Hormones, Cognition and Dementia: State of the Art and Emergent Therapeutic Strategies

by Edited by Eef Hogervorst , Victor W. Henderson , Robert B. Gibbs , Roberta Diaz Brinton

• ISBN13: 9780521899376
• ISBN10: 0521899370
• Edition: 1st
• Format: Hardcover
• Copyright: 2009-10-30
• Publisher: Cambridge University Press

Summary

A decade ago, oestrogen-containing hormone therapy was viewed as a promising strategy for the prevention and treatment of dementia and age-related cognitive decline. However, treatment trials in women with Alzheimer's disease showed that oestrogens did not reverse cognitive impairment, and clinical trials in healthy older women indicated that oestrogens did not prevent cognitive decline. The Women's Health Initiative Memory Study trial even suggested an increased risk of dementia with treatment late in life. What happened? How are we to understand these findings? What are the implications for middle-aged and older women? What about testosterone, and what about men? And where do we go from here? This book brings together world-renowned experts in basic and clinical research on sex steroids, aging, and cognition to integrate existing findings with emerging new data, and offer challenging hypotheses on these key issues.

Author Biography

Eef Hogervorst is Professor Department of Human Sciences, Loughborough University Loughborough, UK; Visiting Senior Research Fellow, Department of Public Health and Primary Care, University of Cambridge, UK; Visiting Professor, Department of Epidemiology and Public Health, University of Respati, Jakarta, Indonesia. Victor W. Henderson is Professor of Health Research Policy (Epidemiology) and of Neurology Neurological Sciences, Stanford University, CA, USA. Robert B. Gibbs is Professor of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA. Roberta Diaz Brinton is Professor of Pharmacology and Pharmaceutical Sciences, Neuroscience and Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.

Table of Contents

List of contributors	p. vii
Preface	p. xi
Estrogens and cognition: perspectives and opportunities in the wake of the Women's Health Initiative Memory Study
Women's Health Initiative Memory Study (WHIMS) program: emerging findings	p. 1
Identifying risk factors for cognitive change in the Women's Health Initiative: a neural networks approach	p. 11
Estrogen therapy - relationship to longevity and prevalent dementia in the oldest-old: the Leisure World Cohort Study and the 90+ Study	p. 25
The critical window hypothesis: hormone exposures and cognitive outcomes after menopause	p. 32
Animal studies that support estrogen effects on cognitive performance and the cholinergic basis of the critical period hypothesis	p. 45
The healthy cell bias of estrogen action through regulating glucose metabolism and mitochondrial function: implications for prevention of Alzheimer's disease	p. 55
Varieties of estrogenic therapy
Alternative estrogenic treatment regimens and the Kronos Early Estrogen Prevention Study - Cognitive and Affective substudy (KEEPS-CA)	p. 65
The use of transdermal 17ß-estradiol in the treatment of Alzheimer's disease	p. 80
Alternative modes of treatment: pulsatile estradiol treatment	p. 87
In search of estrogen alternatives for the brain	p. 93
Potential modulators and modifiers of estrogenic effects
Progesterone regulation of neuroprotective estrogen actions	p. 101
Clinical data of estrogen's effects in the central nervous system: estrogen and mood	p. 110
Different forms of soy processing may determine the positive or negative impact on cognitive function of Indonesian elderly	p. 121
Hypothalamus-pituitary-adrenal axis activity in aging women: its impact on the brain and the potential influence of estradiol	p. 133
Possible genetic factors related to hormone treatment effects
Possible genetic polymorphisms related to sex steroid metabolism and dementia in women	p. 143
Genetics related to sex steroids: implications for Alzheimer's disease	p. 153
Apolipoprotein E, hormone therapy, and neuroprotection	p. 162
Testosterone, gonadotropins, and genetic polymorphisms in men with Alzheimer's disease	p. 171
Testosterone, estradiol and men, and sex hormone binding globulin
Androgens and cognitive functioning in women	p. 179
The role of estradiol in testosterone treatment	p. 187
Endogenous testosterone levels and cognitive aging in men	p. 197
Clinical trials and neuroimaging studies of testosterone in men: insights into effects on verbal memory	p. 208
Testosterone therapy and Alzheimer's disease: potential for treatment and prevention in women	p. 220
Endogenous estradiol and dementia in elderly men: the roles of vascular risk, sex hormone binding globulin, and aromatase activity	p. 228
Testosterone regulates Alzheimer's disease pathogenesis	p. 242
Gonadotropin effects
Involvement of gonadotropins in cognitive function: implications for Alzheimer's disease	p. 251
The role of gonadotropins and testosterone in the regulation of beta-amyloid metabolism	p. 259
Epilogue	p. 269
Concluding remarks	p. 271
Index	p. 275
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