Neurotransmitter - Jan 1995
Focus on Memory Disorders Unit
The Memory Disorders Unit (MDU) at MGH was established in 1982 as a service of the Neurology Department. From the outset, the MDU has been a multi-disciplinary unit comprised of neurologists, social workers, research assistants, a research nurse and the unit coordinator. John H. Growdon is the Director of the Unit; Drs. M. Flint Beal, Bradley T. Hyman, Bruce Price, Allen Bowling, Stephen M. Greenberg, and Teresa Gomez-Isla are other physicians in the Unit; Marsha Tennis is the research nurse; Ari Marcus and Beth Souza are the research associates;, and Melanie Walton is the Unit coordinator. Appointments to the MDU can be made by calling Melanie Walton at 726-1728.
The purpose of the Unit is to offer comprehensive neurological, neuro-psychological, and social service outpatient care for patients with memory disorders. Patients are referred in many ways: from physicians, family, friends, and the local Alzheimer's Association. Initially, the coordinator of the Unit conducts an in-depth telephone interview with a family contact, ensuring that the MDU is the appropriate place for this patient to be seen. We send the family two questionnaires to be completed prior to the initial visit: a family history questionnaire and an activities of daily living inventory. At the time of the visit, one of the research associates reviews these questionnaires with the family contact in order to verify the information. The patient then undergoes a neurological evaluation. Laboratory blood tests, brain imaging, and neuropsychological tests are performed as appropriate. Social services are recommended as necessary. Stephanie Brett-Bell, L.I.C.S.W., Barbara Hawley L.C.S.W., and Boston College intern Heather Nevulis are available to meet with patients and their families to assess social and emotional needs. They provide support and counseling to families and patients who have problems that have been created or aggravated by dementia. The social workers can also provide information about AD and referral to community resources and extended care facilites. Stephanie offers a free monthly support group at MGH for families of patients with memory disorders.Follow up appointments are generally scheduled every 6 months (sooner if a problem arises). There is frequent telephone contact between family members, the Unit coordinator, physician, and social services.
RESEARCH OPPORTUNITIES
The Memory Disorders Unit is an integral clinical unit of the Massachusetts Alzheimer's Disease Research Center (ADRC). The cohort of patients seen in the MDU have the opportunity to participate in a variety of research studies conducted by the ADRC. These include cognitive studies; functional imaging studies; genetic epidemiological studies; and experimental drug studies. Referrals to these projects can be made by calling John Growdon at 726-1728 or Marsha Tennis at 726-1610.
Cognitive Studies
These studies are conducted at the Behavioral Neuroscience Laboratory at MIT under the direction of Prof. Suzanne Corkin. Studies involve tests of memory, language, motor skills, and psycho/physical tests of vision, olfaction and audition. Participants are individuals with mild dementia. Testing requires 3 days to complete and is usually done during outpatient visits to MIT, but accomodations are available for overnight stay at the MIT Medical Department; participants incur no costs.
Functional Neuroimaging
These studies are conducted in collaboration with Prof. Suzanne Corkin at MIT and Dr. Gil Gonzalez at the MGH Neuroimaging Center. The overall goal of the research is to relate cognition in normal aging and AD to alterations in the functional magnetic resonance imaging (fMRI) signal within specific cerebral regions. We use high-speed fMRI to detect the spatial and temporal patterns of neural activation that occur during specific cognitive tasks in normal elderly subjects and patients with AD. Specifically, we examine correlations between fMRI signal and behavior in 3 cognitive domains: long-term explicit memory, visual perception, and motor control. Results from these studies may identify neurophsyiological markers that signal very early AD.
Genetic Epidemiology and APO E
These studies are conducted in conjunction with Dr. Lindsay Farrer, and are embedded in a national multi-institutional effort to identify risk factors that predispose toward the development of AD. We collect family histories of neurological illness on all individuals attending the MDU. These data are used to compute the likelihood that any individual patient has familial or sporadic AD. We also collect information regarding putative environmental risk factors for developing dementia. In association with Drs. Rudy Tanzi and Jonathan Haines, we collect blood for molecular genetic studies from families with multiple instances of AD. In conjunction with Dr. Bradley Hyman, we collect blood from each individual attending the MDU to determine apolipoprotein E genotype. Having the APO e4 allele is a risk factor for developing AD and appears to lower the age of dementia onset. Conversely, the e2 allele, may protect against dementia, or at least delay its onset. An individuals APO E genotype however does not appear to influence the rate of dementia progression.
Investigational Drug Studies
We are now conducting three drug protocols.
AF102B
This is an exploratory pilot project designed to obtain biochemical support for developing treatments that prevent amyloid deposition in brains of AD patients. AF102B is a selective m1 muscarinic agonist. In cell culture and brain slice experiments, m1 agonists increase alpha-secretase processing of amyloid precursor protein and thereby render A-beta fragments that are non-amyloidogenic. The goal of the clinical project is to determine whether an m1 agonist will affect levels of amyloid precursor protein derivatives in blood or CSF of patients with AD. The specific hypothese is that AF102B administration will increase levels of non-amyloidogenic secreted products, and decrease levels of toxic A-beta.
Selegiline
Oxidative metabolic stress can facilitate cell death, and may be implicated in the selective neuronal dysfunction and death that occur in Alzheimer's disease. The aims of this multi-center study are to ascertain if the administration of antioxidants (selegiline, vitamin E, or combination) will delay progression of symptoms of AD. Associated goals of the study are to characterize the disease progression using novel outcome meaures which capture clinically important milestones, and to determine the feasibility of using survival analysis to evaluate drugs for the treatment of AD.
Tropicamide-induced pupil dilitation as a diagnostic test for AD
The purpose of this study is three-fold: (1) to confirm the initial observation that pupil dilitation in response to a dilute solution of tropicamide distinguishes AD patients and control subjects. (2) to determine the optimal dilution of tropicamide for diagnostic purposes, and (3) to determine if the response is limited to AD patients or occurs in patients with other degenerative disorders such as Parkinson's disease, PSP, Huntington's disease, Pick's disease and ALS.
John Growdon, Margy O'Brien
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John Lester (lester@helix.mgh.harvard.edu).