Howard Rosen - US grants

DESCRIPTION (provided by applicant): The goal of this proposal is to provide a program of mentoring, clinical and didactic education, and a research plan that will allow Dr. Howard Rosen to supplement his skills in behavioral neurology and neuroimaging with training in theoretical and experimental models of emotional processing as well as statistical analysis. The particular focus of this proposal is based on the underlying principle that the study of emotional abnormalities in patients with diseases causing dementia will broaden our understanding of these diseases, improve our ability to differentiate them from each other and yield valuable insights into the neuroanatomic basis of emotional processing. Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), the two most common forms of neurodegenerative dementia, are each associated with distinct patterns of behavioral abnormalities. In particular, the diagnosis of FTLD requires the recognition of behavioral signs whose characteristics strongly suggest disorders of emotion. Yet, very few studies have directly assessed emotional processing in AD and FTLD. The proposed research project will compare emotional processing in 46 patients with AD, 46 patients with FTLD, and 46 age-matched controls. Two major aspects of emotional processing will be examined. Emotional understanding (the ability to appreciate emotion in others) will be assessed using bedside measures, and emotional reactivity (the ability to develop appropriate responses to emotional situations) will be studied during the elicitation of emotion with films presented on video in a laboratory setting. Emotional reactivity will be measured via participants' self-report, monitoring of autonomic function (galvanic skin response, heart rate, blood pressure, etc.) and monitoring of behavior (facial actions and somatic movements). The specific hypotheses regarding the experimental groups are 1) the frontal and temporal variants of FTLD (fvFTLD and tvFTLD, respectively) will be associated with deficits in emotional understanding when compared with controls and AD and 2) fvFTLD and tvFTLD will be associated with deficits in emotional reactivity compared with controls and AD. In addition, MRI scans will also be obtained for measurements of frontal cortical and amygdala volumes in order to test two more hypotheses: 1) emotional understanding and reactivity will be correlated with fight amygdala volume in tvFTLD and 2) emotional understanding and reactivity will be correlated with fight frontal cortical volume in fvFTLD.

ABSTRACT NOT PROVIDED

DESCRIPTION (provided by applicant): This proposal describes a plan to study frontotemporal lobar degeneration (FTLD) using the infrastructure established by the Alzheimer's Disease Neuroimaging Initiative (ADNI). FTLD is a common cause of dementia, especially in patients under the age of 65, with large economic and social costs. Over the next few years, potential therapeutic agents for FTLD will likely emerge and require clinical testing. In preparation for these clinical trials, it is important to establish precise, reliable and cost-effective markers for disease progression, to maximize the power of treatment trials to detect disease modifying effects. In the proposed study, 120 patients with FTLD and 120 age-matched controls will be studied with MRI, FDG-PET, and blood, urine and CSF biomarkers over the course of one year to determine the best regions and best methods for following the progression of FTLD. All patients will also undergo PIB-PET scanning, which identifies beta-amyloid plaques associated with Alzheimer's disease. The specific aims of the study are: 1) To identify the regions where FTLD shows greatest longitudinal changes in glucose metabolism, cerebral perfusion, and gray matter volume with the lowest variance, 2) To identify regions where FTLD shows greatest longitudinal changes with lowest variance in white matter tract integrity, 3) To contrast the performance of FDG-PET, ASL perfusion, gray matter volume and white matter tract integrity to detect longitudinal changes in FTLD, 4) To establish the clinical correlates of longitudinal changes in glucose metabolism, perfusion, gray matter volume and white matter integrity in FTLD, 5) To quantify the changes in CSF tau and A-beta1-42 levels and tau/abeta ratios over time in FTLD, and 6) To define the metabolic, structural imaging and CSF biomarker features predicting increased PIB retention with a clinical diagnosis of FTLD. Should these aims be achieved, the proposed study would provide firm data about which regions are the most sensitive indicators for following the course of disease in FTLD, and whether PET is significantly better than MRI for this purpose or visa-versa. The data would also provide estimates from which power could be calculated for clinical studies. All the data will eventually be available in a publicly accessible database for use by other researchers. PUBLIC HEALTH RELEVANCE: The frontotemporal lobar degeneration (FTLD) neuroimaging initiative will provide information on how to use brain images to follow the course of FTLD over time, and what techniques are best for this purpose. This information will be valuable to researchers planning trials of new medications for FTLD, so they can use brain imaging to help decide which drugs show the most promise for treating the disease.

Seeinstructions): The Information and Education Core of the UCSF ADRC was established to provide an educational resource on dementia and cognitive issues in aging for health professionals and lay persons at UCSF, in the Bay Area, nationally and internationally. We have made creation of innovative electronic media, delivered via the internet, an important component of these efforts, as well as collaboration with local and national non-profit institutions such as the NIH's Alzheimer's Disease Education and Referral Center, the Alzheimer's Association and the Association for Frontotemporal Dementia. In addition, an important goal for our ADRC is to reach out to the Bay Area Asian-Pacific Islander population, in order to enhance knowledge about dementia in this medically underserved community and encourage their participation in research. In the first four years, the UCSF ADRC has made excellent strides in achieving these goals, training talented leaders in dementia research as well as many emerging health professionals in other areas of specialization. In the next cycle, we plan to strengthen and expand these efforts. Our specific aims fo>the next cycle will be: 1) To train new leaders in dementia research and to ensure that clinicians training at UCSF have a thorough grounding in the principles of dementia diagnosis and treatment, 2) To build a unique multi-section Web resource for lay people and caregivers, with each section addressing educational needs for a specific disease, including prion diseases, frontotemporal dementia, and Alzheimer's disease, 3) To strengthen our relationship with the San Francisco Chinese-American community and 4) To educate the lay and research communities about non-AD dementias and dementias in minority populations through conferences. RELEVANCE (Seeinstructions): The Education and Information Core serves an important role in the UCSF ADRC, helping to dissminate up- to-date information on dementia diagnosis and treatment to the community and encouraging individuals to participate in dementia research.

DESCRIPTION (provided by applicant): This proposal describes a plan to study lack of awareness of one's disabiltities, called anosognosia, in patients with dementia. Anosognosia contributes to patients' disabilities and frustrates families and caregivers. Lack of awareness may prevent patients from adhering to treatment recommendations, and causes them to pursue potentially risky behaviors that are beyond their limits, requiring supervision to ensure their safety. Although anosognoia is very common in Alzheimer's disease, it is even more common in Frontotemporal dementia, and the reasons for this are not clear. We have developed a model attempting to explain how anosognosia could develop from failures of specific cognitive abilities, including monitoring one's performance and emotion, and we have devised a plan to test whether these factors contribute to anosognosia, and whether the contributing factors differ in patients with Alzheimer's disease and Frontotemporal dementia. We will study 100 healthy older individuals, 50 patients with Alzheimer's disease, and 50 patients with Frontotemporal dementia. We will pursue the following specific aims: A) To define the relative contributions of performance monitoring, other frontal/executive functions, memory, and emotional reactivity to anosognosia in AD and FTD. We hypothesize that: 1) In FTD, performance monitoring and physiological activation during cognitive tasks will be correlated with anosognosia even after accounting for the contributions of memory and executive functions. 2) In AD, but not FTD, memory for recent performance on cognitive testing will make a significant contribution to anosognosia.; We hypothesize that 1) tissue loss in the right medial orbitofrontal cortex will predict physiological activation during testing, behavioral estimates of performance monitoring, and overall level of self-awareness in both FTD and AD [after controlling for the contributions of other relevant brain regions. 2) tissue loss in medial temporal regions (hippocampus, entorhinal cortex, parahippocampal gyrus) will significantly predict overall level of self awareness in AD, after the effects of medial OFC are taken into account.] To examine the relationship between performance monitoring, physiological activation, and anosognosia: We hypothesize that physiological activation during cognitive testing will correlate with behavioral measures of performance-monitoring (post-error slowing [and decreased FOK]) and with overall level of self- awareness across diagnostic groups. If these hypotheses are confirmed, we will have a much clearer idea of why patients with dementia are not aware of their deficits.

? DESCRIPTION (provided by applicant): This is the second renewal application requesting T32 funding for the UCSF Behavioral Neurology Training Program (BNTP), co-directed by Drs. Bruce Miller and Howard Rosen. The BNTP was established at UCSF in 1999 within the UCSF Memory and Aging Center (MAC) to train clinical researchers in behavioral neurology and neurodegenerative disease. Founded in 2004, this T32 is the only program at UCSF that allows junior researchers to gain an integrated understanding of the clinical, epidemiological, genetic, and molecular features of neurodegenerative diseases, and is one of the few programs in the world that provides intensive training on the non-Alzheimer's dementias and non-amnestic forms of AD. The goal of the program is to train postdoctoral clinical researchers for a career in neurodegenerative research. The program is open to MD neurologists, geriatricians and psychiatrists who have completed a residency. A core element of our program is accurate classification of dementia subtypes and prediction of the specific proteins causing neurodegeneration. Our training is designed to impart fellows with the skills to evaluate and quantify the effects of various proteins and other biological factors that cause dementia using clinical assessment and laboratory methods. Training takes place over two years. The first year consists of research rotations through four clinical programs at our center including our program project grant on frontotemporal dementia, our Alzheimer's disease research program, our rapidly progressive dementia program and our clinical trials program. During this year, fellows begin development of their research project with one of the program mentors and develop skills in scientific writing, presentation, and in data analysis using archival data from our clinical and imaging databases. In the second year, fellows are given more unstructured time to continue their research project and plan for grant submissions to support their future career in clinical research. Fifteen fellows have been supported directly by this T32, but the infrastructure developed through the T32 program contributes to the education of many additional postdoctoral fellows. In the upcoming cycle the training program will include improved statistical training and better access to statistical consultation, increased integration with the UCSF Division of Geriatrics, and better utilization of the training and faculty development resources maintained by the UCSF Clinical Translational Sciences Institute (CTSI). The quality and number of applicants for this T32 has grown dramatically, as has the richness of our environment. Therefore we have requested three additional training slots per year in this renewal to support three new fellows per year, and we will open the T32 program to neuropsychologists who have completed their PhD and clinical certification.

PROJECT SUMMARY (See instructions): The proposed project is a plan to add an imaging core to the UCSF Program Project Grant, entitled: Frontotemporal Dementia: Genes, Images and Emotions. This new core for this PPG is a response to the increasing complexity of imaging and increased use of imaging to answer questions related to FTD. Since the inception of this PPG, the number of techniques for brain imaging has expanded significantly. Our group began using structural imaging as the mainstay for anatomical assessment of FTD, and has moved on to embrace diffusion tensor imaging (DTI), arterial spin labelled perfusion (ASL) and intrinsic connectivity functional MRI (ICN fMRI), as well as FDG-PET and PIB-PET. A major goal for the next cycle of the PPG will be to investigate the relative utility of these various techniques, alone or in combination, for diagnosis and for delineating brain-behavior relatioships in FTD. Many of the cores and projects will make use of these various types of imaging modalities. While two other projects will investigate sophisticated new anaytic approaches for multimodality imaging (Project 2) and ICN fMRI (Project 6), this imaging core will facilitate use of images by these projects and the rest of the PPG by ensuring acquistion and archiving of high quality images, performing basic pre-processing, and providing basic imaging data and images. Specifically, Core E will: 1) collect and manage the following MRI sequences at 3Tesla in patients with bvFTD, nfvPPA, svPPA, IvPPA, CBS, PSPS, ALS, memory-predominant cognitive deficits (MEM), asymptomatic carriers of FTLD-causing mutations (MUT) and controls: MP-RAGE, FLAIR, T2-weighted, DTI, ASL perfusion, and ICN fMRI. We will also acquire [18FJFDG and [1 ICjPIB PET scans, 2) preprocess MR images including RF field bias and geometrical distortion corrections and coregistration of all images to each subject's native space, 3) process Tl-weighted images with FreeSurfer (FS) and derive cortical thickness and volumes, regional perfusion, FDG-metabolism, and normalized amyloid tracer binding values for standard ROIs in FS space, 4) consult with Pis and staff serving the other PPG projects and cores on incorporating imaging data into their analyses.

DESCRIPTION (provided by applicant): This proposal requests an R13 conference grant to partially support the Establishing Therapeutic Efficacy for Familial Frontotemporal Degeneration (FTD) conference, scheduled for November 14-16, 2013 at the Four Seasons Hotel in San Francisco, CA. The purpose of this meeting is to assemble leading American and international familial FTD researchers to determine the feasibility of large scale familial FTD efficacy clinical trials and basic principles for their conduct, including the development of consensus criteria for trial enrollment, outcome metrics, and therapeutic agent selection. Recent advances in our understanding of the most common disease-causative genes for familial FTD (tau, progranulin, or C9ORF72) have led to targeted therapeutics that are entering early stage clinical trial pilot studies. This meeting is needed in anticipation of an imminent need for large-scale efficacy studies that will require the coordination of hundreds of individuals across multipl countries, potentially for lengthy trial terms. Approximately 75 leading US and international clinical scientists with diverse backgrounds, including women, minorities and junior investigators are expected to attend, thus representatives from all major FTD treatment centers will be present at this landmark meeting. The conference will establish the size and composition of available patient populations world-wide, develop protocols to address logistical issues for trials decide on the feasibility of specific trial types, identify best trial outcome measures and identif processes to rank available therapeutic agents. Key findings will be summarized and published in a peer-reviewed journal within 6-12 months after the meeting.

PROJECT SUMMARY This is the first renewal application for a K24 award for Dr. Howard Rosen, a behavioral neurologist at the University of California, San Francisco. Dr. Rosen?s research focuses on early recognition and longitudinal tracking of atypical neurodegenerative diseases, in particular frontotemporal dementia (FTD). The work takes place at the UCSF Memory and Aging Center, a large multidisciplinary group dedicated to research, care and education in neurodegenerative diseases. In the first cycle of this project, Dr. Rosen served as a mentor for 21 individuals at various stages of training and accomplished his goals of expanding his research on familial forms of FTD. He helped to implement new strategies for diagnosis of FTD through collaboration with the UCSF Department of Psychiatry. Dr. Rosen also expanded the reach of his educational expertise by leading development of the educational curriculum for a new training program called the Global Brain Health Institute, the mission of which is to address worldwide threats to brain health through training of professionals from a variety of disciplines. With continued K24 funding, Dr. Rosen will continue his leadership of research and training at the MAC, focusing on improving methods for measuring change in FTD for use in clinical trials and expanding collaboration with UCSF Psychiatry. He will improve his expertise as an investigator through selective coursework and collaboration with expert colleagues at UCSF.

CORE E: ABSTRACT This is a proposal to renew the Outreach, Recruitment, and Education Core (Ed Core) for the UCSF Alzheimer's Disease Research Center (ADRC). The core supports the UCSF ADRC by ensuring a steady flow of participants with FTD-spectrum disorders, CJD, amnestic and non-amnestic AD, controls and Chinese- Americans into the Clinical Core, while providing an unparalleled educational environment for emerging researchers and early clinical trainees. The core will focus on four aims, which will continue the current efforts and extend them in the following ways. (1) For Education of Community Professionals, we will maintain outreach to Bay Area professionals with lecturing, organization of conferences, and continued contact with colleagues at the Kaiser Permanente Medical Center (KPMC) in San Francisco. In addition, we will strengthen these efforts by expanding our outreach to KPMC, establishing a new relationship with the HOPE program in Marin County, and organizing a new series of recurring lectures in partnership with the Northern California Alzheimer's Association and other major Bay Area medical centers. (2) For Community Education, we will continue community lectures and maintain and update our web-based resources including our website, Facebook page, Twitter feed, and Blog. In addition, we will improve our website by creating a section on young-onset/non-amnestic subtypes of Alzheimer's disease. (3) For Outreach to Chinese Americans, we will continue our clinical consultation program in Chinatown and partnerships with community organizations to educate laypersons and health providers serving the Chinese American community about neurodegenerative disease. In addition, we will further facilitate the ability of Chinese Americans to participate in research by translating the new UDS neuropsychological battery into Chinese and making these materials available to all centers via NACC, and developing the EXAMINER-C as a frontal assessment battery for Chinese individuals by creating preliminary normative data. (4) For Research and Clinical Training at UCSF, we will maintain our fellowship training programs with a rich set of clinical and experimental resources and continue to welcome medical early clinical trainees to our month long behavioral neurology rotation. In addition, we will enrich and expand these experiences by establishing a new statistical seminar for our clinical research fellows and opening the neurobehavioral rotation to students and postdoctoral fellows in the UCSF Neuroscience program.

CORE F - ABSTRACT This is a proposal to renew the Imaging Core for the UCSF Alzheimer's Disease Research Center (ADRC). The Imaging Core has supported the UCSF ADRC for nearly 10 years by managing acquisition, archiving and processing of high quality structural and functional MRI and PET datasets, and providing these data to ADRC and other investigators. In the coming cycle the Core will pursue the following aims: 1. Collection and archiving of MP-RAGE, FLAIR, T2-weighted, DTI, ASL perfusion, ICN-fMRI, and [18F]Florbetapir PET images, and maintenance of an image database. 2. Preprocessing of MP-RAGE images to correct for scanner-related artifacts and performing integrated image pre-processing for DW-MRI, ASL-MRI, ICN-fMRI, and PET images. 3. Extraction and uploading of data to common database, including processing and editing of T1-weighted images with FreeSurfer (FS) and production of cortical thickness measures and gray and white matter volumes for standard cortical and subcortical regions, and regional perfusion, and normalized amyloid tracer binding values for standard ROIs in FS space. 4. Enhancement of FS-based image processing by creation of disease-specific templates to serve as targets in FS for morphing new research images into standardized space and identifying gray and white matter.

ABSTRACT The imaging core for the program project grant ?Frontotemporal Dementia: Genes, Images and Emotions? has managed the acquisition, storage, distribution and analysis of brain imaging data since the initial funding of the grant. Throughout the life of the project, the imaging core has ensured that images are properly acquired, uniform in quality and that raw and processed images are shared with other PPG researchers and with the other scientific collaborators. The imaging core has also led the development of many new processing pipelines to support the scientific goals of the PPG. For the proposed fourth cycle of this PPG, the imaging core will pursue the following aims: 1) Collection and archiving of images and maintenance of an image database: We will collect and manage the following MRI sequences in age-matched patients with bvFTD, nfvPPA, svPPA, CBS, PSPS, lvPPA, AD and age-matched participants with major depressive disorder (MDD) and bipolar affective disorder (BAD): MP-RAGE, FLAIR, dMRI, ASL perfusion, tf-fMRI and T2-weighted MRI. We will also acquire [18F]AV-1451 and [11C]PIB PET scans. Working with the data management core, we will archive de-identified images on a server accessible to the rest of the PPG investigators and provide tools for locating and retrieving images for analysis. 2) Image preprocessing: We will preprocess MR images including RF field bias and geometrical distortion corrections. We will coregister each subject's dMRI, ASL, tf-fMRI and PET images to their ?native space? as defined by their MPRAGE, 3) Extraction of regional volumetric and molecular data and creation of longitudinal change maps: We will process T1-weighted images with SPM to derive regional gray matter volumes using standard cortical and subcortical regions of interest (ROIs). We will derive regional tau PET and normalized amyloid tracer binding values for standard ROIs. We will create voxel- wise maps for subjects with bvFTD, nfvPPA, svPPA, CBS, PSPS, lvPPA, AD, MDD and BAD quantifying 1- year change in gray matter volume and tau PET signal (for those undergoing longitudinal imaging) in native and standard spaces. Working with the data management core, we will make these values and maps available to other PPG researchers on a secure server, and 4) Consultation on analysis: We will work with PIs and staff serving the other PPG projects and cores on incorporating these and other imaging data into their analyses.

ABSTRACT This is a proposal to fund an Outreach Recruitment and Engagement Core (ORE Core) for the UCSF Alzheimer?s Disease Research Center (ADRC) as part of this application for funding through a P30 grant. The ORE Core will build on our P50 center?s success in establishing a unique identify for our program in the San Francisco Bay Area (Bay Area) and as a national Alzheimer?s center. Our center makes critical contributions to research and care in dementia by studying atypical presentations of dementia, including frontotemporal dementia, early-onset Alzheimer?s disease and prion diseases and contributing data on these types of cases to our national database. We have also established our center as a leader in bringing Chinese Americans into dementia research, contributing 80 percent of the Chinese speaking individuals to our national database, creating tools to facilitate participation in research for people who speak Chinese and publishing research findings on this group. To accomplish these activities, we focus on outreach to professionals and laypersons in the Bay Area to teach about the various symptoms that can signal an oncoming dementia and encourage referrals. We establish satellite clinics in neighborhoods close to large populations that are underserved by expert dementia care underrepresented in dementia research to maximize our exposure to these groups. In the last few years, new faculty appointments and collaborations have allowed us to expand our outreach to Latino Americans, who also make up a large portion of the Bay Area population, and our outreach efforts are leading to recruitment of Latinos into our research program. We have begun to expand outreach to the African American community and we are committed to continuing this activity. In this new P30 application, ORE Core will pursue the following aims: Aim 1: Organize and participate in educational events directed at health professionals and non-professionals (laypersons) to support awareness of brain health and dementia prevention and the variety of symptoms that can occur in neurodegenerative disease in order to promote referrals to our ADRC; Aim 2: Maintain and expand outreach to the Bay Area Chinese and Latino communities through satellite clinics and educational offerings while maintaining a cohort of 100 Chinese-Americans and creating a cohort of 100 Latino-Americans in our ADRC; Aim 3: Implement a zip-code based strategy to increase the representation of individuals in our cohort who have elevated risk for dementia due to social determinants of brain health; Aim 4: Support the Clinical Core to develop culturally and linguistically appropriate assessment tools for deep phenotyping and for measuring vulnerability across different social determinants of health.

ABSTRACT The Imaging Core of the UCSF Alzheimer?s Disease Research Center (ADRC) actively supports the Center by managing acquisition, archiving, and processing of high quality structural and functional MRI and PET datasets and providing these data to ADRC and other investigators. In previous cycles of our P50 center, the Imaging Core has been a leader in applying cutting-edge structural, functional, and molecular imaging techniques to the heterogeneous cohorts followed in the Clinical Core. In this new P30 application, the Imaging Core will pursue the following aims: Aim 1: Collection and archiving of images and maintenance of an image database. We will supervise management of the following MRI and PET sequences from ADRC enrollees: MP-RAGE, FLAIR, T2-weighted, DTI, ASL perfusion, ICN-fMRI, and amyloid and tau PET scans. We will archive de-identified images on a server accessible to the rest of the ADRC investigators and provide tools for locating and downloading images for analysis. We will also upload MRI and PET imaging datasets to the NACC to facilitate sharing, and we will be available to answer questions for investigators interested in using these images. Aim 2: Image quality control and preprocessing: We will employ QC and pre-processing frameworks for MPRAGE, DTI, ASL-MRI, ICN-fMRI, and amyloid and tau PET images, facilitating their use by AD researchers and their integration into multi-modality analyses. Aim 3: Development and dissemination of standard and innovative analytic tools: We will maintain and refine an array of tools to characterize disease related changes in brain volume, white matter microstructure, white matter signal hyperintensity, fMRI-based connectivity, cerebral perfusion, and PET ligand binding, including optimizing pipelines for cross-sectional and longitudinal analyses. We will further develop sophisticated classification engines capable of utilizing multiple forms of data and multiple types of relationships within our data, such as machine-learning based tools and voxel-wise implementation of mixed linear models. Aim 4: Support research training: We will work with the Research Education Component to integrate basic principles of image acquisition and analysis into the research training program and support additional training of individuals who wish to incorporate image analysis into their set of research skills. In pursuing these aims, the Imaging Core will interact extensively with all other ADRC cores, working towards the common goals of improving diagnostic accuracy, forwarding our understanding of disease mechanisms, and enabling drug discovery by improving clinical trial design.

ABSTRACT This is the third renewal application requesting T32 funding for the UCSF Behavioral Neurology Training Program (BNTP), co-directed by Drs. Howard Rosen and Bruce Miller. The BNTP was established at UCSF in 1999 within the UCSF Memory and Aging Center (MAC) to train clinical researchers in behavioral neurology and neurodegenerative disease. Funded in 2005, this T32 program allows emerging researchers to gain an integrated understanding of the clinical, epidemiological, genetic, and molecular features of neurodegenerative diseases, and is one of the few programs in the world that provides intensive training on the non-Alzheimer?s dementias and non-amnestic forms of AD. The goal of the program is to train postdoctoral clinical researchers for a career in neurodegenerative research. The program is open to MD neurologists, geriatricians and psychiatrists who have completed a residency. A core element of our program is accurate classification of dementia subtypes and prediction of the specific proteins causing neurodegeneration. Our training is designed to impart fellows with the skills to evaluate and quantify the effects of various proteins and other biological factors that cause dementia using clinical assessment and laboratory methods. Training takes place over two years. The first year consists of research rotations through four clinical research programs at our center including our program project grant on frontotemporal dementia, our Alzheimer?s disease research program, our rapidly progressive dementia program and our clinical trials program. During this year, fellows begin development of their research project with one of the program mentors and develop skills in scientific writing, presentation, and in data analysis using archival data from our clinical and imaging databases. In the second year, fellows are given more unstructured time to continue their research project and plan for grant submissions to support their future career in clinical research. Over the years, our program has strengthened relationships with UCSF Psychiatry and Geriatrics, and this has influenced our research, recruitment, and approach to training. Twenty- nine fellows have been supported directly by this T32, but the infrastructure developed through the T32 program contributes to the education of many additional postdoctoral fellows. In the upcoming cycle the training program will include additional didactic sessions covering social determinants of health, health economics and policy, along with leadership training.