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

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

Overview

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.

Product Details

ISBN-13:	9780521899376
Publisher:	Cambridge University Press
Publication date:	09/24/2009
Pages:	292
Product dimensions:	7.60(w) x 9.80(h) x 0.80(d)

About the Author

Eef Hogervorst is Professor of Biological Psychology, 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, 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 vii

Preface xi

Section 1 Estrogens and cognition: perspectives and opportunities in the wake of the Women's Health Initiative Memory Study

1 Women's Health Initiative Memory Study (WHIMS) program: emerging findings Mark A. Espeland Sally A. Shumaker Patricia E. Hogan Susan M. Resnick 1

2 Identifying risk factors for cognitive change in the Women's Health Initiative: a neural networks approach Stephan Bandelow Mark A. Espeland Victor W. Henderson Susan M. Resnick Robert B. Wallace Laura H. Coker Eef Hogervorst 11

3 Estrogen therapy - relationship to longevity and prevalent dementia in the oldest-old: the Leisure World Cohort Study and the 90+ Study Claudia H. Kawas Mar?a M. Corrada Annlia Paganini-Hill 25

4 The critical window hypothesis: hormone exposures and cognitive outcomes after menopause Victor W. Henderson 32

5 Animal studies that support estrogen effects on cognitive performance and the cholinergic basis of the critical period hypothesis Robert B. Gibbs 45

6 The healthy cell bias of estrogen action through regulating glucose metabolism and mitochondrial function: implications for prevention of Alzheimer's disease Roberta Diaz Brinton 55

Section 2 Varieties of estrogenic therapy

7 Alternative estrogenic treatment regimens and the Kronos Early Estrogen Prevention Study - Cognitive and Affective substudy (KEEPS-CA) Carey E. Gleason Whitney Wharton Cynthia M. Carlsson Sanjay Asthana 65

8 The use of transdermal 17?-estradiol in the treatment of Alzheimer's disease Whitney Wharton Sanjay Asthana Carey E. Gleason 80

9 Alternative modes of treatment: pulsatile estradiol treatment Jin Li Farook Al-Azzawi 87

10 In search of estrogen alternatives for the brain Liqin Zhao Roberta Diaz Brinton 93

Section 3 Potential modulators and modifiers of estrogenic effects

11 Progesterone regulation of neuroprotective estrogen actions Christian J. Pike Jenna C. Carroll 101

12 Clinical data of estrogen's effects in the central nervous system: estrogen and mood Bevin N. Powers Katherine E. Williams Tonita E. Wroolie Anna Khaylis Natalie L. Rasgon 110

13 Different forms of soy processing may determine the positive or negative impact on cognitive function of Indonesian elderly Eef Hogervorst Linda Kushandy Wita Angrianni Yudarini Sabarinah Theresia Ninuk Vita Priantina Dewi Amina Yesufu Tony Sadjimim Philip Kreager Tri Budi W. Rahardjo 121

14 Hypothalamus-pituitary-adrenal axis activity in aging women: its impact on the brain and the potential influence of estradiol Oliver T. Wolf 133

Section 4 Possible genetic factors related to hormone treatment effects

15 Possible genetic polymorphisms related to sex steroid metabolism and dementia in women Eef Hogervorst Stephan Bandelow Chris Talbot 143

16 Genetics related to sex steroids: implications for Alzheimer's disease Chris Talbot 153

17 Apolipoprotein E, hormone therapy, and neuroprotection Robert G. Struble Mary E. McAsey 162

18 Testosterone, gonadotropins, and genetic polymorphisms in men with Alzheimer's disease Eef Hogervorst Stephan Bandelow Donald Lehmann 171

Section 5 Testosterone, estradiol and men, and sex hormone binding globulin

19 Androgens and cognitive functioning in women Barbara B. Sherwin 179

20 The role of estradiol in testosterone treatment Monique M. Cherrier 187

21 Endogenous testosterone levels and cognitive aging in men Scott D. Moffat 197

22 Clinical trials and neuroimaging studies of testosterone in men: insights into effects on verbal memory Pauline M. Maki 208

23 Testosterone therapy and Alzheimer's disease: potential for treatment and prevention in women Whitney Wharton Sanjay Asthana Carey E. Gleason 220

24 Endogenous estradiol and dementia in elderly men: the roles of vascular risk, sex hormone binding globulin, and aromatase activity Majon Muller Mirjam I. Geerlings 228

25 Testosterone regulates Alzheimer's disease pathogenesis Christian J. Pike Emily R. Rosario 242

Section 6 Gonadotropin effects

26 Involvement of gonadotropins in cognitive function: implications for Alzheimer's disease Gemma Casadesus Kathryn J. Bryan George Perry Mark A. Smith 251

27 The role of gonadotropins and testosterone in the regulation of beta-amyloid metabolism Giuseppe Verdile Ralph N. Martins 259

28 Epilogue Wulf H. Utian 269

29 Concluding remarks Eef Hogervorst Victor W. Henderson Robert B. Gibbs Roberta Diaz Brinton 271

Index 275

Editorial Reviews

Reviewer: Leah H Rubin, PhD (University of Illinois at Chicago College of Medicine)
Description: This book reassesses whether sex hormones are promising candidates for the treatment of dementia and age-related cognitive declines. To discuss this issue, it brings together basic science and clinical research studies that use a variety of experimental and observational methodologies to address inconsistencies between the negative effects of estrogen found in the Women's Health Initiative Memory Study (WHIMS) and data showing that estrogen may have a protective effect on age-related cognitive declines and dementia.
Purpose: The purpose is "to re-examine some of the basic and clinical underpinnings of our current knowledge in areas related to sex steroid hormones, cognitive aging, and dementia." This is important, given that a large percent of our population is elderly, the population is aging, and no known treatment completely reverses the effects of brain aging and dementia. World-renowned experts in basic and clinical research cover this topic comprehensively.
Audience: The intended audience includes gynecologists, endocrinologists, neurologists, psychologists, and behavioral neuroscientists. The book also would be useful to graduate students in psychology and behavioral neuroscience. Having some background in statistics will help.
Features: Part 1 of the book's six parts summarizes the most recent data from WHIMS and discusses alternative explanations for the negative results reported in WHIMS, including the critical window theory and the healthy cell bias. Possible alternative hormone treatments are discussed in part 2. Part 3 describes possible modifiers of the effect of estrogen on the brain including the role of progesterone regulation on estrogen, and estrogen's effect on mood and the hypothalamic-pituitary-adrenal axis. Part 4 covers possible genetic factors related to sex hormone metabolism, Alzheimer's disease, and apolipoprotein E. Parts 5 and 6 conclude with reviews of the relevance of testosterone and gonadotropins to the brain, cognition, and Alzheimer's disease in both women and men. The editor's introductions at the beginning of each chapter are the best part of the book. They help to weave together the individual chapters into a cohesive whole. Each chapter is well referenced.
Assessment: This is an excellent book for understanding where the field stands today regarding sex hormones for the treatment of brain aging and dementia.

Doody's Review Service

"Part 1 of the book's six parts summarizes the most recent data from WHIMS and discusses alternative explanations for the negative results reported in WHIMS, including the critical window theory and the healthy cell bias. Possible alternative hormone treatments are discussed in part 2. Part 3 describes possible modifiers of the effect of estrogen on the brain including the role of progesterone regulation on estrogen, and estrogen's effect on mood and the hypothalamic-pituitary-adrenal axis. Part 4 covers possible genetic factors related to sex hormone metabolism, Alzheimer's disease, and apolipoprotein E. Parts 5 and 6 conclude with reviews of the relevance of testosterone and gonadotropins to the brain, cognition, and Alzheimer's disease in both women and men. The editor's introductions at the beginning of each chapter are the best part of the book. They help to weave together the individual chapters into a cohesive whole. Each chapter is well referenced....This is an excellent book for understanding where the field stands today regarding sex hormones for the treatment of brain aging and dementia."
—Doody's Review Service

From the Publisher

Reviewer: Leah H Rubin, PhD(University of Illinois at Chicago College of Medicine)
Description: This book reassesses whether sex hormones are promising candidates for the treatment of dementia and age-related cognitive declines. To discuss this issue, it brings together basic science and clinical research studies that use a variety of experimental and observational methodologies to address inconsistencies between the negative effects of estrogen found in the Women's Health Initiative Memory Study (WHIMS) and data showing that estrogen may have a protective effect on age-related cognitive declines and dementia.
Purpose: The purpose is "to re-examine some of the basic and clinical underpinnings of our current knowledge in areas related to sex steroid hormones, cognitive aging, and dementia." This is important, given that a large percent of our population is elderly, the population is aging, and no known treatment completely reverses the effects of brain aging and dementia. World-renowned experts in basic and clinical research cover this topic comprehensively.
Audience: The intended audience includes gynecologists, endocrinologists, neurologists, psychologists, and behavioral neuroscientists. The book also would be useful to graduate students in psychology and behavioral neuroscience. Having some background in statistics will help.
Features: Part 1 of the book's six parts summarizes the most recent data from WHIMS and discusses alternative explanations for the negative results reported in WHIMS, including the critical window theory and the healthy cell bias. Possible alternative hormone treatments are discussed in part 2. Part 3 describes possible modifiers of the effect of estrogen on the brain including the role of progesterone regulation on estrogen, and estrogen's effect on mood and the hypothalamic-pituitary-adrenal axis. Part 4 covers possible genetic factors related to sex hormone metabolism, Alzheimer's disease, and apolipoprotein E. Parts 5 and 6 conclude with reviews of the relevance of testosterone and gonadotropins to the brain, cognition, and Alzheimer's disease in both women and men. The editor's introductions at the beginning of each chapter are the best part of the book. They help to weave together the individual chapters into a cohesive whole. Each chapter is well referenced.
Assessment: This is an excellent book for understanding where the field stands today regarding sex hormones for the treatment of brain aging and dementia.