CURRENT CLINICAL NEUROLOGY - PART 1 pptx

Vascular DementiaCerebrovascular Mechanisms and Clinical Management Pawtucket, Rhode Island; Department of Clinical Neurosciences, Brown Medical School, Providence, RI... ALOIA,P h D • D

Vascular Dementia

C U R R E N T C L I N I C A L N E U R O L O G Y

Daniel Tarsy, MD, SERIES EDITOR

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Vascular Dementia

Cerebrovascular Mechanisms and Clinical Management

Pawtucket, Rhode Island;

Department of Clinical Neurosciences,

Brown Medical School, Providence, RI

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Series Editor’s Introduction

The understanding and treatment of dementia remains one of the greatest challenges ing the contemporary clinical neuroscientist This is obviously not surprising given the com-plex infrastructure that forms the basis for what we consider the higher brain functions ofmemory, language, thought, abstract reasoning, motivation, and emotion Progressive de-mentia is, by and large, a disorder of the aging brain Running parallel to the aging of braintissue is aging of the cerebrovascular system, which is necessary to meet the brain’s demandfor a large volume of blood flow Therein lies the problem that has historically been put verysimply: is dementia a result of a primary degenerative disease of the brain or a result of aprogressive impairment in it’s blood supply? The 19th-century view was that dementiaresulted from vascular insufficiency Later, with more sophisticated neuropathology, theconcept arose that dementia was caused by a primary neurodegenerative process whichattacked cortical neurons However, well into the latter part of the 20th century, the popularconcept that cerebral arteriosclerosis—commonly known as “hardening of the arteries”—was the basis for dementia continued to hold sway Eventually, however, Alzheimer’s dis-ease became the principal culprit and even found its way into the popular lexicon Appearing

fac-to confirm the neurodegenerative view, there quickly followed the discovery of additionalneuropathologic and clinical entities such as Lewy body dementia, frontotemporal demen-tia, progressive supranuclear palsy, and corticobasal degeneration to name just a few

As indicated by the editors of this volume, the pendulum appears to have swung too farfrom vascular dementia Even while knowledge of the primary degenerative disorders wasevolving, more respectable concepts of arteriosclerotic dementia, such as multi-infarct demen-tia and subcortical dementia, began to emerge Binswanger’s disease even made a respectablecomeback Until recently however, Alzheimer’s disease and vascular dementia continued

to be considered distinctive with a polarization of opinion as to which of these was moreimportant etiologically As it turns out, the truth may lie somewhere in the middle Theeditors of this volume are of this mindset and have collected a group of distinguished expertswho provide the clinical and laboratory evidence that vascular dementia is a genuine entityand that a mutually exclusive separation between primary degenerative and vasculardementias is difficult to support Going further, if one accepts the concept of vasculardementia, the existence of a “mixed dementia” must also be considered In the end, thequestion remains as to whether vascular and degenerative dementias simply coexist or

whether there is an important pathophysiologic interaction between the two processes lar Dementia: Cerebrovascular Management and Clinical Management lays out the guide-

Vascu-lines for understanding this debate and points the way to future research which should clarifythe question, lead to better understanding of the cause of these disorders, and produce effec-tive methods for their prevention and treatment

Daniel Tarsy, MD

Department of Neurology Beth Israel Deaconess Medical Center

Harvard Medical School

Boston, MA

Preface

The intent of Vascular Dementia: Cerebrovascular Mechanisms and Clinical ment is to address the many recent advances in cardiovascular and cerebrovascular medi-cine and the impact of these on the lives of older adults by examining the state-of-the-artresearch on vascular dementia (VaD) A distinguishing feature of this work is its interdisci-plinary nature We have assembled work from contributors in multiple related fields, includ-ing both human and animal studies, in order to advance our collective understanding ofVaD A second distinguishing feature is that we have devoted one-third of our text to theexamination of the interactions between VaD and Alzheimer’s disease (AD) We believethat this combined approach will enhance patient care, as well as promote future research.One may ask whether yet another summary of work in the field of VaD is necessary,given the number of review papers and recent texts devoted to the topic However, it isimportant to note that research conducted over the recent “Decade of the Brain” has brought

Manage-to light both consensus and controversy regarding the identity of VaD, and as a result thefield is in constant flux No better example of this could be scripted than the topics of discus-sion at a recent international conference on VaD Attended by many prolific contributors tothe field, the debates were charged and the range of discussion was provocative In one openforum debate, the very existence of VaD as a construct was under question Data from autopsystudies were presented which argued that pure VaD was such a rare phenomenon that theconstruct barely warranted clinical and research attention By contrast, in a separate debate,the discussion focused on whether all cases of sporadic AD were manifestations of VaD.This bipolar conceptualization of VaD is the primary impetus behind our book

In addition, though AD has been the central focus of research for several decades, thependulum has begun to move towards a greater interest in cerebrovascular disease Thislikely reflects the ever-growing population of older adults with cerebrovascular disease, aswell as studies conducted in recent years describing important interactions between vasculardisease and the expression of cognitive deficits in AD There is now a growing consensusthat clear, clinical, and pathological distinctions between these two conditions sometimescannot be made in individual patients We are certainly not the first group to describe thispending paradigm shift, as others (i.e., Roman, Hachinski, et al.) have offered this observa-tion in public forum However, it is from our own observations and empirical studies that wecame to appreciate this conceptualization of dementia research, and eventually concludedthat the time was right to synthesize the literature in an effort to move science forward

Vascular Dementia: Cerebrovascular Mechanisms and Clinical Management is divided

into six sections Part I is focused on introducing VaD as a construct Part II describes thebasic mechanisms associated with aging that may have an important role in the development

of VaD Part III identifies the impact of VaD on cognitive status, psychiatric health, and theability of patients to complete important activities of daily living Part IV describes the appli-cation of neuroimaging methods to investigate VaD, with particular attention directed towardboth functional and structural imaging methods Part V is devoted to the topic of interactions

between VaD and AD Finally, Part VI reviews pharmacological management of VaD Thissection also addresses the impact of VaD on perceived quality of life of patients and caregiverburden, two rarely addressed issues in the scientific community.

We developed the book to be of interest to both clinicians and basic scientists The topicscovered are broad in nature and capture work from both the bench and the exam room.Chapters are also provided that address issues likely new to those who practice or conductresearch within a circumscribed specialty area The contributors have skillfully identifiedthe important discoveries of the previous years, explored where this field of research iscurrently headed, and emphasized the critical topics that require a more intensive researchfocus Overall, we hope the book will serve as a valuable reference for the current state ofknowledge regarding VaD as well as a guide for future studies

Series Editor’s Introduction v Preface vii Contributors xi

Part I Introduction

1 The Aging Population and the Relevance of Vascular Dementia

Kelly L Lange and Robert H Paul 3

2 Clinical Forms of Vascular Dementia

Gustavo C Román 7

3 The Neuropathological Substrates of Vascular-Ischemic Dementia

Kurt A Jellinger 23

4 Diagnosis of Vascular Dementia: Conceptual Challenges

José G Merino and Vladimir Hachinski 57

Part II Basic Mechanisms of Vascular Dementia

5 Cerebral Hemodynamics in the Elderly

Jorge M Serrador, William P Milberg, and Lewis A Lipsitz 75

6 The CADASIL Syndrome and Other Genetic Causes

of Stroke and Vascular Dementia

Stephen Salloway and Sophie Desbiens 87

7 Estrogen, the Cerebrovascular System, and Dementia

Sharon X C Yang and George A Kuchel 99

8 Effects of Hypertension in Young Adult and Middle-Aged Rhesus Monkeys

Mark B Moss and Elizabeth M Jonak 113

Part III The Impact of Vascular Dementia on Cognitive, Psychiatric, and Daily Living

9 The Cognitive Profile of Vascular Dementia

Angela L Jefferson, Adam M Brickman, Mark S Aloia,

and Robert H Paul 131

10 Progression of Cognitive Impairments Associated

With Cerebrovascular Disease

Sally Stephens, Raj Kalaria, Rose Anne Kenny, and Clive Ballard 145

11 Neuropsychiatric Correlates of Vascular Injury:

Vascular Dementia and Related Neurobehavioral Syndromes

Anand Kumar, Helen Lavretsky, and Ebrahim Haroon 157

12 Functional Impairment in Vascular Dementia

Patricia A Boyle and Deborah Cahn-Weiner 171

ix

x Contents

Part IV Neuroimaging of Vascular Dementia

13 Functional Brain Imaging of Cerebrovascular Disease

Ronald Cohen, Lawrence Sweet, David F Tate, and Marc Fisher 181

14 Contributions of Subcortical Lacunar Infarcts

to Cognitive Impairment in Older Persons

Dan Mungas 211

15 White Matter Hyperintensities and Cognition

David J Moser, Jason E Kanz, and Kelly D Garrett 223

16 Poststroke Dementia: The Role of Strategic Infarcts

Anelyssa D’Abreu and Brian R Ott 231

Part V Interactions Between Vascular Dementia and Alzheimer’s Disease

17 Understanding Incidence and Prevalence Rates

in Mixed Dementia

John Gunstad and Jeffrey Browndyke 245

18 Vascular Basement Membrane Abnormalities and Alzheimer’s Disease

Edward G Stopa, Brian D Zipser, and John E Donahue 257

19 Amyloid Beta and the Cerebral Vasculature

Paula Grammas 267

20 Cerebrovascular Disease and the Expression of Alzheimer’s Disease

Margaret M Esiri and Zsuzsanna Nagy 275

21 The Neuropsychological Differentiation Between Alzheimer’s Disease

and Subcortical Vascular Dementia

David J Libon, Stephen Scheinthal, Dana L Penney, and Rod Swenson 281

Part VI Clinical Management of Vascular Dementia

22 Pharmacological Treatment of Vascular Dementia

Timo Erkinjuntti, Gustavo Román, Serge Gauthier,

and Kenneth Rockwood 297

23 Understanding and Managing Caregiver Burden

in Cerebrovascular Disease

Geoffrey Tremont, Jennifer Duncan Davis, and Mary Beth Spitznagel 305

24 Quality of Life in Patients With Vascular Dementia

Rebecca E Ready and Brian R Ott 323

25 Approaches to Neuroprotection and Recovery Enhancement

After Acute Stroke

Marc Fisher and Magdy Selim 331

Index 341 About the Editors 355

Contributors

MARK S ALOIA,P h D • Department of Psychiatry and Human Behavior, Brown Medical School,

Providence, RI

CLIVE BALLARD • Wolfson Research Centre, University of Newcastle upon Tyne, Newcastle, UK

PATRICIA A BOYLE,P h D • Department of Neurology, Boston University School of Medicine,

SOPHIE DESBIENS,BS • Department of Biomedical Engineering, Boston University, Boston, MA

JOHN E DONAHUE,MD • Division of Neuropathology, Department of Pathology, Brown Medical

School, Providence, RI

TIMO ERKINJUNTTI,MD • Memory Research Unit, Department of Neurology, Helsinki University

Central Hospital, Helsinki, Finland

MARGARET M ESIRI,MD • Department of Clinical Neurology, University of Oxford;

Department of Neuropathology, Oxford Radcliffe NHS Trust, Oxford, UK

MARC FISHER,MD • Department of Neurology, University of Massachusetts Medical School,

Worcester, MA

KELLY D GARRETT,P h D • Utah State University, Logan, UT

SERGE GAUTHIER,MD • MCSA Alzheimer’s Disease Research Unity, McGill Center

for Studies on Aging, McGill University, Montreal, Canada

PAULA GRAMMAS,P h D • Department of Pathology and the Oklahoma Center for Neuroscience,

University of Oklahoma Health Sciences Center, Oklahoma City, OK

JOHN GUNSTAD,P h D • Department of Psychiatry and Human Behavior, Brown Medical School,

Providence, RI

VLADIMIR HACHINSKI,MD,FRCP(C),DSC • Department of Clinical Neurological Sciences, University

of Western Ontario, London Health Sciences Centre, London, Ontario, Canada

EBRAHIM HAROON,MD • Department of Psychiatry and Biobehavioral Sciences, UCLA School

of Medicine, Los Angeles, CA

ANGELA LEE JEFFERSON,P h D • Department of Psychiatry and Human Behavior, Brown Medical

School, Providence, RI

KURT A JELLINGER,MD • Institute of Clinical Neurobiology and University of Vienna, Vienna, Austria

ELIZABETH M JONAK,P h D • Yerkes National Primate Center, Emory University, Atlanta, GA

RAJ KALARIA • Wolfson Research Center, University of Newcastle upon Tyne, Newcastle, UK

JASON E KANZ,P h D • Department of Psychiatry, University of Iowa Carver College of Medicine,

Iowa City, IA

xii Contributors

ROSE ANNE KENNY • Wolfson Research Center, University of Newcastle upon Tyne, Newcastle, UK

GEORGE A KUCHEL,MD • University of Connecticut Center on Aging, University of Connecticut

Health Center, Farmington, CT

ANAND KUMAR,MD • Department of Psychiatry and Biobehavioral Sciences, UCLA School

of Medicine, Los Angeles, CA

KELLY L LANGE,MD • Department of Psychology, San Diego State University and Department

of Psychiatry, School of Medicine, University of California at San Diego, San Diego, CA

HELEN LAVRETSKY,MD • Department of Psychiatry and Biobehavioral Sciences, UCLA School

of Medicine, Los Angeles, CA

DAVID J LIBON,P h D • Department of Psychiatry, Center for Aging, School of Osteopathic Medicine,

University of Medicine and Dentistry of New Jersey, Stratford, NJ

LEWIS A LIPSITZ,MD • Division on Aging, Harvard Medical School, Hebrew Rehabilitation Center

for Aged, Beth Israel Deaconess Medical Center, Boston, MA

JOSÉ G MERINO,MD,MP HIL • Department of Neurology, University of Florida, Shands

Jacksonville, Jacksonville, FL

WILLIAM P MILBERG,P h D • Department of Psychiatry, Harvard Medical School and West Roxbury

Department of Veteran Affairs Medical Center, Boston, MA

DAVID J MOSER,P h D • Department of Psychiatry, University of Iowa Carver College of Medicine,

Iowa City, IA

MARK B MOSS,P h D • Department of Anatomy and Neurobiology and Department of Neurology,

Boston University School of Medicine, Boston, MA and Yerkes National Primate Center, Emory University, Atlanta, GA

DAN MUNGAS,P h D • Department of Neurology, University of California at Davis, Sacramento, CA

ZSUZSANNA NAGY,MD • Department of Pharmacology, University of Birmingham, Birmingham, UK

BRIAN R OTT,MD • Department of Clinical Neurosciences, Brown Medical School, Providence, RI

ROBERT H PAUL,P h D • Department of Psychiatry and Human Behavior, Brown Medical School,

Providence, RI

DANA L PENNEY,P h D • Department of Neurology, Lahey Clinic, Burlington, MA

REBECCA E READY,P h D • Department of Psychiatry and Human Behavior, Brown Medical School,

Providence, RI

KENNETH ROCKWOOD,P h D • Geriatric Medicine Research Unit, Queen Elizabeth II Health Science

Center, Dalhousie University, Halifax, Nova Scotia, Canada

GUSTAVO C ROMÁN,MD • Geriatric Research Education and Clinical Center, Department

of Neurology, University of Texas Health Science Center at San Antonio

and the Audie L Murphy Memorial Veterans Administration Hospital, San Antonio, TX

STEPHEN SALLOWAY,MD,MS • Departments of Clinical Neurosciences and Psychiatry and Human

Behavior, Brown Medical School; Department of Neurology, Butler Hospital, Providence, RI

STEPHEN SCHEINTHAL,DO • Department of Psychiatry, Center for Aging, School of Osteopathic

Medicine, University of Medicine and Dentistry of New Jersey, Stratford, NJ

MAGDY SELIM,MD,P h D • Department of Neurology, Harvard Medical School, Beth Israel Deaconess

Medical Center, Boston, MA

JORGE M SERRADOR,P h D • Division on Aging, Harvard Medical School, Beth Isreal Deaconess

Medical Center, Boston, MA

MARY BETH SPITZNAGEL,MS • Department of Psychiatry and Human Behavior, Brown Medical

School, Providence, RI

SALLY STEPHENS • Wolfson Research Center, University of Newcastle Upon Tyne, Newcastle, UK

EDWARD G STOPA,MD • Division of Neuropathology, Department of Pathology, Brown Medical

School, Providence, RI

LAWRENCE SWEET,P h D • Department of Psychiatry and Human Behavior, Brown Medical School,

SHARON X C YANG,MD • University of Connecticut Center on Aging, University of Connecticut

Health Center, Farmington, CT

BRIAN D ZIPSER,MD • Division of Neuropathology, Department of Pathology, Brown Medical

School, Providence, RI

Aging and Vascular Dementia 1

Introduction

I

2 Lange and Paul

Aging and Vascular Dementia 3

3

From: Current Clinical Neurology

Vascular Dementia: Cerebrovascular Mechanisms and Clinical Management

Edited by: R H Paul, R Cohen, B R Ott, and S Salloway © Humana Press Inc., Totowa, NJ

1 The Aging Population and the Relevance of Vascular Dementia

Kelly L Lange and Robert H Paul

1 INTRODUCTION

Changes occur in nearly every body system with advanced age Many adults successfully ate these transitions; nevertheless, physiologic changes and disease processes emerge with longerlifespan Numerous age-related changes in physical and psychological conditions can be addressedwith advances in medical procedures and pharmacological treatment; however, there are inevitableconsequences of prolonging life and the immediate effects on individuals extend to their families, thehealthcare system, and society at large In short, increased longevity introduces several financial andmedical challenges and has ramifications for quality of life in a large proportion of the world population.The significance of health among the elderly remains a paramount concern because of their chang-ing demographics In 2000, 35 million people in the United States were at least 65 yr old, accountingfor one of every eight Americans, with similar figures represented in most developed countries Pro-jections about the growth of this group indicate an expected doubling of the older population by 2030

negoti-to 70 million individuals, with individuals over the age of 65 accounting for one of every four cans As recently as the past decade (between 1990 and 2000) the number of adults aged 65 or older

Ameri-increased by 12% (1) The Ameri-increased prevalence of the older generation raises important questions

about their physical and mental health

Many older individuals express significant concern about potential loss of cognitive function andthe development of dementia with advanced age By no means is this a focus restricted to modernsociety Impaired thinking ability associated with advanced age was recognized by the Egyptians in

2000BC , and some records suggest that dementia was so ubiquitous among the elderly that it wasconsidered a “normal” aspect of the aging process by Plato and other scholars of the day This asser-

tion was debated then with no less vigor than it is currently (see ref 2) History aside, there is no

question regarding the overwhelming prevalence of the condition today Currently, more than 4 lion individuals in the United States are diagnosed with dementia, and the expected prevalence ispredicted to top 16 million by 2050 if the primary contributors to dementia are not controlled Thecurrent individual and societal costs of dementia are no less striking, and the magnitude of theseeffects will continue to parallel the changing demographics throughout the coming years

mil-Determining the etiology of dementia in the elderly has been a moving target In the distant past, cerebrovascular disease (CVD) was identified as the primary etiology of dementia EarlyFrench neurologists described discrete vascular lesions in the brain that were presumed to underliedeclines in mental functions Binswanger promulgated this model in 1894, reporting that arterioscle-rosis and associated reductions in brain perfusion were responsible for mental decline in older adult-