Front Cover
DIAGNOSIS AND MANAGEMENT IN DEMENTIA
DIAGNOSIS AND MANAGEMENT IN DEMENTIA
Copyright
Contents
Contributors
Foreword
Preface
I - Dementia: introductory chapters and setting the scene
1 - Mixed dementia: a neuropathological overview
Mini-dictionary of terms
Introduction
Incidence of mixed dementia
Unmixed and mixed Alzheimer disease
Unmixed and mixed lewy body disease
List of abbreviations
Unmixed and mixed frontotemporal lobar degeneration
Progressive supranuclear palsy
Amyotrophic lateral sclerosis
Corticobasal degeneration
Vascular dementia
Clinical diagnosis of mixed dementia
Key facts of mixed dementia
Summary points
References
2 - Vascular dementia: an overview
List of abbreviations
Mini-dictionary of terms
Introduction
Epidemiology and risk factors
Clinical features
Diagnosis
Cognitive assessment
Neuroimaging
Neuropathological features
Management and treatment options
Conclusions
Key facts of vascular dementia
Summary points
References
3 - Small vessel disease and dementia
List of abbreviations
Small vessel disease: the problem
Small vessel disease: concepts and imaging features
Small subcortical infarcts and lacunar strokes
White matter changes
Enlarged perivascular spaces
Cerebral microbleeds and other hemorrhagic lesions
Brain atrophy
Cortical microinfarcts
Detection of small vessel disease: imaging
Classification and pathogenesis of small vessel disease
Small vessel disease and cognitive impairment: subtypes
Small vessel disease and cognitive impairment: clinical features
Conclusions
Key facts
References
4 - Linking amyotrophic lateral sclerosis and frontotemporal dementia
Introduction.

Clinical features underlying the link between frontotemporal dementias and motor neuron disease
Pathological hallmarks underlying the link between frontotemporal dementia and ALS
FTLD-TDP
FTLD-FUS, FTLD-UPS
Genetics underlying the link between frontotemporal dementias and motor neuron disease
C9FTLD/ALS
TARDBP mutations, chromosome 1p36.22
Fused-in-sarcoma mutations, chromosome 16p11.2
VCP mutations, chromosome 9p13
CHMP2B mutations/frontotemporal dementia-3, chromosome 3p11
SQSTM1 mutations, chromosome 5q35
UBQLN2 mutations, chromosome Xp11.21
Conclusion
Key points
Summary points
References
5 - Mortality in dementia: linking in the role of delirium
List of abbreviations
Mini-dictionary of terms
Introduction
Delirium superimposed on dementia
Cognitive and functional decline in delirium superimposed on dementia
Does delirium play a role in dementia mortality?
Final considerations
Key facts of delirium superimposed on dementia
Summary points
References
6 - Midlife diabetes and the risk of dementia: understanding the link
Mini-dictionary of terms
Introduction
Evidence supporting the risk of dementia in diabetes
Potential pathoetiological mechanisms
Hyper- and hypoglycemia
Insulin resistance
Neuroinflammation
Glucocorticoid excess
Vascular pathology
Diabetes-related risk factors for dementia
Neuroimaging in patients with type 2 diabetes mellitus
Interventions to mitigate the risk of dementia in type 2 diabetes
Intensive Glycemic control
Metformin
Other oral hypoglycemics
Diet and exercise
Treatment strategies
Conclusion
Key facts of diabetes
Summary points
References
7 - Gait and dementia
List of abbreviations
Mini-dictionary of terms
Introduction
The measurement of gait.

Subjective description of gait
Quantitative measurement of gait
Different conditions under which gait can be assessed
Gait as a marker of mild cognitive impairment and dementia
Gait as a marker of mild cognitive impairment
Gait speed and mild cognitive impairment
Gait speed under dual-task and mild cognitive impairment
Other gait measures and mild cognitive impairment
Gait as a marker of dementia
Gait speed and dementia
Gait speed under dual-task and dementia
Other gait measures and dementia
Gait as a predictor of cognitive decline, mild cognitive impairment, and dementia
Gait as a predictor of cognitive decline and mild cognitive impairment
Gait as a predictor of dementia
Gait speed as a predictor of dementia
Motoric cognitive risk syndrome
Other gait measures
Dual-task walking as a predictor of dementia
Gait and biomarkers of dementia
β-Amyloid
Apolipoprotein E polymorphism ε4 allele
Brain atrophy and vascular disease
Summary points
Key facts of gait
References
8 - The role of blood pressure and hypertension in dementia
List of abbreviations
Mini-dictionary of terms
Introduction
Blood pressure and cognitive function
Hypertension as a risk factor for dementia
Alzheimer's dementia
Vascular dementia
Blood pressure in relation to brain structural and molecular changes
The physiology of hypertension-related brain changes
Vascular remodeling
Cerebral perfusion and autoregulation
Blood pressure and Alzheimer's disease neurobiology
Antihypertensive clinical trials for improving cognition
Conclusions
Key facts of hypertension
Summary points
References
9 - Genetics of dementia: a focus on Alzheimer's disease
List of abbreviations
Introduction
Genetics of Alzheimer's disease related to its pathophysiology.

Genes related to cognition involved in Alzheimer's disease
Conclusion
Definitions
Key facts of cognition
Summary points
References
10 - Clinical and pathological phenotypes in dementia: a focus on autosomal dominant frontotemporal dementia
List of abbreviations
Mini-dictionary of terms
Introduction
Genetics of frontotemporal dementia
Clinical symptoms of frontotemporal dementia
Behavioral variant frontotemporal dementia
Semantic dementia
Progressive nonfluent aphasia
Neuropathology of frontotemporal dementia
Genotype-phenotype correlations in autosomal dominant frontotemporal dementia
Microtubule-associated protein tau
Granulin precursor gene
Chromosome 9 open reading frame 72 gene
Chromatin-modifying protein 2B gene
Valosin-containing protein
Sequestosome 1
Fused in sarcoma gene
Ubiquilin 2 gene
Optineurin gene
Triggering receptor expressed on myeloid cells 2 gene
TANK-binding kinase 1 gene
Coiled-coil-helix-coiled-coil-helix domain-containing 10 gene
Double mutants in frontotemporal dementia
Conclusions
Key facts
Summary points
References
11 - Environmental and genetic risk factors for dementia
List of abbreviations
Mini-dictionary of terms
Introduction
Why are the risk factors of dementia important?
Environment-wide mapping of risk factors
Environmental risk factors
Genetic risk factors
Mendelian randomization studies
Biases in observational studies for dementia
Conclusions
Summary points
Acknowledgment
References
12 - Lipids, brain ageing, dementia, and lipidomics
List of abbreviations
Mini-dictionary of terms
Introduction
Plasma lipids
Plasma lipids and the brain over the lifespan
The role of lipids in brain ageing and cognition
Lipid-derived metabolites and neurotoxicity.

Protein-lipid interactome and the role of lipids in proteotoxicity
Fatty acids in ageing and dementia
Lipids in dementia and dementia biomarkers
Key facts
Key facts of plasma lipidomics
Key facts on the function of lipids in the brain
Summary points
Acknowledgments
References
13 - The 5×FAD mouse model of Alzheimer's disease
List of abbreviations
Mini-dictionary of terms
Introduction
Amyloid pathology
Neuroinflammation
Behavioral aspects of the model
Synaptic plasticity and long-term potentiation
Vascular pathology
Neuronal loss/synaptic dysfunctions
Tau pathology
Gender issue
Drawbacks of the 5×FAD mouse model
Advantages of the 5×FAD mouse model
Conclusion
Key facts of neurovascular pathology
Summary points
Acknowledgments
References
II - Biomarkers, psychometric instruments and diagnosis
14 - Use of cerebrospinal fluid in diagnosis of dementia
List of abbreviations
Mini-dictionary of terms
Introduction
Alzheimer disease
Amyloid beta-related biomarkers
Abeta peptides
Abeta-generating enzymes
sAPP peptides
Abeta oligomers
TAU-related biomarkers
Total tau
Posphorylated tau
Tau isoforms
Clinical use of CSF biomarkers in AD
Synaptic biomarkers
CSF biomarkers of microglial activation
Vascular cognitive impairment
Biomarkers of blood-brain barrier
Biomarkers of extracellular matrix breakdown
Biomarkers of white matter damage
Frontotemporal dementia
CSF neurofilament
CSF TDP-43
CSF progranulin
CSF AD biomarkers
Synucleinopathies
Parkinson's disease dementia
Dementia with lewy bodies
Key facts
Summary points
References
15 - Salivary biomarkers in Alzheimer's disease
List of abbreviations
Mini-dictionary of terms
Introduction.

Types of salivary biomarkers in Alzheimer's disease and methods of analysis.