About

James Brewer is a neurologist and neuroscientist whose primary research interest is human memory. He has developed functional and structural magnetic resonance imaging (MRI) approaches to study memory processes in volunteers with healthy memory and in patients with memory impairment. Dr. Brewer has developed and applied advanced neuroimaging approaches for early detection of Alzheimer’s disease in the clinical setting and as a measure of the efficacy of new drugs under development. He conducted studies that led to FDA and European regulatory clearance of a widely used tool for brain structure analysis, which has been used to assess brain atrophy in over a million clinical patients. As the director of the UCSD Shiley-Marcos Alzheimer’s Disease Research Center and the Imaging Core for the multi-institutional Alzheimer’s Disease Cooperative Study, he oversees brain imaging of all enrolled subjects. Dr. Brewer received his medical and research degrees at Stanford Medical School, pursued neurology residency training at Johns Hopkins, and joined UC San Diego's faculty in 2004. He is Professor and Chair of the Department of Neurosciences and holds a secondary appointment in the Department of Radiology. His research interests include the development and clinical application of imaging biomarkers for Alzheimer’s disease and other neurodegenerative disorders, aiming to develop rational care pathways for improved differential diagnosis and predictive prognosis using genetic and biomarker information.

Research topics

• Medicine
• Internal medicine
• Machine Learning
• Psychiatry
• Computer Science
• Artificial Intelligence
• Psychology
• Theoretical computer science
• Pharmacology
• Pathology
• Econometrics
• Nuclear medicine
• Oncology
• Mathematics
• Biology
• Genetics
• Data science
• Chemistry
• Bioinformatics

Selected publications

• Effects of exercise on cognition and Alzheimer's biomarkers in a randomized controlled trial of adults with mild cognitive impairment: The EXERT study

  Alzheimer s & Dementia · 2025-04-01 · 16 citations

  articleOpen access

  INTRODUCTION: The EXERT study (Exercise in Adults with Mild Memory Problems) was a Phase 3, multicenter, randomized controlled trial that examined effects of exercise on cognition and other measures of brain health in sedentary older adults with amnestic mild cognitive impairment (MCI). METHODS: Participants were randomized to moderate-high intensity aerobic training (AX) or low-intensity stretching/balance/range of motion (SBR) for 18 months. Exercise was supervised for the first 12 months. Assessments were administered at baseline and every 6 months. The primary outcome was a global cognitive composite. RESULTS: A total of 296 participants were enrolled, and intervention adherence was high (supervised session attendance: AX = 81%, SBR = 87%). Intervention effects on cognition did not differ for AX and SBR (regression = -0.078, standard error [SE] = 0.074; p = 0.3). Notably, there was no 12 month cognition decline for either group, and mean 12 month hippocampal volume loss for both groups was low at 0.51%. DISCUSSION: Exercise intensity did not differentially affect cognitive trajectory. Intervention delivery was successful (high adherence) and cognition remained stable over 12 months for both MCI groups, an association that warrants further study. HIGHLIGHTS: Exercise in Adults with Mild Memory Problems (EXERT) was a large multisite randomized controlled trial of moderate-high intensity aerobic training versus lower-intensity flexibility and balance exercise in sedentary older adults with amnestic mild cognitive impairment (MCI). A sensitive and validated measure of global cognitive function, the Alzheimer's Disease Assessment Scale-Cognition supplemented with tests of executive function (ADAS-Cog-Exec), was used to assess intervention efficacy with 12 months of supervised exercise. There was no intervention group difference on the 12-month cognitive trajectory of the ADAS-Cog-Exec. Intervention delivery was successful (high adherence), and cognition remained stable over 12 months for both exercise groups. Regular supported moderate-high or lower-intensity exercise may stall decline in adults with amnestic MCI, but further investigation is needed.

  PublisherOA PDFDOI

• The Consortium for Clarity in ADRD Research Through Imaging (CLARiTI): Overview of consortium sites and anticipated enrollment

  UNC Libraries · 2025-11-14

  articleOpen access

  INTRODUCTION The Consortium for Clarity in Alzheimer's disease related dementias (ADRD) Research Through Imaging (CLARiTI) is a study that aims to collect standardized imaging and plasma biomarkers on 2000 Clinical Core participants enrolled across all Alzheimer's Disease Research Centers (ADRC) sites. We sought to summarize the known heterogeneity across centers regarding scientific focus and initial enrollment plans for CLARiTI. METHODS We developed and distributed a survey capturing information on the 36 CLARiTI site's theme/expertise, recruitment plans, and the intersection of CLARiTI with other ADRC imaging efforts. RESULTS Anticipated CLARiTI enrollees spanned 11 different categories of suspected etiologies underlying impairment. A wide range of risk factors were endorsed across sites regarding the enrollment of unimpaired individuals. Variability also existed regarding site‐level strategies in enrollment into CLARiTI versus other imaging efforts. DISCUSSION We anticipate that the 2000 individuals that will enroll into CLARiTI will reflect the clinical heterogeneity already in place across the ADRC network. Highlights The ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) will leverage and contribute to the existing Alzheimer's Disease Research Centers (ADRC) program by supporting standardized imaging and plasma collection across all centers. We summarize the variation in scientific focus and enrollment plans across ADRC sites participating in CLARiTI. The anticipated CLARiTI cohort will reflect the clinical heterogeneity that already exists across the ADRC network. CLARiTI will contribute to scientific goals related to the detection of multi‐etiological signatures relevant for Alzheimer's disease and related disorders (ADRDs).

  PublisherDOI

• Transcriptome profiling of cerebrospinal fluid in Alzheimer's disease reveals molecular dysregulations associated with disease

  Alzheimer s & Dementia Translational Research & Clinical Interventions · 2025-07-01 · 1 citations

  articleOpen access

  BACKGROUND: Despite the increasing prevalence of neurodegenerative diseases, the molecular characterization of brain pathologies remains challenging due to limited tissue access. Cerebrospinal fluid (CSF) contains a significant proportion of brain-derived molecular contents, and characterizing these molecules has served as a proxy for evaluating molecular dysregulation in the brain. Here we have characterized the CSF cell-free messenger RNA (cf-mRNA) transcriptome and identified genes and pathways altered in Alzheimer's disease (AD). METHODS: We performed cf-mRNA sequencing on 52 human CSF samples and further compared their transcriptomic profiles to matched plasma samples. In addition, we also investigated the cf-mRNA profiles of CSF in individuals with AD as well as non-cognitively impaired (NCI) controls. RESULTS: The molecular content of CSF cf-mRNA was distinct from that of plasma cf-mRNA, with a substantially higher number of brain-associated genes identified in CSF. A large set of dysregulated gene transcripts from CSF was detected in the AD subjects, and these gene transcripts were able to discriminate AD from NCI subjects. Notably, the gene transcripts were enriched in biological processes closely associated with AD, such as brain development and synaptic signaling. In addition, we discovered a subset of gene transcripts that exhibited a high correlation in matched CSF and plasma samples from AD subjects. CONCLUSIONS: This study not only reveals the novel cf-mRNA content of CSF but also highlights the potential of CSF cf-mRNA profiling as a tool to garner pathophysiological insights into AD. Highlights: Cell-free messenger RNA (cf-mRNA) sequencing was performed on 52 human cerebrospinal fluid (CSF) samples.CSF exhibited a distinct transcriptional profile with a higher prevalence of brain-associated genes compared to plasma.Dysregulated genes in Alzheimer's disease (AD) CSF effectively distinguished AD from non-cognitively impaired controls.CSF cf-mRNA profiling holds potential as a tool for gaining pathophysiological insights into AD.

  PublisherDOI

• The Consortium for Clarity in ADRD Research Through Imaging (CLARiTI): Overview of consortium sites and anticipated enrollment

  Alzheimer s & Dementia · 2025-11-01

  articleOpen access

  INTRODUCTION: The Consortium for Clarity in Alzheimer's disease related dementias (ADRD) Research Through Imaging (CLARiTI) is a study that aims to collect standardized imaging and plasma biomarkers on 2000 Clinical Core participants enrolled across all Alzheimer's Disease Research Centers (ADRC) sites. We sought to summarize the known heterogeneity across centers regarding scientific focus and initial enrollment plans for CLARiTI. METHODS: We developed and distributed a survey capturing information on the 36 CLARiTI site's theme/expertise, recruitment plans, and the intersection of CLARiTI with other ADRC imaging efforts. RESULTS: Anticipated CLARiTI enrollees spanned 11 different categories of suspected etiologies underlying impairment. A wide range of risk factors were endorsed across sites regarding the enrollment of unimpaired individuals. Variability also existed regarding site-level strategies in enrollment into CLARiTI versus other imaging efforts. DISCUSSION: We anticipate that the 2000 individuals that will enroll into CLARiTI will reflect the clinical heterogeneity already in place across the ADRC network. HIGHLIGHTS: The ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) will leverage and contribute to the existing Alzheimer's Disease Research Centers (ADRC) program by supporting standardized imaging and plasma collection across all centers. We summarize the variation in scientific focus and enrollment plans across ADRC sites participating in CLARiTI. The anticipated CLARiTI cohort will reflect the clinical heterogeneity that already exists across the ADRC network. CLARiTI will contribute to scientific goals related to the detection of multi-etiological signatures relevant for Alzheimer's disease and related disorders (ADRDs).

  PublisherOA PDFDOI

• WTP1.05 Lessons learnt from an interprofessional surgical teaching forum: motivations for learning and opportunities for multidisciplinary team-building

  British journal of surgery · 2025-08-01

  article

  Abstract Background Interprofessional education (IPE) occurs when two or more professions learn together to enhance collaboration and improve patient care. The 2015 Improving Surgical Training report recommends developing cross-professional competencies, which can be readily facilitated through IPE. We describe and evaluate the implementation and impact of an interprofessional surgical teaching forum and explore the motivations for learning and personal learning outcomes from the general surgery multidisciplinary team. Methods A weekly teaching program was established, by a coordinating team of educators, with the option to attend in-person or virtually. Educational activities included journal clubs, M&M meetings, and quality improvement presentations. Feedback from participants was collected via an online form to assess the quality of teaching and identify key learning points and self-reported motivations for attendance. Results Data were collected from 88 interprofessional attendees over ten sessions. The forum was well-received, with average ratings of 4.72±0.55/5 for material quality and 4.67±0.60/5 for delivery quality. Motivations for attending varied across grades and disciplines, and included continued professional development, specific interest in topics, team-building and interdisciplinary collaboration. The majority of learning points centred on new management strategies and awareness of specific guidelines, with suggestion of resultant changes in clinical practice. Conclusions We describe successful implementation of an interdisciplinary surgical teaching forum, with high quality ratings and strong engagement from surgical professionals of all grades. These findings highlight the demand for interprofessional education within surgery and emphasise the need for multidisciplinary collaboration in both attending and organising such activities.

  PublisherDOI

• eP52 Enhancing Acute Pancreatitis Management through a Multidisciplinary Upper Gastrointestinal Team Approach: A Closed Loop Audit

  British journal of surgery · 2025-01-01

  articleOpen access

  Abstract Aims Pancreatitis is a severe, acute inflammatory condition of the pancreas, potentially leading to life-threatening complications. This closed-loop audit assessed the impact of a newly established multidisciplinary Upper GI (UGI) team on the management of acute pancreatitis patients at Chelsea and Westminster Trust. Methods This closed-loop audit analysed 131 patients admitted with acute pancreatitis over two 6-month periods in 2023 and 2024. Data were prospectively collected on diagnostic timing, Glasgow score calculations, imaging, and referral practices, comparing these metrics to the first audit cycle. The first cycle occurred concurrently with the introduction of the in-hospital UGI team. Interventions following the initial audit included establishing weekly benign UGI multidisciplinary team (MDT) meetings with gastroenterology and radiology specialists, streamlining the ERCP pathway, creating a "hot" cholecystectomy pathway, and implementing targeted education within the surgical department. Results The second audit cycle demonstrated substantial improvements. Glasgow score calculation within 48 hours increased to 50%. Escalation of severe pancreatitis cases to higher care rose from 0% to 60%. Imaging within 24 hours achieved 100% compliance. The median time from admission to ERCP decreased to 5 days. Cholecystectomy rates within 2 weeks improved from 75% to 100%, and the transfer of non-gallstone pancreatitis cases to gastroenterology increased from 33% to 50%. Conclusion The audit highlighted significant advancements in acute pancreatitis management, including earlier diagnosis, timely surgical interventions, and enhanced multidisciplinary care, underscoring the positive impact of the implemented measures.

  PublisherOA PDFDOI

• Overcoming Barriers to Latino Participation in Alzheimer's Disease Research

  The International Journal of Aging and Human Development · 2024-08-16 · 6 citations

  article

  There is a critical need to increase Latino participation in research on Alzheimer's disease and related disorders (ADRD). Applying principles of community-based participatory research, we convened a community advisory board (CAB) to identify barriers and recommend strategies to increase participation of older Latinos in a longitudinal observational research study of ADRD at the Shiley-Marcos Alzheimer's Disease Research Center. Six major barriers were identified and programmatic changes to overcome them were implemented. Changes resulted in a nearly three-fold increase in the number of Latino individuals recruited, with the proportion of all newly recruited participants who were Latino increasing from 12.2% to 57.4%. Newer Latino recruits were more representative of the elderly Latino population in San Diego County than those recruited pre-CAB and remained highly agreeable to blood draw and neuroimaging, though less so to lumbar puncture and autopsy. Results demonstrate the value of CAB involvement in enhancing diversity in ADRD research.

  PublisherDOI

• Multiomics analysis to explore blood metabolite biomarkers in an Alzheimer’s Disease Neuroimaging Initiative cohort

  Scientific Reports · 2024-04-02 · 26 citations

  articleOpen access

  Abstract Alzheimer's disease (AD) is a neurodegenerative disease that commonly causes dementia. Identifying biomarkers for the early detection of AD is an emerging need, as brain dysfunction begins two decades before the onset of clinical symptoms. To this end, we reanalyzed untargeted metabolomic mass spectrometry data from 905 patients enrolled in the AD Neuroimaging Initiative (ADNI) cohort using MS-DIAL, with 1,304,633 spectra of 39,108 unique biomolecules. Metabolic profiles of 93 hydrophilic metabolites were determined. Additionally, we integrated targeted lipidomic data (4873 samples from 1524 patients) to explore candidate biomarkers for predicting progressive mild cognitive impairment (pMCI) in patients diagnosed with AD within two years using the baseline metabolome. Patients with lower ergothioneine levels had a 12% higher rate of AD progression with the significance of P = 0.012 (Wald test). Furthermore, an increase in ganglioside (GM3) and decrease in plasmalogen lipids, many of which are associated with apolipoprotein E polymorphism, were confirmed in AD patients, and the higher levels of lysophosphatidylcholine (18:1) and GM3 d18:1/20:0 showed 19% and 17% higher rates of AD progression, respectively (Wald test: P = 3.9 × 10 –8 and 4.3 × 10 –7 ). Palmitoleamide, oleamide, diacylglycerols, and ether lipids were also identified as significantly altered metabolites at baseline in patients with pMCI. The integrated analysis of metabolites and genomics data showed that combining information on metabolites and genotypes enhances the predictive performance of AD progression, suggesting that metabolomics is essential to complement genomic data. In conclusion, the reanalysis of multiomics data provides new insights to detect early development of AD pathology and to partially understand metabolic changes in age-related onset of AD.

  PublisherOA PDFDOI

• AMBRA1 is a predictive biomarker of melanoma response to targeted therapy

  EJC Skin Cancer · 2024-01-01

  articleOpen access

  conceptual framework we present here for melanoma may be broadly applicable to ALDH High cancer stem cell subpopulations in other cancer types, as ALDH isoforms potentially cooperate with lineage specific master transcription factors (often from developmental lineages) that are co-opted to regulate tumour cell states.

  PublisherOA PDFDOI

• Sex differences in interacting genetic and functional connectivity biomarkers in Alzheimer’s disease

  GeroScience · 2024-04-10 · 6 citations

  articleOpen access
  PublisherOA PDFDOI

Recent grants

• NIH Grant K23NS050305

  NIH · $878k · 2009

• Core G: Research Education Core

  NIH · $47.3M · 2019–2029

• NIH Grant K02NS067427

  NIH · $927k · 2015

• NIH Grant R01AG034062

  NIH · $1.3M · 2018

Frequent coauthors

• Keith A. Johnson

  Massachusetts General Hospital

  765 shared

• D. Cheng

  567 shared

• Joseph C. Wu

  486 shared

• Marcelo F. Di Carli

  Harvard University

  405 shared

• Carl K. Hoh

  University of California, San Diego

  405 shared

• Monte S. Buchsbaum

  University of California, Irvine

  405 shared

• Steven E. Arnold

  Harvard University

  364 shared

• Carolyn C. Meltzer

  University of Southern California

  324 shared