Diagnosis and Management in Dementia

The Neuroscience of Dementia, Volume 1

Colin R Martin, Victor R Preedy, Colin R. Martin, Victor R. Preedy

• Publisher: Academic Press
• Year: 2020
• Print ISBN:
  9780128158548
• eBook ISBN:
  9780128158555
• Topic: Medicine
• Subtopic: Physiology

Diagnosis and Management in Dementia: The Neuroscience of Dementia, Volume 1 consolidates different fields of dementia into a single book, covering a range of subjects, including Alzheimer's disease, Lewy body dementia, mixed dementia, vascular dementia, physical activity, risk factors, mortality, biomarkers, SPECT, CT, MRI, questionnaires, nutrition, sleep, delirium, hearing loss, agitation, aggression, delusions, anxiety, depression, hallucinations, psychosis, senile plaques, tau and amyloid-beta, neuroinflammation, molecular biology, and more. With an impact on millions globally, and billions of research dollars being invested in dementia research, this book will stimulate research in the area and inform researchers. - Offers comprehensive coverage of a broad range of topics related to dementia - Serves as a foundational collection for neuroscientists and neurologists on the biology of dementia and brain dysfunction - Contains in each chapter an abstract, key facts, mini dictionary of terms, and summary points to aid in understanding - Provides unique sections on specific subareas, intellectual components, and knowledge-based niches that will help readers navigate key areas for research and further clinical recommendations - Features preclinical and clinical studies to help researchers map out key areas for research and further clinical recommendations - Serves as a "one-stop" source for everything you need to know about dementia

Part I

Dementia: introductory chapters and setting the scene

Outline

1. Chapter 1. Mixed dementia: a neuropathological overview
2. Chapter 2. Vascular dementia: an overview
3. Chapter 3. Small vessel disease and dementia
4. Chapter 4. Linking amyotrophic lateral sclerosis and frontotemporal dementia
5. Chapter 5. Mortality in dementia: linking in the role of delirium
6. Chapter 6. Midlife diabetes and the risk of dementia: understanding the link
7. Chapter 7. Gait and dementia
8. Chapter 8. The role of blood pressure and hypertension in dementia
9. Chapter 9. Genetics of dementia: a focus on Alzheimer's disease
10. Chapter 10. Clinical and pathological phenotypes in dementia: a focus on autosomal dominant frontotemporal dementia
11. Chapter 11. Environmental and genetic risk factors for dementia
12. Chapter 12. Lipids, brain ageing, dementia, and lipidomics
13. Chapter 13. The 5×FAD mouse model of Alzheimer's disease

Chapter 1

Mixed dementia

a neuropathological overview

Jacques De Reuck Degenerative & vascular cognitive disorders. Lille, France

Abstract

The definitive diagnosis of mixed dementias can be made only by an extensive neuropathological examination. These diseases are mainly observed in elderly patients and further increase during the aging process even when they started as a single illness. They are for 85% of patients due to a combination of Alzheimer, Lewy body, and vascular pathology. The last can be due to cerebral amyloid angiopathy or arteriosclerotic cerebrovascular disease. However, some neurodegenerative diseases remain mainly unmixed, such as frontotemporal lobar degeneration, amyotrophic lateral sclerosis, progressive supranuclear palsy, and corticobasal degeneration. This can mainly be explained by the favorable vascular profile of the patients with these diseases. The clinical diagnosis of most mixed neurodegenerative and cerebrovascular dementia diseases can be suspected by means of magnetic resonance imaging and positron emission tomography of the brain, using glucose, amyloid, and tau tracers.

Keywords

7.0-tesla magnetic resonance imaging; Alzheimer pathology; Amyotrophic lateral sclerosis; Corticobasal degeneration; Frontotemporal lobar degeneration; Lewy body pathology; Mixed dementia; Neuropathology; Progressive supranuclear palsy; Unmixed dementia

List of abbreviations

AD Alzheimer disease

ALS amyotrophic lateral sclerosis

CAA cerebral amyloid angiopathy

CBD corticobasal degeneration

CoMBs cortical microbleeds

CoMIs cortical microinfarcts

FTLD frontotemporal lobar degeneration

FUS type fused sarcoma type

LBD Lewy body disease

MRI magnetic resonance imaging

PET positron emission tomography

PSP progressive supranuclear paralysis

TDP type TAR DNA-binding protein type

VaD vascular dementia

WMCs white matter changes

Mini-dictionary of terms

Mixed dementia severe cognitive deficiency due to a combination of different neurodegenerative and/or cerebrovascular diseases.

Neuropathological examination postmortem evaluation of the brain to confirm the clinical suspected diagnosis.

Postmortem MRI this allows the detection of additional postmortem brain lesions, in particular the distribution of small cerebrovascular lesions, and the iron content.

Neurodegenerative diseases progressive diffuse diseases affecting mainly neurons, leading to a global cerebral dysfunction.

Vascular dementia severe cognitive disturbances due to the progressive accumulation of small and large cerebrovascular lesions.

Introduction

The etiological diagnosis of mixed dementia diseases can be made with certainty only after death by an extensive examination of the brain (Jellinger & Attems, 2007). According to several clinicopathological surveys, the main clinical diagnosis is confirmed in 43% up to 86% of cases by the neuropathological evaluation (Suemoto et al., 2017). This correlation has increased significantly from 65% up to 96% since the development of new biomarkers such as magnetic resonance imaging (MRI), positron emission tomography (PET), cerebrospinal fluid analysis, and genetic markers (Jellinger, 2009).

In the Lille Memory Clinic the clinical diagnosis of Alzheimer disease (AD) is confirmed in 94% of the cases, Lewy body disease (LBD) in 80%, vascular dementia (VaD) in 100%, and mixed AD–VaD in 93% by the neuropathological examination (Bombois et al., 2008). Early previously obtained informed consent from the patients themselves or later from the nearest family allows the autopsy for diagnostic and scientific purposes. The brain tissue samples are acquired from the Neuro-Bank of Lille University, federated to the Centre des Resources Biologiques, which acts as an institutional review board.

The standard procedure for the neuropathological diagnosis of the dementia types consists of examining samples from the primary motor cortex; the associated frontal, temporal, and parietal cortices; the primary and secondary visual cortex; the cingulate gyrus; the basal nucleus of Meynert; the amygdaloid body; the hippocampus; the basal ganglia; the mesencephalon; the pons; the medulla; and the cerebellum. The slides from paraffin-embedded sections are stained with hematoxylin–eosin, Luxol fast blue, and Prussian Perl. In addition, immunostaining for protein tau, β-amyloid, α-synuclein, prion protein, TDP-43, and ubiquitin is performed (De Reuck, 2012a). Fused sarcoma (FUS) histochemistry is carried out in the cases of frontotemporal lobar degeneration (FTLD) that are tau and TDP-43 negative (De Reuck et al., 2016d). In addition, small cerebrovascular lesions can be quantified on microscopical examination of a large complete coronal section of a cerebral hemisphere at the level of the mammillary body.

Postmortem 7.0-tesla MRI is an additional useful tool. Three to six coronal sections of a cer...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• Contributors
• Foreword
• Preface
• Part I. Dementia: introductory chapters and setting the scene
• Part II. Biomarkers, psychometric instruments and diagnosis
• Part III. Pharmacological treatments for dementia
• Part IV. Non-pharmacological treatments and procedures
• Index