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Board of Honors Tutors
Dr. Marilyn Albert
Director, Gerontology Research Unit
Massachusetts General Hospital
Harvard Medical School
albert@psych.mgh.harvard.edu
(617) 726-5571
The
Gerontology Research Unit is focused on two primary themes: the cognitive
changes associated with age and their neurophysiologic correlates, and the
cognitive changes associated with Alzheimer's disease (and other major dementing
disorders) and their neurophysiologic or genetic correlates. Most of the work is multi-disciplinary in nature and includes:
neuropsychology, neurology, psychiatry, neuroradiology, genetics and geriatrics.
Age-Related Changes of Cognition in Health and Disease (P01-AG04953): This Program Project is longest running grant in the Gerontology Research Unit, having first been funded in 1980. Originally, half of the project focussed on normal aging and half on Alzheimer's disease (AD). The currently funded grant focuses on the boundary between aging and AD. It involves persons with recent declines in memory, who may or may not be in the very early stages of AD. The study initially recruited 124 questionable subjects (i.e., CDR = 0.5 or very mildly impaired persons) and 41 controls, who are being followed longitudinally to determine which individuals develop the full clinical syndrome of AD. All subjects and their collateral source (a person who has regular contact with them) were given a structured interview by a skilled clinician and then coded according to the status of their memory problems at baseline (i.e., CDR 0.5 or 0.0). The subjects then received MRI scans, SPECT scans and quantified EEGs. The structured interview is being readministered annually to subjects and collaterals, and various types of follow-up imaging and neuropsychological testing are being conducted. Plans are in place to recruit a second cohort of subjects, with similar characteristics to the first. These subjects will receive neuropsychological testing, SPECT scans and fMRI scans at baseline. As with the first cohort, all subjects will be followed annually with the semi-structured interview. Dr. Albert is the Principal Investigator. Collaborators from MGH involve investigators from the Psychiatry Department (Dr. Bates), the NMR Center (Dr. Rosen), and the Department of Neurology (Drs. Tanzi, Hyman, Kennedy and Makris). Collaborators at Brigham and Women's Hospital involve investigators from the Department of Radiology (Drs. Johnson, Kikinis and Guttman) and Neurology (Dr. Sperling).Collaborators also include investigators from the Department of Anatomy and Neurobiology at Boston University (Drs. Moss and Killiany), the Department of Psychology at Harvard College and the Heller School at Brandeis University and (Dr. Jones). Dr. McArdle (from the University of Virginia) is a consultant.
Predictors of Severity in Alzheimer's Disease (R01-AG07370): This is a multi-center longitudinal study in which AD patients are evaluated every 6 months, starting when they are mildly impaired. The goal of the original study, which was funded in 1989, was to identify factors that help predict the course of AD. In the past, the focus has been on assessments of extrapyramidal signs and psychiatric symptoms. A new cohort of individuals is about to be recruited that will use a similar approach to identify factors that help identify patients with Lewy Body Dementia without AD from those who have both disorders. Approximately 60 patients per site will be recruited, for a total of 240 overall. Neuropathological analyses of the original cohort by Dr. Brad Hyman will be ongoing. (MGH, Johns Hopkins and Columbia University). This study is coordinated by investigators at Columbia, under the direction of Dr. Yaakov Stern. Dr. Albert is the Principal Investigator at MGH.
Inference of Emotion & Mental States in Patients with Alzheimer's Disease (P01-AG04390): This project is part of a grant entitled "Harvard/HRCA Research Nursing Home" and has been ongoing since 1989. It is primarily conducted at the Hebrew Rehabilitation Center for Aged (HRCA), a 720-bed chronic care facility. The goal of the study is to assess the way in which AD patients infer emotion in others (i.e., from facial expressions, body gesture and postures) and their ability to infer mental states in others (i.e., their knowledge or beliefs). These latter studies examine an area known as 'Theory of Mind'. Dr. Albert is the Principal Investigator. Dr. Deborah Zaitchik, in our Unit, is taking the leadership in designing the study tasks.
Ethical Issues in the Genetics of Alzheimer’s Disease (R01- HG01831): This study is examining a variety of ethical and legal issues as they apply to the genetics of Alzheimer’s Disease. The participants in this study are the relatives of the sibling pairs with Alzheimer’s disease we recruited for the study described above. Their attitude toward genetic testing and other ethical and legal issues related to genetics will be examined, in their knowledge about genetics will be examined. The primary care physicians of these individuals will also be evaluated and will complete a continuing education course (presented on video) concerning ethical and legal issues related to genetic testing. Dr. Blacker (in our Unit) is the Principal Investigator of this study.
Genetic Linkage Studies of Alzheimer's Disease (R01-MH60009): The goal of this study is to conduct genetic linkage studies on the sibling pairs identified in a study previously conducted in our Unit. In that study, 155 sibling pairs with Alzheimer’s Disease were identified. Clinical information about them was obtained and their blood was transformed to produce ongoing supplies of DNA for genetic linkage studies. The Center for Inherited Diseases Research (CIDR)(an arm of the Human Genome Project at NIH) is currently conducting a total genomic search with these samples. We, and investigators at Johns Hopkins and the University of Alabama, have been funded to follow-up on hits from this total genome search. Dr. Rudolph Tanzi (Director of the Genetics of Aging Unit in the Department of Neurology at MGH) and Dr. Deborah Blacker (in our Unit) are the Co-PIs of the currently funded study. The cells and the clinical data are also considered a national resource and are available to investigators throughout the field.
Dana Foundation Grant on Memory and Aging: This research project, funded by the Dana Foundation, involves pertain primarily to neuroimaging studies of young and elderly humans and rhesus monkeys. A series of focused studies utilizing fMRI scans are underway. The goal is examine age-related changes in memory in relation to functional and structural changes in the brain. Dr. Albert is the Principal Investigator. The studies involve investigators in the Psychiatry Department at MGH (Dr. Bates), the NMR Unit at MGH (Drs. Rosen), the CMA Unit at MGH (Dr. Kennedy), the Neurology Department at Brigham & Women's Hospital (Dr. Sperling), the Department of Statistics at McLean (Dr. Lange) and Harvard University (Dr. Schacter).
Use of fMRI as a Marker of Drug Efficacy: The goal of this study, which is funded by SmithKline Beecham Pharmaceuticals) is to determine whether fMRI can be used to assess drug efficacy. Participants in the study are young male volunteers. They receive 4 fMRI scans during which an explicit memory task is presented. During two of the scans no drug is given. During two of the scans, two different drugs are given in a double-blind fashion, both of which alter memory processing. The reliability of the fMRI signal changes off drug will be assessed, and differential responses to the drugs will be explored. Dr. Albert is the Principal Investigator of the study. Dr. Sperling (of Brigham & Women’s Hospital), Dr. Diana Rosas (of MGH), and Dr. Nicholas Lange (of McLean Hospital) are Co-Investigators.
MacArthur Foundation Research Network on Successful Aging: This is a research network funded by the MacArthur Foundation that consists of 15 scientists across the U.S. The primary goal is an exploration of the factors that permit some elderly individuals to function at a high level to a very old age. This network has been ongoing since 1984. As part of this research effort, investigators at Harvard participated in an epidemiologic study in which data from 1200 high functioning individuals, pertaining to cognitive, functional, psychosocial and physiological function were gathered at three sites (Harvard, Yale, and Duke). Subjects were first evaluated between 1987 and 1989, and then reevaluated between 1991 and 1992. A second follow-up was just completed during 1996-1997. The primary analyses have focused on the predictors of maintenance of high function in this elderly cohort, with the goal of developing intervention trials designed to retard declines with age. Dr. Albert is the Principal Investigator at MGH.
Drug Studies: Two drug trials are currently underway in the Unit. One is examining the effect of Cylcoserine on cognitive function in patients with AD. This is an open-labeled study. The other trial is examining the effect of Remeron on depression in older individuals. This is a double-blind trial. Patients are carefully monitored throughout both trials for side-effects and receive periodic medical evaluations. A number of AD patients are also being followed who are on Aricept.
Career Development Awards: Two members of the Unit are funded by Career Development Awards. Both are utilizing functional Magnetic Resonance Imaging (fMRI) to study explicit memory in aging and Alzheimer’s Disease. Dr. Sperling is studying face-name association with a number of different tasks. Dr. Bates is examining spatial and feature visual processing in relation to aging and AD.
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