Mediterranean diet adherence and cognitive function in older, UK adults: The EPIC-Norfolk study

Background In Mediterranean countries, adherence to a traditional Mediterranean dietary pattern (MedDiet) is associated with better cognitive function and reduced dementia risk. It is unclear if similar benefits exist in non-Mediterranean regions. Objective To examine associations between MedDiet adherence and cognitive function in an older, UK population. To investigate whether associations differed between individuals with high versus low cardiovascular disease (CVD) risk. Design We conducted an analysis in 8009 older individuals with dietary data at Health Check 1 (1993-1997) and cognitive function data at Health Check 3 (2006-2011) of the European Prospective Investigation of Cancer, Norfolk (EPIC-Norfolk). Associations were explored between MedDiet adherence and global and domain specific cognitive test scores and risk of poor cognitive performance in the entire cohort, and when stratified according to CVD risk status. Results Higher MedDiet adherence defined by the Pyramid MedDiet score was associated with better global cognition (β±SE=-0.012±0.002; P<0.001), verbal episodic memory (β±SE=-0.009±0.002; P<0.001), and simple processing speed (β±SE=-0.002±0.001; P=0.013). Lower risk of poor verbal episodic memory (OR(95%CI)=0.784 (0.641,0.959); P=0.018), complex processing speed (OR(95%CI)=0.739 (0.601,0.907); P=0.004), and prospective memory (OR(95%CI)=0.841 (0.724,0.977); P=0.023) was also observed for the highest versus lowest Pyramid MedDiet tertiles. The effect of a one-point increase in Pyramid score on global cognitive function was equivalent to 1.7 fewer years of cognitive ageing. MedDiet adherence defined by the MEDAS score (mapped using both binary and continuous scoring) showed similar, albeit less consistent, associations. In stratified analyses, associations were evident in individuals at higher CVD risk only (P<0.05). Conclusions Higher adherence to the MedDiet is associated with better cognitive function and lower risk of poor cognition in older, UK adults. This evidence underpins the development of interventions to enhance MedDiet adherence, particularly in individuals at higher CVD risk, aiming to reduce the risk of age-related cognitive decline in non-Mediterranean populations

Feasibility and acceptability of a multi-domain intervention to increase Mediterranean diet adherence and physical activity in older UK adults at risk of dementia: Protocol for the MedEx-UK randomised controlled trial

Introduction Dementia prevalence continues to increase, and effective interventions are needed to prevent, delay or slow its progression. Higher adherence to the Mediterranean diet (MedDiet) and increased physical activity (PA) have been proposed as strategies to facilitate healthy brain ageing and reduce dementia risk. However, to date, there have been no dementia prevention trials in the UK focussed on combined dietary and PA interventions. This study aims to: (1) assess feasibility and acceptability of a theory-underpinned digital and group-based intervention for dementia risk reduction in an 'at risk' UK cohort; (2) evaluate behaviour change responses to the intervention; and, (3) provide information on cognitive, neurological, vascular and physiological outcomes to inform the design of a follow-on, full-scale efficacy trial. Methods One hundred and eight participants aged 55 to 74 years with a QRISK2 score of ≥10% will be recruited to take part in this 24-week multi-site study. Participants will be randomised into three parallel arms: (1) Control; (2) MedDiet; and, (3) MedDiet+PA. The study will evaluate a personalised website, group session and food delivery intervention to increase MedDiet adherence and PA in older adults at risk of dementia. Diet and PA will be monitored prior to, during and following the intervention. Feasibility, acceptability and hypothesised mediators will be assessed in addition to measures of cognitive function, brain structure/perfusion (MRI), vascular function and metabolic markers (blood, urine and faecal) prior to, and following, the intervention. Discussion This trial will provide insights into the feasibility, acceptability and mechanism of effect of a multi-domain intervention focussed on the MedDiet alone and PA for dementia risk reduction in an 'at risk' UK cohort. Ethics and dissemination The study has received NHS REC and HRA approval (18/NI/0191). Findings will be disseminated via conference presentations, public lectures, and peer-reviewed publications. Trial registration details ClinicalTrials.gov NCT03673722

OPTIMA prelim: a randomised feasibility study of personalised care in the treatment of women with early breast cancer

Abstract Background There is uncertainty about the chemotherapy sensitivity of some oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers. Multiparameter assays that measure the expression of several tumour genes simultaneously have been developed to guide the use of adjuvant chemotherapy for this breast cancer subtype. The assays provide prognostic information and have been claimed to predict chemotherapy sensitivity. There is a dearth of prospective validation studies. The Optimal Personalised Treatment of early breast cancer usIng Multiparameter Analysis preliminary study (OPTIMA prelim) is the feasibility phase of a randomised controlled trial (RCT) designed to validate the use of multiparameter assay directed chemotherapy decisions in the NHS. Objectives OPTIMA prelim was designed to establish the acceptability to patients and clinicians of randomisation to test-driven treatment assignment compared with usual care and to select an assay for study in the main RCT. Design Partially blinded RCT with adaptive design. Setting Thirty-five UK hospitals. Participants Patients aged ≥ 40 years with surgically treated ER-positive HER2-negative primary breast cancer and with 1–9 involved axillary nodes, or, if node negative, a tumour at least 30 mm in diameter. Interventions Randomisation between two treatment options. Option 1 was standard care consisting of chemotherapy followed by endocrine therapy. In option 2, an Oncotype DX® test (Genomic Health Inc., Redwood City, CA, USA) performed on the resected tumour was used to assign patients either to standard care [if ‘recurrence score’ (RS) was > 25] or to endocrine therapy alone (if RS was ≤ 25). Patients allocated chemotherapy were blind to their randomisation. Main outcome measures The pre-specified success criteria were recruitment of 300 patients in no longer than 2 years and, for the final 150 patients, (1) an acceptance rate of at least 40%; (2) recruitment taking no longer than 6 months; and (3) chemotherapy starting within 6 weeks of consent in at least 85% of patients. Results Between September 2012 and 3 June 2014, 350 patients consented to join OPTIMA prelim and 313 were randomised; the final 150 patients were recruited in 6 months, of whom 92% assigned chemotherapy started treatment within 6 weeks. The acceptance rate for the 750 patients invited to participate was 47%. Twelve out of the 325 patients with data (3.7%, 95% confidence interval 1.7% to 5.8%) were deemed ineligible on central review of receptor status. Interviews with researchers and recordings of potential participant consultations made as part of the integral qualitative recruitment study provided insights into recruitment barriers and led to interventions designed to improve recruitment. Patient information was changed as the result of feedback from three patient focus groups. Additional multiparameter analysis was performed on 302 tumour samples. Although Oncotype DX, MammaPrint®/BluePrint® (Agendia Inc., Irvine, CA, USA), Prosigna® (NanoString Technologies Inc., Seattle, WA, USA), IHC4, IHC4 automated quantitative immunofluorescence (AQUA®) [NexCourse BreastTM (Genoptix Inc. Carlsbad, CA, USA)] and MammaTyper® (BioNTech Diagnostics GmbH, Mainz, Germany) categorised comparable numbers of tumours into low- or high-risk groups and/or equivalent molecular subtypes, there was only moderate agreement between tests at an individual tumour level (kappa ranges 0.33–0.60 and 0.39–0.55 for tests providing risks and subtypes, respectively). Health economics modelling showed the value of information to the NHS from further research into multiparameter testing is high irrespective of the test evaluated. Prosigna is currently the highest priority for further study. Conclusions OPTIMA prelim has achieved its aims of demonstrating that a large UK clinical trial of multiparameter assay-based selection of chemotherapy in hormone-sensitive early breast cancer is feasible. The economic analysis shows that a trial would be economically worthwhile for the NHS. Based on the outcome of the OPTIMA prelim, a large-scale RCT to evaluate the clinical effectiveness and cost-effectiveness of multiparameter assay-directed chemotherapy decisions in hormone-sensitive HER2-negative early breast would be appropriate to take place in the NHS

Effects of the COVID-19 associated United Kingdom lockdown on physical activity in older adults at high risk of cardiovascular disease: a mixed methods perspective from the MedEx-UK multicenter trial

Introduction: Physical inactivity and sedentary behaviour are linked to increased risk of cardiovascular disease, infections and dementia, as well as placing a significant economic burden on healthcare systems. The implementation of COVID-19 pandemic lockdown measures aimed at reducing virus transmission posed challenges to the opportunity to be physically active. This study investigates how the first UK COVID-19 lockdown affected objectively measured physical activity in older adults at higher risk of cardiovascular disease.Methods: We studied 48 individuals aged 55-74 years (81.3% female) with self-reported PA levels &lt; 90 min/week and a QRISK2 score ≥ 10 (indicative of a ≥ 10% risk of a major cardiovascular event in the next 10 years) without mild cognitive impairment or dementia. Physical activity data was collected using objective wrist-based activity monitors and analysed across three time periods, usual activity (pre-pandemic), the precautionary phase when the UK began advising on limiting social contact and finally during the first UK lockdown period was collected (27 January 2020 and 07 June 2020). Data was analysed using linear mixed effects model was used to investigate PA levels over the measured 12-week period. Effects of BMI, age, deprivation score and baseline PA levels on PA across the three measurement periods were also examined. Focus-group and individual interviews were conducted, and data were thematically analysed.Results: Average daily step count (−34% lower, p &lt; 0.001) and active energy expenditure (−26% lower, p &lt; 0.001) were significantly lower during the precautionary period compared with the usual activity period. Physical activity remained low during the UK lockdown period. Participants with a lower BMI engaged in significantly more (+45% higher daily steps p &lt; 0.001) physical activity and those over 70 years old were more physically active than those under 70 years across the 12-week period (+23% higher daily steps p &lt; 0.007). The risk of COVID-19 infection and restrictions because of lockdown measures meant some individuals had to find alternative methods to staying physical active. Participants described a lack of access to facilities and concerns over health related to COVID-19 as barriers to engaging in physical activity during lockdown. For some, this resulted in a shift towards less structured activities such as gardening or going for a walk.Discussion: The data presented shows that lockdown measures during the COVID-19 pandemic significantly reduced physical activity among older individuals at risk of cardiovascular disease, particularly those with a higher body mass index. To support this population group in staying active during future lockdowns, a multifaceted strategy is needed, emphasizing psychosocial benefits and home-based physical activity. The MedEx-UK study was pre-registered with ClinicalTrials.gov (NCT03673722)