Feasibility and acceptability of NIDUS-professional, a training and support intervention for homecare workers caring for clients living with dementia: a cluster-randomised feasibility trial.

INTRODUCTION: In the first randomised controlled trial of a dementia training and support intervention in UK homecare agencies, we aimed to assess: acceptability of our co-designed, manualised training, delivered by non-clinical facilitators; outcome completion feasibility; and costs for a future trial. METHODS: This cluster-randomised (2:1) single-blind, feasibility trial involved English homecare agencies. Intervention arm agency staff were offered group videocall sessions: 6 over 3 months, then monthly for 3 months (NIDUS-professional). Family carers (henceforth carers) and clients with dementia (dyads) were offered six to eight complementary, individual intervention sessions (NIDUS-Family). We collected potential trial measures as secondary outcomes remotely at baseline and 6 months: HCW (homecare worker) Work-related Strain Inventory (WRSI), Sense of Competence (SoC); proxy-rated Quality of Life (QOL), Disability Assessment for Dementia scale (DAD), Neuropsychiatric Inventory (NPI) and Homecare Satisfaction (HCS). RESULTS: From December 2021 to September 2022, we met agency (4 intervention, 2 control) and HCWs (n = 62) recruitment targets and recruited 16 carers and 16/60 planned clients. We met a priori progression criteria for adherence (≥4/6 sessions: 29/44 [65.9%,95% confidence interval (CI): 50.1,79.5]), HCW or carer proxy-outcome completion (15/16 (93.8% [69.8,99.8]) and proceeding with adaptation for HCWs outcome completion (46/63 (73.0% [CI: 60.3,83.4]). Delivery of NIDUS-Professional costs was £6,423 (£137 per eligible client). WRSI scores decreased and SoC increased at follow-up, with no significant between-group differences. For intervention arm proxy-rated outcomes, carer-rated QOL increased, HCW-rated was unchanged; carer and HCW-rated NPI decreased; DAD decreased (greater disability) and HCS was unchanged. CONCLUSION: A pragmatic trial is warranted; we will consider using aggregated, agency-level client outcomes, including neuropsychiatric symptoms.

Subjective caregiver burden and coping in family carers of dependent adults and older people: A systematic review and meta-analysis.

Subjective caregiver burden is highly prevalent in family caregivers. Despite several studies investigating the relationship between subjective caregiver burden and coping strategies, results remain inconsistent. The aim of our study was to systematically review current literature on the relationship between subjective caregiver burden and coping in family carers of dependent adults and older people. A secondary objective was to analyse possible sources of heterogeneity in the estimated effect. The study design was a systematic review with meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) guidelines. We searched several international databases (CINAHL, LILACS, PsycINFO and PubMed) up to February 2024. We performed several subgroup analyses to examine whether study design, methodological quality or care recipient dependency influenced results. Of the 1064 records identified in our search, a total of 80 studies met inclusion criteria. We found a significant association between greater use of dysfunctional coping and higher levels of subjective caregiver burden ( r ‾ $\overline{r}$  = 0.400; 95% CI = 0.315, 0.478); higher use of second-order active coping was significantly associated with lower caregiver burden ( r ‾ $\overline{r}$  = -0.213; 95% CI = -0.316, -0.105). Problem-focused coping showed no statistically significant association with levels of subjective burden; emotion-focused coping was associated with caregiver burden only after controlling for confounding variables ( r ‾ $\overline{r}$  = -0.258; 95% CI = -0.441, -0.055); several individual strategies of this dimension such as acceptance ( r ‾ $\overline{r}$  = -0.135; 95% CI = -0.238, -0.028), positive reappraisal ( r ‾ $\overline{r}$  = -0.178; 95% CI = -0.255, -0.099) and religious coping ( r ‾ $\overline{r}$  = -0.083; 95% CI = -0.162, -0.002), were associated with lower burden. We found that several dimensions of coping strategies are significantly associated with levels of subjective caregiver burden experienced by carers. These results can inform future research evaluating the effectiveness of interventions aimed at improving carers' mental health.

A psychosocial goal-setting and manualised support intervention for independence in dementia (NIDUS-Family) versus goal setting and routine care: a single-masked, phase 3, superiority, randomised controlled trial.

BACKGROUND: Although national guidelines recommend that everyone with dementia receives personalised post-diagnostic support, few do. Unlike previous interventions that improved personalised outcomes in people with dementia, the NIDUS-Family intervention is fully manualised and deliverable by trained and supervised, non-clinical facilitators. We aimed to investigate the effectiveness of home-based goal setting plus NIDUS-Family in supporting the attainment of personalised goals set by people with dementia and their carers. METHODS: We did a two-arm, single-masked, multi-site, randomised, clinical trial recruiting patient-carer dyads from community settings. We randomly assigned dyads to either home-based goal setting plus NIDUS-Family or goal setting and routine care (control). Randomisation was blocked and stratified by site (2:1; intervention to control), with allocations assigned via a remote web-based system. NIDUS-Family is tailored to goals set by dyads by selecting modules involving behavioural interventions, carer support, psychoeducation, communication and coping skills, enablement, and environmental adaptations. The intervention involved six to eight video-call or telephone sessions (or in person when COVID-19-related restrictions allowed) over 6 months, then telephone follow-ups every 2-3 months for 6 months. The primary outcome was carer-rated goal attainment scaling (GAS) score at 12 months. Analyses were done by intention to treat. This trial is registered with the ISRCTN registry, ISRCTN11425138. FINDINGS: Between April 30, 2020, and May 9, 2021, we assessed 1083 potential dyads for eligibility, 781 (72·1%) of whom were excluded. Of 302 eligible dyads, we randomly assigned 98 (32·4%) to the control group and 204 (67·5%) to the intervention group. The mean age of participants with dementia was 79·9 years (SD 8·2), 169 (56%) were women, and 133 (44%) were men. 247 (82%) dyads completed the primary outcome, which favoured the intervention (mean GAS score at 12 months 58·7 [SD 13·0; n=163] vs 49·0 [14·1; n=84]; adjusted difference in means 10·23 [95% CI 5·75-14·71]; p<0·001). 31 (15·2%) participants in the intervention group and 14 (14·3%) in the control group experienced serious adverse events. INTERPRETATION: To our knowledge, NIDUS-Family is the first readily scalable intervention for people with dementia and their family carers that improves attainment of personalised goals. We therefore recommend that it be implemented in health and care services. FUNDING: UK Alzheimer's Society.

Coping and anxiety symptoms in family carers of dependent older people: Mediation and moderation effects of subjective caregiver burden.

INTRODUCTION: Coping responses influence anxiety symptoms experienced by informal carers. However, only a few studies have investigated the longitudinal association between coping responses and anxiety symptoms in family carers. We also currently have limited knowledge on the mediating or moderating influence of subjective caregiver burden on this relationship over time. The aim of the present study was to investigate the longitudinal relationship between coping and anxiety symptoms in family carers of dependent older people, and examine the mediating or moderating role of subjective caregiver burden over time. DESIGN: Prospective longitudinal study. METHODS: We recruited and enrolled participants from a probability sample of 132 family carers of older dependent relatives. We measured coping strategies, anxiety symptoms, subjective caregiver burden, and several covariates (sex and intensity of care) at baseline and at 1-year follow-up. We used generalized estimating equations with multiple imputations to examine associations over time. RESULTS: Considering both direct and indirect effects through subjective burden, anxiety symptoms were positively associated with proactive coping (B = 0.13), planning (B = 0.15), self-distraction (B = 0.24), denial (B = 1.15), venting (B = 0.94) and self-blame (B = 0.90), and negatively associated with positive reframing (B = -0.83) and acceptance (B = -0.75). Subjective caregiver burden moderated the relationship between anxiety symptoms and planning, and the use of denial as a form of coping. CONCLUSIONS: Our results show that subjective caregiver burden is an important moderator and mediator of the longitudinal association between coping responses and anxiety symptoms in carers. CLINICAL RELEVANCE: Proactive coping and planning when subjective burden is low, self-distraction, denial, venting, and self-blame significantly increase levels of anxiety and caregiver burden in carers over time. Acceptance and positive reframing however as coping responses are associated with lower levels of anxiety and caregiver burden long-term. Our findings highlight the need for a multi-dimensional approach in future caregiving interventions.

Biomarkers associated with cognitive impairment in post-traumatic stress disorder: A systematic review of current evidence.

OBJECTIVE: This systematic review aimed at synthesizing current evidence on biomarkers associated with cognitive impairment (CI) in Post-Traumatic Stress Disorder (PTSD). METHODS: A systematic literature search was conducted for studies assessing biomarkers associated with CI in PTSD. RESULTS: Of the 10,149 titles screened, 8 studies met our inclusion criteria. In a single longitudinal study, MRI volumes, Aß and tau accumulation were not associated with CI in PTSD. Studies on structural imaging reported no significant association between morphological changes and CI. Two studies on diffusion neuroimaging showed abnormalities in white matter tracts which were cross-sectionally associated with CI in PTSD. Similarly, lower resting-state functional connectivity in neocortical networks, and elevated tau in the neocortex were also cross sectionally associated with CI. Two single studies on biochemical biomarkers showed that sixteen novel plasma proteins and lower BDNF, indicative of genetic vulnerabilities associated with neural and synaptic dysfunctions commonly observed in neurodegeneration, were cross-sectionally associated with CI in PTSD. Overall, evidence is of low quality. CONCLUSIONS: Longitudinal research utilizing large representative samples of trauma exposed populations are needed to establish the utility of specific biomarkers in monitoring cognitive decline in PTSD.

A systematic review and meta-analysis of the association between anxiety symptoms and coping in family carers of dependent people aged 18 and over.

Anxiety symptoms are prevalent in family carers of dependent people. Despite accumulating evidence in the area, there are still inconsistent findings on the association between carer anxiety symptoms and coping strategies. The aim of our study was to systematically analyse the relationship between anxiety symptoms and coping strategies in carers of dependent adults aged 18 years and older, and examine possible sources of heterogeneity in the results. The study design was a systematic review and meta-analysis. We searched several international databases (Pubmed, CINAHL, PsycINFO and LILACS) from June 2022 up to February 2023. We followed the preferred reporting items for systematic reviews and meta-analyses statement and performed several subgroup analyses to examine whether study design, cause of dependency and whether or not controlling for various biases influenced results. Forty-one studies were included in the review. We found significant associations between greater use of dysfunctional coping and higher anxiety symptoms. Greater use of problem-focused coping was associated with lower anxiety symptoms in carers of frail older people, but higher anxiety in carers of people surviving cancer. Emotion-focused coping and some of its individual strategies, such as acceptance and positive reappraisal, in probabilistic samples, were associated with lower anxiety symptoms across all groups. Most of the studies included in this review were cross-sectional. Evidence overall indicates that only specific dimensions and strategies of coping are significantly associated with anxiety symptoms in family carers. These findings should be considered when developing future interventions supporting carers.

Artificial intelligence for dementia prevention.

INTRODUCTION: A wide range of modifiable risk factors for dementia have been identified. Considerable debate remains about these risk factors, possible interactions between them or with genetic risk, and causality, and how they can help in clinical trial recruitment and drug development. Artificial intelligence (AI) and machine learning (ML) may refine understanding. METHODS: ML approaches are being developed in dementia prevention. We discuss exemplar uses and evaluate the current applications and limitations in the dementia prevention field. RESULTS: Risk-profiling tools may help identify high-risk populations for clinical trials; however, their performance needs improvement. New risk-profiling and trial-recruitment tools underpinned by ML models may be effective in reducing costs and improving future trials. ML can inform drug-repurposing efforts and prioritization of disease-modifying therapeutics. DISCUSSION: ML is not yet widely used but has considerable potential to enhance precision in dementia prevention. HIGHLIGHTS: Artificial intelligence (AI) is not widely used in the dementia prevention field. Risk-profiling tools are not used in clinical practice. Causal insights are needed to understand risk factors over the lifespan. AI will help personalize risk-management tools for dementia prevention. AI could target specific patient groups that will benefit most for clinical trials.

Association between Social Support and Depressive Symptoms in Informal Caregivers of Adult and Older Dependents: A Systematic Review and Meta-Analysis.

Social support is an important determinant of a carer's mental health. In recent decades, despite many studies reporting on the relationship between social support and depressive symptoms in informal caregivers of adult and older dependents, there are no systematic reviews synthesizing the available evidence. The purpose of the present study was to perform a systematic review and meta-analysis on the relationship between social support and depressive symptoms in informal caregivers of adults and older dependent people. We searched PubMed, CINAHL (EBSCO), PsycINFO (ProQuest), and Scopus, up to 15 January 2023 for studies. We applied no date or language limits to our search. A random-effects model was used to pool effect estimates. The included studies were also independently assessed for quality. Publication bias was evaluated by funnel plots, Egger's regression test, and the Trim and Fill method. Ninety-three studies were included in the review, reporting on a total of 15,431 informal caregivers. We found a moderate negative association between perceived social support and caregiver depressive symptoms (78 studies; r = -0.35, 95% CI = -0.39, -0.31; low heterogeneity and low risk of publications bias) and a small negative association between received social support and caregiver self-reported depressive symptoms (12 studies; r = -0.14, 95% CI = -0.20, -0.07; low heterogeneity and low risk of publications bias). Our results indicate that social support is a clinically relevant construct for carer well-being and an important protective factor for depressive symptoms in informal caregivers of adult and older dependents.

Artificial intelligence for dementia-Applied models and digital health.

INTRODUCTION: The use of applied modeling in dementia risk prediction, diagnosis, and prognostics will have substantial public health benefits, particularly as "deep phenotyping" cohorts with multi-omics health data become available. METHODS: This narrative review synthesizes understanding of applied models and digital health technologies, in terms of dementia risk prediction, diagnostic discrimination, prognosis, and progression. Machine learning approaches show evidence of improved predictive power compared to standard clinical risk scores in predicting dementia, and the potential to decompose large numbers of variables into relatively few critical predictors. RESULTS: This review focuses on key areas of emerging promise including: emphasis on easier, more transparent data sharing and cohort access; integration of high-throughput biomarker and electronic health record data into modeling; and progressing beyond the primary prediction of dementia to secondary outcomes, for example, treatment response and physical health. DISCUSSION: Such approaches will benefit also from improvements in remote data measurement, whether cognitive (e.g., online), or naturalistic (e.g., watch-based accelerometry).

A predictive model of carer resilience in dementia family caregiving: A structural equation modelling approach.

OBJECTIVES: This study aimed to investigate the mediating effects of quality of the caregiving relationship and other carer and person with dementia variables in predicting carer resilience over time. METHOD: Carers of people with mild and moderate dementia in community settings completed baseline (n = 176 dyads) and six-month follow-up assessments (n = 139 dyads). Causal mediation analysis was conducted using Pearson Correlation and Structural Equation Modelling (SEM) to examine longitudinal predictors of carer resilience, and the effect of several mediating person with dementia, and carer factors on carer resilience over time. RESULTS: At 6-month follow-up, higher levels of carer resilience were longitudinally correlated with higher ratings of perceived relationship quality by people with dementia (r = 0.53 p ≤ 0.01), and lower levels of emotional distress symptoms by carer's (r = -0.59 p ≤ 0.01). Mediation analyses showed that people with dementia perspectives of the quality of the caregiving relationship mediated the relationship between carer distress specific to neuropsychiatric symptoms (ß = -0.32, p ≤ 0.001) and carer resilience (ß = 0.53, p ≤ 0.001) over time. The final SEM provided a good fit for the data (X 2  = 0.12, p = 0.72, CFI = 1.00, NFI = 0.99, and Root Mean Square Error of Approximation = 0.001). CONCLUSION: Higher ratings of perceived relationship quality by people with dementia, and lower levels of carer emotional distress predicted higher carer resilience at follow-up. People with dementia perspectives of the quality of the caregiving relationship mediated the relationship between carer distress specific to neuropsychiatric symptoms and carer resilience over time. Our findings indicate that interventions aimed at strengthening the caregiving relationship might have a protective long-term effect for carer resilience in dementia caregiving.

The Relationship between Social Support and Anxiety Symptoms in Informal Carers: A Systematic Review and Meta-Analysis.

BACKGROUND: Providing care can be challenging for informal carers and increases the risk of mental health problems, such as experiencing clinical symptoms of anxiety. While strengthening social support for informal carers is a common recommendation to reduce this risk, no systematic review or meta-analysis to date has examined the relationship between social support and anxiety symptoms in informal carers. The aim of our study was to systematically review the current evidence on the association between perceived and received social support and anxiety symptoms in informal carers of dependent adults and older people, and to comment on the quality of the evidence. METHODS: We searched PubMed, CINAHL (EBSCO), PsycINFO (ProQuest), Scopus, and LILACS up to 31 March 2021 for articles reporting on the association between caregiver anxiety symptoms and social support. A random-effects model was used to pool estimates, and each study was rated for quality using pre-specified criteria. Publication bias was assessed using a funnel plot and Egger's regression test, which was adjusted using trim and fill analysis. RESULTS: From the 2180 identified articles, 35 studies met our inclusion criteria, reporting on 5036 informal carers in total. We found a moderate negative association between perceived social support and caregiver anxiety symptoms (r = -0.31, 95% CI = -0.35, -0.27) and a small, negative association between received social support and caregiver anxiety (r = -0.15, 95% CI = -0.22, -0.08). CONCLUSION: The levels of perceived social support showed a significant negative association with caregiver anxiety symptoms. Policymakers and those working directly with informal carers should consider the development of targeted social support interventions that specifically enhance the levels of perceived social support to reduce symptoms of anxiety in informal carers.

Harnessing the potential of machine learning and artificial intelligence for dementia research.

Progress in dementia research has been limited, with substantial gaps in our knowledge of targets for prevention, mechanisms for disease progression, and disease-modifying treatments. The growing availability of multimodal data sets opens possibilities for the application of machine learning and artificial intelligence (AI) to help answer key questions in the field. We provide an overview of the state of the science, highlighting current challenges and opportunities for utilisation of AI approaches to move the field forward in the areas of genetics, experimental medicine, drug discovery and trials optimisation, imaging, and prevention. Machine learning methods can enhance results of genetic studies, help determine biological effects and facilitate the identification of drug targets based on genetic and transcriptomic information. The use of unsupervised learning for understanding disease mechanisms for drug discovery is promising, while analysis of multimodal data sets to characterise and quantify disease severity and subtype are also beginning to contribute to optimisation of clinical trial recruitment. Data-driven experimental medicine is needed to analyse data across modalities and develop novel algorithms to translate insights from animal models to human disease biology. AI methods in neuroimaging outperform traditional approaches for diagnostic classification, and although challenges around validation and translation remain, there is optimism for their meaningful integration to clinical practice in the near future. AI-based models can also clarify our understanding of the causality and commonality of dementia risk factors, informing and improving risk prediction models along with the development of preventative interventions. The complexity and heterogeneity of dementia requires an alternative approach beyond traditional design and analytical approaches. Although not yet widely used in dementia research, machine learning and AI have the potential to unlock current challenges and advance precision dementia medicine.

Coping and depressive symptoms in family carers of dependent adults aged 18 and over: A systematic review and meta-analysis.

Being a family carer is associated with increased risk of experiencing depressive symptoms. Despite many decades of research investigating the association between coping strategies and depressive symptoms in carers results across studies remain contradictory. The objective of this study was to systematically review evidence on the association between depressive symptoms and coping strategies in carers of dependent people aged 18 and over and investigate potential sources of heterogeneity of findings. The study design was a systematic review and meta-analysis. We searched Pubmed, CINAHL, PsycINFO and LILACS up to April 2021. We performed meta-analyses following the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement and several subgroup analyses to investigate whether cause of caring dependency, study design, and controlling for several biases influenced results. Fifty-nine studies met our inclusion criteria. We found a robust and statistically significant association between greater use of dysfunctional coping and higher depressive symptoms. Greater use of emotion-focussed coping was associated with fewer depressive symptoms only in studies controlling for confounding bias. Use of problem-focussed coping was related to fewer depressive symptoms in carers of frail older people. The combined use of both problem-focussed and emotion-focussed coping was associated with lower symptoms of depression. Our review concludes that the broad domain of dysfunctional coping is consistently associated with higher levels of depressive symptoms in carers. After controlling for confounders, emotion-focussed coping and several of its individual strategies were consistently associated with fewer depressive symptoms. Whilst problem-focussed coping and some of its individual strategies are also associated with lower depressive symptoms, these strategies may not be as helpful in all caregiving groups.

Association between anxiety symptoms and Alzheimer's disease biomarkers in cognitively healthy adults: A systematic review and meta-analysis.

OBJECTIVE: Anxiety has been identified as both a risk factor and prodromal symptom for Alzheimer's disease (AD) and related dementias, however, the underlying neurobiological correlates remain unknown. The aim of this systematic review and meta-analysis was to examine the association between anxiety symptoms and two defining markers of AD neuropathology: amyloid-beta (Aß) and tau. METHODS: Systematic literature searches were conducted across 5 databases. Studies investigating the relationship between anxiety and AD neuropathology (i.e., Aß and/or tau) in cognitively healthy adults were eligible. Where possible, effect sizes were combined across studies, for Aß and tau separately, using random-effects meta-analyses. Sensitivity analyses were performed to assess whether results differed according to anxiety type (i.e., state and trait) and biomarker assessment modality (i.e., positron emission tomography and cerebrospinal fluid). RESULTS: Twenty-seven studies reporting data from 14 unique cohorts met eligibility criteria. Random-effects meta-analyses revealed no associations between self-reported anxiety symptoms and either Aß (13 studies, Fisher's z = 0.02, 95% confidence interval [CI] -0.01-0.05, p = 0.194) or tau (4 studies, Fisher's z = 0.04, 95% CI -0.02-0.09, p = 0.235). Results remained unchanged across sensitivity analyses. CONCLUSIONS: In cognitively healthy adults, meta-analytic syntheses revealed no associations between anxiety symptoms and either Aß or tau. There is a critical need, however, for larger studies with follow-up periods to examine the effect of anxiety symptom onset, severity, and chronicity on AD neuropathology. Additionally, further research investigating other potential neurobiological correlates is crucial to advance scientific understanding of the relationship between anxiety and dementia.

Effectiveness of treatments for people living with severe dementia: A systematic review and meta-analysis of randomised controlled clinical trials.

BACKGROUND: Dementia is a progressive neurodegenerative syndrome that has no cure. Although a significant proportion of people with dementia progress into the severe stages of the disease, evidence on the clinical effectiveness of treatments for people with severe dementia remains limited. AIMS: To systematically review the effectiveness of pharmacological and non-pharmacological treatments for people living with severe dementia and assess the quality of the evidence. METHOD: We searched MEDLINE, EMBASE, PsycINFO, CINAHL and online clinical trial registers up to January 2022, for Randomised Controlled Trials (RCT) in people living with severe dementia. Quality and risk of bias were assessed independently by two authors. RESULTS: A total of 30 trials met our inclusion criteria of which 14 evaluated the effectiveness of pharmacological treatments, and 16 evaluated a non-pharmacological intervention. Pharmacological treatments: Meta-analyses indicated that pharmacological treatments (donepezil: 10 mg, 5 mg; galantamine: 24 mg; memantine: 10 mg) are associated with better outcomes compared to placebo for: severity of symptoms (standardized mean difference (SMD) 0.37, 95% CI 0.26-0.48; 4 studies; moderate-certainty evidence), activities of daily living (SMD 0.15, 95% CI 0.04-0.26; 5 studies; moderate-certainty evidence), and clinical impression of change (Relative Risk (RR) 1.34, 95% CI 1.14-1.57; 4 studies; low-certainty evidence). Pharmacological treatments were also more likely to reduce mortality compared to placebo (RR 0.60, 95% CI 0.40-0.89; 6 studies; low-certainty evidence). Non-pharmacological treatments: Five trials were included in the meta-analyses of non-pharmacological interventions (multi-sensory stimulation, needs assessment, and activities-based interventions); results showed that non-pharmacological interventions may reduce neuropsychiatric symptoms of dementia compared to usual care (SMD -0.33, 95% CI -0.59 to -0.06; low certainty evidence). CONCLUSIONS: There is moderate-certainty evidence that pharmacological treatments may decrease disease severity and improve function for people with severe dementia. Non-pharmacological treatments are probably effective in reducing neuropsychiatric symptoms but the quality of evidence remains low. There is an urgent need for high-quality evidence for other outcomes and for developing service-user informed interventions for this under-served group.

Non-affective psychotic disorders and risk of dementia: a systematic review and meta-analysis.

Non-affective psychotic disorders have been associated with an increased risk of developing dementia. However, research in this area remains limited, highlighting the need for an up-to-date systematic review and meta-analysis of the evidence. We aimed to systematically review and quantify the risk of dementia associated with psychotic disorders. We searched four electronic databases for longitudinal studies investigating non-affective psychotic disorders and subsequent dementia. We used random-effects meta-analyses to pool estimates across studies and assessed risk of bias for each study. Non-affective psychotic disorders were associated with increased risk of all-cause dementia; pooled risk ratio (RR) = 2.52, 95% confidence interval (CI) (1.67-3.80), I2 = 99.7%, n = 12,997,101; 11 studies, with high heterogeneity between studies. Subgroup analyses indicated stronger associations in studies with shorter follow-up periods, conducted in non-European countries, published after 2020, and where ≥60% of the sample were female. The risk was higher in people aged <60 years at baseline, in typical and late-onset psychotic disorders versus very late-onset psychosis, in broader psychotic disorders vs schizophrenia, and in prospective vs retrospective studies. Associations remained after excluding low quality studies (pooled RR = 2.50, 95% CI (1.71-3.68), I2 = 99.0%). Our review finds a substantial association between psychotic disorders and subsequent dementia. Our findings indicate that psychotic disorders are a potentially modifiable risk factor for dementia and suggest that individuals with psychotic disorders need to be closely monitored for cognitive decline in later life. Further research is needed to investigate the mechanisms underlying the association between psychotic disorders and dementia.

Risk factors for apathy in Alzheimer's disease: A systematic review of longitudinal evidence.

BACKGROUND: Apathy is frequent and persistent in Alzheimer's disease (AD), associated with poor prognosis and carer distress; yet our knowledge of risk factors remains limited. AIMS: To identify risk factors associated with apathy incidence and progression in AD over time. METHODS: We systematically reviewed evidence based on longitudinal studies assessing risk factors for apathy in AD up to June 2021. Two authors independently assessed article eligibility and rated quality. RESULTS: 13,280 articles were screened, of which 13 met inclusion criteria. Studies had a mean follow-up of 2.7 years reporting on a total of 2012 participants. Most findings were based on single studies of moderate quality evidence. Risk factors increasing apathy onset were: being a carrier of the T allele of the PRND gene polymorphism, and having high levels of the IL-6 and TNFα cytokines at baseline. Risk factors for apathy worsening were: reduced inferior-temporal cortical thickness, taking antidepressants, being an ApoE ε4 carrier, living longer with AD, lower cognitive test scores, higher baseline apathy, premorbid personality traits (lower agreeableness, higher neuroticism), and higher midlife motivational abilities. CONCLUSIONS: Although results are limited by the small number of studies, this review identified specific genetic, neurobiological, AD specific, and dispositional factors that may increase risk of apathy onset and worsening in AD.

Psychological treatments for depression and anxiety in dementia and mild cognitive impairment.

BACKGROUND: Experiencing anxiety and depression is very common in people living with dementia and mild cognitive impairment (MCI). There is uncertainty about the best treatment approach. Drug treatments may be ineffective and associated with adverse effects. Guidelines recommend psychological treatments. In this updated systematic review, we investigated the effectiveness of different psychological treatment approaches. OBJECTIVES: Primary objective To assess the clinical effectiveness of psychological interventions in reducing depression and anxiety in people with dementia or MCI. Secondary objectives To determine whether psychological interventions improve individuals' quality of life, cognition, activities of daily living (ADL), and reduce behavioural and psychological symptoms of dementia, and whether they improve caregiver quality of life or reduce caregiver burden. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE, Embase, four other databases, and three trials registers on 18 February 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared a psychological intervention for depression or anxiety with treatment as usual (TAU) or another control intervention in people with dementia or MCI. DATA COLLECTION AND ANALYSIS: A minimum of two authors worked independently to select trials, extract data, and assess studies for risk of bias. We classified the included psychological interventions as cognitive behavioural therapies (cognitive behavioural therapy (CBT), behavioural activation (BA), problem-solving therapy (PST)); 'third-wave' therapies (such as mindfulness-based cognitive therapy (MBCT)); supportive and counselling therapies; and interpersonal therapies. We compared each class of intervention with control. We expressed treatment effects as standardised mean differences or risk ratios. Where possible, we pooled data using a fixed-effects model. We used GRADE methods to assess the certainty of the evidence behind each result. MAIN RESULTS: We included 29 studies with 2599 participants. They were all published between 1997 and 2020. There were 15 trials of cognitive behavioural therapies (4 CBT, 8 BA, 3 PST), 11 trials of supportive and counselling therapies, three trials of MBCT, and one of interpersonal therapy. The comparison groups received either usual care, attention-control education, or enhanced usual care incorporating an active control condition that was not a specific psychological treatment. There were 24 trials of people with a diagnosis of dementia, and five trials of people with MCI. Most studies were conducted in community settings. We considered none of the studies to be at low risk of bias in all domains.  Cognitive behavioural therapies (CBT, BA, PST) Cognitive behavioural therapies are probably slightly better than treatment as usual or active control conditions for reducing depressive symptoms (standardised mean difference (SMD) -0.23, 95% CI -0.37 to -0.10; 13 trials, 893 participants; moderate-certainty evidence). They may also increase rates of depression remission at the end of treatment (risk ratio (RR) 1.84, 95% CI 1.18 to 2.88; 2 studies, with one study contributing 2 independent comparisons, 146 participants; low-certainty evidence). We were very uncertain about the effect of cognitive behavioural therapies on anxiety at the end of treatment (SMD -0.03, 95% CI -0.36 to 0.30; 3 trials, 143 participants; very low-certainty evidence). Cognitive behavioural therapies probably improve patient quality of life (SMD 0.31, 95% CI 0.13 to 0.50; 7 trials, 459 participants; moderate-certainty evidence) and activities of daily living at end of treatment compared to treatment as usual or active control (SMD -0.25, 95% CI -0.40 to -0.09; 7 trials, 680 participants; moderate-certainty evidence). Supportive and counselling interventions Meta-analysis showed that supportive and counselling interventions may have little or no effect on depressive symptoms in people with dementia compared to usual care at end of treatment (SMD -0.05, 95% CI -0.18 to 0.07; 9 trials, 994 participants; low-certainty evidence). We were very uncertain about the effects of these treatments on anxiety, which was assessed only in one small pilot study. Other interventions There were very few data and very low-certainty evidence on MBCT and interpersonal therapy, so we were unable to draw any conclusions about the effectiveness of these interventions. AUTHORS' CONCLUSIONS: CBT-based treatments added to usual care probably slightly reduce symptoms of depression for people with dementia and MCI and may increase rates of remission of depression. There may be important effect modifiers (degree of baseline depression, cognitive diagnosis, or content of the intervention). CBT-based treatments probably also have a small positive effect on quality of life and activities of daily living. Supportive and counselling interventions may not improve symptoms of depression in people with dementia. Effects of both types of treatment on anxiety symptoms are very uncertain. We are also uncertain about the effects of other types of psychological treatments, and about persistence of effects over time. To inform clinical guidelines, future studies should assess detailed components of these interventions and their implementation in different patient populations and in different settings.

Anger and Dementia Caregiving: A Systematic Review of the Effects of Anger and Hostility on Caregivers' Physical Health.

Background: Anger is commonly experienced by family caregivers of people living with dementia yet its effect on caregivers' physical health remains unknown. Objective: The primary aim of this study was to systematically review current evidence on the effects of anger and hostility on caregivers' physical health. Methods: We searched Medline, EMBASE, PubMed, and PsycINFO up to January 2022. Two review authors independently extracted data on study characteristics, study quality, and effect sizes of associations of anger and hostility with caregiver health outcomes. Results: We found eight studies examining the effects of anger and hostility on caregivers' physical health reporting on a total of 937 participants, of which four were cross-sectional and four were longitudinal. Overall findings indicated that higher levels of anger and hostility exerted a negative effect on caregivers' physical health. Higher anger control was longitudinally associated with increased weight gain (ß= 1.13, p < 0.001), whereas higher anger out predicted higher glucose dysregulation at long-term follow-up (r = 0.27, p < 0.05). Higher levels of caregiver hostility were associated with increased risk of chronic low-grade inflammation long-term (r = 0.18, p < 0.05), and increased risk of cognitive decline over time (r = -0.16, p < 0.05). Conclusion: Our review provides the first systematic synthesis of the evidence demonstrating the harmful effects of anger and hostility on dementia caregivers' health and highlights the need for preventative interventions to support family caregivers experiencing high levels of anger.