Ideal Cohort Research Articles

Forecasting Africa’s fertility decline by female education groups

While female education has long been recognized as a key driver of fertility decline during the process of demographic transition and most population projection models consider it implicitly or explicitly in their forecasts of overall fertility, there still is need for a method to forecast education-specific fertility trends directly. Here we propose a method for projecting education-specific fertility declines for cohorts of women in Sub-Saharan Africa based on all available demographic and health surveys data for African countries (including 1.03Mio cases). We study at different levels of aggregation (sample clusters, strata, and national) the associations between ideal family size and completed cohort fertility for education groups, on the one hand, and the average level of education in those units, on the other. The consistently very strong empirical associations suggest a plausible narrative by which a higher prevalence of educated women in a spatial unit influences the fertility levels of women in all specific education categories. Empirical associations between education-specific cohort fertility trends at the national level and newly available quality-adjusted human capital data for these cohorts are then operationalized to produce education-specific population projections as they are needed for-among other uses-the shared socioeconomic pathways scenarios that are widely used in the climate change research community. Sensitivity analyses including out-of-sample projections support the validity of the proposed method which is then applied to 37 African countries.

Navigating the COVID-19 pandemic two years on: experiences of carers of people with dementia from the British IDEAL cohort

We explored carers’ experiences during the COVID-19 pandemic in England to identify long-term impacts and implications, and to suggest future support for caregivers. Data were collected during COVID-19 rapid response studies from carers participating in a British longitudinal cohort study. Semi-structured interview data were compared to accounts from previous interviews conducted during the first 18 months of the pandemic. There was indication of some return to pre-pandemic lifestyles, but without appropriate support, carers risked reaching crisis point. Evidence points to a requirement for assessment and management of support needs to ensure well-being and sustainable dementia caregiving.

Using impedance planimetry (EndoFLIP) to determine ideal distensibility ranges for esophageal motility disorders

ObjectiveUse of impedance planimetry (EndoFLIP) has shown distensibility index ranges associated with improved patient-reported outcomes after antireflux surgery. Questions remain whether the previously described ideal distensibility index range can be used for patients with esophageal motility disorders. We hypothesized that patients with esophageal motility disorders would have a different ideal distensibility range for optimal outcomes. MethodsA retrospective review of a prospectively maintained gastroesophageal database was performed for all patients undergoing Toupet and Nissen fundoplication and impedance planimetry. Demographic data, perioperative outcomes, and quality-of-life indicators (Reflux Symptom Index, Gastroesophageal Reflux Disease-Health Related Quality of Life Questionnaire, and gas/bloat and dysphagia scores) were analyzed and compared between patients by use of the χ2 and Wilcoxon rank-sum tests. ResultsFrom 2015 to 2024, 475 patients underwent laparoscopic fundoplication and impedance planimetry evaluation. Of those, 160 had a final distensibility index score in the ideal range, 165 with a final distensibility index score <2.5, and 150 with a final distensibility index >3.6. In the ideal-range cohort, there were no statistically significant differences between those with normal and abnormal motility in regards to outcomes or quality of life indicators. In the low distensibility index cohort, patients with abnormal motility had worse Gastroesophageal Reflux Disease-Health Related Quality of Life Questionnaire, gas/bloat, and dysphagia scores at 1 year postoperatively compared with those with normal motility. More patients in the low distensibility index cohort required dilations postoperatively, and more patients in the high distensibility index cohort had recurrences compared with those in the ideal range cohort. ConclusionThe previously described ideal distensibility index range of 2.5–3.6 for patients undergoing laparoscopic fundoplication may be used for patients with certain esophageal motility disorders.

Differences in trajectories of quality of life according to type of dementia: 6-year longitudinal findings from the IDEAL programme

BackgroundPeople with different types of dementia may have distinct symptoms and experiences that affect their quality of life. This study investigated whether quality of life varied across types of dementia and over time.MethodsThe participants were 1555 people with mild-to-moderate dementia and 1327 carers from the IDEAL longitudinal cohort study, recruited from clinical services. As many as possible were followed for up to 6 years. Diagnoses included were Alzheimer’s disease, vascular dementia, mixed Alzheimer’s and vascular dementia, Parkinson’s disease dementia, dementia with Lewy bodies, and frontotemporal dementia. Self- and informant-rated versions of the Quality of Life in Alzheimer’s Disease scale were used. A joint model, incorporating a mixed effects model with random effects and a survival model to account for dropout, was used to examine whether quality of life varied by dementia type at the time of diagnosis and how trajectories changed over time.ResultsThe strongest associations between dementia type and quality of life were seen around the time of diagnosis. For both self-ratings and informant ratings, people with Parkinson’s disease dementia or dementia with Lewy bodies had lower quality of life scores. Over time there was little change in self-rated scores across all dementia types (− 0.15 points per year). Informant-rated scores declined over time (− 1.63 points per year), with the greatest decline seen in ratings by informants for people with dementia with Lewy bodies (− 2.18 points per year).ConclusionsSelf-rated quality of life scores were relatively stable over time whilst informant ratings showed a steeper decline. People with Parkinson’s disease dementia or dementia with Lewy bodies report particularly low levels of quality of life, indicating the importance of greater attention to the needs of these groups.

Selenium levels and their association with thyroid autoimmunity and severe preeclampsia in pregnancy: Insights from a prospective ideal breast milk cohort study.

This study aimed to assess selenium status in South Korean pregnant women and its impact on maternal thyroid function and pregnancy outcomes. 'Ideal Breast Milk (IBM) Cohort Study' included 367 pregnant women out of 442 participants and categorized into three groups based on plasma selenium levels: deficient (< 70 μg/L), suboptimal (70-99 μg/L), and optimal (≥ 100 μg/L). During the second or third trimester, various blood parameters, including selenium, thyroid-stimulating hormone, free T4, free T3, and anti-thyroid peroxidase antibody levels, were measured. Thyroid parenchymal echogenicity was assessed as another surrogate marker for thyroid autoimmunity using ultrasonography. The median plasma selenium was 98.8 (range: 46.7-206.4) μg/L, and 30 individuals (8%) were categorized as deficient, while 164 (45%) were classified in the suboptimal group. Selenium deficiency was associated with markers of autoimmune thyroiditis, including positive anti-thyroid peroxidase antibody results (13.3 (deficient) vs 4.6 (optimal) %, P = 0.031) and thyroid parenchymal heterogeneity on ultrasound (33.3 (deficient) vs 14.6 (suboptimal) vs 17.3 (optimal) %, P = 0.042), independently of gestational age. The incidence of severe preeclampsia was higher in the group not taking selenium supplements, particularly among those with twin pregnancies, compared to the group taking selenium supplements (0 (selenium supplement) vs 9.0 (no supplement) %, P = 0.015). Pregnant women experience mild selenium deficiency, which can lead to significant health issues including maternal thyroid autoimmunity and obstetrical complications during pregnancy. Guidelines for appropriate selenium intake according to the stage of pregnancy and the number of fetuses are needed.

Living Alone With Mild-to-Moderate Dementia Over a Two-Year Period: Longitudinal Findings From the IDEAL Cohort

ObjectivesTo compare the experiences of people with dementia living alone or with others and how these may change over two years. DesignWe analysed longitudinal data from three assessment waves, one year apart, in the British IDEAL cohort. SettingParticipants with mild-to-moderate dementia were recruited through National Health Service providers, where possible with a family caregiver, and interviewed at home. ParticipantsThe current analyses include 281 people with dementia living alone and 1,244 living with others at baseline; follow-up data were available for 200 and 965 respectively at time 2 and 144 and 696 respectively at time 3. For those living alone, 140 nonresident caregivers contributed at baseline, 102 at time 2 and 81 at time 3. For those living with others, 1,127 family caregivers contributed at baseline, 876 at time 2 and 670 at time 3. MeasurementsAssessments covered: cognitive and functional ability; self-reported perceptions of health, mood, social engagement, quality of life, satisfaction with life and well-being; use of in-home and community care; and transitions into residential care. ResultsPeople living alone tended to have better cognitive and functional ability and were more frequent users of in-home care. However, they experienced poorer physical, social, and psychological health and reduced quality of life, satisfaction with life, and well-being. These differences persisted over time and rates of transition into residential care were higher. ConclusionsTo facilitate continuing in place for people with dementia living alone, a dual focus on supporting functional ability and add ressing psychosocial needs is essential in the context of an enabling policy framework.

“I think I exactly know why I am here”: what do mature female students tell us about their experiences on a foundation programme

ABSTRACT The concept of the ideal student is one that has generated much research across many disciplines across the globe and continues to stimulate debate about teaching and learning within higher education. This paper explores the concept of the ideal student in relation to the experiences of mature female students enrolled onto a Foundation Programme in Business and Management. Although some Foundation Programmes are intended to recruit international students, most are conceived for school-leavers who are deemed to be the ideal cohort for this programme by the university. As such, there exists the potential for a disconnect between the concept of an ideal student which is generally associated with an implied curriculum model and the experiences of mature students. This paper explored the experiences of mature female students on a Foundation Programme at an English Business School that prepares students for undergraduate study. The research involved interviews with five mature female students, three of whom are mothers. The findings were analysed using Interpretative Phenomenological Analysis and challenges the concept of the ideal student as useful theoretical model upon which to construct the curriculum. This paper also conceptualises the mature student learning journey through the PIPE support model.

Longitudinal Trajectories of Stress and Positive Aspects of Dementia Caregiving: Findings From the IDEAL Programme.

Understanding what influences changes over time in caregiver well-being is important for the development of effective support. This study explores differences in trajectories of caregiver stress and positive aspects of caregiving (PAC). Caregivers of community-dwelling individuals with mild-to-moderate dementia at baseline from the IDEAL cohort were interviewed at baseline (n = 1,203), 12 months (n = 917), and 24 months (n = 699). Growth mixture models identified multiple growth trajectories of caregiver stress and PAC in the caregiver population. Associations between study measures and trajectory classes were examined using multinomial logistic regression and mixed-effects models. Mean stress scores increased over time. A 4-class solution was identified: a "high" stable class (8.3%) with high levels of stress, a "middle" class (46.1%) with slightly increasing levels of stress, a "low" class (39.5%) with initial low levels of stress which slightly increased over time, and a small "increasing" class (6.1%) where stress level started low but increased at a steeper rate. Mean PAC scores remained stable over time. A 5-class solution was identified: 3 stable classes ("high," 15.2%; "middle," 67.6%; "low" 9.3%), a small "increasing" (3.4%) class, and 1 "decreasing" class (4.5%). For stable classes, positive ratings on study measures tended to be associated with lower stress or higher PAC trajectories and vice versa. Those with "increasing" stress also had worsening trajectories of several study measures including depression, relationship quality, competence, and ability to cope. The findings highlight the importance of identifying caregivers at risk of increased stress and declining PAC and offering them targeted support.

'Caring beyond capacity' during the coronavirus pandemic: resilience and family carers of people with dementia from the IDEAL cohort.

Family carers of people with dementia have reported increased caring demands during the COVID-19 pandemic. The aim of this qualitative study was to explore seven family carers' accounts of dementia caregiving one year into the COVID-19 pandemic in England in relation to carer resilience. Themes described the complex challenges of caring during the pandemic, with interviewees burned out and 'caring beyond capacity' due to unmet needs within the caring role, therein highlighting the limitations of building individual resilience only. Timely practical support for carers is essential to protect their well-being and to ward against the potential consequences of carer burnout.

Doing dementia differently: A range of co-produced resources from the IDEAL programme

This article introduces different free resources for people with dementia, carers and professionals working within dementia care. All were produced as part of the IDEAL research programme, drawing on the wealth of evidence created as part of this large cohort longitudinal study. Explaining the background, the creation process and where to find each resource, the article directs readers towards resources readily available for use, as well as information about forthcoming resources.Four ready-to-use resources are described in detail. The Living with Dementia Toolkit is a comprehensive suite of resources for people with dementia and carers. It also features lots of different people with dementia and carers sharing their stories in their own words. The Toolkit is being widely used in NHS and third-sector settings, as well as by community groups. My Life Questionnaire is a new measure of living well which was co-produced with people living with mild-to-moderate dementia and scientifically validated with the IDEAL cohort. ‘The World Turned Upside Down’ began as a play and became a documentary film which can be used to raise awareness, promote discussion and within educational or continuing professional development settings. ‘The Bridge’ is an opera about the experience of living with dementia through the diagnostic process and how a husband and wife manage following diagnosis. Both artistic productions involved people with lived experience advising the performers on how to portray dementia authentically.

LONGITUDINAL FACTORS ASSOCIATED WITH LIVING WELL IN PEOPLE WITH MILD TO MODERATE DEMENTIA

Abstract Understanding the factors associated with quality of life can help us become more effective in optimizing the potential for people with mild-to-moderate dementia to ‘live well’. Identifying individuals at risk of declining quality of life could help to target support more appropriately. We used longitudinal data from 1749 individuals with mild-to-moderate dementia participating in the IDEAL cohort. Assessments took place on entry and at 12, 24, 48, 72 and 96 months. Using mixed effects modelling we examined change in quality of life, as measured by QoL-AD, since time of diagnosis, and looked at time-invariant and time-varying measures and their association with decline in quality of life at 6 years. Mean quality of scores life were stable over our six year follow up period. However, we were able to identify some individuals whose quality of life declined by varying amounts over this period. A larger decline was associated with being male and older, and those with a decline in quality of life had worsening cognitive function and increasing depression in the years following diagnosis. Our results show that quality of life does not decline for most people following a diagnosis of dementia. However, for those that did decline we were able to identify key factors associated with this decline. This model allows us to investigate further factors that may influence living well in people with dementia, and identify, at diagnosis, those most ‘at risk’ of decline and identify potential remediating factors that could inform potential intervention to mitigate this decline.

SOCIAL HEALTH IN PEOPLE WITH DEMENTIA AND THEIR CARERS. PRELIMINARY FINDINGS FROM THE IDEAL PROGRAM

Abstract WHO defines health as a state of complete physical, mental, and social wellbeing. There is an extensive literature examining physical and mental health in later life and, typically, measures of healthy ageing focus upon physical and/or mental health. In the IDEAL dementia research programme we investigated social health outcomes because of their importance in understanding the experience of ‘living well’ for people with dementia. Using data from the IDEAL cohort study, we examined the prevalence and predictors of social isolation in 1,052 people with mild-to-moderate dementia and 928 caregivers who were followed up at 12 and 24 months. Social isolation was assessed using the six-item Lubben Social Network Scale where a score of less than 12 suggests participants are at risk of social isolation. Linear mixed models showed that both people with dementia and caregivers experienced increased social isolation across the two-year period. At baseline 29% of people with dementia were categorised as being socially isolated compared with 14% of caregivers. For both people with dementia and caregivers, loneliness and depression were associated with greater social isolation whilst increased cultural engagement mitigated the impact of social isolation. For people with dementia cognition, the number of green and blue spaces nearby and higher trust in the local community were also important factors. Interventions aimed at increasing cultural engagement and interaction with blue and green spaces may go some way to reducing social isolation.

Dyadic influences on awareness of condition in people with dementia: findings from the IDEAL cohort.

The discrepancy between caregiver-ratings and self-ratings of abilities is commonly used to assess awareness in people with dementia. We investigated the contribution of caregiver and dyadic characteristics to the difference in perspective between caregiver-informants and people with dementia about difficulties experienced, when considering awareness of condition. We conducted exploratory cross-sectional analyses using data from the IDEAL cohort. Participants were 1,038 community-dwelling people with mild-to-moderate dementia, and coresident spouse/partner caregivers. The Representations and Adjustment to Dementia Index (RADIX) checklist reporting difficulties commonly experienced in dementia was completed by 960 caregiver-informants and 989 people with dementia. Difference in scores was calculated for 916 dyads. Demographic information, cognition, informant-rated functional ability and neuropsychiatric symptoms were recorded for the person with dementia. Self-reported data were collected on mood, comorbidity, religion, importance of religion, relationship quality, and caregiver stress. For most dyads, caregivers reported more RADIX difficulties than people with dementia. Caregiver RADIX ratings were more closely associated with informant-rated functional ability and neuropsychiatric symptoms than with cognition. More RADIX difficulties and higher stress were reported by female caregivers. Greater RADIX difference was associated with more caregiver stress, and older age but less depression in people with dementia. Few dyadic characteristics were important, but caregiver stress was higher where caregivers reported more RADIX difficulties and/or the difference in perspective was greater, whereas partners with dementia reported better mood. In addition to offering information about awareness of condition, the caregiver rating and difference in perspectives could indicate where more support is needed.

Resilience in caregivers of people with mild-to-moderate dementia: findings from the IDEAL cohort

ObjectivesA novel model of resilience was tested in caregivers of people with mild-to-moderate dementia and was extended to explore whether including self-efficacy, optimism, and self-esteem improved its predictive value.DesignCross-sectional.SettingData from the IDEAL cohort were used.ParticipantsThe study comprised 1222 caregivers of people with dementia.MeasurementsA composite resilience score was calculated from five measures. Multivariable regressions were used to investigate factors associated with resilience.ResultsGreater resilience was associated with being older, being male, and caregiving for older people with dementia. Greater resilience was also observed when people with dementia had fewer functional difficulties and/or fewer neuropsychiatric symptoms, there was a stronger dyadic relationship, and the caregiver had fewer social restrictions, less neuroticism, and greater perceived competence. Surprisingly, caregiver self-efficacy, optimism, and self-esteem were unrelated to resilience.ConclusionCaregivers of people with mild-to-moderate dementia generally scored well for resilience. Resilience was associated with both the personal characteristics of caregivers and level of care need among people with dementia. Future work is needed to determine whether the caregivers in this cohort appeared resilient because the care recipients had relatively low care needs and consequently placed fewer demands on caregiver well-being than would be the case where dementia is more advanced.

Simvastatin restores pulmonary endothelial function in the setting of pulmonary over-circulation

Statin therapy is a cornerstone in the treatment of systemic vascular diseases. However, statins have failed to translate as therapeutics for pulmonary vascular disease. Early pulmonary vascular disease in the setting of congenital heart disease (CHD) is characterized by endothelial dysfunction, which precedes the more advanced stages of vascular remodeling. These features make CHD an ideal cohort in which to re-evaluate the potential pulmonary vascular benefits of statins, with a focus on endothelial biology. However, it is critical that the full gamut of the pleiotropic effects of statins in the endothelium are uncovered. The purpose of this investigation was to evaluate the therapeutic potential of simvastatin for children with CHD and pulmonary over-circulation, and examine mechanisms of simvastatin action on the endothelium. Our data demonstrate that daily simvastatin treatment preserves endothelial function in our shunt lamb model of pulmonary over-circulation. Further, using pulmonary arterial endothelial cells (PAECs) isolated from Shunt and control lambs, we identified a new mechanism of statin action mediated by increased expression of the endogenous Akt1 inhibitor, C-terminal modifying protein (CTMP). Increases in CTMP were able to decrease the Akt1-mediated mitochondrial redistribution of endothelial nitric oxide synthase (eNOS) which correlated with increased enzymatic coupling, identified by increases in NO generation and decreases in NOS-derived superoxide. Together our data identify a new mechanism by which simvastatin enhances NO signaling in the pulmonary endothelium and identify CTMP as a potential therapeutic target to prevent the endothelial dysfunction that occurs in children born with CHD resulting in pulmonary over-circulation.

Evaluating 'living well' with mild-to-moderate dementia: Co-production and validation of the IDEAL My Life Questionnaire.

We aimed to co-produce and validate an accessible, evidence-based questionnaire measuring 'living well' with dementia that reflects the experience of people with mild-to-moderate dementia. Nine people with dementia formed a co-production group. An initial series of workshops generated the format of the questionnaire and a longlist of items. Preliminary testing with 53 IDEAL cohort participants yielded a shortlist of items. These were tested with 136 IDEAL cohort participants during a further round of data collection and assessed for reliability and validity. The co-production group contributed to decisions throughout and agreed the final version. An initial list of 230 items was reduced to 41 for initial testing, 12 for full testing, and 10 for the final version. The 10-item version had good internal consistency and test-retest reliability, and a single factor structure. Analyses showed significant large positive correlations with scores on measures of quality of life, well-being, and satisfaction with life, and expected patterns of association including a significant large negative association with depression scores and no association with cognitive test scores. The co-produced My Life Questionnaire is an accessible and valid measure of 'living well' with dementia suitable for use in a range of contexts.

The associations between personality traits and quality of life, satisfaction with life, and well-being over time in people with dementia and their caregivers: findings from the IDEAL programme

BackgroundCross-sectional evidence indicates that certain personality traits may influence how well people with dementia and their caregivers are able to live alongside the condition. However, no studies to date have explored these associations longitudinally. The present study aimed to explore whether each of the Five-Factor personality traits were associated with change over two years in perceptions of ‘living well’ for people with dementia and their caregivers. ‘Living well’ was conceptualized as a composite of quality of life, satisfaction with life, and subjective well-being.MethodsData were analyzed from 1487 people with dementia and 1234 caregivers who took part in the IDEAL cohort. Participants were categorized into low, medium, and high groups for each trait using stanine scores. Latent growth curve models investigated associations between these groups and ‘living well’ scores for each trait at baseline and at 12 and 24 months. Covariates included cognition in people with dementia and stress in caregivers. A Reliable Change Index was calculated against which to evaluate changes in ‘living well’ scores over time.ResultsAt baseline, neuroticism was negatively associated with ‘living well’ scores for people with dementia, while conscientiousness, extraversion, openness, and agreeableness were positively associated. For caregivers, neuroticism was negatively associated with ‘living well’ scores at baseline while conscientiousness and extraversion were positively associated. ‘Living well’ scores were mostly stable over time with no influence of personality traits on observed changes.ConclusionsFindings suggest that personality traits, particularly neuroticism, have a meaningful impact on how people with dementia and caregivers rate their capability to ‘live well’ at baseline. Over time ‘living well’ scores for each personality trait group were largely stable. Studies utilizing longer follow-up periods and more appropriate measures of personality are needed to corroborate and extend the findings of the present study.

Does awareness of condition change over time in people with mild‐to‐moderate dementia? Longitudinal findings from the IDEAL cohort

AbstractBackgroundAlthough awareness is known to vary in people with dementia, little is known about longitudinal trajectories of awareness of condition in people with mild‐to‐moderate dementia. Exploring this could help understand the concepts around awareness, and reasons for apparent impaired awareness, relevant to person‐centered care.MethodWe used longitudinal data from the IDEAL programme for 917 community‐dwelling people diagnosed with mild‐to‐moderate dementia. Using a validated checklist, we assessed awareness of personal difficulties associated with dementia at three timepoints over two years. Changes in awareness from baseline were examined. Focusing on people with low awareness at baseline, we used case‐matching to compare characteristics between people who gained awareness over time, and those who continued with low awareness.ResultAt baseline, 83 people showed low awareness of personal dementia‐related difficulties. Following up this group, after attrition we examined data for 49 people at T2 and 25 people at T3. Most people remaining in the study had gained awareness at T2 and T3. Gains were seen up to four or more years after diagnosis. Five people continued to deny any of the common difficulties associated with dementia at all timepoints. These five reported slightly more comorbid conditions than matched cases. Few other distinguishing features were evident but in comparison, the people who came to acknowledge difficulties showed greater deterioration in cognitive and functional ability by T3.ConclusionOver time, self‐reported awareness of dementia‐related difficulties can change in people with mild‐to‐moderate dementia. Awareness gains, seen in most people remaining in the study at T2 and T3, may have been prompted by deteriorating abilities. Reasons for ongoing low awareness were difficult to establish and may relate to individual circumstances including comorbidity. This highlights the individual complexity and dynamic nature of awareness in dementia and challenges the concept of impaired awareness as a fixed disease‐related condition.

The role of anemia and haemoglobin concentration on cognitive function in the Longitudinal Ageing Study of India‐Diagnostic Assessment of Dementia (LASI‐DAD)

AbstractBackgroundAnemia is a condition characterised by low haemoglobin concentration, which is common in elderly populations. In India, anemia is widely researched in childhood development and women of reproductive age, although studies in older populations are lacking. The Longitudinal Ageing Study India ‐ Diagnosis of Dementia (LASI‐DAD) dataset is an ideal cohort to better understand the potential impact of anaemia and changes in blood haemoglobin and cognition in an elderly dataset.Method2,758 respondents from the LASI‐DAD cohort, aged 60 or older, had venous blood samples taken for complete blood count and harmonised cognitive function tests. Haemoglobin concentration was used as the exposure in the linear regression models. Cognition data from in‐depth cognitive tests and informant interviews used the Harmonized Cognitive Assessment Protocol (HCAP). A summary value for each of the 11 tests was used as the outcome. We corrected for age and gender in the basic model with the full model also containing adjustments for rural location, smoking and BMI.ResultCases of anemia are more common in older and rural participants in the Indian population. We found a positive association between haemoglobin concentration and all the harmonised cognitive test measures except the visuospatial measures (b = 0.038 ‐ 0.072 p &lt; 0.05). The strongest association was identified for memory‐based measures (immediate episodic, delayed episodic and recognition, b = 0.045 ‐ 0.072 p &lt; 0.05). This was supported by an association between the general cognitive score and the other red blood count tests including the derived measure mean corpuscular haemoglobin concentration (b = 0.06 p = 0.0001) and Red Cell Distribution Width (b = ‐0.11 p &lt; 0.0001).ConclusionWe have established for the first time in a large South Asian population that anaemia may be an important potentially modifiable risk factor for low cognitive function. As the LASI‐DAD cohort expands to include new timepoints it will be possible to run longitudinal analysis to examine the causal relationship between these measures.

Abstract GS5-10: Utility of the 70-gene MammaPrint test for prediction of extended endocrine therapy benefit in patients with early-stage breast cancer in the IDEAL Trial

Abstract Background: The IDEAL trial showed no significant benefit of 5 years extended endocrine therapy (EET) using letrozole in postmenopausal patients with hormone receptor positive (HR+) breast cancer (BC) versus 2.5 years. Genomic classifiers may assist with treatment decisions by predicting EET benefit. The 70-gene MammaPrint (MP) test classifies tumors as having a higher or lower risk of distant metastasis in HR+ early-stage BC. A MP lower risk result can be further classified as either Ultra-Low risk or Low risk of distant metastasis. In the NSABP B42 trial, MP predicted a statistically significant absolute benefit from EET in patients with a MP Low Risk result. Here, we aimed to determine the utility of MP in identifying a subgroup of patients enrolled in the IDEAL trial for which 5 years of EET is beneficial compared to 2.5 years. Methods: A total of 869 patients had available primary tumor tissue for testing. MP results were available for 545/869 patients, of which 515 did not have an event at 2.5 year after randomization and were used for our analyses. The MP result for each patient was calculated by Agendia while blinded to patient clinical outcomes. The primary endpoint was distant recurrence (DR). Secondary endpoints were recurrence free interval (RFI) and breast cancer free interval (BCFI) as defined by STEEP criteria. Patients were classified as higher risk (score -1.000 - 0) or lower risk (score 0.001 - 1.000). Lower risk tumors were further classified as either MP Ultra-Low (score &amp;gt; 0.355) or MP Low Risk (score ≥ 0.001, ≤ 0.355). Likelihood ratio test based on stratified Cox proportional hazards (PH) model were used to evaluate treatment by risk group interaction. Differences in endpoints between treatment groups were assessed by stratified log-rank tests. Hazard ratios (HR) and 95% Confidence Intervals (CI) were computed based on the stratified Cox PH model. Results: The clinical characteristics of the 515 IDEAL samples with a MP result were comparable to the whole IDEAL cohort (n=1820). Within the 2.5 year EET group, 50.6% (n=134) were MP higher risk and 49.4% (n=131) MP lower risk, of which 14.5% (n=19/131) were MP Ultra-Low. Within the 5 year EET group, 50.0% (n=125) were MP higher risk and 50.0% (n=125) MP lower risk, of which 11.2% (n=14/125) were MP Ultra-Low. Among patients with MP lower risk tumors, 5 years vs. 2.5 years of EET resulted in a significant absolute benefit of 9.8% for DR (HR=0.42, [95% CI 0.174-0.996]), 9.8% for RFI (HR=0.43, [95% CI 0.198-0.934]), and 8.8% (HR=0.53, [95% CI 0.264-1.055]) for BCFI, whereas patients with MP higher risk tumors did not derive significant benefit (Table 1). Within the MP lower risk group, 5 year vs 2.5 year EET benefit was more pronounced in MP Low tumors, which exhibited a significant benefit of 10.1% for DR (HR=0.32, [95% CI 0.116-0.866]), 11.7% for RFI (HR=0.35, [95% CI 0.147-0.824]), and 9.7% for BCFI (HR=0.48, [95% CI 0.225-1.015]); MP Ultra Low tumors did not derive significant benefit. Treatment-by-risk group interaction was statistically significant for RFI. Conclusion: A significant EET benefit was observed for MammaPrint lower risk tumors but not for MP higher risk tumors. MammaPrint Low tumors exhibited the largest absolute benefit of 5 years of EET compared to 2.5 years. Consistent with the findings in the NSABP B42 trial, the results from this second randomized trial provide clinically meaningful implications in patient selection for extended endocrine therapy. Table 1. IDEAL: 10-year outcome analysis comparing 5 years vs. 2.5 years of EET using letrozole stratified by MP risk. **MammaPrint Lower Risk &amp; Higher Risk (n=515) and *** MammaPrint Low Risk &amp; High Risk (n=482) Citation Format: Gerrit-Jan Liefers, Elma Meershoek-Klein Kranenbarg, Marjolijn Duijm-de Carpentier, Cornelis J.H. van de Velde, Miranda Kleijn, Christa Dreezen, Andrea Menicucci, Laura van’t Veer, William Audeh. Utility of the 70-gene MammaPrint test for prediction of extended endocrine therapy benefit in patients with early-stage breast cancer in the IDEAL Trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS5-10.