Predictors of primary care psychological therapy outcomes for depression and anxiety in people living with dementia: evidence from national healthcare records in England.

BACKGROUND: Psychological therapies can be effective in reducing symptoms of depression and anxiety in people living with dementia (PLWD). However, factors associated with better therapy outcomes in PLWD are currently unknown. AIMS: To investigate whether dementia-specific and non-dementia-specific factors are associated with therapy outcomes in PLWD. METHOD: National linked healthcare records were used to identify 1522 PLWD who attended psychological therapy services across England. Associations between various factors and therapy outcomes were explored. RESULTS: People with frontotemporal dementia were more likely to experience reliable deterioration in depression/anxiety symptoms compared with people with vascular dementia (odds ratio 2.98, 95% CI 1.08-8.22; P = 0.03) or Alzheimer's disease (odds ratio 2.95, 95% CI 1.15-7.55; P = 0.03). Greater depression severity (reliable recovery: odds ratio 0.95, 95% CI 0.92-0.98, P < 0.001; reliable deterioration: odds ratio 1.73, 95% CI 1.04-2.90, P = 0.04), lower work and social functioning (recovery: odds ratio 0.98, 95% CI 0.96-0.99, P = 0.002), psychotropic medication use (recovery: odds ratio 0.67, 95% CI 0.51-0.90, P = 0.01), being of working age (recovery: odds ratio 2.03, 95% CI 1.10-3.73, P = 0.02) and fewer therapy sessions (recovery: odds ratio 1.12, 95% CI 1.09-1.16, P < 0.001) were associated with worse therapy outcomes in PLWD. CONCLUSIONS: Dementia type was generally not associated with outcomes, whereas clinical factors were consistent with those identified for the general population. Additional support and adaptations may be required to improve therapy outcomes in PLWD, particularly in those who are younger and have more severe depression.

Psychological therapies for depression and cardiovascular risk: evidence from national healthcare records in England.

AIMS: People with depression are up to 72% more at risk to develop cardiovascular disease (CVD) in their lifetime. Evidence-based psychotherapies are first-line interventions for the treatment of depression and are delivered nationally in England through the National Health Service via the Improving Access to Psychological Therapy (IAPT) primary care programme. It is currently unknown whether positive therapy outcomes may be associated with cardiovascular risk reduction. This study aimed to examine the association between psychotherapy outcomes for depression and incident CVD. METHODS AND RESULTS: A cohort of 636 955 individuals who have completed a course of psychotherapy was built from linked electronic healthcare record databases of national coverage in England: the national IAPT database, the Hospital Episode Statistics (HES) database, and the HES-ONS (Office of National Statistics) mortality database. Multivariable Cox models adjusting for clinical and demographic covariates were run to estimate the association between reliable improvement from depression and the risk of subsequent incidence of cardiovascular events. After a median follow-up of 3.1 years, reliable improvement from depression symptoms was associated with a lower risk of new onset of any CVD [hazard ratio (HR): 0.88, 95% confidence interval (CI): 0.86, 0.89], coronary heart disease (HR: 0.89, 95% CI: 0.86, 0.92), stroke (HR: 0.88, 95% CI: 0.83, 0.94), and all-cause mortality (HR: 0.81, 95% CI: 0.78, 0.84). This association was stronger in the under 60 compared with the over 60 for all outcomes. Results were confirmed in sensitivity analyses. CONCLUSION: Management of depression through psychological interventions may be associated with reduced risk of CVD. More research is needed to understand the causality of these associations.

Associations between psychological therapy outcomes for depression and incidence of dementia.

BACKGROUND: Depression is an important, potentially modifiable dementia risk factor. However, it is not known whether effective treatment of depression through psychological therapies is associated with reduced dementia incidence. The aim of this study was to investigate associations between reduction in depressive symptoms following psychological therapy and the subsequent incidence of dementia. METHODS: National psychological therapy data were linked with hospital records of dementia diagnosis for 119808 people aged 65+. Participants received a course of psychological therapy treatment in Improving Access to Psychological Therapies (IAPT) services between 2012 and 2019. Cox proportional hazards models were run to test associations between improvement in depression following psychological therapy and incidence of dementia diagnosis up to eight years later. RESULTS: Improvements in depression following treatment were associated with reduced rates of dementia diagnosis up to 8 years later (HR = 0.88, 95% CI 0.83-0.94), after adjustment for key covariates. Strongest effects were observed for vascular dementia (HR = 0.86, 95% CI 0.77-0.97) compared with Alzheimer's disease (HR = 0.91, 95% CI 0.83-1.00). CONCLUSIONS: Reliable improvement in depression across psychological therapy was associated with reduced incidence of future dementia. Results are consistent with at least two possibilities. Firstly, psychological interventions to improve symptoms of depression may have the potential to contribute to dementia risk reduction efforts. Secondly, psychological therapies may be less effective in people with underlying dementia pathology or they may be more likely to drop out of therapy (reverse causality). Tackling the under-representation of older people in psychological therapies and optimizing therapy outcomes is an important goal for future research.

Role of cardiometabolic risk in the association between accumulation of affective symptoms across adulthood and mid-life cognitive function: national cohort study.

BACKGROUND: Affective symptoms are associated with cognition in mid-life and later life. However, the role of cardiometabolic risk in this association has not been previously examined. AIMS: To investigate how cardiometabolic risk contributes to associations between affective symptoms and mid-life cognition. METHOD: Data were used from the National Child Development Study (NCDS), a sample of people born in Britain during one week in 1958. Measures of immediate and delayed memory, verbal fluency and information processing speed and accuracy were available at age 50. Affective symptoms were assessed at ages 23, 33 and 42 years and a measure of accumulation was derived. A cardiometabolic risk score was calculated from nine cardiometabolic biomarkers at age 44. Path models were run to test these associations, adjusting for sex, education, socioeconomic position and affective symptoms at age 50. RESULTS: After accounting for missing data using multiple imputation, path models indicated significant indirect associations between affective symptoms and mid-life immediate memory (ß = -0.002, s.e. = 0.001, P = 0.009), delayed memory (ß = -0.002, s.e. = 0.001, P = 0.02) and verbal fluency (ß = -0.002, s.e. = 0.001, P = 0.045) through cardiometabolic risk. CONCLUSIONS: These findings suggest that cardiometabolic risk may play an important role in the association between affective symptoms and cognitive function (memory and verbal fluency). Results contribute to understanding of biological mechanisms underlying associations between affective symptoms and cognitive ageing, which can have implications for early detection of, and intervention for, those at risk of poorer cognitive outcomes.

Bidirectional relation between affective symptoms and cognitive function from middle to late adulthood: a population-based birth cohort study.

OBJECTIVES: There is an association between affective symptoms and cognition. However, the direction of this association remains unclear. This study aimed to test bidirectional relationships between affective symptoms and cognition from middle to late adulthood. METHOD: Data were available from the MRC National Survey of Health and Development (NSHD), a prospective birth cohort of 5362 people born in 1946. Affective symptoms and cognition were measured at ages 53, 60-64, and 69. Latent scores of affective symptoms were derived and cross-lagged models were fitted for affective symptoms with verbal memory and processing speed. RESULTS: Results revealed an inverse cross-sectional association between affective symptoms and verbal memory (ß=-0.18, SE=0.04, p<.001) and processing speed (ß=-0.13, SE=0.06, p=.05) at age 53, but not at ages 60-64 or 69. Affective symptoms at age 53 predicted lower verbal memory at age 60-64 (ß=-0.58, SE=0.27, p=.03), and affective symptoms at age 60-64 predicted lower verbal memory (ß=-0.64, SE=0.29, p=.03) and processing speed (ß=-1.27, SE=0.41, p=.002) at age 69. Verbal memory and processing speed did not predict subsequent affective symptoms. CONCLUSION: Affective symptoms predict poorer verbal memory and processing speed over a period of 16 years, but not vice versa.

Accumulation of affective symptoms and midlife cognitive function: The role of inflammation.

BACKGROUND: The aim of the present study was to test whether C-Reactive Protein (CRP), a proxy measure of inflammation, is elevated in people with higher childhood and adulthood affective symptoms and whether elevated CRP predicts midlife cognitive function. METHODS: Data were used from the National Child Development Study (n = 6276). Measures of memory, verbal fluency, information processing speed and accuracy were available in midlife (age 50). Affective symptoms were assessed in childhood (ages 7, 11, 16) and in adulthood (ages 23, 33, 42, 50). The level of plasma CRP was measured at age 44. Pathway models, unadjusted and fully adjusted for sex, education, childhood socioeconomic position, childhood cognitive ability and affective symptoms at age 50, were fitted to test direct associations between affective symptoms and midlife cognitive function, and indirect associations via the inflammatory pathway (CRP level). RESULTS: In a fully adjusted model, there were significant indirect associations between adulthood affective symptoms and immediate memory (ß = -0.01, SE = 0.003, p = .03) and delayed memory (ß = -0.01, SE = 0.004, p = .03) via CRP. In addition, there were significant indirect associations between affective symptoms in childhood and immediate memory (ß = -0.001, SE = 0.00, p = .03) and delayed memory (ß = -0.001, SE = 0.001, p = .03), via adulthood affective symptoms and associated CRP. Independent of CRP, there was a significant direct association between adulthood affective symptoms and information processing errors (ß = 0.47, SE = 0.21, p = .02). There were no direct or indirect associations between affective symptoms and verbal fluency or information processing speed. CONCLUSIONS: CRP at age 44 is elevated in people with higher affective symptoms from age 7 to 42, and elevated CRP is associated with poorer immediate and delayed memory at age 50.

Affective symptoms across the life course and resilience in cognitive function.

Background: Little is known about what factors can modify the relationship between affective symptoms and cognitive function across the life course.Aim: To investigate a number of factors that can contribute to resilience in cognitive function in relation to affective symptoms, using data from the National Child Development Study.Subjects and methods: Adult affective symptoms were measured using the Malaise Inventory Scale (ages 23, 33, 42 and 50). Measures of immediate and delayed memory, verbal fluency and information processing accuracy (age 50) were used to derive measures of resilience in cognitive function-better than predicted cognition, when accounting for experiences of affective symptoms. Factors contributing to resilience in cognitive function were informed by a literature review and included sex, childhood cognitive ability, education, household socio-economic position (SEP), midlife SEP, and APOE genotype. Linear regression and structural equation modelling approaches were used for analyses.Results: Higher childhood cognitive ability, educational level, midlife SEP and female sex contributed to better than predicted cognitive function in relation to affective symptoms (i.e. resilience), with particularly consistent effects for memory. No effects on resilience were revealed for APOE genotype.Conclusion: Understanding factors contributing to resilience in cognitive function in those with affective symptoms can inform interventions to promote healthy cognitive ageing for those at risk.

Longitudinal associations of affective symptoms with mid-life cognitive function: evidence from a British birth cohort.

BACKGROUND: Affective disorders are associated with poorer cognition in older adults; however, whether this association can already be observed in mid-life remains unclear. AIMS: To investigate the effects of affective symptoms over a period of 30 years on mid-life cognitive function. First, we explored whether timing (sensitive period) or persistence (accumulation) of affective symptoms predicted cognitive function. Second, we tested how different longitudinal trajectories of affective symptoms were associated with cognitive function. METHOD: The study used data from the National Child Development Study. Memory, verbal fluency, information processing speed and accuracy were measured at age 50. Affective symptoms were measured at ages 23, 33, 42 and 50 and used to derive longitudinal trajectories. A structured modelling approach compared a set of nested models in order to test accumulation versus sensitive period hypotheses. Linear regressions and structural equation modelling were used to test for longitudinal associations of affective symptoms with cognitive function. RESULTS: Accumulation of affective symptoms was found to be the best fit for the data, with persistent affective symptoms being associated with poorer immediate memory (b = -0.07, s.e. = 0.03, P = 0.01), delayed memory (b = -0.13, s.e. = 0.04, P < 0.001) and information processing accuracy (b = 0.18, s.e. = 0.08, P = 0.03), but not with information processing speed (b = 3.15, s.e. = 1.89, P = 0.10). Longitudinal trajectories of repeated affective symptoms were associated with poorer memory, verbal fluency and information processing accuracy. CONCLUSIONS: Persistent affective symptoms can affect cognitive function in mid-life. Effective management of affective disorders to prevent recurrence may reduce risk of poor cognitive outcomes and promote healthy cognitive ageing. DECLARATION OF INTEREST: None.

Bidirectional Associations of Depressive Symptoms and Cognitive Function Over Time.

Importance: Cognitive decline and depressive symptoms often co-occur among older adults, and they share several mechanisms. Despite the fact that cognitive dysfunction has been linked to increased depressive symptoms, the directionality of this association remains unclear. Objective: To examine whether there is a bidirectional association between depressive symptoms and cognitive function in English adults aged 50 years or older throughout a 16-year follow-up period. Design, Setting, and Participants: This cohort study included a nationally representative sample of community-dwelling English adults aged 50 years or older. The current analysis included 8268 eligible participants with relevant data. These participants were examined every other year from 2002 and 2003 until 2018 and 2019, resulting in a follow-up period of up to 16 years. Data were analyzed from July to November 2023. Main Outcomes and Measures: The bivariate dual change score models were used to estimate the multivariable associations between depressive symptoms and cognitive function, which were interchangeably used as exposures and outcomes. Cognitive measures include memory and verbal fluency tests, while the Center for Epidemiologic Studies Depression Scale evaluated depressive symptoms. Results: The study population of 8268 participants had a mean (SD) age of 64 (10) years at the study baseline, and 4517 participants (55%) were female. Higher depressive symptoms were cross-sectionally associated with poorer memory (ß intercept, -0.018; standard error [SE], 0.004; P < .001) and verbal fluency (ß intercept, -0.009; SE, 0.004; P = .02) at study baseline. A steeper linear change in depressive symptoms was associated with an accelerated memory change (ß intercept, -0.253; SE, 0.079; P = .001), and a linear change in memory was associated with an acceleration in depressive symptoms over time (ß intercept, 0.016; SE, 0.006; P = .005). This bidirectional change was not observed with verbal fluency. Conclusions and Relevance: In this study, greater depressive symptoms were associated with poorer memory at the study baseline and steeper memory change over time. A gradual linear change in depressive symptoms contributed to accelerated memory loss and vice versa, suggesting that psychological mood and memory performance are intrinsically associated.

Effectiveness of Cognitive Stimulation Therapy (CST) for mild to moderate dementia: A systematic literature review and meta-analysis of randomised control trials using the original CST protocol.

AIMS: We aimed to conduct a systematic literature review and meta-analysis to evaluate the efficacy of the original 14 session Cognitive Stimulation Therapy (CST) protocol in improving cognitive function and related outcomes in people with mild to moderate dementia. METHODS: Four databases were searched, up to May 2023, for randomized controlled trials of CST using the original protocol. Pre- and post-test means and measures of dispersion for intervention and control groups were extracted for each reported outcome and used to calculate effect sizes. Effect sizes were grouped by outcome and pooled in inverse variance weighted random effects models. RESULTS: Twelve studies were identified as meeting inclusion criteria. Of these, ten were given either a 'high' or 'medium' quality rating. The pooled results indicated that CST had a significant beneficial impact on global cognition, language, working memory, depression, neuropsychiatric symptoms, communication, self-reported quality of life and severity of dementia. CONCLUSIONS: CST as delivered in adherence to the original 14-session protocol is an efficacious treatment for mild to moderate dementia with improvements in cognition, affective symptoms and quality of life demonstrated from global trials.

A review of the literature on wellbeing and modifiable dementia risk factors.

Wellbeing-defined broadly as experiencing one's life as enjoyable and fulfilling-has been associated with lower risk for Alzheimer's disease and related dementias. The mechanisms underlying this association are largely unknown. However, prior research and theory suggest that wellbeing impacts health behaviors and biological systems that are relevant to cognitive and brain health. Several of these factors have also been identified by the 2020 Lancet Commission on Dementia Prevention, Intervention, and Care as modifiable dementia risk factors. In the current review, we summarize and evaluate the evidence for associations between wellbeing and each of the 12 Lancet Commission risk factors. We found relatively consistent evidence for associations between higher wellbeing and lower levels of most of the risk factors: physical inactivity, social isolation, smoking, depression, hypertension, diabetes, hearing loss, traumatic brain injury, and air pollution. By contrast, we found evidence for only modest associations between wellbeing and education and mixed evidence for associations of wellbeing with alcohol use and body weight. Although most of the reviewed evidence was observational, longitudinal and experimental evidence suggests that many of the observed associations are likely bidirectional. These findings suggest that modifiable dementia risk factors may be mediators (i.e., intermediate steps in the causal chain) and/or confounders (i.e., variables that impact both wellbeing and dementia, and thus could induce a spurious association) of the association between wellbeing and dementia. We conclude by discussing next steps to test mediation hypotheses and to account for potential confounding in the relation between wellbeing and dementia.

Examining the Lancet Commission risk factors for dementia using Mendelian randomisation.

BACKGROUND: Dementia incidence is increasing across the globe and currently there are no disease-modifying pharmaceutical treatments. The Lancet Commission on dementia identified 12 modifiable risk factors which explain 40% of dementia incidence. However, whether these associations are causal in nature is unclear. OBJECTIVE: To examine the modifiable risk factors for dementia as identified in the Lancet Commission review using Mendelian randomisation (MR) to establish if, based on genetic evidence, these associations with different dementia subtypes are causal in nature. METHODS: Publicly available genome-wide association study data were used for 10 risk factors and Alzheimer's disease (AD), frontotemporal dementia and dementia with Lewy bodies. Two-sample MR using the inverse varianceweighted method was conducted to test for causal relationships. Weighted median MR and MR-Egger were used to test for pleiotropic effects. RESULTS: Genetic proxied risk for higher levels of smoking (OR: 0.80 (95% CI: 0.69; 0.92), p=0.002), obesity (OR: 0.87 (95% CI: 0.82; 0.92), p<0.001) and blood pressure (OR: 0.90 (95% CI: 0.82; 0.99), p=0.035) appeared to be protective against the risk of AD. Post hoc analyses indicated these associations had pleiotropic effects with the risk of coronary artery disease. Genetic proxied risk of educational attainment was found to be inconsistently associated with the risk of AD. CONCLUSIONS AND IMPLICATIONS: Post hoc analysis indicated that the apparent protective effects of smoking, obesity and blood pressure were a result of survivor bias. The findings from this study did not support those presented by the Lancet Commission. Evidence from causal inference studies should be considered alongside evidence from epidemiological studies and incorporated into reviews of the literature.

Associations between psychological intervention for anxiety disorders and risk of dementia: a prospective cohort study using national health-care records data in England.

BACKGROUND: Meta-analyses support an association between anxiety in older adulthood and dementia. The aim of this study was to use routinely collected health data to test whether treatment of anxiety disorders through psychological intervention is associated with a lower incidence of dementia. METHODS: In this prospective cohort study, data from nationally provided psychological therapy services in England termed Improving Access to Psychological Therapies from 2012 to 2019 were linked to medical records, including dementia diagnoses as defined by the tenth edition of the International Classification of Diseases, up to 8 follow-up years later. Inclusion criteria were as follows: (1) patients who were aged 65 years and older; (2) patients with a probable anxiety disorder; and (3) those with no previous or current diagnosis of dementia. Cox proportional hazards models were constructed to test whether reliable improvement in anxiety following psychological intervention was associated with future dementia incidence. The primary outcome was all-cause dementia and cases were identified using ICD-10 dementia codes from Hospital Episode Statistics, Mental Health Services Dataset, and mortality data. For main analyses, hazards ratios (HRs) are presented. FINDINGS: Data from 128 077 people aged 65 years and older attending a nationally provided psychological intervention service in England were linked to medical records. 88 019 (69·0%) of 127 064 participants with available gender data were women and 39 585 (31·0%) were men. 111 225 (95·9%) of 115 989 with available ethnicity data were of White ethnicity. The mean age of the sample was 71·55 years (SD 5·69). Fully adjusted models included data from 111 958 people after 16 119 were excluded due to missing data on key variables or covariates. 4510 (4·0%) of 111 958 participants had a dementia diagnosis. The remaining 107 448 (96·0%) were censored either at date of death or when the final follow-up period available for analyses was reached. People who showed reliable improvement in anxiety had lower rates of later dementia diagnosis (3·9%) than those who did not show reliable improvement (5·1%). Reliable improvement in anxiety following psychological intervention was associated with reduced incidence of all-cause dementia (HR 0·83 [95% CI 0·78-0·88]), Alzheimer's disease (HR 0·85 [0·77-0·94]), and vascular dementia (HR 0·80 [0·71-0·90]). Effects did not differ depending on anxiety disorder diagnosis. INTERPRETATION: Results showed that reliable improvement in anxiety from psychological therapy was associated with reduced incidence of future dementia. There are multiple plausible explanations for this finding and further research is needed to distinguish between these possibilities. Missing data in the sample limit reliability of findings. FUNDING: Alzheimer's Society, Medical Research Council, Wellcome Trust, and UCLH National Institute for Health and Care Research Biomedical Research Centre.

Effectiveness of primary care psychological therapy services for treating depression and anxiety in autistic adults in England: a retrospective, matched, observational cohort study of national health-care records.

BACKGROUND: Autistic adults report a higher prevalence of anxiety and depression than adults without identified autism but have poorer access to appropriate mental health care. Evidence-based psychological therapies are recommended in treatment guidelines for autistic adults, but no study has investigated their effectiveness in large samples representative of the autistic population accessing routine care. This study aimed to examine therapy outcomes for autistic adults in a primary care service. METHODS: In this retrospective, matched, observational cohort study of national health-care records, we used the MODIFY dataset that used linked electronic health-care records, including national data, for individuals who accessed psychological therapy in primary care in Improving Access to Psychological Therapies (IAPT) services in 211 clinical commissioning group areas in England, UK. All adults aged 18 years or older who had completed a course of IAPT in 2012-19 were eligible, and were propensity score matched (1:1) with a comparison group without identified autism. Exact matching was used, when possible, for a range of sociodemographic factors. Primary outcomes were routine metrics that have been nationally defined and used to evaluate IAPT treatments: reliable improvement, reliable recovery, and reliable deterioration. Secondary outcomes were calculated pre-post treatment changes in scores for Patient Health Questionnaire-9, Generalised Anxiety Disorder Assessment-7, and Work and Social Adjustment Scale measures. Subgroup analyses investigated differential effects across a range of sociodemographic factors. FINDINGS: Of 2 515 402 adults who completed at least two sessions of IAPT in 2012-19, 8761 had an autism diagnosis (5054 [57·7%] male and 3707 [42·3%] female) and 1 918 504 did not (631 606 [32·9%] male and 1 286 898 [67·0%] female). After propensity score matching, 8593 autistic individuals were matched with an individual in the comparison group. During IAPT treatment, symptoms of depression and generalised anxiety disorder decreased for most autistic adults, but symptoms were less likely to improve in the autism group than in the comparison group (4820 [56·1%] of 8593 autistic adults had reliable improvement vs 5304 [61·7%] of 8593 adults in the matched group; adjusted odds ratio [ORadj] 0·75, 95% CI 0·70-0·80; p<0·0001) and symptoms were more likely to deteriorate (792 [9·2%] vs 619 [7·2%]; ORadj 1·34, 1·18-1·48; p<0·0001). In the comparison group, improved outcomes were associated with employment and belonging to a higher socioeconomic deprivation category, but this was not the case for autistic adults. INTERPRETATION: Evidence-based psychological therapy for depression or anxiety might be effective for autistic adults but less so than for adults without identified autism. Treatment moderators appear different for autistic individuals, so more research is needed to allow for better targeted and personalised care. FUNDING: Alzheimer's Society.

"Better Living with Non-memory-led Dementia": protocol for a feasibility randomised controlled trial of a web-based caregiver educational programme.

BACKGROUND: Non-memory-led dementias such as posterior cortical atrophy (PCA), primary progressive aphasia (PPA) and behavioural variant frontotemporal dementia (bvFTD) are low prevalent and often affect individuals under the age of 65. Tailored educational and support resources for caregivers of people living with these dementia phenotypes are scarce and unevenly distributed geographically. Web-based educational programmes are emerging as promising alternatives to improve caregiver self-efficacy and well-being. Here, we present the protocol of a study aiming to assess the feasibility of a co-produced online educational programme for caregivers of people living PCA, PPA and bvFTD: the Better Living with Non-memory-led Dementia programme. METHODS: A randomised controlled feasibility trial will be conducted on a sample of 30 caregivers of people living with PCA, PPA and bvFTD. Participants will be recruited among members of the support organisation Rare Dementia Support (based at UCL in the UK). The intervention group will be given access to an 8-week co-produced web-based educational programme consisting of 6 modules addressing education about PCA, PPA and bvFTD and support strategies for the person with dementia and for the caregiver. The control group will receive treatment as usual (TAU). Feasibility will be measured through feasibility of recruitment, clinical measurement tools and acceptability. Clinical measures will be used to assess preliminary efficacy and data on completion rates, missing data and variability used to decide on measures to be included in a full-scale trial. Allocation ratio will be 2:1 (intervention:control) stratified by diagnosis. Feasibility of recruitment and acceptability will be assessed. Clinical measures will be administered at baseline and 8-week and 3-month post-randomisation. The control group will be offered access to the intervention at the completion of data collection. Participants will be unblinded, and all measures will be self-reported online. DISCUSSION: Online-delivered educational programmes show potential for improving care competency of caregivers and may contribute to overcoming geographical inequalities in local provision of support services. This pilot study will inform a fully powered international trial to determine the effectiveness of Better Living with Non-memory-led Dementia. TRIAL REGISTRATION: This trial has been registered prospectively on the Clinical Trials Registry on 1st September 2022, registration number NCT05525377.

Childhood reading problems and cognitive ageing across mid to later life.

BACKGROUND: Little research has investigated long-term associations of childhood reading with cognitive ageing. The aim of this study was to test longitudinal associations between childhood reading problems and cognitive function from mid-adulthood (age 43) to early old age (age 69), and whether associations were mediated by education. METHODS: Data were from the MRC National Survey of Health and Development, a prospective population-based birth cohort. Reading problems were measured at age 11 using a reading test. Verbal memory and processing speed were measured at ages 43, 53, 60-64 and 69 and Addenbrooke's Cognitive Examination (ACE) was administered at age 69. Linear mixed models and path analyses were used to test: (1) associations between reading problems and verbal memory and processing speed trajectories; (2) associations between reading problems and ACE-III scores; (3) whether associations were mediated by education. RESULTS: Reading problems were associated with poorer verbal memory at intercept but not rate of decline (N=1726), and were not associated with processing speed intercept or decline (N=1730). There were higher rates of scores below ACE-III clinical thresholds (<82 and <88) in people with reading problems compared with those without. Reading problems were associated with poorer total ACE-III scores and all domain scores at age 69 (N=1699). Associations were partly mediated by education. CONCLUSION: Reading problems in childhood were associated with poorer cognitive function in early old age, and associations were partly mediated by education.

Positive psychological constructs and association with reduced risk of mild cognitive impairment and dementia in older adults: A systematic review and meta-analysis.

Understanding factors associated with dementia risk is important for informing future interventions aimed at dementia prevention. There is accumulating evidence for the association between depression and risk of dementia, however less is known about the association between positive psychological factors and dementia incidence. This review aims to synthesise evidence regarding the association between positive psychological constructs (PPCs) and later risk of MCI and dementia in adults aged 50 and over. Literature searches were conducted in Medline, PsycINFO, and Scopus until March 2021. Papers reporting on the association between at least one PPC and later risk of MCI or dementia in people aged 50 + without cognitive impairment at baseline were included. Results from the meta-analyses revealed that purpose in life was significantly associated with a reduced risk of dementia (HR = 0.81, 95% CI [0.78, 0.85], p < .001), however results for positive affect were non-significant (HR = 0.94, 95% CI [0.76, 1.15], p = .54). Results for other PPCs are described narratively. Mixed findings for different PPCs highlight the importance of investigating these factors individually. Understanding which factors may play a protective role in their association with risk of mild cognitive impairment and dementia could have important implications for informing dementia prevention interventions.

Positive psychological constructs and cognitive function: A systematic review and meta-analysis.

AIM: To synthesise evidence regarding the association between positive psychological constructs (PPCs) and cognitive function in adults aged 50 +. METHODS: Literature searches: Medline, PsycINFO, and Scopus (inception to February 2022). Studies were included if they reported on the association between at least one PPC and one objective measure of cognitive function in people aged 50 + without cognitive impairment at baseline. Where at least two studies reported on the same PPC and cognitive outcome, estimates were pooled through meta-analysis. FINDINGS: In total, 37 studies were included. There was evidence of cross-sectional associations for 'meaning in life' (verbal fluency: b = 0.09, 95 %CI [0.07, 0.11], p < .001; memory: b = 0.10, 95 %CI [0.08, 0.12], p < .001), 'purpose in life' (verbal fluency: b = 0.07, 95 %CI [0.05, 0.08], p < .001; memory: r = 0.13, 95 %CI [0.08, 0.18], p < .001), and positive affect (cognitive state: r = 0.25, 95 %CI [0.14, 0.36], p < .001; memory: r = 0.05, 95 %CI [0.02, 0.08], p < .001) with various domains of cognitive function. However, no significant results were found for life satisfaction (p = .13) or longitudinal studies investigating positive affect and memory (p = .48). Other PPCs were included in narrative syntheses only. IMPLICATIONS: Purpose and meaning in life may be sensible primary targets for interventions to promote healthy cognitive aging. More longitudinal and causal inference research is needed to better understand this association and its implications for clinical practice.

Salivary cortisol in longitudinal associations between affective symptoms and midlife cognitive function: A British birth cohort study.

Affective disorders are associated with accelerated cognitive ageing. However, current understanding of biological mechanisms which underlie these observed associations is limited. The aim of this study was to test: 1) Whether cortisol acts as a pathway in the association between depressive or anxiety symptoms across adulthood and midlife cognitive function; 2) Whether cortisol is associated with later depressive or anxiety symptoms, and cognitive function. Data were used from the National Child Development Study (NCDS), a sample of infants born in mainland UK during one week of 1958. A measure of the accumulation of affective symptoms was derived from data collected from age 23 to 42 using the Malaise Inventory Scale. Salivary cortisol measures were available at age 44-45. Cognitive function (memory, fluency, information processing) and affective symptoms were assessed at the age of 50. Path models were run to test whether salivary cortisol explained the longitudinal association between depressive or anxiety disorder symptoms and cognitive function. Direct effects of affective symptoms are shown across early to middle adulthood on cognitive function in midlife (memory and information processing errors). However, there were no effects of affective symptoms on cognitive function through cortisol measures. Additionally, cortisol measures were not significantly associated with subsequent affective symptoms or cognitive function at the age of 50. These results do not provide clear evidence to suggest that cortisol plays a role in the association between affective symptoms and cognitive function over this period of time. These findings contribute to our understanding of how the association between affective symptoms and cognitive function operates over time.

Effectiveness of primary care psychological therapy services for the treatment of depression and anxiety in people living with dementia: Evidence from national healthcare records in England.

Background: Depression and anxiety are common and deleterious in people living with dementia (PLWD). It is currently unknown whether routinely provided psychological therapy can help reduce these symptoms in PLWD. This study aimed to investigate improvements in depression and anxiety symptoms over the course of therapy offered in primary care psychological therapy services in PLWD and to compare outcomes to people without dementia. Methods: National data from Improving Access to Psychological Therapies services (IAPT) across England linked with Hospital Episode Statistics data, the Mental Health Services Dataset, and HES-ONS mortality data were used to identify 1,549 PLWD who completed a course of psychological treatment in IAPT between 2012-2019 and a propensity score matched control group without identified dementia. Outcome measures included pre-post intervention changes in depression (PHQ-9) and anxiety (GAD-7) symptoms and therapy outcomes (reliable improvement, recovery, deterioration). Findings: Symptoms of depression (t(1548)=31·05, p<·001) and anxiety (t(1548)=30·31, p<·001) improved in PLWD over the course of psychological therapy with large effect sizes (depression: d=-0·83; anxiety: d=-0·80). However, PLWD were less likely to reliably improve (OR=·75, 95%CI[·63,·88], p<·001) or recover (OR=·75, 95%CI[·64,·88], p=·001), and more likely to deteriorate (OR=1·35, 95%CI[1·03,1·78], p=·029) than a matched control sample without dementia. Interpretation: Psychological therapy may be beneficial for PLWD with depression or anxiety, but it is currently not as effective as for people without dementia. More research is needed to improve access to psychological therapies and to understand this discrepancy and how therapies can be adapted to further improve outcomes. Funding: This work was supported by the Alzheimer's Society.