This pilot study is addressing the major clinical problem of anemia in the elderly, which has been associated with reduced survival and increased risk of functional decline, cognitive impairment and death. Although parenteral treatment with erythropoietin and related compounds is being used increasingly for anemia in the elderly population, this therapy is only partially effective, and is also expensive and burdensome.

Dr. Ganz’s group has recently identified the peptide hormone, hepcidin, a key systemic regulator of iron homeostasis, as the main mediator of anemia of inflammation. Therefore, using hepcidin as a target, the proposed pilot study aims to identify new compounds for the treatment of anemia of inflammation and other anemias of unknown causes. The project will first develop a high throughput screen for hepcidin antagonists, then screen a 30,000 small molecule NIH library for these antagonists, confirm positive candidates with additional in vitro tests, and finally, test selected compounds in a mouse model.

It is hoped that this research will ultimately lead to the development of effective anemia treatments that will result in improved functional status in seniors.

This pilot project aims to evaluate two potential treatments for cognitive deficits, including those associated with Alzheimer’s disease (AD), that affect the health and independence of older Americans. Decline in cognitive function in older persons is not only a leading cause of institutionalization (in the case of dementia syndromes), but at milder levels may contribute to depression, vulnerability and diminished quality of life.

Based on certain biochemical data and epidemiological associations between type 2 diabetes and AD, the proposed work will evaluate two small molecule mimetics of insulin and brain-derived neurotrophic factor on several key signaling pathways, on tau modification and accumulation, on amyloid deposition, and on synaptic and cognitive deficits. Using tissue culture technologies and animal models, this project aims to identify whether these promising treatments will result in neuroprotection and/or cognitive enhancement. The research is, therefore, highly relevant to many causes of cognitive decline, including Alzheimer’s disease, stroke, and multi-infarct dementia. Moreover, a neuroprotective agent that also enhances cognitive function would permit effects to be evident in a relatively short-term clinical trial, compared to the prolonged trials required to detect slowing of neurodegeneration.

Upper-Extremity Function Following Yoga for Hyperkyphosis
Year 16 (2006-2007)
George Salem, PhD – gsalem@usc.edu
Associate Professor of Biokinesiology & Physical Therapy, USC School of Medicine

This pilot will add important new outcomes that measure upper extremity biomechanics and functioning to the ongoing NIH-funded Yoga for Hyperkyphosis Study ( R01 HD04834, Greendale, PI). The parent R-01 is a single blind, randomized controlled trial (RCT) designed to investigate whether a specifically designed Hatha (movement-based) Yoga intervention can reduce hyperkyphosis (excess forward curvature of the thoracic spine), increase height, improve physical function (mainly of the lower extremities), and enhance mood and quality of life in older men and women with hyperkyphosis.

Not substantively assessed in the funded investigation, however, are the potential effects of the Yoga program on scapular posturing and upper-extremity-dependent function. In part, the omission of upper-extremity (UE) outcomes from the original R-01 was due to lack of adequate technical methods to measure UE function and the absence of access to the required, highly specialized biomechanics expertise and laboratory infrastructure. This pilot will bring the requisite content knowledge and laboratory infrastructure to the project.

The preservation or restoration of UE functional capability is important for seniors because this capability underlies the ability to perform many ADLs (e.g. carrying, dressing or cooking) and ultimately maintain independence. Moreover, scapular posturing and UE function are likely to be improved by an intervention program targeting hyperkyphosis, because previous studies have documented strong associations between increased thoracic curvature and: 1) excessive scapular protraction, 2) altered scapulohumeral mechanics, 3) decreased UE range of motion, and 4) reduced UE functional performance.

Using novel UE biomechanical assessment techniques developed in his laboratory, Dr. Salem will quantify scapulohumeral kinematic patterns (patterns that increase range of motion and reduce the risk of impingement syndromes) during functional and maximum-reach tasks among participants in the Yoga for Hyperkyphosis study. He will also conduct timed tests of UE multiple-repetition function. To our knowledge, this study will be the first to quantify the baseline UE function and biomechanics of elders with hyperkyphosis.

This study will provide novel information about whether Yoga can improve UE function in those with hyperkyphosis.

This pilot will develop and test an innovative intervention for the treatment of persistent fatigue among older breast cancer survivors (BCS). Women aged 60 years or greater constitute the majority of BCS and fatigue is the most common and disabling symptom among women successfully treated for breast cancer. Fatigue negatively impacts mood, social relationships, and conduct of daily activities and diminishes overall quality of life

In a prior, single-armed, pilot study by Dr. Bower found that Iyengar yoga was a highly effective intervention for persistent fatigue among middle-aged breast cancer survivors. However, the Iyengar yoga intervention used in her prior work will require substantial modification for an older age group. Older women will likely have physical limitations and/or reservations about being in certain positions that are believed to be central to the Iyengar yoga intervention’s effectiveness (for example, back-bending or being upside down in inverted postures). Thus, this pilot proposes to create a program for use in older women, to evaluate its feasibility and to obtain a preliminary estimate of effectiveness.

The pilot will utilize a randomized study design wherein 40 BCS, aged 60-75 years, who have persistent cancer-related fatigue, will be randomly assigned to either active treatment (a 3-month Iyengar yoga intervention) or a wait-list control group (who will be given vouchers for free Yoga classes with the same Iyengar instructor after the study is over). The yoga intervention will be designed to combat fatigue, according to the precepts of the Iyengar School, but the poses will be modified to be accessible to older women. Outcomes will include assessments of fatigue, behavioral symptoms, quality of life, physical performance, and side effects of the yoga program.

Last Updated: November 21, 2006 © 2000 UCLA GeroNet