External validation of dementia risk models is essential to assess generalisability and clinical utility. We evaluated 12 prediction models, including 10 dementia-specific and two cardiovascular-based models, in the EPIC-Norfolk cohort (n = 25,423) with up to 30 years of follow-up. Performance was assessed using discrimination, calibration, competing risks, and power analyses, stratified by follow-up and sex. Five models were fully validated and seven partially. The CAIDE, CAIDE-APOE, and DRS showed moderate performance declines, while the FRS and CHA₂DS₂-VASc demonstrated good calibration and strong transportability, supporting the value of vascular risk factors in predicting dementia. The UKBDRS maintained high discrimination (>0.80) despite partial validation. Performance was generally lower in women, especially for CAIDE and DRS. Calibration was acceptable in most fully validated models, though several were underpowered. Simplified models focusing on core vascular and lifestyle predictors may offer scalable, clinically relevant tools for dementia risk stratification.

Chronic obstructive pulmonary disease (COPD) symptoms of dyspnea and chest tightness overlap with some symptoms of panic attacks, the hallmark feature of panic disorder (PD). Our objective was to quantify PD prevalence in COPD from a systematic review and meta-analysis. A database search from inception to January 2025 was performed using five electronic databases. Eligible studies utilized structured clinical psychiatric interviews to identify PD in adult populations with COPD derived from inpatient, outpatient, or general population sampling. Twenty-one studies met inclusion criteria, with most from Asia (k = 9), reporting data from 1847 persons with COPD, 860 healthy controls, and 450 persons with comorbidities other than COPD. The prevalence of PD in persons with COPD was 12.5

Direct exposure to fires and floods adversely impacts mental health, although less is known about youth wellbeing after compounding natural hazards in short time frames. A youth sample aged 16-25 years completed self-report measures of adjustment disorder, alcohol/substance misuse and dependence, depression, anxiety and stress symptoms, and climate change anxiety after drought, bushfire and flood events in New South Wales. From 877 respondents, direct exposure to compounding (i.e., ≥ 2) natural hazards occurred in 182 persons and single hazard in 267. Compounding hazards increased odds for alcohol/substance misuse and dependence (adjusted odds ratio [OR] 2.19, 95% confidence interval [CI] 1.39-3.45) and anxiety (adjusted OR 1.55, 95% CI 1.04-2.30) by comparison to single hazard exposure. There was no interaction between compound hazard and life stressors (quantified by the Adjustment Disorder New Module-8). The association between compounding hazard exposure with mental health was mediated by climate change anxiety; full mediation for adjustment disorder, depression, anxiety, and stress, and partial mediation for alcohol/substance misuse and dependence. Compounding natural hazard exposure may have specific rather than global mental health impacts and is mediated by climate change anxiety. Youth may require specific support to recover from compounding hazards to promote wellbeing and manage climate change anxiety.

Depression is a major modifiable risk factor for dementia, yet most prediction models treat it as a homogeneous exposure, despite evidence that risk varies among people with depression. This study aimed to identify key modifiers of the depression-dementia association to inform the development of tailored prediction models. A narrative synthesis was conducted, incorporating (1) an umbrella review of nine meta-analyses examining the depression-dementia association; (2) a systematic review of depression-related medication use on dementia risk; and (3) findings from three Lancet Commission reports on dementia (2017, 2020, and 2024). Seven key modifiers were identified that influenced the reliability and direction of risk estimates: demographic factors, assessment methods, depression severity, follow-up duration, depression timing and trajectory, the outcome predicted (e.g., all-cause vs dementia subtypes), and antidepressant use. Late-life and severe depression conferred the highest risk, with associations being stronger for vascular dementia than for Alzheimer's disease. Clinical diagnoses yielded higher risk estimates compared to symptomatic rating scales. Duration of follow-up was associated with contradictory directional effects. Antidepressant use was associated with increased dementia risk. However, class-specific analyses were inconclusive due to extreme heterogeneity. The Lancet Commission emphasized late-life and mid-life depression as key modifiable risk factors. Multiple clinical, methodological, and temporal factors influence dementia risk estimates in individuals with depression. The findings support developing depression-specific dementia risk models that prioritize high-risk subgroups. Recommendations include distinguishing between symptom-based and clinical diagnostic approaches, addressing heterogeneity in timing and severity, modeling reverse causation, and validating models across diverse populations.

BACKGROUND:Blood pressure (BP) variability and cumulative BP load are significantly associated with cardiovascular disease risk beyond mean systolic BP, but less is known regarding their associations with cognitive decline/dementia and whether these associations differ by cognitive function at baseline or by sex. The aims of this study were to determine associations of different BP parameters with cognitive decline/dementia in patients with type 2 diabetes and explore differences by mild cognitive impairment at baseline and sex. METHODS:Using data from the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) study, BP parameters were calculated from an 18-month exposure window comprising measurements at 3, 4, 6, 12, and 18 months, after randomization. Logistic regression was used to estimate the odds ratio (OR) per SD higher and 95% CI for the associations of BP parameters with the composite outcome of cognitive decline (≥3 points from baseline on the Mini-Mental State Examination) or clinical diagnosis of dementia. RESULTS:Of the 11 140 ADVANCE participants, 9586 patients had 5 complete BP measurements within the 18-month exposure window. After a mean follow-up of 3.5 years, 1674 (17.5%) participants were diagnosed with cognitive decline and/or dementia. Overall, variability and baseline pulse pressure (PP), but not BP load, were associated with higher odds of cognitive decline/dementia (OR: variability in systolic BP, 1.11 [95% CI, 1.05-1.17]; diastolic BP, 1.11 [95% CI, 1.05-1.17]; PP, 1.05 [95% CI, 1.00-1.11]; mean arterial pressure, 1.13 [95% CI, 1.07-1.19]; and baseline PP, 1.19 [95% CI, 1.13-1.25]). There were no differences by mild cognitive impairment at baseline or sex. CONCLUSIONS:Higher BP variability and baseline PP, but not mean BP or BP load, were associated with higher odds of cognitive decline/dementia in patients with type 2 diabetes. BP variability and PP may be important therapeutic markers for the preservation of brain health. REGISTRATION:URL: https://clinicaltrials.gov; Unique Identifier: NCT00145925.

Earlier clinical trials have investigated the efficacy of auricular stimulation for hypertension, but the overall evidence regarding the effect of non-invasive auricular stimulation on blood pressure (BP) reduction remains unclear. This systematic review summarizes the effects of non-invasive auricular stimulation on cardiovascular haemodynamics. We searched for studies published in English through PubMed, ICHUSHI, and Cochrane Central Library databases and reviewed randomized controlled trials involving adults. Data collection and analysis were performed on the relationships of non-invasive auricular electrical stimulation and acupressure with changes in haemodynamics. A meta-analysis was conducted on the effects of non-invasive auricular stimulation on systolic BP (SBP), diastolic BP (DBP), and heart rate (HR). In the primary analysis, effect sizes were extracted from 18 studies for a total analytic sample of n = 959. Non-invasive auricular stimulation significantly reduced in SBP [weighted mean difference (WMD) = -4.435 mmHg, 95% confidence interval (CI) (-7.037 to -1.832)], DBP [WMD = -2.212 mmHg, 95% CI (-3.734 to -0.690)], and HR [WMD = -3.069 beats/min, 95% CI (-5.389 to -0.749)]. Overall, heterogeneity in each analysis was high, which could be explained by the stimulation duration and baseline values of SBP, DBP, and HR. There were no serious adverse events across all 18 studies. Enhancing vagus nerve activity through non-invasive auricular stimulation leads to clinically safe reductions in BP and HR. Further studies are needed to clarify whether non-invasive auricular stimulation can be used as a viable treatment for hypertension.

Visit-to-visit blood pressure (BP) variability (VVV) is a risk factor for cognitive impairment and cognitive decline, but several studies have recently shown that VVV also increases the risk of Alzheimer's disease (AD). Although the relationship between VVV and AD has been extensively studied, its pathophysiology is instructive due to its association with vascular stiffness, cerebral circulatory failure, decreased cardiac function, and AD pathology such as amyloid β and tau-proteins. This review article focuses on the relationship between VVV and cognitive function and summarizes recent studies and the underlying pathophysiology that appears to be mediated by systemic hemodynamic disruption.

CONTEXT:Elevated homocysteine levels are associated with brain atrophy and dementia, with B vitamin supplementation a possible low-cost intervention to help mitigate the deleterious impacts on brain health. However, prior meta-analyses have produced inconsistent results, with unexplained heterogeneity, while the quality of evidence has not been assessed. OBJECTIVE:This systematic review, meta-analysis, and meta-regression sought to quantify the effect of B vitamin supplementation on global cognitive function in older adults. DATA SOURCES:PubMed, Embase, PsychInfo, Scopus, and the Cochrane Library databases were searched for randomized controlled trials (RCTs) from inception to June 20, 2024. DATA EXTRACTION:Eligible RCTs were derived from populations aged ≥60 years, with interventions of 26 weeks or longer comprising vitamin(s) B6, B9, or B12 of any dose or administration route, compared with placebo or usual dementia care. Studies must also have quantified global cognitive function at baseline and at end of treatment. DATA ANALYSIS:Seventeen RCTs, including 5275 participants, were identified. A small to moderate improvement (Hedges' g = 0.423; 95% CI: 0.188 to 0.657) in global cognitive function after supplementation was observed with considerable heterogeneity (I2 = 92.71; Grading of Recommendations, Assessment, Development, and Evaluations [GRADE] = very low certainty). A meta-regression identified that statistical outliers and single-blinded studies contributed to the pooled g and heterogeneity. Omitting these studies resulted in a small effect (g = 0.110; 95% CI: 0.034 to 0.186), with negligible heterogeneity (I2 = 15.39; GRADE = high certainty). The effect size did not differ between classifications of cognitive impairment (ie, intact cognition, mild cognitive impairment, and dementia) in subgroup analysis (P = .729). CONCLUSION:The pooled findings indicated there is high-certainty evidence that vitamin B6, B9, or B12 supplementation has a very small benefit on global cognitive function in older adults. SYSTEMATIC REVIEW REGISTRATION:PROSPERO registration no. CRD42024553717.

Introduction:Blood pressure variability (BPV) is a marker of vascular and autonomic regulation, and emerging evidence links BPV with anxiety and depression. Limited research has explored central BPV, and secondly whether sleep modulates the association between BPV with anxiety and depression. Study design:Eighty-eight adults from clinical and community settings underwent 24-hour ambulatory blood pressure monitoring to assess central and brachial BPV, including augmentation index (AIx), mean arterial pressure (MAP), and pulse pressure (PP). Psychological symptoms were evaluated using the Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire (PHQ-9), and Sleep Condition Indicator (SCI). Correlation and regression analyses were conducted, adjusting for age and gender. Mediation analyses explored the role of sleep disturbances in BPV-mood relationships. Results:Higher central BPV was associated with lower anxiety symptom severity, for somatic and cognitive symptoms (e.g., trouble relaxing: rs = -0.28, p < 0.01), whereas brachial BPV showed minimal associations. No significant relationships emerged between BPV and depressive symptoms after adjustment. AIx demonstrated significant negative associations with sleep-related issues, with stronger effects seen when adjusting for age and gender (β = -0.04, p < 0.01). Mediation analysis revealed sleep-related issues partially mediated the BPV-anxiety relationship. Discussion:Findings suggest that central BPV is more strongly associated with cognitive and somatic anxiety symptoms than depressive symptoms, with sleep disturbances potentially mediating this relationship. These results support BPV's role in autonomic dysfunction, emphasizing the need for longitudinal research to clarify its role in mental health.

Background:Identifying modifiable risk factors is crucial for dementia prevention, a global health concern. Depression is considered a risk factor for dementia, but the temporal dynamics across the life course remain inconclusive. Therefore, we aimed to systematically assess the relationship between the timing of depression assessment and risk of all-cause late-life dementia. Methods:We conducted an umbrella review and meta-analysis to assess incident dementia in individuals with non-current history of depression. PubMed and Ovid Embase, MEDLINE, and PsycInfo were searched from inception up to February 17, 2025. Systematic reviews with meta-analyses investigating the association between depression and incident late-life dementia were included. From eligible reviews, we also extracted data from studies reporting dementia risk as hazard ratios (HRs), analysing the timing of depression measurement using random-effects models for meta-analysis. This study is registered with PROSPERO, CRD42021249706. Findings:Of the 7763 records identified, nine reviews were eligible for inclusion of the umbrella review. One review was judged to be of moderate quality, while the others were either low (n = 3) or critically low (n = 5). For our meta-analyses, 18 studies reporting depression onset in later life (n = 901,762 participants, n = 7595 incident dementia cases) and seven studies on depression assessed during midlife (n ≥ 2,501,269 participants, n ≥ 276,929 incident dementia cases) were included. All studies in the meta-analyses were deemed to be of good quality, with no strong evidence of publication bias. Pooled HRs indicated depression present in late-life (HR 1.95, 95% CI: 1.68-2.26; I 2 = 77.5%) and midlife (HR 1.56, 95% CI: 1.12-2.18; I 2 = 97.5%) significantly increased risk of all-cause dementia. Interpretation:The findings suggest that depression across the life course may increase dementia risk; however, substantial heterogeneity and review quality should be considered when interpreting the strength of this evidence. A life course approach to the treatment and prevention of depression may help reduce the burden of dementia, but this will require scaling up access to effective mental health care for vulnerable populations. Further research is needed to clarify if the stronger late-life association reflects depression as an immediate risk factor or an early manifestation of neurodegenerative processes. Funding:National Institute for Health and Care Research, UK Research and Innovation, and Saudi Arabian Cultural Mission.

Atrial fibrillation (AF) is associated with an increased risk of dementia, even in the absence of stroke. Risk factor management (RFM), a newly defined pillar of AF management, reduces AF burden and symptoms. However, data on brain health endpoints are lacking. This study investigated the impact of RFM and other pillars of AF management on cognitive impairment in AF. 215 patients with a clinical diagnosis of AF and without a diagnosis of dementia were recruited (RECORD-AF, ANZCTR ACTRN12621001506886). Retrospective medical records audit, prospective assessments, and participant interviews were conducted. Cognitive assessment was conducted by blinded trained personnel using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Successful RFM was defined as weight loss to BMI<27 or ≥10% weight loss, treatment of OSA, alcohol intake <3SD/week and heart failure, hypertension and diabetes as per standard guidelines, and smoking cessation. RBANS index scores were regressed on demographic, comorbidities, RFM and AF-related variables in hierarchical linear regressions. Missing data was dealt with using multiple imputations with chained equations and a pooled analysis from 10 imputations. 196 participants completed RBANS for the cognitive function assessment. The mean age was 65.4 ± 10 years, 51% paroxysmal AF (PAF), 60% males and the median CHA2DS2VA score = 2 [1-3]. All received oral anticoagulation appropriate for CHA2DS2VA score. The mean RBANS index score was 94.4 ± 12.7. The visuospatial domain was most affected (RBANS 83.7 ± 13.5). Cognitive scores 1.5 SD below normative means were observed in 9.7% of the participants for the indexed RBANS and in 20.9% for immediate memory, 37.8% for visuospatial, 3.6% for language, 4.1% for attention and 15.3% for delayed memory domains. There was no association between risk factors at the time of AF diagnosis and cognitive function (β=-3, p=0.45). The number of unmanaged modifiable risk factors at RBANS was associated with poorer performance on immediate memory (β=-3, p=0.01), attention (β=-2.9, p=0.01), and total index score (β=-1.8, p=0.02) in analyses adjusted for age, sex, education, stroke, depression, CHA2DS2VA and AF severity. Compared to rate control, rhythm control was protective for the attention domain (β=7, p=0.01), and there was a trend toward improved total index RBANS scores (β=3.9, p=0.07). However, the benefit of rhythm control on cognition was no longer observed in the presence of un-modified risk factors (β=-3.08, p = 0.004 for rhythm*RF interaction term). Early impairment in cognitive function is common in individuals with AF. Successful risk factor management is associated with a lower risk of cognitive impairment. [LJP1]Correct?

OBJECTIVES:This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To determine the effects of psychological interventions for depression in people with diabetes mellitus.

Hoarding disorder (HD) is characterized by an accumulation of possessions owing to acquisition behaviors or absence of discarding, resulting in clutter severe enough to cause emotional distress, impair functioning, and preclude the use of living spaces for their intended purposes. HD is associated with significant psychiatric and physical health comorbidities. Evidence demonstrates an increased cardiovascular response, high prevalence of heart disease, and sudden cardiac death in patients with HD and yet treatment outcomes for patients with comorbid cardiovascular diseases remain unreported. A psychology referral was made for a patient with heart failure (HF) who underwent a structured clinical interview within their domicile and met criteria for adolescent-onset HD (27-year history). Treatment outcomes for this case are described, as well as the cognitive-behavioral therapy (CBT) modifications required for the patient, living in squalor and facing eviction. Results demonstrated modest improvements in HD symptoms from pretreatment to posttreatment. To ensure HF patients are involved in sorting/discarding tasks during CBT, modifications are necessary to compensate for high fatigability and dizziness to reduce the risk for serious adverse events including syncope and falls.

Introduction Cumulative blood pressure metrics may provide greater precision for measuring temporal risk exposure, especially in later life where data are mixed regarding associations of high blood pressure (BP) on cognitive function. We examined the relationship between greater cumulative exposure to high BP in later life and several domains of cognitive function. Methods Individual cognitive assessment scores and BP measurements in older adults (age ≥70 years) at baseline and over approximately 8 years of follow-up were available in the population-based Canadian Victoria Longitudinal Study (VLS) and Swedish Gothenburg H70 Birth Cohort Studies (H70). Linear mixed models were used to quantify associations between cumulative systolic and diastolic BP and change in cognitive scores. Results Each additional 100mmHg increase in cumulative BP was related to greater decline in the Rey Auditory Verbal Learning Test (RAVLT) List A, trials 1-5 total score over follow-up: -0.23 (95% confidence interval [CI] -0.32, -0.13) for systolic BP and -0.41 (95%CI -0.58, -0.23) for diastolic BP. Similarly increases cumulative systolic and diastolic BP were related to greater declines Digit Symbol Substitution Task (DSS) scores: -0.59 (95%CI -0.80, -0.38) and -1.04 (95% CI -1.40, -0.67), respectively. There were no associations of cumulative BP and temporal changes in general cognition, other measures of verbal episodic memory, or semantic fluency. Conclusions Higher cumulative BP is associated with greater declines in RAVLT measured immediate memory span and complex attention, information processing speed and visuospatial scanning in older adults, but the scale of change is small. Additional research is required to further define these relationships and identify opportunities for prevention.

BackgroundThe effects of climate change on mental health are becoming widely recognized. Mental health can be impacted through direct and indirect exposure to natural hazards, as well as through the overarching awareness of climate change and the resultant environmental decline—the latter is termed eco-anxiety. Exposure to natural hazards also increases eco-anxiety, further compounding mental health impacts. Young people are especially vulnerable to the mental health impacts of climate change and have higher rates of eco-anxiety than other age groups. Those in rural areas are also more likely to be impacted by natural hazards, further underscoring the need to support this population. To date, there remains scant evidence regarding how to support young people with eco-anxiety, and few interventions, especially for children, have been evaluated. There is a need for further research to inform treatment for young people for climate change–related distress. ObjectiveThis study pilots a novel group-based mental health and resilience intervention in relation to eco-anxiety. Specifically, this project aims to explore the acceptability, feasibility, and clinical utility of a group-based eco-anxiety intervention. MethodsThe project is an exploratory pilot assessing the acceptability, feasibility, and clinical utility of a group-based intervention using a pre-post design with a single group. A minimum sample of 12 children aged 10-14 years located in a rural area and with exposure to at least one natural hazard will be enrolled in this study. In order to assess clinical utility, changes from preintervention to postintervention in distress, resilience, and climate emotions will be assessed. To do so, children will complete measures of psychological distress (subjective units of distress, Depression Anxiety Stress Scale-21–youth version), climate emotions, and resilience (Resilience Scale for Children-10) before and after the intervention. Acceptability will be assessed post intervention through a series of Likert scale and open-ended questions. Feasibility will be assessed through enrollment and the proportion of participants completing the full intervention. Eligible children will take part in a novel 5-module group-based intervention designed to build resilience, promote nature connectedness, build social support, and foster meaning-focused coping. ResultsThis study has received ethics board approval by the University of New England’s Human Research Ethics Committee (HE23-080). This study will be conducted from late 2024 to 2025. As of March 2025, 28 children have been enrolled in the study. ConclusionsRural children and young people are an especially vulnerable population for the mental health impacts of climate change. To date, the evidence base for interventions for treating eco-anxiety remains sparse, especially for young people and children who typically have higher rates of eco-anxiety than older age groups. This study will provide preliminary evidence of a group-based treatment for children and adolescents experiencing eco-anxiety that can inform practitioners. Trial RegistrationAustralia and New Zealand Clinical Trials Registry ACTRN12624001287527; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=388545 International Registered Report Identifier (IRRID)PRR1-10.2196/69005

The adverse impacts of climate change on mental health is a burgeoning area, although findings are inconsistent. The emerging concept of eco-anxiety represents distress in relation to climate change and may be related to mental health. The aim of this study was to explore the relationship between eco-anxiety with validated mental health outcomes, specifically psychological distress and symptoms of major affective disorders. Systematic review. EBSCO, ProQuest, and Web of Science databases were searched to February 2024 for studies of adult samples quantifying eco-anxiety (exposure, i.e. fear, worry or anxiety in relation to climate change) and symptoms of psychological distress and major affective disorders (outcomes), as assessed by validated measures. Full text review of 83 studies was performed, and k = 35 studies were included in the review (N = 45 667, 61

BackgroundNatural hazards are increasing in frequency and intensity due to climate change. Many of these natural disasters cannot be prevented; what may be reduced is the extent of the risk and negative impact on people and property. Research indicates that the 2019-2020 bushfires in Australia (also known as the “Black Summer Bushfires”) resulted in significant psychological distress among Australians both directly and indirectly exposed to the fires. Previous intervention research suggests that communities impacted by natural hazards (eg, earthquakes, hurricanes, and floods) can benefit from interventions that integrate mental health and social support components within disaster preparedness frameworks. Research suggests that disaster-affected communities often prefer the support of community leaders, local services, and preexisting relationships over external supports, highlighting that community-based interventions, where knowledge stays within the local community, are highly beneficial. The Community-Based Disaster Mental Health Intervention (CBDMHI) is an evidence-based approach that aims to increase disaster preparedness, resilience, social cohesion, and social support (disaster-related help-seeking), and decrease mental health symptoms, such as depression and anxiety. ObjectiveThis research aims to gain insight into rural Australian’s recovery needs post natural hazards, and to enhance community resilience in advance of future fires. Specifically, this research aims to adapt the CBDMHI for the rural Australian context and for bushfires and second, to assess the acceptability and feasibility of the adapted CBDMHI in a rural Australian community. MethodsPhase 1 consists of qualitative interviews (individual or dyads) with members of the target bushfire-affected rural community. Analysis of these data will include identifying themes related to disaster preparedness, social cohesion, and mental health, which will inform the adaptation. An initial consultation phase is a key component of the adaptation process and, therefore, phase 2 will involve additional discussion with key stakeholders and members of the community to further guide adaptation of the CBDMHI to specific community needs, building on phase 1 inputs. Phase 3 includes identifying and training local community leaders in the adapted intervention. Following this, leaders will co-deliver the intervention. The acceptability and feasibility of the adapted CBDMHI within the community will be evaluated by questionnaires and semistructured interviews. Effectiveness will be evaluated by quantifying psychological distress, resilience, community cohesion, psychological preparedness, and help-seeking intentions. ResultsThis study has received institutional review board approval and commenced phase 1 recruitment in October 2022. ConclusionsThe study will identify if the adapted CBDMHI is viable and acceptable within a village in the Northern Tablelands of New South Wales, Australia. These findings will inform future scale-up in the broader rural Australian context. If this intervention is well received, the CBDMHI may be valuable for future disaster recovery and preparedness efforts in rural Australia. These findings may inform future scale-up in the broader rural Australian context. International Registered Report Identifier (IRRID)DERR1-10.2196/53454