A Nutritional Formulation for Cognitive Performance and Mood in Alzheimer’s Disease and Mild Cognitive Impairment: A Phase II Multi-site Randomized Trial with an Open-label Extension

Background: It is increasingly recognized that interventions for dementia must shift towards prevention to obtain maximal efficacy and any significant degree of disease modification. Nutritional supplementation with single agents has shown varied results, suggesting the need for combinatorial intervention. Methods: We conducted a 3-month, randomized, multi-site, phase II study in which 141 individuals diagnosed with Alzheimer’s disease (AD) and 34 individuals with Mild Cognitive Impairment received a nutraceutical formulation (NF; folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) or indistinguishable placebo under double-blind conditions, followed by an open-label extension in which all individuals received NF for a total of 1yr. An additional 38 individuals with AD received NF under open-label conditions from baseline for 1yr. The primary outcome was defined as cognitive performance. Secondary outcomes were defined as behavioral and psychological symptoms of dementia and activities of daily living. Results: Participants randomized to NF improved statistically within 3 months in cognitive performance as ascertained by Clox-1 and the Dementia Rating Scale, and their caregivers reported improvement in Neuropsychiatric Inventory. Participants receiving NF either continued to improve or maintained their baseline performance during open-label extensions. Participants randomized to placebo did not improve, but during open-label extensions displayed similar improvement within 3 months to that of participants initially randomized to NF. Caregivers reported no change in Activities of Daily Living for either cohort. Conclusions: These findings confirm and extend prior phase I studies in which NF improved or maintained cognitive performance and behavioral symptoms for individuals with AD, and improved cognitive performance for community-dwelling individuals without dementia. In published studies with transgenic mice NF reduced PS-1 expression, beta and gamma secretase activity, Abeta deposits, phospho-tau, homocysteine and oxidative damage, and increased acetylcholine and glutathione. This comprehensive impact of NF on AD-related neuropathology supports the possibility that NF may harbor disease-modifying properties

Task force on immigration and higher education in Central Massachusetts

In August 2007, the Colleges of Worcester Consortium, Inc. created a task force to examine the issue of immigration and higher education in Central Massachusetts. It has become increasingly clear from recent demographic and economic studies and projections that the population in the northeast, and certainly in Central Massachusetts, is showing minimal growth. There is evidence that a decline in the “native-born” population is caused by significant out-migration due to a number of factors, including the high cost of living, limited career opportunities and a declining birth rate. The limited population growth that is evident is due primarily to the recent influx of immigrants to this area, with the most significant numbers in Worcester coming from Ghana, Brazil, the Dominican Republic, Kenya, El Salvador, Albania and Liberia. It is also clear that the area’s economy is becoming more knowledge-based with an increasing percentage of all new jobs requiring some form of postsecondary education. According to the 2007 Massachusetts Department of Workforce Development’s Job Vacancy Survey, 38 percent of current job vacancies in Massachusetts require an associate’s degree or higher. This represents an increase from 30 percent in 2003. Consequently, the level of education that the immigrant population attains is of vital importance to everyone—not only to immigrant students and their families but also to the economic well-being of the entire region. The Task Force was charged with researching the barriers to higher education faced by this new wave of immigrants and suggesting recommendations to address those barriers. The 36-member Task Force was made up of representatives from Consortium member institutions; federal, state and local governments; community and faithbased organizations; the Worcester Public Schools; the Massachusetts Board of Higher Education; and the Massachusetts Immigrant and Refugee Advocacy (MIRA) Coalition. Meetings were held over six months, during which the Task Force identified three main barriers faced by immigrant communities in accessing higher education, and sub-committees were created to work on each of these. Speakers were invited to present on topics of interest. Two public hearings were held, the first of which was conducted at Worcester State College in October. It attracted community representatives, as well as college and high school faculty and administrators. The second hearing, held at the downtown branch of Quinsigamond Community College (QCC) in December, was attended by immigrants (English for Speakers of Other Languages – ESOL and GED) students as well as QCC staff.Published versio

Increased Risk for Malignancies in 131 Affected CTLA4 Mutation Carriers

Background: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a negative immune regulator on the surface of T cells. In humans, heterozygous germline mutations in CTLA4 can cause an immune dysregulation syndrome. The phenotype comprises a broad spectrum of autoinflammatory, autoimmune, and immunodeficient features. An increased frequency of malignancies in primary immunodeficiencies is known, but their incidence in CTLA-4 insufficiency is unknown.Methods: Clinical manifestations and details of the clinical history were assessed in a worldwide cohort of 184 CTLA4 mutation carriers. Whenever a malignancy was reported, a malignancy-specific questionnaire was filled.Results: Among the 184 CTLA4 mutation carriers, 131 were considered affected, indicating a penetrance of 71.2%. We documented 17 malignancies, which amounts to a cancer prevalence of 12.9% in affected CTLA4 mutation carriers. There were ten lymphomas, five gastric cancers, one multiple myeloma, and one metastatic melanoma. Seven lymphomas and three gastric cancers were EBV-associated.Conclusion: Our findings demonstrate an elevated cancer risk for patients with CTLA-4 insufficiency. As more than half of the cancers were EBV-associated, the failure to control oncogenic viruses seems to be part of the CTLA-4-insufficient phenotype. Hence, lymphoproliferation and EBV viral load in blood should be carefully monitored, especially when immunosuppressing affected CTLA4 mutation carriers