ABSTRACT The analysis tools and statistical methods used in large neuroimaging research studies differ from those applied in clinical contexts, making it unclear whether these techniques can be translated to a memory clinic setting. The Oxford Brain Health Clinic (OBHC) was established in 2020 to bridge this gap between research studies and memory clinics. We optimised the UK Biobank imaging framework for the memory clinic setting by integrating enhanced quality control (QC) processes (MRIQC, QUAD, and DSE decomposition) and supplementary dementia‐informed analyses (lobar volumes, NBM volumes, WMH classification, PSMD, cortical diffusion MRI metrics, and tract volumes) into the analysis pipeline. We explored associations between resultant imaging‐derived phenotypes (IDPs) and clinical phenotypes in the OBHC patient population ( N = 213), applying hierarchical FDR correction to account for multiple testing. 14%–24% of scans were flagged by automated QC tools, but upon visual inspection, only 0%–2.4% of outputs were excluded. The pipeline successfully generated 5683 IDPs aligned with UK Biobank and 110 IDPs targeted towards dementia‐related changes. We replicated established associations and found novel associations between brain metrics and age, cognition, and dementia‐related diagnoses. The imaging protocol is feasible, acceptable, and yields high‐quality data that is usable for both clinical and research purposes. We validated the use of this methodology in a real‐world memory clinic population, which demonstrates the potential of this enhanced pipeline to bridge the gap between big data studies and clinical settings.

AbstractWith promising disease-modifying therapies (DMTs) emerging and good evidence to support risk reduction in the delay of dementia onset and progression, it is important to understand the profile of patients attending memory assessment services to estimate what proportion of patients might benefit from different types of interventions. The Oxford Brain Health Clinic (OBHC) is a psychiatry-led, clinical-research service that offers memory clinic patients detailed clinical assessments and equal access to research opportunities as part of their secondary care pathway. In this work, we describe the characteristics of OBHC patients in terms of demographics, diagnoses and prevalence of potentially modifiable risk factors compared with a cohort of healthy volunteers and the average memory clinic population. Our results suggest that high research consent rates (91.5%) in the OBHC resulted in a highly representative cohort of the clinical population. Based on Lecanemab trial inclusion criteria, 24.6% of the OBHC population may be suitable for further investigation into DMTs. Furthermore, 67.4% of OBHC patients have at least one potentially modifiable risk factor that may benefit from lifestyle interventions, particularly those focused on depression, sleep and physical activity.

Personalised risk reduction is a key driver for the nascent UK Brain Health Clinic (BHC) network, with increasing evidence that modifying dementia risk could delay or prevent disease progression. Livingston et al. (2020) demonstrated a number of risk factors for dementia, including less formal education (identified as no secondary education), excessive alcohol consumption (>21 units/week), obesity (BMI >30), depression and presence of an ApoE Ɛ4 allele; whilst increased physical activity has been associated with reduced risk and sleep duration is suggested to have a U-shaped association with dementia risk. The aim of this study was to understand the prevalence of these risk factors within a typical UK memory clinic population. The Oxford BHC is a joint clinical and research assessment service for Oxford Health NHS Foundation Trust memory clinic patients (O’Donoghue et al., 2022). It aims to provide detailed clinical assessment and equal access to research opportunities. Between August 2020 and May 2022, 152 BHC patients (93.2%) consented to their clinical data, including subsequent diagnosis, being used for research purposes (mean age = 78.2 years, range 65-101 years; 52.6% female). Self-reported questionnaires collected education (N = 124), alcohol consumption (M SASQ, N = 150), depressive symptoms (PHQ9, N = 148), physical activity (IPAQ, N = 152) and sleep (PSQI, N = 152). BMI was calculated from height and weight measured at BHC appointment (N = 146) and ApoE Ɛ genotyping from saliva sampling (N = 76). Preliminary results show 7% of patients reported no formal qualifications, 1% consumed 6 or more units of alcohol daily/almost daily, 15.7% had a BMI >30 and 45% showed mild-severe symptoms of depression. Inappropriate sleep was reported by 13%, 71% engaged in less than 150 minutes of physical activity a week and 41% had an ApoE Ɛ4 allele (see Figure 1). In this population, we found a relatively small prevalence of low education and alcohol consumption, but a large proportion of patients could benefit from interventions focused on improving mood and physical activity. Ongoing analysis aims to create a weighted composite risk score for this population and explore relationships with primary diagnosis, cognition and measures of brain health including hippocampal volume and white matter hyperintensities.

With the advent of disease modifying treatments for dementia, it is essential to restructure memory clinic services to provide accurate and early diagnosis to enable precision therapies and recruitment to clinical trials. The Oxford Brain Health Clinic (BHC) offers a comprehensive clinical and embedded research assessment in the patient pathway, including a research-quality brain MRI scan (using the UK Biobank protocol), well-tolerated by patients (Griffanti et al., 2022, Neuroimage:Clinical). In this study we investigated whether the images obtained from BHC patients were of sufficient quality for clinical/diagnostic purposes (i.e. to provide a radiology report) and research purposes (i.e. suitable to extract quantitative measures with automated software) and whether the scan quality was related to patients’ characteristics (capacity, frailty, anxiety, cognitive impairment - CI), to inform future triage to Brain Health Clinics. T1 and FLAIR scans from 138 BHC patients were reported by a radiologist and independently rated as high, medium or low quality for research purposes (consensus between 2 raters). The following patients’ characteristics were evaluated: capacity (yes/no), Rockwood Clinical Frailty Scale (more frail if 5 or more), anxiety before/during the scan (low/not-low), Addenbrooke’s Cognitive Examination III (ACE-III, score above or below 82). A two-sided Fisher-Freeman-Halton test was run to test the association between scan quality (3 classes) and patients characteristics (2 classes for each independent variable). Bonferroni-adjusted post-hoc comparisons were performed between scan quality classes using 2×2 Fisher’s Exact Tests. The radiologist was able to provide a clinical report for all scans. Over 90% of scans were rated high or medium quality for research purposes (Fig.1). No significant associations were observed between patients’ characteristics and FLAIR quality. T1 quality was significantly associated with patients’ capacity (p = 0.001, more low-quality images from patients lacking capacity, Fig.2) and frailty (p = 0.014, more low-quality images from frailer patients, Fig.3). Research-quality MRI scans in memory clinic are useful for both clinical and research purposes. For research comprised of high-quality MRI, relatively generous thresholds relating to frailty and capacity could be considered to balance the trade-off between inclusivity (i.e. increasing representativeness) and adherence to protocols.

INTRODUCTION:Despite major advances in the field of neuroscience over the last three decades, the quality of assessments available to patients with memory problems in later life has barely changed. At the same time, a large proportion of dementia biomarker research is conducted in selected research samples that often poorly reflect the demographics of the population of patients who present to memory clinics. The Oxford Brain Health Clinic (BHC) is a newly developed clinical assessment service with embedded research in which all patients are offered high-quality clinical and research assessments, including MRI, as standard.METHODS AND ANALYSIS:Here we describe the BHC protocol, including aligning our MRI scans with those collected in the UK Biobank. We evaluate rates of research consent for the first 108 patients (data collection ongoing) and the ability of typical psychiatry-led NHS memory-clinic patients to tolerate both clinical and research assessments.ETHICS AND DISSEMINATION:Our ethics and consenting process enables patients to choose the level of research participation that suits them. This generates high rates of consent, enabling us to populate a research database with high-quality data that will be disseminated through a national platform (the Dementias Platform UK data portal).

Since August 2020, the Oxford Brain Health Clinic (BHC) has seen over 200 NHS memory clinic patients (O’Donoghue et al., 2022). In addition to high-quality cognitive and lifestyle assessments and opportunities for research participation, patients receive a clinical MRI scan (T1-weighted, T2-FLAIR, and SWI) and can consent to additional research scans (diffusion MRI – dMRI, resting-state functional MRI – rfMRI, and arterial spin labelling - ASL) aligned to the UK Biobank (Griffanti et al., 2022). In this project, we aimed to automatically extract imaging-derived phenotypes (IDPs) from the different imaging modalities acquired at the BHC and perform unimodal group-level analyses to explore associations with cognition and diagnoses in this real-world memory clinic population. As of January 2023, scans were analysed from 176 BHC patients, 101 of whom completed the additional research MRI scans. Cognitive scores (ACE-III total score, N = 166) were available from the BHC appointment, and subsequent diagnoses (N = 118) were extracted from electronic healthcare records. Scans were processed using the UK Biobank pipeline (Alfaro-Almagro et al., 2018), adapted to include previously described modifications (Griffanti et al., 2022). All IDPs were deconfounded for age, sex, and head size. We calculated Spearman correlations with ACE-III cognitive scores and group comparisons (Kruskal-Wallis tests) between 3 diagnostic groups: dementia, MCI, and no dementia-related diagnosis. Results were corrected for multiple comparisons (false discovery rate with Benjamini-Hochberg procedure; FDR-adjusted p = 0.000016). 11 IDPs significantly correlated with ACE-III (Figure 1). Four voxel-based morphometry temporal lobe measures, 3 FreeSurfer temporal lobe measures, FIRST left hippocampal volume, and SIENAX peripheral grey matter volume positively correlated with ACE-III, in line with known dementia-related atrophy patterns (Figure 2). dMRI mean diffusivity in the bilateral parahippocampal part of the cingulum negatively correlated with ACE-III, highlighting white matter disruption (Figure 3). No FDR-corrected differences were found between diagnostic groups. Using an unselected patient population, all of whom have a degree of memory problems, this work provides real-world validation of associations that are well-established in the research context. This represents a key step towards integrating research-quality imaging in the memory clinic. Imaging and clinical variables are planned to be available through DPUK.

The Oxford Brain Health Clinic (BHC) is a joint clinical-research service that provides memory clinic patients and clinicians access to high-quality assessments not routinely available, including brain MRI aligned with the UK Biobank imaging study (UKB).In this work we present how we 1) adapted the UKB MRI acquisition protocol to be suitable for memory clinic patients, 2) modified the imaging analysis pipeline to extract measures that are in line with radiology reports and 3) explored the alignment of measures from BHC patients to the largest brain MRI study in the world (ultimately 100,000 participants).Adaptations of the UKB acquisition protocol for BHC patients include dividing the scan into core and optional sequences (i.e., additional imaging modalities) to improve patients' tolerance for the MRI assessment. We adapted the UKB structural MRI analysis pipeline to take into account the characteristics of a memory clinic population (e.g., high amount of white matter hyperintensities and hippocampal atrophy). We then compared the imaging derived phenotypes (IDPs) extracted from the structural scans to visual ratings from radiology re-ports, non-imaging factors (age, cognition) and to reference distributions derived from UKB data.Of the first 108 BHC attendees (August 2020-November 2021), 92.5 % completed the clinical scans, 88.0 % consented to use of data for research, and 43.5 % completed the additional research sequences, demonstrating that the protocol is well tolerated. The high rates of consent to research makes this a valuable real-world quality research dataset routinely captured in a clinical service. Modified tissue-type segmentation with lesion masking greatly improved grey matter volume estimation. CSF-masking marginally improved hippocampal segmentation. The IDPs were in line with radiology reports and showed significant associations with age and cognitive per-formance, in line with the literature. Due to the age difference between memory clinic patients of the BHC (age range 65-101 years, average 78.3 years) and UKB participants (44-82 years, average 64 years), additional scans on elderly healthy controls are needed to improve reference distributions. Current and future work aims to integrate automated quantitative measures in the radiology reports and evaluate their clinical utility.

The Oxford Brain Health Centre (BHC) provides real-world research data, aligned with the UK Biobank imaging study (UKB), routinely captured in a clinical service from patients under-represented in dementia research. In this work we present how we 1) adapted the UKB MRI acquisition protocol to be suitable for memory clinic patients, 2) modified the imaging analysis pipeline to extract measures that are in line with radiology reports and 3) compare measures from BHC patients to the biggest brain MRI study in the world (ultimately 100,000 participants). Adaptations of the UKB acquisition protocol for BHC patients include dividing the scan into core and optional sequences to improve patients’ tolerance. We adapted the UKB structural MRI analysis pipeline to extract quantitative measures from the scans, taking into account the characteristics of a memory clinic population (e.g. high level of white matter hyperintensities, WMH, causing misclassifications in tissue-type segmentation). We compared the measurements extracted from the scans to visual ratings from radiology reports and to reference distributions derived from UKB data. Of the 108 BHC attendees since August 2020 (average age 78.5 years, range 65-101 years, 50.9% female), 100 (92.6%) completed the clinical scans, 100 (92.6%) consented to use of data for research, and 69 (63.9%) consented to additional research sequences, demonstrating that the protocol is well tolerated. Modified tissue-type segmentation improved grey matter volume estimation, which showed stronger correlation with visual ratings of global atrophy after correction (r=-0.34; p=0.001) than with the original analysis pipeline (r=-0.31; p=0.002). Correlations between hippocampal volumes and MTA scale (r(L)=-0.59, r(R)=-0.71) and between WMH volume and Fazekas scale (r=0.78) were also significant (p<0.001). Because UKB participants are younger than memory clinic patients, additional scans on elderly healthy controls are planned to improve reference distributions to detect pathological deviations. Measures from BHC patients within UKB age range are comparable to those from UKB participants, with several patients falling in the lower percentiles. We adapted UKB research imaging for clinical practice. Current and future work aims to integrate automated quantitative measures in the radiology reports and evaluate their clinical utility.

Launched in August 2020, the Oxford Brain Health Centre (BHC) is the UK's first psychiatry-led joint clinical-research service providing high-quality assessments and increasing research opportunities for patients with memory problems. By embedding research in the NHS service, the BHC aims to address gaps between clinical practice and research advances into dementia. This abstract describes the first 60 referrals from the BHC pilot. Patients from Oxford Health NHS Foundation Trust memory clinics were referred to the BHC for assessment prior to their diagnostic appointment. At the BHC, patients completed clinical assessments - MRI scan, cognitive assessment and questionnaires – and could consent to use of clinical data for research, additional research assessments, and recontact about future research. Accompanying relatives completed a clinical informant interview and could consent to recontact about research. Patient/relative feedback was obtained via questionnaires. Between August and December 2020, the BHC received 60 referrals. 38% were returned to the memory clinic for reasons relating to the patient (n=9, e.g. patient unable to travel to the centre), the referral (n=3, e.g. patient already seen in clinic), or the MRI scan (n=11, e.g. claustrophobia, MR contraindication). BHC appointments occurred on average 26 days (range: 5-63) after referral from the memory clinic. Only 3% did not attend. Of the 33 attendees in 2020, 58% were female, average age was 77.5 years (66-90), and average ACE-III score was 66.8 (9– 98; max: 100). 97% of patients consented to use of clinical data for research, 88% to additional research assessments, and 69% to recontact about research. 81% of relatives consented to recontact about research. Service-user feedback was consistently high; 100% of responding patients were satisfied with the BHC service, particularly highlighting positive interactions with staff. Since launching, we have demonstrated the feasibility of an integrated clinical-research service for people with memory problems and demonstrated extremely high research uptake in this population. Evaluation of referrals, procedures, impact on diagnosis, and health economics at the end of the 6-month pilot will inform sustainability and scalability of Oxford BHC to provide a model for a specialist service that can be adopted throughout the NHS.