Experts present new research at 2011 Alzheimer's Association ICAD

Experts from the Center of Excellence on Brain Aging at NYU Langone Medical Center will present new research at the 2011 Alzheimer's Association International Conference on Alzheimer's disease (ICAD) to be held in Paris, France from July 16 - 21. Of particular interest is the presentation about mild cognitive impairment in retired football players, with Stella Karantzoulis, PhD, and the selected "Hot Topics" presentation about a new experimental approach to targeting amyloid plaques, with Fernando Goni, PhD. Each presentation is embargoed as noted below.

The FAST: A Brief, Practical, Comprehensive, Valid Functional Assessment for Alzheimer's Disease (AD) Staging, Diagnosis and Differential Diagnosis in the Primary Care Setting

Barry Reisberg, MD, professor in the Department of Psychiatry, NYU School of Medicine

Patients with Alzheimer's disease often display impairment in daily living skills upon diagnosis. There are many tools available to assist in evaluating the progression of the disease. The FAST (Functional Assessment Staging) scale, is a brief and easy-to-use tool primary care physicians can employ to follow the course of aging.

Supporting Caregivers

Mary S. Mittelman, Dr PH, research professor in the Department of Psychiatry, NYU School of Medicine

Family caregivers are essential to the care of people with dementia. Depending on the severity of dementia, their roles can include decision-making, advocating for the person with dementia in the health care system, providing personal care, homemaking and financial planning, and managing formal care services. Caregiving can cause physical, psychological, social, and financial burdens, increasing the risk of depression and physical illness, which may lead to burnout and even greater societal costs. Therefore, support for family caregivers is essential. Interventions can help caregivers and support should be considered an integral part of good comprehensive care for persons with dementia.

TOMM40 poly-T Variants Influence Sensitivity to Lorezapam-induced Impairment in Healthy Elderly

Nunzio Pomara, MD, professor, Department of Psychiatry, NYU School of Medicine, director of Geriatric Psychiatry, Nathan S. Kline Institute

Healthy and cognitively-intact elderly carriers of APOE e4, an established risk factor for late-onset Alzheimer's disease(LOAD), display more pronounced memory deficits following acute administration of lorazepam, a drug used to alleviate anxiety, than non-e4 carriers. However, among non-e4 carriers, there is considerable individual variability. Researchers found a biomarker that could help predictor which individuals were more likely to have suffer memory losses associated with the drug.

Impact of Hormone Replacement Therapy (HRT) Usage on Seven Year Outcome of Older Persons with Subjective Cognitive Impairment

Barry Reisberg, MD, professor in the Department of Psychiatry, NYU School of Medicine

In this study of 91 women with subjective cognitive impairment, 22 received hormone replacement therapy either as estrogen or estrogen-progesterone combined. Of the HRT group, 45.5% progressed to either mild cognitive impairment or dementia over a 7-year period. The researchers conclude that HRT did not influence the progression of SCI. Systematic longitudinal investigation of possible effects of other medications on progression of SCI to MCI/dementia is required to identify substances that may regulate or prevent this process.

Characterization of Mild Cognitive Impairment in Retired NFL Players

Stella Karantzoulis, PhD, assistant professor in the Department of Neurology, NYU Comprehensive Epilepsy Center, NYU Langone Medical Center

It has been suggested that retired American football players may be at increased risk for late-life cognitive disorders although this has not yet been definitively established. Isolated findings have been reported of chronic traumatic encephalopathy in athletes who have been exposed to repetitive head trauma. In this study, 41 retired NFL athletes were compared to two groups; a demographically-matched cognitive intact cohort and a clinical sample of patients with amnestic (forgetfulness) on a neurocognitive series of tests. Results indicated that the prevalence of mild cognitive impairment (MCI) within the sample of retired athletes appears to be higher than epidemiological studies would predict. The researchers conclude that MCI may be more common in retired NFL athletes than in the general population.

Immunization with a pseudo-phosphorylated tau epitope clears tau pathology in a mouse model.

Pavan Krishnamurthy, PhD, instructor in the Department of Physiology and Neuroscience, NYU School of Medicine

Immunotherapy holds great promise for Alzheimer's disease (AD) and other conformational disorders. Recent studies have shown that immunization with an AD specific phospho-tau immunogen Tau379-408[P-Ser396,404] alleviates brain levels of aggregated tau and slows the progression of motor deficits or prevents cognitive impairments in two different tangle models. To assess potential epitope specificity and safety of this promising therapeutic effect, the researchers examined several tau epitopes. The results support the feasibility of tau immunotherapy.

An Evidence-based Caregiver Intervention: Translation from Research to Practice

Mary Mittelman, DrPH, research professor in the Department of Psychiatry, NYU Langone Medical Center

The NYU Caregiver Intervention (NYUCI) is a multi-component individualized intervention for spouse caregivers of people with Alzheimer's disease. The underlying premise of the intervention is that improving social support can have significant positive impact on the well-being of the caregiver. Intervention includes individual counseling for the primary caregiver and family counseling for the spouse and other family members within a fixed period of time and ongoing support as requested for the entire course of the illness. Results suggest a short course of intensive counseling and readily available supportive maintenance that includes not only the spouse caregiver, but also other family members, can have long-lasting effects on the well-being of spouse caregivers. The structure of the NYUCI permits flexibility of content, making it an ideal intervention for diverse cultures.

Hyperglycemia increases amyloid accumulation and exacerbates cerebrovascular pathology in Alzheimer's disease model animals.

Ayodeji A. Asuni, PhD, research professor in the Department of Neurology, NYU School of Medicine

Hyperglycemia is a metabolic abnormality defining diabetes. Misfolding and accumulation of abnormally conformed amyloid-β and associated neurodegenerative cascades underpins Alzheimer's disease (AD) pathogenesis. Epidemiological studies have repeatedly demonstrated increased coincidence of AD pathology in diabetes patients, and the clinical course of AD is often hastened in subjects with diabetes. Despite these associations, the association is unclear. This study focused on defining the relationship between hyperglycemia (hGly) and the Aβ pathology in AD transgenic (Tg) animals. The researchers found that chronic hyperglycemia is strongly associated with exacerbation of Aβ pathology in AD Tg mice, and primarily aggravated cerebral amyloid angiopathy (CAA), which is allied with increased damage to blood vessel integrity. It also promoted formation of Aβ oligomers which enhances Aβ toxicity.

Conformation Directed Immunomodulation Effectively Targeting amyloid plaques, CAA and neurofibrillary tangle pathology in Model Mice

Fernando Goni, PhD, research associate professor in the Department of Neurology, NYU School of Medicine

Alzheimer's disease is the most common of the conformational neurodegenerative disorders. Current treatments for AD are largely symptomatic and minimally effective. Issues with previous immunotherapeutical approaches include: the potential of toxicity from autoimmune encephalitis, tau related pathology not being addressed, and the need to effectively clear congophilic angiopathy (CAA). For the current study a novel immunomodulatory therapeutic approach was developed using polymerized British amyloidosis (pABri) related peptides with no homology to any human protein; and polymerized-non-fibrillized-Aβ1-42 peptide (pAβ42), to help overcome these limitations of vaccination. In the past it has been demonstrated that pABri can induce behavioral benefits in APP/PS1 Tg mice associated with reductions in Aβ oligomers. This approach was tested in mice with both plaques and tangle pathology (3xTg mice) and mice with extensive CAA (TgSwDI). The pABri inoculated animals made low titers of IgM and IgG recognizing the original antigen and oligomerized Aβ42. Animals inoculated with pAβ42 had high titers of anti-Aβ peptides plain or oligomerized. All animals remained healthy and without noticeable autoimmune complications for the length of the experiment. Histological analysis showed reduction of both amyloid and tau pathology.