remained significant only for clinical severity (ß=0.20, p=0.041) but not WMH (ß=0.17, p=0.066).

Our results demonstrate that systemic vascular burden is associated with an “accelerated aging” pattern on clinical and white matter outcomes in autosomal dominant FTLD. Specifically, mutation carriers with greater vascular burden show poorer neurobehavioral outcomes for their chronological age. When separating vascular risk from disease, risk was associated with higher age-related WMH burden, whereas disease was associated with poorer age-related clinical severity of mutation carriers. This pattern suggests preferential brain-related effects of vascular risk factors, while the functional impact of such factors may be more closely aligned with fulminant vascular disease. Our results suggest cardiovascular health may be an important, potentially modifiable risk factor to help mitigate the cognitive and behavioral disturbances associated with having a pathogenic variant of autosomal dominant FTLD. Future studies should continue to examine the neuropathological processes underlying the impact of cardiovascular risk in FTLD to inform more precise recommendations, particularly as it relates to lifestyle interventions.

Tissue inhibitor of metalloproteinases 2 (TIMP2) is produced peripherally, crosses the blood-brain barrier, and improves synaptic plasticity and hippocampal-dependent cognition in aged mice; however, the role of TIMP2 in human cognitive aging is unclear. We examined associations of circulating TIMP2 levels in blood with a known plasticity-inducing behavior, physical activity, and cognitive functioning among older adults along the Alzheimer’s disease continuum.

Participants included 84 community-dwelling older adults (meanage = 78.8; 57% female; 82% cognitively normal; 14% MCI; 4% mild dementia; 35% PET Aß+) enrolled in the UC San Francisco Memory and Aging Center. All participants completed 30 days of observational FitbitTM monitoring to quantify physical activity (average daily steps), as well as a comprehensive in-person visit including blood draw (proteins assayed on SOMAscan platform), [18F]AV-45 positron emission tomography (PET) to quantify brain beta-amyloid (centiloids), and neuropsychological assessment. Composite cognitive z-scores were calculated for memory (California Verbal Learning Test-II [CVLT-II] and Benson Figure Recall), semantic processing (animal fluency and Boston Naming Test), and executive functioning (digits backwards span, Stroop inhibition, modified trail making test, lexical fluency, and design fluency). Multiple linear regression examined TIMP2 as a function of physical activity, covarying for age and PET centiloids. Additional regression models separately examined cognitive z-scores as a function of TIMP2, covarying for age, sex, education, PET centiloids, and body mass index (BMI).

TIMP2 was not significantly correlated with age, sex, education, or PET centiloids (ps > 0.05); however, TIMP2 was negatively correlated with BMI (r = -0.23, p = 0.036). Greater average daily steps related to higher levels of TIMP2 (b = 0.30, 95%CI = 0.04-0.55, p = 0.022). TIMP2 also related to better semantic processing (b = 0.28, 95%CI = 0.04-0.51, p = 0.021) and executive functioning (b = 0.26, 95%CI = 0.03-0.49, p = 0.028). TIMP2 did not significantly relate to memory (p > 0.05).

Greater physical activity was associated with higher concentrations of blood factor TIMP2, which in turn related to better cognitive functioning independent of Alzheimer’s disease pathology burden. These results support previous mouse models by broadly replicating relationships between TIMP2 and cognition in humans, while also uniquely demonstrating an association between TIMP2 and physical activity, a modifiable protective factor in both typical and diseased cognitive aging. Our domain-specific results, however, suggest that benefits of TIMP2 in humans may involve a broader neuroanatomical network than the hippocampal-specific effects previously shown in mice. Although exact mechanisms of TIMP2 need further examination, TIMP2 is known to be enriched in human umbilical cord plasma, has been shown to be involved in cell-growth promoting activities, and may relate to increased neural plasticity in older age. Further examination of TIMP2 and other novel blood-based proteins as potential therapeutic targets for improved cognitive aging, including in the presence of Alzheimer’s disease, is warranted.

Subjective cognitive decline (SCD, i.e., perceived cognitive decline without neuropsychological deficits) is associated with Alzheimer’s disease pathology and increased risk for cognitive impairment but is heterogenous in etiology and has been linked to other factors including personality and depression. Mental wellbeing (i.e., the perception and functioning of social, emotional, and health-related aspects of one’s life) has been associated with subjective memory complaints, but its relationship with other subjective cognitive domains is poorly understood. Further characterizing the relationship between mental wellbeing and SCD could refine understanding of SCD and inform development of interventions that prevent progression to objective cognitive decline. This study aimed to describe the relationship between mental wellbeing and subjective decline in multiple cognitive domains and examine whether this relationship differs between older adults with normal cognition and those with mild cognitive impairment (MCI).

Community-dwelling older adults (normal: n = 58, Mage = 73.7±5.6; MCI: n = 43, Mage = 75.9±6.1) completed the Everyday Cognition scale, a validated self-report measure of SCD, and the RAND-36 Health Survey, a validated self-report measure of health-related quality of life which includes a mental wellbeing subscale. Spearman’s rank correlations were conducted between self-reported mental wellbeing and each self-reported cognitive domain (i.e., memory, language, visuospatial, and executive function) for the Normal Cognition and MCI groups.

Worse mental wellbeing was associated with worse subjective language and executive function in the normal group, rs(56) = -.42, p =.001; rs(56) = -.37, p =.005, but not for the MCI group, rs(41) = -.23, p =.15; rs(41) = -.12, p =.46. Worse mental wellbeing was associated with worse subjective visuospatial function in the MCI group, rs(41) = -.39, p =.009, but not in the normal group, rs(56) = -.11, p =.39. For both groups, worse mental wellbeing was associated with worse subjective memory, rs(56) = -.45, p < .001; rs(41) = -.37, p =.02. While this correlation was greater in the normal group, the difference was not significant (z = 0.38, p =.71).

These results suggest that perceptions of mental wellbeing are related to perceptions of cognitive decline in multiple domains, and that the specific domains involved differ between normal and MCI groups. The differential associations may mean perception of specific cognitive domains more strongly affect mental wellbeing, or mental wellbeing more acutely influences perception of those domains. The overall observed relationship between SCD and mental wellbeing may have several explanations: the impact of broader health perceptions may extend to cognitive perception, behavioral changes associated with poor wellbeing may reduce subjective cognitive function, or worse subjective cognitive function may lead to negative experiences of wellbeing. Future longitudinal investigation could inform causal inferences. The more limited associations between mental wellbeing and SCD among MCI individuals may point to the role of decreased self-awareness (due to cognitive impairment) precluding detection of subtle changes in cognition or wellbeing. This study highlights the importance of better understanding mental wellbeing in experiences of SCD in both normal and MCI older adults to improve cognitive and mental health outcomes.

Quantitative Susceptibility Mapping (QSM) is an MRI-based technique that sensitively measures in-vivo iron deposition via relaxation and magnetic susceptibility of brain tissue. Iron is essential for brain homeostasis, including oxidative metabolism, formation and maintenance of neural networks, and myelin synthesis. While increased levels of iron deposition occur during normal aging, high levels may have detrimental effects. Previous work has linked excessive brain iron accumulation to oxidative stress, beta-amyloid and tau toxicity, neurodegeneration, and cognitive dysfunction, particularly memory loss. Physical activity, on the other hand, correlates with higher synaptic integrity and memory performance, even in the presence of neuropathology. To date, it is unknown how physical activity may affect iron deposition-related cognition changes. We examined the moderating role of physical activity on the relationship between QSM hippocampal iron deposition and verbal memory in typically aging adults.

62 cognitively unimpaired older adults from the UCSF Memory and Aging Center (age mean(SD) = 78.34(7.28) years; 56% women; education mean(SD) = 17.94(1.72) years; 85% non-Hispanic White) completed neuropsychological testing and brain MRI during annual research visits, followed by Fitbit™ physical activity monitoring for 30 days. Average total daily steps were aggregated. Participants completed 3T Prisma neuroimaging with QSM, and regional iron deposition levels were quantified. All subjects also underwent diffusion tensor imaging (fractional anisotropy). Verbal memory was assessed via long delay free recall scores from the California Verbal Learning Test II (CVLT-II). Linear regression examined verbal memory as a function of hippocampal QSM (bilateral), physical activity, and their interaction. Models covaried for age, sex, and education. Additional models separately examined left and right hippocampal QSM, as well as subcortical QSM to determine lateralization and specificity of verbal memory effects to hippocampal iron deposition, respectively.

Univariably, higher bilateral hippocampal QSM correlated with worse verbal memory (r= 0.35; p= 0.015). Adjusting for demographics, physical activity moderated the relationship between bilateral hippocampal QSM and verbal memory (ß= 0.41, p= 0.011), such that at higher levels of physical activity, the negative relationship between hippocampal QSM and verbal memory was significantly attenuated. Results persisted when adjusting for DTI integrity of the uncinate fasciculus and fornix white matter tracts. Lateralization models were both significant, suggesting that results were not dominantly driven by either left (ß= 0.34, p= 0.048), or right (ß=0.31, p= 0.035) hippocampal QSM. In contrast, subcortical QSM did not correlate with memory performance (r= 0.13, p > 0.05) or interact with physical activity on verbal memory outcomes (p > 0.05).

Physical activity significantly moderated the negative relationship between hippocampal QSM and verbal memory performance. Higher exercise engagement may buffer the adverse effect of hippocampal iron deposition on memory, potentially through its role in maintenance of myelin and synaptic integrity and/or protecting against other neurotoxic events (e.g., oxidative stress, neuronal cell death). Our results support that physical activity continues to be a modifiable risk factor that may offer a protective role in neurobiological pathways of memory and cognitive decline.

Excessive and persistent fear of clusters of holes, also known as trypophobia, has been suggested to reflect cortical hyperexcitability and may be associated with mental health risks. No study, however, has yet examined these associations in representative epidemiological samples.

To examine the prevalence of trypophobia in a population-representative youth sample, its association with mental health and functioning, and its interaction with external stress.

A total of 2065 young people were consecutively recruited from a household-based epidemiological youth mental health study in Hong Kong. Trypophobia, symptoms of anxiety, depression and stress, and exposure to personal stressors were assessed. Logistic regression was used to assess the relationships between trypophobia and mental health. Potential additive and interaction effects of trypophobia and high stress exposure on mental health were also tested.

The prevalence of trypophobia was 17.6%. Trypophobia was significantly associated with severe symptoms of anxiety (odds ratio (OR) = 1.83, 95% CI = 1.32–2.53), depression (OR = 1.78, 95% CI = 1.24–2.56) and stress (OR = 1.68, 95% CI = 1.11–2.53), even when accounting for sociodemographic factors, personal and family psychiatric history, resilience and stress exposure. Dose–response relationships were observed, and trypophobia significantly potentiated the effects of stress exposure on symptom outcomes, particularly for depressive symptoms. Those with trypophobia also showed significantly poorer functioning across domains and poorer health-related quality of life.

Screening for trypophobia in young people may facilitate early risk detection and intervention, particularly among those with recent stress exposure. Nevertheless, the generally small effect sizes suggest that other factors have more prominent roles in determining recent mental health outcomes in population-based samples; these should be explored in future work.