The Massachusetts Alzheimer's Disease Research Center, established in 1984, proposes to continue and expand its research into the underpinnings of Alzheimer's and related dementias with 5 major goals. First, we will focus on the earliest stages of the disease process, when symptoms and signs are subtle, or even undetectable, by bringing to bear an integrated multidisciplinary team of clinicians and scientists. Second, we will continue to provide critical infrastructure and resources to support Alzheimer disease and dementia related research across a range of institutions including Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, and the Harvard School of Public Health as well as supporting national initiatives. Third, we will innovate with technical developmental projects in each Core, targeting the boundaries of cognitive ageing and disease. Fourth, we are committed to mentoring, educating, and developing future leaders through formal training or mentoring programs in each Core. Fifth, we continue to reach out to the surrounding community in order to communicate the urgency of understanding this devastating disease, and to enhance recruitment of a diverse pool of subjects and patients for critical studies. These broad aims are distributed among the mandated Administration, Clinical, Data Management and Statistics, Neuropathology and Outreach Cores, along with a new Neuroimaging Core. Each Core provides support for, and helps catalyze, the MADRC's mission, including active participation in national programs (e.g. NACC, ADNI, ADCS, ADGC, DIAN), more than 40 local clinical initiatives, and pilot projects. Three small R01 style projects leverage these Cores and are designed to marry cutting edge science with the clinical programs. Project 1, led by a new junior investigator, Dr Hedden, uses state-of-the art fMRI and Connectome techniques (a new technology that illuminates white matter pathways) as well as quantitative structural MRI approaches to study the neural system basis of the earliest cognitive impairments. Project 2, led by Dr Gomez-Isla (a senior investigator recruited to our Center in the current grant period) combines resources with 5 other ADCs to define the neuropathological phenotype of individuals who are amyloid imaging-positive and cognitively normal. Project 3, led by Dr Hyman, explores a new transgenic mouse model of Alzheimer disease that develops tangles in entorhinal cortex and widespread plaques and compares it to human neuropathological samples - to examine experimentally the neural system biology of this early point in the disease process. Together these efforts are aimed at targeting early disease phenotypes - as national efforts towards early intervention and prevention strategies unfold. Along with parallel ongoing multidisciplinary studies of established dementias, we believe the MADRC has made, and is well positioned to continue to make, strong contributions to Alzheimer research.

Public Health Relevance

The Massachusetts Alzheimer Disease Research Center is an integrated program of clinicians and scientists focused on understanding and contributing to the care and treatment of patients with Alzheimer's disease and similar disorders. Our major focal point is on learning about early disease manifestations - ideally during the period of the disease even before clear symptoms have emerged. We plan complementary clinical, neuroimaging, neuropathological, and laboratory studies that cut across many disciplines. Each element of the study contributes to National programs, and also serves as a vessel for innovation and for teaching of the next generation of investigators targeting this devastating disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Specialized Center (P50)
Project #
3P50AG005134-34S2
Application #
9378821
Study Section
Special Emphasis Panel (ZAG1)
Program Officer
Silverberg, Nina B
Project Start
1997-04-01
Project End
2019-03-31
Budget Start
2017-08-01
Budget End
2018-03-31
Support Year
34
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114
Schaffert, Jeff; LoBue, Christian; White, Charles L et al. (2018) Traumatic brain injury history is associated with an earlier age of dementia onset in autopsy-confirmed Alzheimer's disease. Neuropsychology 32:410-416
Lee, Catherine; Betensky, Rebecca A; Alzheimer's Disease Neuroimaging Initiative (2018) Time-to-event data with time-varying biomarkers measured only at study entry, with applications to Alzheimer's disease. Stat Med 37:914-932
Wachinger, Christian; Reuter, Martin; Klein, Tassilo (2018) DeepNAT: Deep convolutional neural network for segmenting neuroanatomy. Neuroimage 170:434-445
Brenowitz, Willa D; Han, Fang; Kukull, Walter A et al. (2018) Treated hypothyroidism is associated with cerebrovascular disease but not Alzheimer's disease pathology in older adults. Neurobiol Aging 62:64-71
Gallagher, Damien; Kiss, Alex; Lanctot, Krista L et al. (2018) Toward Prevention of Mild Cognitive Impairment in Older Adults With Depression: An Observational Study of Potentially Modifiable Risk Factors. J Clin Psychiatry 80:
Matsouaka, Roland A; Singhal, Aneesh B; Betensky, Rebecca A (2018) An optimal Wilcoxon-Mann-Whitney test of mortality and a continuous outcome. Stat Methods Med Res 27:2384-2400
Barnes, Josephine; Bartlett, Jonathan W; Wolk, David A et al. (2018) Disease Course Varies According to Age and Symptom Length in Alzheimer's Disease. J Alzheimers Dis 64:631-642
Buckley, Rachel F; Mormino, Elizabeth C; Amariglio, Rebecca E et al. (2018) Sex, amyloid, and APOE ?4 and risk of cognitive decline in preclinical Alzheimer's disease: Findings from three well-characterized cohorts. Alzheimers Dement 14:1193-1203
Jacobs, Heidi I L; Hedden, Trey; Schultz, Aaron P et al. (2018) Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals. Nat Neurosci 21:424-431
Rieckmann, Anna; Johnson, Keith A; Sperling, Reisa A et al. (2018) Dedifferentiation of caudate functional connectivity and striatal dopamine transporter density predict memory change in normal aging. Proc Natl Acad Sci U S A 115:10160-10165

Showing the most recent 10 out of 966 publications