Robert P. Friedland, MD - US grants

Alzheimer's disease (AD) remains a diagnosis of exclusion. However, research criteria have been developed to allow for pre-mortem diagnosis with relatively high validity, reliability and sensitivity. The Clinical Core is responsible for recruiting, evaluating and maintaining a population of subjects with AD and healthy age-matched controls who are available for investigation, and for facilitating analyses of data from these activities. There are 4 components to the Clinical Core: 1. Patient Registry Component; 2. Neuropsychology Component; 3. Psychopathology Component; 4. Data Management and Analysis Component (DMAC). The functions of the Patient Registry Component are to recruit, characterize, and re-evaluate cases and controls; and to coordinate research activities of subjects and caregivers, including CERAD activities and autopsy. The Neuropsychology Component tests subjects to provide quantitative measures of disease effects, using a standardized evaluation. The Psychopathology Component provides assessments of current psychopathology, as well as personal and family history of psychopathology. The functions of DMAC are to facilitate the collection and computerization of data, maintain the database, to assist investigators in the design and execution of data analysis plans, and to support the information management needs of cores and projects.

DESCRIPTION (Adapted from the Applicant's Abstract): In a population based study of AD, we have screened all elderly residents of Wadi Ara, an Arab community near Tel Aviv in northern Israel, and observed an unusually high prevalence (20.5% of those >60 years, 60.5% of those >85 years). This prevalence is higher than that found anywhere else in the world, even after adjustment for age, education and gender, and apparently is not due to increased frequency of the APOE epsilon-4 allele. We hypothesize that the increased prevalence of AD in this genetic isolate is caused by the presence of AD susceptibility alleles which are over-represented because of mating patterns in this closed population which has few founders. In this application we propose to study extensively all persons residing in this community ages 60 and older (numbering 855 at the time of the last survey including 168 persons meeting NINDS/ADRDA criteria for AD). We will obtain from each subject risk/protective factor data (including smoking, blood pressure, head trauma, education, diet, physical and mental activity levels, occupation and medication history) and blood samples for biochemical and DNA studies. Family informants will be used to construct detailed pedigrees. Our scientific aims are: (1) Estimate the life-time risk of AD in first-degree relatives of prevalent cases using survival techniques and compare these estimates to those obtained for relatives of cognitively normal subjects and for relatives of AD cases in other populations; (2) Localize the gene(s) causing AD in this population using a homozygosity mapping approach. In order to rapidly screen for markers linked to the disease, one AD affected and one elderly nondemented from each of several families from the same tribal group (hamula) will be genotyped with 400 polymorphic microsatellite markers spaced less than 10 cM apart. Suspect chromosomal regions will be pursued by genotyping all subjects individually with markers spaced at 2 cM intervals. A variety of analytical techniques including both parametric (lod score) and non-parametric (affected relative, sib-transmission-disequilibrium and allele-frequency-dependent homozygosity mapping) approaches will be employed to assess the marker data for linkage to AD; (3) Examine genes from candidate regions identified in aim 2 by SSCP/CSGE; and direct sequencing for polymorphisms which may directly influence AD susceptibility; (4) Analyze the effects of non-genetic factors (singly and in combination with each other and with linked genetic markers or candidate gene polymorphisms) on risk of AD. Identifying specific genes and elucidating their mechanisms and the nature of gene/environment interactions will be a major achievement. Results from this study may have immediate impact on the development of new treatment or prevention strategies.

DESCRIPTION (From the application): Alzheimer's disease is a major health problem and the leading cause of dementia in the Americas and Europe. Although there has been little work on dementia in the Middle East, there is evidence from our studies in Arabs residing in Israel that Alzheimer's disease has an extraordinarily high prevalence in Arabs (20% over 60, 60% over 85 years of age). This high prevalence is over three times higher than in other population, even after correcting for the effects of age, gender and education. This is an important issue because of the progressive aging of the populations of the Middle East as we enter the 21 st century. Public awareness of dementia in the Middle East is low, and many cases do not receive medical attention. The goals of this Symposium are to focus attention on neurodegenerative disorders of the aged in the Middle East, to raise scientific, medical and social, awareness of these disorders, and to enhance communication between Arab and Jewish medical and scientific personnel. It is anticipated that the meeting will lead to other studies of the disease in Middle East populations an area with unique features valuable for research, including a high rate of consanguinity, high fat diet and smoking. A target audience of clinicians, scientists, nurses, social workers, representatives of government and other agencies, pharmaceutical and biotechnology companies will attend the meeting to be held in Cyprus, April 18 and 19, 2001. Attendees will be from Egypt, Saudi Arabia, Jordan and other Arab States as well as From Israel, Europe, and North America. Topics to be covered include dementia basic science, diagnosis, history, management and treatment, and ethics, with consideration of unique cultural traditions in Arab and Jewish populations.

[unreadable] DESCRIPTION (provided by applicant): Interest in the vascular causes of various brain disorders including Alzheimer's disease, vascular dementia, mild cognitive impairment, depression, and other behavioral disorders has grown immensely over the last decade. Stroke, hypertension, diabetes and hyperlipidemia have all been shown to be risk factors for Alzheimer's disease. Recent evidence also suggests that Alzheimer's disease and vascular dementia may be delayed or even prevented by treatment of vascular risk factors such as hypertension and hyperlipidemia. The potential implications of these findings span a diverse arena of both scientific and clinical interest. It is increasingly apparent that a forum for discussion and education on vascular causes of these various brain disorders is needed. Such a forum would also develop research strategies to address key issues in cerebrovascular diseases. To this end, The First Congress of the International Society for Vascular Behavioral and Cognitive Disorders (VAS-COG) proposes to bring diverse basic science and clinical research interest together for the study of vascular causes of various brain disorders, as well as to serve as a vehicle for the dissemination of this information, patient advocacy and training of researchers. This meeting will present in one large Congress the most recent advances in the field, including diagnostic and therapeutic developments by internationally recognized opinion leaders. [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Alzheimer's disease is a major health problem and the leading cause of dementia in America and Europe. Although there has been little work done on dementia in the Middle East, there is evidence--from our studies in Arabs residing in Israel--that Alzheimer's disease has a high prevalence in Arabs (20% over 60, 60% over 85 years of age). This high prevalence is over three times higher than in other populations, even after correcting for the effects of age, gender and education. This is an important issue because of the progressive aging of the population of the Middle East as we enter the 21st century. Public awareness of dementia in the Middle East is low, and in many cases does not receive medical attention. The goals of this Symposium are to focus attention on neurodegenerative disorders of the aged in the Middle East, to raise scientific, medical and social awareness of these disorders, and to enhance communication amongst medical and scientific personnel in the region. It is anticipated that the meeting will lead to other studies in Middle East populations, an area with unique features valuable for research, including a high rate of consanguinity, high fat diet, and smoking. A target audience of clinicians, scientists, nurses, social workers, government representatives and other agencies, pharmaceutical and other biotechnology companies will attend the meeting to be held in Istanbul, Turkey, May 1-3, 2003. Attendees will be from Egypt, Saudi Arabia, Jordan, Qatar, Bahrain, and other Arab states, as well as from Europe, Israel and North America. Topics to be covered include dementia, basic science, diagnoses, history, management and treatment, and ethics, with consideration of the unique cultural traditions of Arab and Jewish populations.

[unreadable] DESCRIPTION (provided by applicant): Interest in the vascular causes of various brain disorders including Alzheimer's disease, vascular dementia, mild cognitive impairment, depression, and other behavioral disorders has grown immensely over the last decade. Stroke, hypertension, diabetes and hyperlipidemia have all been shown to be risk factors for Alzheimer's disease. Recent evidence also suggests that Alzheimer's disease and vascular dementia may be delayed or even prevented by treatment of vascular risk factors such as hypertension and hyperlipidemia. The potential implications of these findings span a diverse arena of both scientific and clinical interest. It is increasingly apparent that a forum for discussion and education on vascular causes of these various brain disorders is needed. Such a forum would also develop research strategies to address key issues in cerebrovascular diseases. To this end, the Second Congress of the International Society for Vascular Behavioral and Cognitive Disorders (VAS-COG) will bring diverse basic science and clinical research interest together for the study of vascular causes of various brain disorders, as well as to serve as a vehicle for the dissemination of this information, patient advocacy and training of researchers. We will build upon the success of our first meeting (Goteborg, 2003) at which 636 participants (out of which 225 were women) were brought together to disseminate knowledge on vascular causes of various brain disorders, including Alzheimer's disease, vascular dementia, mild cognitive impairment, depression, and other behavioral disorders. Our second event will present in one large Congress the most recent advances in the field, including diagnostic and therapeutic developments by internationally recognized opinion leaders. [unreadable] [unreadable]