Myron F. Weiner

Bio: Myron F. Weiner is an academic researcher from University of Texas Southwestern Medical Center. The author has contributed to research in topics: Dementia & Montreal Cognitive Assessment. The author has an hindex of 53, co-authored 235 publications receiving 11272 citations.

Early role of vascular dysregulation on late-onset Alzheimer’s disease based on multifactorial data-driven analysis

Abstract: Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD-abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions.

Normative data for the Montreal Cognitive Assessment (MoCA) in a population-based sample

Abstract: Objective: To provide normative and descriptive data for the Montreal Cognitive Assessment (MoCA) in a large, ethnically diverse sample. Methods: The MoCA was administered to 2,653 ethnically diverse subjects as part of a population-based study of cardiovascular disease (mean age 50.30 years, range 18–85; Caucasian 34%, African American 52%, Hispanic 11%, other 2%). Normative data were generated by age and education. Pearson correlations and analysis of variance were used to examine relationship to demographic variables. Frequency of missed items was also reviewed. Results: Total scores were lower than previously published normative data (mean 23.4, SD 4.0), with 66% falling below the suggested cutoff ( Conclusion: These findings highlight the need for population-based norms for the MoCA and use of caution when applying established cut scores, particularly given the high failure rate on certain items. Demographic factors must be considered when interpreting this measure.

High-Dose B Vitamin Supplementation and Cognitive Decline in Alzheimer Disease: A Randomized Controlled Trial

Abstract: Context Blood levels of homocysteine may be increased in Alzheimer disease (AD) and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Even in the absence of vitamin deficiency, homocysteine levels can be reduced by administration of high-dose supplements of folic acid and vitamins B 6 and B 12 . Prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess their effect on cognitive decline. Objective To determine the efficacy and safety of B vitamin supplementation in the treatment of AD. Design, Setting, and Patients A multicenter, randomized, double-blind controlled clinical trial of high-dose folate, vitamin B 6 , and vitamin B 12 supplementation in 409 (of 601 screened) individuals with mild to moderate AD (Mini-Mental State Examination scores between 14 and 26, inclusive) and normal folic acid, vitamin B 12 , and homocysteine levels. The study was conducted between February 20, 2003, and December 15, 2006, at clinical research sites of the Alzheimer Disease Cooperative Study located throughout the United States. Intervention Participants were randomly assigned to 2 groups of unequal size to increase enrollment (60% treated with high-dose supplements [5 mg/d of folate, 25 mg/d of vitamin B 6 , 1 mg/d of vitamin B 12 ] and 40% treated with identical placebo); duration of treatment was 18 months. Main Outcome Measure Change in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog). Results A total of 340 participants (202 in active treatment group and 138 in placebo group) completed the trial while taking study medication. Although the vitamin supplement regimen was effective in reducing homocysteine levels (mean [SD], −2.42 [3.35] in active treatment group vs −0.86 [2.59] in placebo group; P Conclusion This regimen of high-dose B vitamin supplements does not slow cognitive decline in individuals with mild to moderate AD. Trial Registration clinicaltrials.gov Identifier: NCT00056225

High-Dose B Vitamin Supplementation and Cognitive Decline in Alzheimer Disease

Abstract: Context Blood levels of homocysteine may be increased in Alzheimer disease (AD) and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Even in the absence of vitamin deficiency, homocysteine levels can be reduced by administration of high-dose supplements of folic acid and vitamins B6 and B12. Prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess their effect on cognitive decline.

A randomized controlled trial of prednisone in Alzheimer’s disease

Abstract: To the Editor: We read with interest the article by Aisen et al.,1 who found that low doses of prednisone are not effective in AD. In the article, inflammatory processes are discussed in the pathophysiology of dementia, and corresponding therapeutic approaches are pursued. However, no clear clinical evidence for this exciting hypothesis has been established yet. To acquire information about the inflammatory activity of patients with expected dementia transferred to our ward, we investigated eosinophilic cationic protein (ECP) in serum. ECP is a sensitive marker of inflammatory processes and often used as a marker in clinical studies.2 We have 41 patients (mean age 73.8 years, SD 7.8; 7 men, 34 women) in our study. …

Standards of Medical Care in Diabetes

Abstract: XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Effects of stress throughout the lifespan on the brain, behaviour and cognition

Abstract: Chronic exposure to stress hormones, whether it occurs during the prenatal period, infancy, childhood, adolescence, adulthood or aging, has an impact on brain structures involved in cognition and mental health. However, the specific effects on the brain, behaviour and cognition emerge as a function of the timing and the duration of the exposure, and some also depend on the interaction between gene effects and previous exposure to environmental adversity. Advances in animal and human studies have made it possible to synthesize these findings, and in this Review a model is developed to explain why different disorders emerge in individuals exposed to stress at different times in their lives.

Neuroinflammation in Alzheimer's disease

Abstract: Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.