Anne-Marie Minihane’s research while affiliated with University of East Anglia and other places

Purpose Inadequate reporting of nutrition data can hinder the success of nutrition health policies. CONSORT provides guidance for reporting of randomised controlled trials (RCTs) and is required by most journals today, yet reporting of nutrition interventions may benefit from a more tailored approach. A Federation of European Nutrition Societies working group was created to improve quality and completeness of reporting of nutrition trials, and our work to date features a proposal for a CONSORT extension specific to nutrition RCTs. The present manuscript describes a Delphi survey conducted to gather opinion from a wider panel of nutrition and health experts and related interest-holders on our proposal. Methods We invited 138 potentially eligible participants to take part in the Delphi survey from a representative spread of expertise and geography. We employed a Likert scale with comments for our 32-item proposal in round 1, and a dichotomous scale with comments for our 29-item proposal in round 2. Threshold for agreement was set at ≥ 80% for both rounds. Results Forty-seven potentially eligible participants responded to our invitation, 38 completed the first round and 36 completed the second. N = 23 (72%) items achieved ≥ 80% in round 1, and 100% of items in round 2. Three items were dropped or merged following round 1. A third Delphi round was not required to obtain consensus. Conclusions This Delphi expert consensus proposes a 29-item checklist specific to the reporting of nutrition RCTs and will inform further development of guidance through forthcoming consensus meetings.

Background Reported effects of Hormone Replacement Therapy (HRT) on late‐life neurodegenerative disease are inconsistent. Variability in the timing and formulation of HRT, plus whether an individual carries an Apolipoprotein (APOE) e4 genetic risk variant for Alzheimer’s Disease (AD), likely contribute to conflicting results. Additionally, whilst many studies have focused exclusively on the effects of exogenous oestrogen, the inclusion of testosterone in HRT appears protective against AD pathology, specifically in APOE e4 carriers. This project will investigate whether the introduction of HRT affects cognition in mid‐life, including whether benefits are influenced by HRT formulation, timing of initiation, and APOE genotype. Methods Peri and early postmenopausal women (minimum n = 500) being newly prescribed HRT will be recruited from Newson Health specialist menopause clinics. Participants will complete a suite of online cognitive tasks targeting domains sensitive to preclinical AD (e.g., perceptual discrimination, spatial navigation), alongside questionnaires capturing cognitive, physical, and behavioural menopause symptoms, at baseline, 4‐months, and 12‐months. A tissue sample will be collected for APOE genotype analysis. HRT prescription and circulating blood‐hormone levels will also be available from clinic records. Results Existing cohort data (n = 10,222) from Newson Health indicates 97% patients present at clinic with memory or concentration complaints. Pilot data for this study (n = 85, mean age 56.48 years, peri/postmenopausal women) showed HRT users (relative to non‐users) were significantly quicker on a perceptual 'odd‐one‐out’ task (p = .025) and trended to show better lure discrimination on an object mnemonic similarity task (p = .064). This project builds on this by testing whether the introduction of HRT influences cognition longitudinally, including whether effects differ by HRT formulation (estrogen/+progesterone/+testosterone), timing of initiation relative to menopause, and APOE genotype. Exploratory analysis will consider whether predicted benefits of HRT are moderated by non‐cognitive menopause symptoms, cardiovascular health, and wider lifestyle factors. Conclusions Exploring the impact of HRT on cognition, specifically in interaction with the leading genetic risk factor for AD, will further research into how we can promote women’s brain health from mid‐life. Additionally, this research will inform best‐practices for HRT prescription, considering possible effects on late‐life neurodegenerative disease.

Background Despite an urgent need for multi-domain lifestyle interventions to reduce dementia risk, there is a lack of interventions which are informed by theory- and evidence-based behaviour change strategies, and no interventions in this domain have investigated the feasibility or effectiveness of behaviour change maintenance. We tested the feasibility, acceptability and cognitive effects of a personalised theory-based 24-week intervention to improve Mediterranean diet (MD) adherence alone, or in combination with physical activity (PA), in older-adults at risk of dementia, defined using a cardiovascular risk score. Methods Participants (n = 104, 74% female, 57–76 years) were randomised to three parallel intervention arms: (1) control, (2) MD, or (3) MD + PA for 24 weeks and invited to an optional 24-week follow-up period with no active intervention. Behaviour change was supported using personalised targets, a web-based intervention, group sessions and food provision. The primary outcome was behaviour change (MD adherence and PA levels), and the secondary outcomes included feasibility and acceptability, cognitive function, cardiometabolic health (BMI and 24-h ambulatory blood pressure) and process measures. Results The intervention was feasible and acceptable with the intended number of participants completing the study. Participant engagement with group sessions and food provision components was high. There was improved MD adherence in the two MD groups compared with control at 24 weeks (3.7 points on a 14-point scale (95% CI 2.9, 4.5) and 48 weeks (2.7 points (95% CI 1.6, 3.7)). The intervention did not significantly change objectively measured PA. Improvements in general cognition (0.22 (95% CI 0.05, 0.35), memory (0.31 (95% CI 0.10, 0.51) and select cardiovascular outcomes captured as underpinning physiological mechanisms were observed in the MD groups at 24 weeks. Conclusions The intervention was successful in initiating and maintaining dietary behaviour change for up to 12 months which resulted in cognitive benefits. It provides a framework for future complex behaviour change interventions with a range of health and well-being endpoints. Trial registration ClinicalTrials.gov NCT03673722.

The trace element selenium is known to protect against oxidative damage which is known to contribute to cognitive impairment with ageing (1,2) . The aim of this study was to explore the association between selenium status (serum selenium and selenoprotein P (SELENOP)) and global cognitive performance at baseline and after 5 years in 85-year-olds living in the Northeast of England. Serum selenium and SELENOP concentrations were measured at baseline by total reflection X-ray fluorescence (TXRF) and enzyme-linked immunosorbent assay (ELISA), respectively, in 757 participants from the Newcastle 85+ study. Global cognitive performance was assessed using the Standardized Mini-Mental State Examination (SMMSE) where scores ≤25 out of 30 indicated cognitive impairment. Logistic regressions explored the associations between selenium status and global cognition at baseline. Linear mixed models explored associations between selenium status and global cognition prospectively after 5 years. Covariates included sex, body mass index, physical activity, high sensitivity C-reactive protein, alcohol intake, self-rated health, medications and smoking status. At baseline, in fully adjusted models, there was no increase in odds of cognitive impairment with serum selenium (OR 1.004, 95% CI 0.993-1.015, p = 0.512) or between SELENOP (OR 1.006, 95% CI 0.881-1.149, p = 0.930). Likewise, over 5 years, in fully adjusted models there was no association between serum selenium and cognitive impairment (β 7.20 E-4 ± 5.57 E-4 , p = 0.197), or between SELENOP and cognitive impairment (β 3.50 E-3 ± 6.85 E-3 , p = 0.610). In this UK cohort of very old adults, serum selenium or SELENOP was not associated with cognitive impairment at baseline and 5 years. This was an unexpected finding despite SELENOP’s key role in the brain and the observed associations in other studies. Further research is needed to explore the effect of selenium on global cognition in very old adults.

A key component of disease prevention is the identification of at-risk individuals. Microbial dysbiosis and microbe-derived metabolites (MDM) can influence the central nervous system, but their role in disease progression and as prognostic indicators is unknown. To identify preclinical factors associated with Alzheimer’s disease (AD), we compared gut microbiome and metabolome profiles of cognitively healthy subjects, subjective cognitive impairment (SCI) participants and mild cognitive impairment (MCI) participants (n=50 per group, matched for age, BMI and sex), targeting metabolites previously associated with cognitive health (TMAO, bile acids, tryptophan, p -cresol and their derivatives). 16S rRNA bacterial microbiome sequencing and targeted LC-MS/MS were employed for faecal microbiome speciation and serum MDM quantification. Microbiome beta diversity differed between healthy controls and SCI participants. Multiple linear regression modelling highlighted five serum metabolites (indoxyl sulfate, choline, 5-hydroxyindole acetic acid, indole-3-propionic acid (IPA) and kynurenic acid) significantly altered in preclinical AD. Neuroprotective metabolites, including choline, 5-hydroxyindole acetic acid and IPA, exhibited lower concentrations in SCI and MCI in comparison to controls, while the cytotoxic metabolite indoxyl sulfate had higher levels. A Random Forest algorithm with multiclass classification confirmed and extended our results, identifying six metabolites (indoxyl sulfate, choline, 5-hydroxyindole acetic acid, IPA, kynurenic acid, kynurenine) as predictors of early cognitive decline, with an area under the curve of 0.74. In summary, a combined statistical and machine learning approach identified MDM as a novel composite risk factor for the early identification of future dementia risk.

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 < 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 < 0.001) and active energy expenditure (−26% lower, p < 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 < 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 < 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).

Background The Eatwell guide reflects the UK government's recommendations for a healthy and balanced diet. Previous research has identified associations between healthy eating patterns and both cardiovascular and brain health, although there is little evidence specifically focusing on the Eatwell Guide. To date no research has investigated associations between the Eatwell Guide and risk for future dementia. Methods Data from the PREVENT dementia cohort study baseline visit was used in this analysis. Binary and graded Eatwell Guide scores (BEWG, GEWG) were created from a self-reported Food Frequency Questionnaire. The CAIDE score was included as the primary outcome measure to represent risk for future Alzheimer’s disease. Secondary outcome measures included cardiometabolic health measures and brain health measures. Generalised additive models were run in R. Results A total of 517 participants were included in the analysis, with a mean BEWG score of 4.39 (± 1.66) (out of a possible 12 points) and GEWG score of 39.88 (± 6.19) (out of a possible 60 points). There was no significant association between either Eatwell Guide score and the CAIDE score (BEWG β: 0.07, 95% confidence interval (CI): -0.07, 0.22; GEWG β: 0.02, 95% CI: -0.02, 0.06) or any measures of brain health. There was a significant association between higher GEWG score and lower systolic and diastolic blood pressure and body mass index (BMI) (systolic β: -0.24, 95% CI: -0.45, -0.03; diastolic β: -0.16, 95% CI: -0.29, -0.03; BMI β: -0.09, 95% CI: -0.16, -0.01). Conclusions Although not directly associated with the CAIDE score, the Eatwell Guide dietary pattern may be beneficial for dementia prevention efforts through the modification of hypertension and obesity, which are both known risk factors for dementia. Future work could replicate these findings in other UK-based cohorts as well as further development of Eatwell Guide scoring methodologies.

Background Anthocyanin and blueberry intakes positively associated with cognitive function in population-based studies and cognitive benefits in randomized controlled trials of adults with self-perceived or clinical cognitive dysfunction. To date, adults with metabolic syndrome (MetS) but without cognitive dysfunction are understudied. Objectives Cognitive function, mood, alertness, and sleep quality were assessed as secondary end points in MetS participants, postprandially (>24 h) and following 6-mo blueberry intake. Methods A double-blind, randomized controlled trial was conducted, assessing the primary effect of consuming freeze-dried blueberry powder, compared against an isocaloric placebo, on cardiometabolic health >6 mo and a 24 h postprandial period (at baseline). In this secondary analysis of the main study, data from those completing mood, alertness, cognition, and sleep assessments are presented (i.e., n = 115 in the 6 mo study, n = 33 in the postprandial study), using the following: 1) Bond-Lader self-rated scores, 2) electronic cognitive battery (i.e., testing attention, working memory, episodic memory, speed of memory retrieval, executive function, and picture recognition), and 3) the Leeds Sleep Evaluation Questionnaire. Urinary and serum anthocyanin metabolites were quantified, and apolipoprotein E genotype status was determined. Results Postprandial self-rated calmness significantly improved after 1 cup of blueberries (P = 0.01; q = 0.04; with an 11.6% improvement compared with baseline between 0 and 24 h for the 1 cup group), but all other mood, sleep, and cognitive function parameters were unaffected after postprandial and 6-mo blueberries. Across the ½ and 1 cup groups, microbial metabolites of anthocyanins and chlorogenic acid (i.e., hydroxycinnamic acids, benzoic acids, phenylalanine derivatives, and hippuric acids) and catechin were associated with favorable chronic and postprandial memory, attention, executive function, and calmness. Conclusions Although self-rated calmness improved postprandially, and significant cognition-metabolite associations were identified, our data did not support strong cognitive, mood, alertness, or sleep quality improvements in MetS participants after blueberry intervention. This trial was registered at clinicaltrials.gov as NCT02035592.