Front Cover 1
Diet and Nutrition in Dementia and Cognitive Decline 4
Copyright Page 5
Contents 6
List of Contributors 14
Preface 22
Foreword 24
I. Introductory Aspects, Specific Conditions, and Basic Mechanisms in Dementia and Cognitive Decline 26
1 Cognitive Impairment and Dementia 28
List of Abbreviations 28
Introduction 28
Mild Cognitive Impairment 28
History and Development of Mild Cognitive Impairment 28
Subtypes of MCI 29
Epidemiology of MCI 29
Pathophysiology of Cognitive Decline 30
Risk Factors for Cognitive Decline 30
Current Diagnostic Criteria for MCI and AD 32
Preclinical Stages of Dementia 32
Core Clinical Criteria of “MCI Due to AD” 32
Research Criteria of “MCI Due to AD” 33
Diagnosis of Dementia 34
Treatment of Cognitive Decline 34
Applications to Other Areas of Cognitive Decline 34
Practical Issues 35
Summary Points 35
References 35
2 Alzheimer’s Disease 38
List of Abbreviations 38
Introduction 38
Clinical Symptoms 39
Neuropathology 39
Metabolic Disturbances 41
Therapeutics 42
Diagnostic Tools 43
Practical Issues 44
Summary Points 45
References 45
3 Amyotrophic Lateral Sclerosis and Dementia 48
List of Abbreviations 48
Introduction 48
Clinical Features, Diagnosis, and Care 49
Riluzole 50
Multidisciplinary Care 50
Nutrition 50
Respiration 51
Palliative Care and Hospice 51
Symptomatic Treatments 51
Epidemiology 51
Incidence and Mortality 51
Risk Factors 53
Measuring Progression 54
Clinical Features That Predict Survival 54
Clinical Trials 55
Applications to Other Dementias 56
Practical Issues 57
Summary Points 57
References 57
4 Corticobasal Degeneration and Dementia 60
List of Abbreviations 60
Introduction 60
Clinical Features 61
Neuropathology 61
Gross Features 61
Histopathology 62
Molecular Pathology 62
Neuroimaging 64
Diagnosis 64
Causes 65
Application to Other Dementias 65
Practical Issues 66
Summary Points 67
References 67
5 Creutzfeldt–Jakob Disease and Dementia 70
List of Abbreviations 70
Introduction 70
Prion Protein in Health and Disease 70
Etiological Classification of Human Prion Diseases 71
Neuropathological Aspects 72
Molecular Basis of Phenotypic Variability 74
Clinical Symptoms 74
Sporadic CJD 74
Iatrogenic CJD 74
Variant CJD 75
Genetic CJD 75
Sporadic and Familial Fatal Insomnia 75
GSS Disease and PrP Cerebral Amyloid Angiopathy 76
Differential Diagnosis 76
Currently Available and Routinely Used Laboratory Tests 76
Neuroimaging 76
Electroencephalogram 76
Cerebrospinal Fluid 76
Applications to Other Areas of Cognitive Decline 77
Practical Issues 77
Summary Points 79
References 79
6 Frontotemporal Lobar Degeneration 82
List of Abbreviations 82
Introduction 82
Diagnostic Criteria of bvFTD 83
Genetics: Autosomal-Dominant Inherited Mutations and Pathogenic-Related Mechanisms 84
MAPT 85
GRN 86
C9ORF72 87
Additional Genes 88
Final Remarks 88
Applications to Other Dementias 89
Practical Issues 89
Summary Points 89
Acknowledgment 90
References 90
7 Gaucher Disease and Dementia 92
List of Abbreviations 92
Introduction 92
Neuronopathic GD 93
Pathological Mechanisms 94
Establishment of an In Vitro GD Model to Study Neurodegenerative Mechanisms 95
Applications to Other Dementia 96
GD and Parkinson’s Disease 96
GD and Dementia with Lewy Bodies 96
Practical Applications 97
Therapeutic Approaches for GD 97
Clinical Applications to Other Dementia 98
Summary Points 98
Acknowledgments 98
References 98
8 Huntington’s Disease and Dementia: From Transgenic Models to Molecular Neuropathology 102
List of Abbreviations 102
Introduction 102
Neuropathology and Dementia in HD 103
Cognitive Changes in HD 104
HD Transgenic Models 105
Truncated Models 105
Full-Length Models 105
Knockin Models 105
Other Genetic HD Models 105
Molecular Etiology of HD 108
Mutant HTT Misfolding and Protein Aggregation 108
Energy Metabolism and Oxidative Stress 108
Glutamatergic Neurotransmission and Excitotoxicity 110
NMDA Receptor Signaling 110
Glutamate Uptake 110
Dysregulated Corticostriatal Neuronal Processing as a Key Driver of HD Neuropathology 110
Conclusion 112
Applications to Other Areas of Cognitive Decline 113
Practical Issues 113
Summary Points 113
References 113
9 Dementia with Lewy Bodies 116
List of Abbreviations 116
Introduction 116
Clinical Features 117
Neuropathology 117
Gross Features 117
Histopathology 118
Molecular Pathology 120
Neuroimaging 120
Diagnosis 121
Causes 121
Application to Other Dementias 121
Practical Issues 122
Summary Points 123
References 123
10 Normal Pressure Hydrocephalus: Etiology, Diagnosis, Treatment, and Putative Nutritional and Lifestyle Risk Facto ... 126
List of Abbreviations 126
Hydrocephalus 126
The Clinical Syndrome of NPH 128
Etiology of NPH: Idiopathic and Secondary 129
Applications to Other Dementias 129
Diagnosis of NPH 130
Surgical Management of NPH 131
Diet and Nutrition in iNPH 132
Summary 133
Summary Points 133
References 135
11 Cognitive Decline and Dementia in Parkinson’s Disease 138
List of Abbreviations 138
Introduction 138
History 138
Concepts and Pathophysiology 139
Epidemiology 139
Etiology and Risk Factors 139
Clinical Features and Diagnosis 139
Motor Features 139
Non-Motor Features 140
Neuroimaging 140
Functional Imaging 140
Cognitive Dysfunction in PD 141
Epidemiology of Cognitive Decline and Dementia in PD 141
Risk Factors for PDD 141
Neuropathology in PD and PDD 141
Clinical Picture Spectrum 142
Cognitive Domains 142
Memory 142
Executive Functions 142
Attention 142
Visuospatial Functions 142
Language/Speech 142
PD-MCI Diagnostic Criteria 142
Criteria for the Diagnosis and Specific Guidelines for PD-MCI (Figure 11.2) 143
Subtype Classification of PD-MCI 144
PDD Diagnostic Criteria 144
Behavioral Alterations in PD 145
Treatment 145
General Considerations 145
Treatment of PDD and Neuropsychiatric Symptoms 146
Applications to Other Areas of Cognitive Decline 147
Practical Issues 147
Summary Points 148
References 148
12 Pick’s Disease: The Evolution of Theory and Knowledge in Neurodegenerative Tauopathies 152
List of Abbreviations 152
Classical Conceptualization 153
Conceptual Evolution: Micropathology Guides Construct Development 153
The Essentials of Tau Protein 154
Tau and Pathology 155
Conceptual Evolution: From “Pick’s Disease” to FTLD 157
FTLD-Tau with Pick bodies 158
Epidemiology 158
Pathological Findings 158
Clinical Presentation 158
Applications to Other Dementia 159
Practical Issues 160
Summary Points 161
Acknowledgments 161
References 161
13 Posterior Cortical Atrophy and Dementia 164
Introduction 164
Prevalence 164
Pathophysiology 164
Risk Factors 164
Clinical Features 164
Non-Cognitive Symptoms 165
Cognitive Symptoms 166
Some Examples of PCA Presentations 166
Case 1 166
Case 2 166
Practical Issues 166
Differential Diagnosis 167
Diagnostic Features 167
Diagnostic Testing 167
Neuroimaging 168
Structural Imaging 168
Functional Neuroimaging 168
Application to Other Dementias 168
Treatment 168
Summary Points 169
Acknowledgment 169
References 169
14 Progressive Supranuclear Palsy and Dementia 172
List of Abbreviations 172
Progressive Supranuclear Palsy 172
General Aspects 172
Epidemiology 172
Pathology and Neurobiology 173
Clinical Manifestation 173
Differential Diagnosis 174
Diagnostic Workup 175
Clinical Investigation 175
Imaging 175
Biofluid Markers 175
Therapy 176
Cognitive Decline and Dementia in PSP 177
Epidemiology 177
Pathology and Neurobiology 177
Clinical Manifestation 177
Executive Function and Cognitive Slowing 177
Neuropsychiatric Symptoms 177
Social Cognition 177
Memory 178
Language 178
Differential Diagnosis 178
Diagnostic Workup 178
Neuropsychological Assessment 178
Imaging 178
Biofluid Markers 178
Therapy 179
Application to Other Areas of Cognitive Decline 179
Practical Issues 180
Summary Points 180
References 180
15 Cognitive Vascular Impairment: An Overview of Clinical, Diagnosis, and Treatment 184
Introduction 184
Definition and Diagnostic Criteria 184
Definition of VaD 185
Definition of VaMCI 185
Mechanisms of Disease 186
Pathophysiological Subtypes of VCI 188
Mixed AD/CVD 188
Clinical Evaluation 189
Neuropsychological Assessment 189
Neuroimaging 189
Treatment 189
Summary Points 190
References 190
16 Wernicke–Korsakoff Syndrome and Dementia 192
List of Abbreviations 192
Introduction 192
Historical Perspectives 193
Epidemiology of WKS 193
Thiamine Metabolic Functions 193
Mechanisms Leading to Thiamine Deficiency in WKS 193
Pathology and Neurological Damage in WKS 195
Clinical Features of WKS 196
Diagnosis of WKS 196
Treatment of WKS 197
Applications to Other DementiaS 197
Alcohol-Related Dementia 197
ARD and Its Relationship to Other Dementias 198
Treatment of ARD 198
Conclusions 199
Practical Issues 199
Summary Points 199
References 199
17 Rare and Unusual Dementias 202
List of Abbreviation 202
Introduction 202
Degenerative Causes 202
Vitamin-Related Deficiencies 203
Metal and Other Toxicities 204
Infectious Causes 205
Prion Diseases 206
Endocrinal and Metabolic Causes 207
Brain Trauma and Other Injuries 208
Neoplastic and Paraneoplastic Disorders 208
Autoimmune and Inflammatory Causes 209
Summary Points 209
References 209
18 Dementia: An Overview of Risk Factors 212
List of Abbreviations 212
Introduction 212
Epidemiology of Dementia and Risk Factors 213
Vascular Risk Factors and Dementia Why Was it Explored? 214
Nonmodifiable Risk Factors 214
Aging 214
Apolipoprotein E 215
Genetic Causes 215
Alzheimer’s Disease 216
Vascular Cognitive Impairment 216
Frontotemporal Dementia 216
Modifiable Risk Factors 217
Hypertension 217
Diabetes Mellitus 218
Hyperlipidemia 218
Smoking 219
Elevated Plasma Homocysteine 219
Atrial Fibrillation 219
Application to Other Dementias 219
Practical Issues 220
Conclusion 221
Summary Points 221
Acknowledgment 221
References 221
19 Setting the Scene: Cognitive Decline and the Default American Lifestyle 224
List of Abbreviations 224
The Brain’s Metabolic Needs 224
The Default American Lifestyle 225
Energy, Human, and Other 225
How Bounty Becomes Deficit 226
Body Mass Trajectories and Trends 227
BMI and Threats to Cognitive Function 227
Bioaccumulation and Pharm-accumulation 228
The New Majority: Old or Obese 231
Applications to Other Areas of Cognitive Decline 231
Practical Issues 232
Summary Points 232
Acknowledgments 232
References 232
20 Malnutrition in the Elderly 236
List of Abbreviations 236
Introduction 236
Nutritional Status in the Elderly (Definition and Prevalence) 236
Pathophysiology (Determinants and Consequences) 237
Nutritional Status Evaluation 240
Prevention of Malnutrition 243
Nutritional Intervention 243
Applications to Dementia or to Other Areas of Cognitive Decline 244
Practical Issues 244
Summary Points 245
References 245
21 Chronic Inflammation and Innate Immunity in Alzheimer’s Disease—Role of Diet 248
List of Abbreviations 248
Signatures of Inflammation Associated with Chronic Diseases of Midlife 248
Proinflammatory Chronic Disease in Midlife and Risk of AD and Dementia in Later Life 250
Effects of Antiinflammatory Therapy Use in Midlife on Attenuating Risk of AD and Dementia in Later Life 251
Effects of Antiinflammatory Dietary Profiles on Attenuating Risk of AD and Dementia in Later Life 251
Signatures of Inflammation Associated with Aging, Dementia, and AD 252
Effects of Immunomodulating Therapies on Progression of Dementia and AD 254
Applications to AD 255
Applications to Other Dementias 255
Practical Issues 256
Summary Points 256
References 256
22 Pathophysiological Mechanisms on How Nutritionally Related Components Can Have a Negative Impact on Cognition: The Examp ... 260
List of Abbreviations 260
Introduction 260
Metabolism of Homocysteine 261
Plasma Homocysteine 261
Homocysteine Metabolism in the Brain 261
Homocysteine and Brain Cells 262
Neurons 262
Astrocyte 263
Microglia 263
Neurogenesis 263
Blood–Brain Barrier 263
Animal Models of Hyperhomocysteinemia 263
Vitamin B Deficient Models 263
Non-Vitamin B Deficiency Models 264
Homocysteine Exacerbates AD Pathology 264
Applications to Vascular Dementia 264
Practical Issues 264
Conclusion 265
Summary Points 265
References 265
23 Body Composition and Cognitive Function: A Review with Focus on Aging and Disease 268
Introduction 268
Causes of Weight Loss and Changes in Body Composition During Aging 268
Body Composition and Cognitive Function in Healthy Subjects 269
Body Composition and Cognitive Function in Subjects with Cognitive Impairment 269
Applications to Other Areas of Cognitive Decline 273
Practical Issues 273
Summary Points 273
References 274
II. General Aspects, Nutritional Factors, and Specific Conditions in Dementia and Cognitive Decline 276
24 Whole of Diet Approaches: Evaluating the Evidence for Healthy Policy Guidelines, the Mediterranean, Vegetarian, Paleolit ... 278
List of Abbreviations 278
Introduction 279
Dietary Patterns Based on Health Policy Guidelines 279
Mediterranean Diet 281
Vegetarian Diets 282
Paleolithic Diet 283
Okinawa Diet 283
Ketogenic Diet 284
Caloric Restriction 284
Concluding Remarks 285
Practical Issues 286
Summary Points 286
Acknowledgments 287
References 287
25 Mediterranean Diet and Cognitive Health 290
List of Abbreviations 290
Introduction 290
The Mediterranean Diet: Basic Concepts 290
The MeDi: Overall Health Benefits 291
Assessment of MeDi Adherence 291
MeDi and Cognitive Health 292
Results from Cross-Sectional Studies 292
MeDi and Cognitive Decline 296
MeDi and Risk of MCI 303
MeDi and Risk of Dementia 304
MeDi and Subsequent Dementia Course 305
RCT: MeDi as Nutritional Intervention 305
Applications to Other Dementia 306
Practical Issues 306
Summary Points 307
References 307
26 Japanese Perspectives on Dietary Patterns and Risk of Dementia 310
List of Abbreviations 310
Introduction 310
The Burden of Dementia in Japan 311
Epidemiological Findings of Dietary Patterns and Risk of Dementia in Japanese Communities 311
Dairy Constituents and Risk of Dementia 312
Soybean Products and Risk of Dementia 314
Rice and Risk of Dementia 315
Other Dietary Factors Associated with Dementia Risk 316
Conclusion 316
Application to Other Subtypes of Dementia 317
Practical Issues 317
Summary Points 317
References 318
27 Western Diet and Cognitive Impairment 320
List of Abbreviations 320
Introduction 320
Effects of Obesity and Diet in Westernized Societies on Human Cognitive Functioning 321
Western Diet and Impaired Hippocampal-Dependent Learning and Memory 322
Underlying Neuroendocrine Mechanisms 323
Insulin 325
Leptin 325
Ghrelin 326
Applications to Other Areas of Cognitive Decline 327
A “Vicious Cycle” of Obesity and Cognitive Decline 327
Practical Issues 328
Summary Points 328
References 328
28 Dehydration in Elderly: Impact on Cognition 332
Introduction 332
The Physiology of Dehydration 332
Dehydration and Cognitive Impairment 333
Halting and Reversing Cognitive Impairment 335
Preventing Dehydration in the Elderly 335
Detecting and Treating Dehydration in the Elderly 337
Further Research 338
Summary Points 338
Practical Issues 339
References 339
29 Oral Health as Prerequisite of Nutrition Status in the Elderly 342
Introduction 342
Influential Factors on the Elderly in the Intake of Appropriate Diet 343
Periodontal Disease 343
Dental Caries 343
Xerostomia 344
Tooth Loss 344
Denture Fit 345
Oral Mucosa Lesions 345
Tongue Alterations 347
Applications to Other Areas of Cognitive Decline 347
Final Remarks 347
Practical Issues 347
Summary Points 348
References 348
30 Fruit and Vegetable Consumption and Cognitive Decline 350
List of Abbreviations 350
Introduction 350
Observed Associations Between Fruit and Vegetable Consumption and Measures of Cognitive Function 350
Fruits and Vegetables Combined 358
Vegetables 358
Subclasses of Vegetables 359
Root Vegetables 359
Cruciferous Vegetables 359
Allium 359
(Green) Leafy Vegetables 359
Fruiting Vegetables 360
Yellow Vegetables 360
Mushrooms 360
Legumes 360
Fruits 360
Subclasses of Fruits 360
Citrus Fruits 360
Berries 361
Nuts 361
Other Subclasses of Fruits 361
Juices 361
Other Subclasses 361
Is Fruit and Vegetable Consumption Beneficial for Maintenance of Cognitive Function? 361
Methodological Considerations 362
Varying Results Among Studies 362
Long-Term Effect of Lifestyle on Cognitive Function 363
Possible Mechanisms 364
Applications to Other Dementias or Other Areas of Cognitive Decline 364
Conclusion 364
Practical Issues 365
Summary Points 365
References 365
31 Medical Foods and Dietary Approaches in Cognitive Decline, Mild Cognitive Impairment, and Dementia 368
List of Abbreviations 368
Introduction 368
Effects of Dietary Supplementation on Cognitive Function—Biological Plausibility 369
Evaluating the Evidence 369
Observational Studies 369
Interventional Studies 369
Anecdotal Reports 370
Diet and Cognitive Function 370
Cognitive Decline 370
Risk for MCI 371
Risk for AD 371
Specific Dietary Supplements 372
Cognitive Decline 372
Ginkgo Biloba 372
Omega-3 Fatty Acids 372
Acetyl-L-Carnitine 373
Individual Vitamins 373
Vitamin A (Beta-Carotene) 373
Vitamin B 373
Vitamins C and E 373
Vitamin D 373
Multivitamins 373
Mild Cognitive Impairment 374
Ginkgo Biloba 374
Omega-3 Fatty Acids 374
Individual Vitamins 375
Alzheimer’s Disease 375
Ginkgo Biloba 375
Omega-3 Fatty Acids 375
Coenzyme Q10/Idebenone 375
Alpha-Lipoic Acid 375
Acetyl-l-Carnitine 375
Individual Vitamins 375
Medical Foods 376
Treatment of MCI and AD with Medical Foods 376
Ketone Bodies 376
INM-176 376
Cerefolin NAC 377
Souvenaid 377
Conclusions 378
Applications to Other Dementias 378
Practical Issues 378
Summary Points 378
Acknowledgments 379
References 379
32 Polymorphism and Cognition: The Example of Folate and MTHFR C677T 382
List of Abbreviations 382
Introduction 383
Chemistry, Source, and Metabolism 383
Chemistry 383
Sources 383
Metabolism 383
Absorption 383
Conversion 384
The Active Form 385
MTHFR 385
The Main Function 385
Folate, MTHFR C677T in Cognition 385
Folate, Homocysteine, and Cognition 385
Plasma Total Homocysteine Levels and MTHFR C667T 386
Folate, MTHFR 677TT Polymorphism, and Cognition 386
The Polymorphism of MTHFR Gene and Diseases 386
Vascular Disease 386
Neural Tube Defects 387
Down Syndrome 387
Stroke 387
Depression 387
Schizophrenia 387
Cancer 387
MTHFR 677TT Genotype and Cognitive Performance 387
MTHFR C677T Polymorphism, Homocysteine, and Cognition 388
Applications to Other Areas of Dementia or Cognitive Decline 389
Conclusions 389
Practical Issues 389
Summary Points 390
Acknowledgment 390
References 390
33 Eating Behavior of Dementia Patients 394
List of Abbreviations 394
Introduction 394
Perspectives from Which to Understand the Puzzling Eating Behavior of Dementia Patients 394
Intelligence That Has Evolved in Order to Deal with Complex Interpersonal Relations 395
A Self-Awareness Model in Order to Understand the Puzzling Words and Deeds of Dementia Patients 395
Evaluation for the Presence of “Theory of Mind” 397
Evaluation for the Presence of “Self-Evaluation” 397
Evaluation for the Presence of “Self-Consciousness” 398
The Puzzling Eating Behavior of Dementia Patients Seen from the Viewpoint of the Self-Awareness Model 398
Stage in Which Patients Passed the “Theory of Mind” Task CDR: Mild–Moderate 399
Stage in Which Patients Passed the “Self-Evaluation” Task but Failed the “Theory of Mind” Task CDR: Moderate–Severe 399
Stage in Which Patients Passed the “Self-Consciousness” Task but Failed the “Self-Evaluation” Task CDR: Severe 399
Stage in Which Patients Fail to Pass the “Self-Consciousness” Task CDR: Severe 400
“Fragile Selves” that Collapse with Loss of “Self-Awareness” 400
Applications to Other Dementias 401
Practical Issues 401
Dementia Patients’ Nutrition 402
Summary Points 402
References 402
34 An Overview of the Association Between Obesity in Later Life and Dementia Risk 404
List of Abbreviations 404
Introduction 404
Is Obesity Associated with Dementia Risk? 405
Is Weight Loss Associated with Dementia Risk? 411
Putative Mechanisms: Causality, Reverse Causality, or Residual Confounding? 411
Applications to Other Areas of Cognitive Decline: Caloric Restriction and Cognition 414
Practical Issues 415
Summary Points 415
References 415
35 Cognitive Decline and Diabetes: A Focus on Linking Mechanisms 418
List of Abbreviations 418
Introduction 418
Applications to Other Areas of Cognitive Decline 419
Pathophysiology of Cognitive Decline Among Diabetic Subjects 420
Abnormal Glucose Metabolism 421
Hyperglycemia 421
Hypoglycemia 422
Glucose Fluctuation 422
Vascular Mechanisms 422
Nonvascular Mechanisms 423
Impaired Insulin Signaling 423
Mitochondrial Dysfunction 424
Adiposity 424
Practical Issues 425
Conclusions 425
Summary Points 425
References 426
36 Dementia and Insulin Resistance: Implications for Diet and Nutrition 428
List of Abbreviations 428
Introduction 428
Insulin and IGF-1 in the Brain 429
Glucose Metabolism and AD 429
Insulin and IGF-1 Signaling in AD 429
Insulin and Oxidative Stress Mechanisms in AD 430
Applications to Other Dementia 431
Insulin, IGF-1 Signaling, and Amyloid in AD 432
Insulin, Inflammation, and AD 432
Role of Diet and Insulin Resistance in AD 433
Practical Issues 434
Summary Points 435
References 435
37 Diabetes, Cognitive Decline, and Genome-Wide Associations 438
List of Abbreviations 438
Introduction 438
Applications to Other Areas of Cognitive Decline 439
Genetics and MCI 441
Genetics and AD 442
Genetics and Type 2 Diabetes 443
Genetic Polymorphisms, MCI, AD, and Diabetes 443
Practical Issues 444
Summary Points 445
References 445
38 MRI of White Matter in Dementia in Relation to Cardiovascular Risks: Implications for Diet and Nutrition 448
List of Abbreviations 448
Introduction 448
WMH IN AD and VaD 450
WMH and LBD 453
Parkinson’s Disease with Dementia 453
Dementia with Lewy Bodies 454
Implications for Medical Preventive Treatment, Lifestyle Factors, Specially Focused on Diet and Nutrition 454
Practical Issues 456
Summary Points 456
References 456
39 Relationship Between Nutritional and Psycho-Functional Status in Alzheimer’s Disease 460
List of Abbreviations 460
Introduction 461
Eligibility Criteria and Search Strategy 462
General Characteristics of Selected Articles 462
Bibliographic Characteristics 466
Study Setting, Participants, and Methodologies 466
Association Between Nutritional and Psycho-Functional Status 466
Nutritional and Psycho-Functional Association in AD 467
Applications to Other Areas of Cognitive Decline 468
Practical Issues 469
Summary Points 470
References 470
40 Ketosis in Mild Cognitive Impairment and Alzheimer’s Disease 472
List of Abbreviations 472
Introduction 472
Applications to Other Areas of Cognitive Decline 473
Practical Issues 473
Brain Energy Metabolism and Aging 473
Hypometabolism and APP Processing 474
Environmental Factors in Hypometabolism 475
Ketogenic Diets 476
Ketosis and AD 477
Ketosis and MCI 478
Conclusion 479
Summary Points 479
Disclosure and Acknowledgments 479
References 479
41 Leptin and Alzheimer’s Disease 482
List of Abbreviations 482
Introduction 482
Leptin 483
Leptin Receptor 483
Leptin Receptor Expression in the CNS 484
Leptin Receptor Signal Transduction 484
Leptin Regulation of Hippocampal Synaptic Plasticity 485
Leptin Induces a Persistent Increase in Excitatory Synaptic Strength in Adult Hippocampus 486
Leptin and the Aging Brain 487
Obesity, Leptin, and AD 487
Neuroprotective Actions of Leptin 487
Leptin and Synaptic Function in AD 489
Conclusions 489
Applications to Other Dementias 489
Practical Issues 490
Summary Points 490
References 490
42 Circulating Oxidative Damage and Antioxidant Defense System Biomarkers in Early Stage Alzheimer’s Disease 494
List of Abbreviations 494
Introduction 494
Oxidative Stress in AD 495
Genetic Susceptibility for AD 495
Circulating Oxidative Stress Biomarkers in AD 496
Antioxidant Defense Systems and AD 496
Applications to Other Dementia 499
Practical Issues 500
Summary Points 500
Acknowledgments 500
References 500
43 The Contribution of Raised Metabolic Rate in the Weight Loss Associated with Alzheimer’s Disease 504
List of Abbreviations 504
Introduction 504
Energy Intake and AD 504
Energy Expenditure and AD 505
Basal Metabolic Rate 505
Adaptive Thermogenesis 508
Physical Activity 508
Applications to Other Areas of Cognitive Decline 508
Practical Issues 508
Summary Points 510
References 510
44 Nutrition and Survival in Patients with Amyotrophic Lateral Sclerosis 512
List of Abbreviations 512
Introduction 512
Practical Issues 515
Summary of Points 515
References 516
45 Eating Disturbance in Frontotemporal Dementia 518
List of Abbreviations 518
Introduction 518
Alteration of Eating Behavior in FTD 519
Characteristics of Eating Behavior in FTD Subtypes 519
Behavioral Variant FTD 519
Semantic Dementia 519
Biology of Eating Disturbance in FTD 520
Implications for Other Dementias 521
Practical Issues 522
Conclusion 523
Summary Points 523
Acknowledgments 524
References 524
46 Oxidative Stress, Micronutrients, and HIV Dementia 526
List of Abbreviations 526
Introduction 526
Pharmacological Treatment of HIV Infection 527
Oxidative Stress, Vitamin E, and HAND 527
Sources of Oxidative Stress in HIV Infection 529
Effects of Vitamin E Administration on HIV Infection 529
Antioxidants and HAND 530
Application to Other Areas of Cognitive Decline 531
Practical Issues 532
Summary Points 532
References 532
47 Homocysteine and Cognitive Decline in Parkinson’s Disease 536
List of Abbreviations 536
Introduction 536
Parkinson’s Disease 536
CI in PD 537
Typical Neuropsychological Profile of CI in PD (Table 47.2) 538
Neuropathology and Pathophysiology 539
Hcy in PD 539
Hcy, B Vitamins, and Levodopa 539
Cognitive Decline, Vitamins, and Hcy 540
Cognitive Decline and Hcy in PD: Highlights 541
Therapeutic Possibilities: Practical Issues 541
Measures to Reduce the Level of Hcy in Patients with PD 541
Supplements of Folic Acid and Vitamin B12 541
Inhibition of COMT 542
Lifestyle 542
Conclusion: Considerations and Limitations 542
Summary Points 543
References 543
48 Focusing on the Effect of Body Mass Index Status in the Risk of Vascular Dementia Development 546
List of Abbreviations 546
Introduction 546
The Reality of Vascular Dementia 546
Relation of Changes in Body Mass Index to VaD 547
Is Obesity in Midlife a Risk Factor for VaD in the Future? 547
Which Category of BMI in Later Life Would Be Related to VaD, Underweight or Overweight? 548
Is Weight Loss a Predictor of VaD? 549
Practical Issues 551
Summary Points 551
References 551
49 Antioxidant Status in Vascular Dementia 554
List of Abbreviations 554
Introduction 554
In Vitro and In Vivo Experiments 555
Studies of Human Patients 557
Diet, Antioxidants, and VaD 559
Applications to Other Dementias 560
Conclusion 560
Practical Issues 560
Summary Points 560
Acknowledgments 561
References 561
50 Gastrointestinal Surgery and Wernicke Encephalopathy 564
List of Abbreviations 564
Introduction 564
Sources of Vitamin B1 565
Vitamin B1 Metabolism (Figure 50.1) 565
Pathophysiology of Brain Damage Due to Thiamine Deficiency 566
Vitamin B1 Mediated Processes in Brain Functions (Figure 50.2) 566
Risk Factors and Clinical Findings in Nonalcoholic WE 567
Malnutrition and/or Absorption Deficit Lead to Thiamine Deficiency, Particularly in the Elderly 567
Complexity of Clinical Picture in Nonalcoholic WE 568
Life-Threatening WE Complicates Gastrointestinal Surgery for Cancer: A Retrospective Case Series Study (Table 50.3) 568
Brain MRI Findings 570
Factors Influencing Outcome and Therapy 570
Postsurgical Complications Negatively Influencing the Outcome 570
Application to Other Dementias and Other Areas of Cognitive Decline 570
Thiamine Deficiency as a Model of Neurodegeneration in AD 570
WE: A Treatable Form of RPD 571
Practical Issues 571
Summary Points 572
References 572
III. Micronutrients in Dementia and Cognitive Decline 576
51 Aluminum and Alzheimer’s Disease 578
List of Abbreviations 578
Introduction 578
Biology of Aluminum 578
Dietary Sources, Absorption, and Pharmacokinetics of Aluminum 579
Aluminum Toxicity and Health Risks 580
Aluminum and the Brain 580
Alzheimer’s Disease 581
Aluminum and Alzheimer’s Disease 582
Practical Issues 584
Conclusions 584
Applications to Other Dementia 584
Summary Points 584
References 585
52 Iron and Copper in Alzheimer’s Disease: A Review 588
List of Abbreviations 588
Introduction 588
The Impact of Supplementation or Depletion 589
Evidence from Observational Studies 590
Brain Levels of Cu and Fe in AD 590
Systemic Levels of Cu and Fe in AD 592
Molecular Considerations 592
Applications to Other Areas of Dementia 593
Practical Issues 593
Summary Points 594
Acknowledgments 594
References 594
53 Neuroimaging of Brain Iron Deposition in Mild Cognitive Impairment and Dementia 598
List of Abbreviations 598
Introduction 598
Imaging Techniques to Detect Brain Iron Deposition 599
Histologically Documented Iron Deposition in Microhemorrhages 600
Focal Iron Deposition (Microhemorrhages) in Normal Aging 600
Focal Iron Deposition in MCI and AD 601
Applications to Other Forms of Dementia 602
Differential Diagnoses of Multiple Microhemorrhages 602
Multiple Microhemorrhages in Hypertensive Leukoencephalophathy 602
Cerebral Amyloid Angiopathy 602
Multiple Cavernomas 602
Global Iron Deposition 602
Global Degenerative Iron Deposition in Normal Aging 604
Global Degenerative Iron Deposition in MCI and AD 604
Dietary and nutritional aspects of iron 604
Applications to Other Areas of Cognitive Decline 605
NBIA in Young Age 605
Practical Issues 606
Individual Level Classification Based on Brain Iron Deposition 606
Summary Points 606
References 606
54 Magnesium and Alzheimer’s Disease: Implications for Diet and Nutrition 610
List of Abbreviations 610
Introduction 610
Magnesium Metabolism in Older Adults 610
Magnesium and Cognitive Function 612
Alzheimer Disease, Oxidative Stress, and Magnesium 614
Neuroprotective Role of Magnesium 614
Conclusions 615
Summary Points 616
References 616
55 Inorganic Mercury and Alzheimer’s Disease—Results of a Review and a Molecular Mechanism 618
List of Abbreviations 618
Background 618
IM and AD 620
Mercury Exposure in Workers 620
Health Effects of Dental Amalgams 620
Mercury Exposure, Accumulation, and Excretion in Alzheimer Patients 620
Experimental Animal and In Vitro Studies 622
A Mechanistic Model of Mercury Toxicity 623
Applications to Other DementiaS 624
Practical Issues 625
Summary Points 625
Acknowledgment 625
References 625
56 Carotenoids in Cognitive Impairment with and without Dementia 628
Introduction: Micronutrients, Oxidative Stress, and Carotenoids 628
Biological Activity of Carotenoids: Implications for Cognitive Impairment-Related Oxidative Stress 629
Carotenoids in the Frame of Nutrition, Aging, and Cognitive Impairment: Applications to Other Areas of Cognitive Decline 630
Practical Issues 632
References 632
57 Homocysteine and Dementia 636
List of Abbreviations 636
Introduction 636
Homocysteine—Metabolism and Possible Mechanisms of Nervous System Injury 637
Homocysteine as a Vascular Risk Factor 638
Homocysteine as a Risk Factor for Neurodegeneration 638
Environmental and Genetic Factors Responsible for Hyperhomocysteinemia 639
Applications to Other Dementias (The Role of Hcy in Different Dementia Syndromes) 640
AD and Hcy 640
VaD and Hcy 641
LBD and Hcy 641
Possible Therapeutic Options 642
Practical Issues 644
Summary Points 644
References 644
58 Vitamin A and Cognitive Impairment 648
Introduction 648
Vitamin A and Nutritional Concerns 649
Sources and Functions 649
Metabolism and Signaling Pathway 649
Vitamin A and Aging: Implications for Metabolism and Signaling Pathway 650
Vitamin A and Cognitive Decline 653
Importance Throughout Life 653
Vitamin A Deficiency: A Nutritional Model That Mimics the Aging Processes 654
Reversibility of Memory Disorders by RA Administration or Vitamin A Supplementation 654
Vitamin A and AD 654
Results from Experimental Studies 654
AD-Related Genes Under the Control of RA 654
RA Hypoactivity Signaling Leads to AD-Related Damage 655
Therapeutic Effects of Retinoids in Animal Models of AD 655
Results from Epidemiological Studies 656
Applications to Other Areas of Cognitive Decline 657
Practical Issues: Dietary Guidelines for Vitamin A Intake for the Elderly 657
Conclusion 658
Summary Points 658
References 659
59 Vitamin B12 and Cognitive Impairment 662
List of Abbreviations 662
Introduction 662
The Vitamin B12 Reference Ranges 663
Malabsorption and Vitamin B12 Deficiency in Older Adults 664
The Prevalence of Vitamin B12 Deficiency in the Elderly 665
Proposed Mechanisms of Disease of Low Vitamin B12 Levels in Neurological Health 665
Vitamin B12 and Cognition in the Elderly 666
Vitamin B12 Supplementation and Cognition in Cognitively Intact Elders 667
Vitamin B12 Supplementation Does Not Improve Cognition in Dementia Patients with Normal Vitamin B12 Levels 668
Vitamin B12 Therapy in Patients Who Are Vitamin B12 Deficient 669
Benefits of Improving Vitamin B12 Levels Through Dietary Intake 670
Applications to Other Areas of Cognitive Decline 670
Practical Issues 671
Summary Points 671
References 671
60 An Overview on Vitamin B12 and Dementia with Behavioral and Executive Disturbances 674
List of Abbreviations 674
Introduction 674
Vitamin B12 and AD 674
Psychiatric Disturbances, Dementia, and VB12D 676
VB12D Can Cause Psychiatric Symptoms via Multiple Mechanisms 677
Hyperhomocysteinemia and Brain Circuits 677
Changes in Myelin and Subcortical Dysfunction 677
Derangement of Methylation Reactions and Synthesis of Transmitters 677
BRAIN ATROPHY 678
VB12D Can Manifest with Symptoms of FTD 678
Pathophysiological Mechanisms Associated with VB12D and Frontal Dysfunction 683
Patients with FTD-Like Syndrome Due to VB12D Meet Diagnostic Criteria for FTD 683
Application to Other Areas of Cognitive Decline 685
Practical Issues 685
Summary Points 686
References 686
61 Potential Role of Vitamin C in the Prevention of Alzheimer’s Disease 688
List of Abbreviations 688
Introduction 688
Practical Issues—Potential Role of VC in AD Prevention FROM Human Studies 689
Potential Role of VC in AD Prevention from Animal Studies 690
Applications of VC to Other Dementias 691
Future Direction 691
Summary Points 691
Acknowledgments 692
References 692
62 Vitamin C and Glutamate Uptake: Implications for Huntington’s Disease 694
List of Abbreviations 694
Introduction 694
Vitamin C Biochemistry 695
Vitamin C in the Brain 696
Striatal Dysfunction in HD 698
Dysregulation of Glutamate and Vitamin C in HD Striatum 699
Upregulation of GLT1 700
Applications to Other DementiaS 701
Practical Issues 701
Summary Points 701
References 702
63 Vitamin D and the Association with Cognitive Performance, Cognitive Decline, and Dementia 704
List of Abbreviations 704
Introduction 705
Sources of Vitamin D 705
Vitamin D Metabolism 705
Why Is the Elderly Population at Risk for Developing a Deficiency? 706
Vitamin D–Mediated Processes in Brain Function 707
Behavioral Correlates of Vitamin D Deficiency in Rodents 707
Vitamin D and Cognitive Performance in Human Population-Based Studies 708
Serum 25(OH)D and Global Cognitive Performance 708
Cross-Sectional Studies 708
Prospective Studies 713
Sex Differences 713
Serum 25(OH)D and Domain-Specific Cognitive Performance 713
Cross-Sectional Studies 713
Prospective Studies 713
Serum 25(OH)D and Magnetic Resonance Imaging Studies in Humans 718
Vitamin D and Cognitive Performance: Evidence from Human Trials 719
Applications to Other Areas of Cognitive Decline 722
Alzheimer’s Disease 722
Other Neuropsychiatric Disorders 722
Practical Issues 722
Summary Points 723
References 723
64 1a,25-Dihydroxyvitamin D3 and Resolvins Improve Immunity to Amyloid-ß in Patients with Alzheimer’s Disease 726
List of Abbreviations 726
Introduction 726
Targets of AD Immunotherapy: Adaptive Immunity Versus Innate Immunity 726
Rationale for AD Prevention by Vitamin D and .-3 Fatty Acids 727
Immune Reactivity of AD Patients 727
Supplementation of Vitamin D3 729
Neuroprotective (Intracranial) and Immune (Extracranial) Effects of Vitamin D and Curcuminoids Against Dementia 730
Neuroprotective and Immune Effects of DHA, Resolvins, and Neuroprotectin D1 730
Effects of 1,25D3 and RvD1 on Aß42 Phagocytosis and Inflammation in Human Macrophages Versus Mouse Models 730
Clinical Trials of DHA 731
Conclusions 731
Summary Points 731
Acknowledgments 732
References 732
65 Vitamin E Status in Niemann–Pick Type C 734
List of Abbreviations 734
Introduction 734
Vitamin E 734
Biological Activity of Vitamin E 734
Antioxidant Function 735
Vitamin E in the CNS 736
Niemann–Pick Disease, Type C 737
Vitamin E and Niemann–Pick Disease Type C 737
Vitamin E as a Therapy for Niemann–Pick Disease Type C? 738
Applications to Other Dementias 739
Practical Issues 739
Summary Points 740
References 740
IV. Lipids, Amino Acids, Proteins, and Alcohol in Dementia and Cognitive Decline 742
66 Olive Oil and Huntington’s Disease 744
List of Abbreviations 744
Introduction 745
Applications to Other Dementias 745
Neurodegenerative Diseases and Mediterranean Diet 745
Practical Issues 746
Beneficial Effects of Mediterranean Diet 746
Oxidative Stress and Inflammation 746
Huntington’s Disease 749
Huntington’s Disease and Oxidative Stress 750
Mediterranean Diet 750
Olive Oil 750
Mediterranean Diet, Olive Oil, and Huntington’s Disease 753
Basic Studies 753
Summary Points 754
References 754
67 The Impact of High Saturated Fat and High Glycemic Index Foods on Cognitive Function and Alzheimer’s Disease Bio ... 758
List of Abbreviations 758
Introduction 758
Longevity and Diet Patterns 758
Components of the Western Diet Worsen Cognition and Increase Risk for AD 759
Western Diet Components, Amyloid, and Tau 759
Western Diet Components and Altered Brain Lipid Chemistry 761
Western Diet Components and Brain Insulin Resistance 762
Inflammation/Oxidation 762
Western Diet, Adipocytes, and Hormones 763
Western Diet Components and Cerebral Blood Flow 763
Gene/Diet Interactions: Does One Diet Fit All? 764
Applications to Other Dementias 764
Practical Issues 764
Conclusion 765
Summary Points 765
References 765
68 Cholesterol Levels and Cognitive Impairments 768
List of Abbreviations 768
Introduction 768
Hypercholesterolemia as an Early Risk Factor for AD 769
Cholesterol Homeostasis Behind the Blood–Brain Barrier 769
Role of apoE in Cerebral Aß Clearance 770
Hypercholesterolemia Affects Aß Cerebral Metabolism 771
Influence of Hypercholesterolemia on the Integrity of the BBB 771
Perspectives 773
Application to Other Areas of Cognitive Decline 774
Practical Issues 774
Summary Points 774
References 774
69 Statins and Reduction of Oxidative Stress in the Aged Brain 778
List of Abbreviations 778
Introduction 778
Aging and Oxidative Stress 778
Alzheimer’s Disease and Metabolic Dysfunction 778
Effect of Statins for AD 779
Simvastatin 780
Atorvastatin 780
Pitavastatin 781
Pravastatin 781
Applications to Other Dementias 782
Practical Issues 783
Summary Points 783
References 784
70 Glutamine as a Potential Neuroprotectant in Alzheimer’s Disease 786
List of Abbreviations 786
Introduction 786
Glutamine Is Multifunctional and Conditionally Essential 786
Glutamine Synthetase Is the Essential Enzyme for In Vivo Glutamine Production 788
Defective Glutamine Metabolism in Aging and AD 789
ß-Amyloid and Glutamine Metabolism 790
Glutamine Metabolism and Inflammation 791
Glutamine and Autophagy 791
Glutamine and Diabetes 792
Glutamine and the Intestine 792
Glutamine and Exercise 792
Applications to Other Brain Diseases 793
Practical Issues 793
Summary Points 794
References 794
71 Dietary Protein, Cognitive Decline, and Dementia 798
List of Abbreviations 798
Introduction 798
Sources of Protein 799
Habitual Protein Intake 799
Protein Metabolism 800
Dietary Protein and Dementia and Cognitive Decline 800
Total Protein 801
Evidence from Observational Studies 801
Evidence from Clinical Trials 801
Individual Amino Acids 801
Tryptophan 804
Tyrosine 805
Applications to Other Areas of Cognitive Decline 805
Practical Issues 805
Summary Points 806
References 806
72 Ethanol and Cognition 810
List of Abbreviations 810
Introduction 810
Direct and Indirect Effects of Ethanol on Cognition 810
Alcoholic Dementia 811
Ethanol as a Neuroprotectant 813
Applications to Other Areas of Cognitive Decline 815
Practical Issues 815
Summary Points 815
References 816
V. Nutraceuticals and Dietary Components in Dementia and Cognitive Decline 818
73 Herbs and Dementia: A Focus on Chinese and Other Traditional Herbs 820
List of Abbreviations 820
Introduction 820
Dietary Herbs and Neuroprotection 820
Huperzine A 823
Bacopa monnieri 823
Applications to Other Areas of Cognitive Decline 825
Practical Issues 826
Conclusion 827
Summary points 827
References 828
74 Chinese Herbs for Cognitive Decline: Historical and Contemporary Applications 830
List of Abbreviations 830
Introduction 830
Memory Disorders and Their Treatment in Pre-Modern China 830
Plants Used for Memory Disorders in the Traditional Pharmacopoeia 831
Traditional Use of Multiingredient Formulae for Memory Disorders 831
Dementia and Memory Disorders in Contemporary Traditional Chinese Medicine 832
Contemporary Clinical Studies on Herbal Formulae for Dementia and Memory 834
Gou Teng San (GTS) (Japanese Name: Chotosan) 836
Yi Gan San (YGS) (Japanese Name: Yokukansan) 836
Selected Single Plants and Extracts 839
Ginseng 839
Polygala tenuifolia 839
Ginkgo biloba 839
Huperzia serrata 840
Applications to Other Areas of Cognitive Decline 840
Practical Issues 840
Summary Points 841
Acknowledgments 842
References 842
75 Multivitamin Supplementation and Cognitive Performance: An Overview of Current Evidence 844
Abbreviation 844
Introduction 844
Vitamin Deficiency in the General Population 844
Vitamin Deficiency and Cognition 844
Supplementing Diet with Multivitamin Formulations 845
Multivitamins and Cognition 845
Multivitamins and Cognition: Other Contributions 847
Applications to Other Areas of Cognitive Decline 848
Practical Issues 848
Future Directions 848
Summary 849
References 849
76 Natural Antioxidants in Dementia: An Overview 852
List of Abbreviations 852
Introduction 852
Characteristics of Natural Antioxidants 853
Polyphenols 854
Resveratrol 854
Ginkgo biloba 854
Curcumin 855
Epigallocatechin Gallate 855
Tannic Acid 856
Genistein and Related Compounds 856
Non-Phenolic Antioxidants 856
Pycnogenol 856
Caffeine and Dementia 857
Murraya koenigii 858
Acetyl-l-Carnitine and Dementia 858
Carnosine and Dementia 858
Other Compounds with Prospective Use for Dementia 858
Applications to Other Dementias 859
Practical Issues 859
Summary Points 859
References 860
77 Nutritional Approaches to Mitigating Cognitive Decline and Maintaining Function in Alzheimer’s Disease: Transgenic Mouse ... 862
Introduction 862
Nutritional Studies Harbor Inherent Compromise 862
Utility of Studies in Transgenic Mouse Models 864
The Timing of Nutritional Intervention Is Critical for Efficacy in Humans 865
A Combinatorial Approach May Provide Maximum Benefit 866
Application to Other Areas of Cognitive Decline 866
Maternal Folate Insufficiency Can Impact Early- and Late-Stage Cognitive Decline 866
Practical Issues 867
Summary Points 869
References 869
78 The Antioxidant Effect of LMN Diet, Rich in Polyphenols and Polyunsaturated Fatty Acids, in Alzheimer’s Disease 872
List of Abbreviations 872
Introduction 872
Alzheimer’s Disease 872
Oxidative Stress 872
Diet as Possible Therapy for AD 872
Healthy Role of Diets Rich in Polyphenols 873
LMN-Rich Diet Has a Beneficial Effect on Neurogenesis and Neuroprotection 873
LMN Diet Increases Survival of SH-SY5Y H2O2 Damaged Cell Line 873
LMN Diet Is Able to Decrease ROS Levels and to Increase Antioxidant Enzyme Expression in Cells 874
LMN Antioxidant Effects Are Even More Pronounced Once in Plasma 875
LMN Intake Allows an Antioxidant Metabolomics Profile Both in Mice and by Acute Intake in Humans 875
Applications to Other Areas of Cognitive Decline 880
Practical Issues 880
Summary Points 881
Acknowledgments 881
References 881
79 Probiotics and Neuroprotection 884
List of Abbreviations 884
Introduction 884
Gut Flora and Nervous System 884
Probiotics 885
Probiotics and Health 886
Probiotics and the CNS 886
Neuroprotective Effects of Probiotics 886
Probiotics and Neurological Disease 888
Antidementia Properties of Probiotics 888
Probiotics and Anxiety Disorder 889
Probiotics and Autism 890
Probiotics and Parkinson’s Disease 890
Probiotics and Multiple Sclerosis 890
Conclusion 891
Practical Issues 891
Summary Points 891
References 892
80 Citrus Flavonoids and Effects in Dementia and Age-Related Cognitive Decline 894
List of Abbreviations 894
Introduction 895
Dietary and Citrus Flavonoids 895
Flavonoids, Neuroprotection, and Dementia 895
Flavonoids as Pharmacological Agents 897
Neuroprotective Signaling Pathways of Flavonoids 897
Citrus Flavonoids, Neuroprotection, and Cognition 898
Molecular Mechanisms Underlying the Neuroprotection and Cognition Enhancement of Citrus Flavonoids 899
Applications of Citrus Flavonoids to Other Dementias 900
Practical Issues of Citrus Flavonoids as Pharmacological Agents 901
Summary Points 902
References 902
81 Caffeine Consumption and Prevention of Cognitive Decline: A Focus on Mechanisms 904
List of Abbreviations 904
Introduction 904
Molecular Targets of Caffeine in the Brain 904
Epidemiologic Studies of Chronic Caffeine Consumption and Cognitive Decline 905
Experimental Studies Assessing Whether Chronic Caffeine Consumption Prevents Cognitive Decline in Rodents 906
Blockade of A1Rs as a Mechanism for Attenuating Cognitive Impairment During Aging 908
Blockade of A2ARs as a Mechanism for Attenuating Cognitive Impairment During Aging 910
Conclusions 912
Applications to Other Areas of Cognitive Decline 912
Practical Issues 912
Summary Points 913
References 913
82 Coffee and the Risk of Dementia and Cognitive Impairment 916
List of Abbreviations 916
Introduction 916
Initial Observational Studies on Coffee Intake and Cognition—Cross-Sectional and Case–Control Studies in Which Coffee Consu ... 916
Initial Observational Studies on Coffee Intake and Cognition with Prospectively Collected Information on Coffee Consumption 917
Possible Neuroprotective Mechanisms of Coffee 922
Applications to Other Dementias 923
Limitations of Studies on Coffee Intake/Practical Issues 924
Exposure Assessment 924
Confounding, Effect Modification, Selection Bias 925
Future Directions 925
Summary Points 926
References 926
83 Tea and Cognitive Health: A Focus on Community-Based Studies 928
List of Abbreviations 928
Introduction 928
Cross-Sectional Studies 929
The Tsurugaya Project 1 (Japan) 929
The Hordaland Health Study (Norway) 930
The Singapore Longitudinal Aging Study: Study 1 930
The Singapore Longitudinal Aging Study: Study 2 931
Longitudinal Studies 933
The Singapore Longitudinal Aging Study 933
The Chinese Longitudinal Healthy Longevity Survey 933
The Cardiovascular Health Study 934
The Cardiovascular Risk Factors, Aging, and Dementia Study 936
Future Research 936
Applications to Other Areas of Cognitive Decline 936
Practical Issues 936
Summary Points 937
References 937
84 Green Tea Effects on Age-Related Neurodegeneration: A Focus on Neuronal Plasticity 940
List of Abbreviations 940
Introduction 940
Green Tea as Nutraceutical 941
The Bioavailability of Catechins 942
Direct and Indirect Neuroprotective Actions of Catechins 942
Green Tea and Age-Related Neurodegeneration 943
Conclusions 946
Application to Other Areas of Cognitive Decline 946
Practical Issues 947
Summary Points 947
Acknowledgments 947
References 947
85 The Role of Grape Powder in Emotional Well-Being and Memory Improvement 950
List of Abbreviations 950
Introduction 950
Oxidative Stress and Memory Impairment 951
Antioxidant Properties of Grapes 951
Applications to Other Forms of Dementias 953
Practical Issues 955
Summary Points 957
Acknowledgment 957
References 957
86 Red Grape Juice and Alzheimer’s Disease 960
List of Abbreviations 960
Introduction 960
Rat Model of AD 960
GJ and Antioxidative Effects 961
GJ and Lipid Profile 961
GJ and Cognition 962
Applications to Other Dementias 964
Practical Issues 964
Summary Points 965
References 965
87 Red Wine, Resveratrol, and Vascular Aging: Implications for Dementia and Cognitive Decline 968
List of Abbreviations 968
Introduction 968
Vascular Aging and Brain Function 968
Increased Arterial Stiffness 968
Endothelial Dysfunction 969
Inflammation 969
Endothelial Replicative Senescence 970
Apoptosis 971
Endothelial Progenitor Cells and Aging 971
Aging and the Brain 971
Structural Brain Alterations 971
Abnormalities in Cerebral Metabolism 972
Neuroendocrine Implications 973
Applications to Other Areas of Cognitive Decline 973
Resveratrol and Red Wine Effects on Cerebral Functions 974
Practical Issues 976
Conclusion 977
Summary Points 977
References 977
88 Role of a-Lipoid Acid and Acetyl-L-Carnitine in Dementia 980
List of Abbreviations 980
Introduction 980
a-Lipoic Acid 981
Homeostasis of Cellular Antioxidants 982
Metabolism of LA 982
Antioxidant Analogs of LA 982
Synthesis of LA Conjugates 984
Acetyl-L-Carnitine 984
Drug Conjugates of L-Carnitine 985
Applications of LA and ALCAR to Other Areas of Cognitive Decline 985
Practical Issues 986
Summary Points 986
References 986
89 Effects of 3-n-Butylphthalide from Celery on Vascular Dementia 988
List of Abbreviations 988
Current Understanding of the Pathological Basis and Treatment of Vascular Dementia 988
NBP: A Chemical Constituent in Celery 989
Overview of Pathogenic Events Underlying VaD Pertaining to the Research on NBP 990
NBP May Interfere with the Aß Metabolic Pathway to Suppress Neurofibrillogenesis 992
NBP Protects Against Oxidative Damage to the Brain 993
NBP Elicits Neuroprotection by Inhibiting Apoptotic Cell Death 993
Applications to Other Areas of Cognitive Decline 994
Practical Issues 994
Summary Points 994
References 995
90 Carnosine and Cognitive Deficits 998
List of Abbreviations 998
Introduction 998
Brain Homeostasis of Carnosine 999
Carnosine in Neurodegeneration 1001
Unifying Events in Progressive Neurodegenerative Disorders 1001
Effects on In Vitro and In Vivo Models of Neurodegeneration 1001
Effects on Oxidative and Nitrosative Stress 1002
Effects on the Metal Dyshomeostasis 1003
Limits of Carnosine Applications 1003
Applications to Other Areas of Cognitive Decline 1004
Carnosine in Hypoxic–Ischemic Brain Damage 1004
Practical Issues 1004
Summary Points 1004
Acknowledgment 1005
References 1005
91 Coenzyme Q10 and Behavior in Huntington’s Disease 1008
List of Abbreviations 1008
Introduction 1008
Mitochondrial Dysfunction and Metabolic Impairment in HD 1008
CoQ10 Treatment in Patients Suffering from HD 1009
CoQ10 Treatment in Genetic Animal Models of HD 1010
Fast-Progressing TG Mouse Models 1010
Slowly Progressing Knock-in Mouse Model of HD 1011
Conclusion 1014
Applications to Other Areas of Cognitive Decline 1014
Practical Issues 1014
Summary Points 1015
References 1015
92 Ferulic Acid and Angelica archangelica Extract in Dementia: Effects on Cognitive Functions and Behavioral and Ps ... 1018
List of Abbreviations 1018
Introduction 1018
Suppressing the Progression of Cognitive Disturbance 1019
Control of BPSD 1021
Problems that Confront Us 1024
Applications to Other Dementias or Other Areas of Cognitive Decline 1024
Practical Issues 1024
Summary Points 1025
References 1025
93 Neuroprotection of Genistein in Alzheimer’s Disease 1028
List of Abbreviations 1028
Introduction 1028
Pharmaceutical and Molecular Effects of Genistein 1030
Applications to Other Areas of Cognitive Decline 1031
Practical Issues 1031
Summary Points 1033
Acknowledgment 1033
References 1033
94 S-Equol, a Metabolite of Soy Daidzein, and Cognitive Function 1036
List of Abbreviations 1036
Introduction 1036
Hormones and Cognitive Function 1037
Brain Mitochondria as a Target for Early Intervention for Cognitive Function 1037
S-equol, a Soy-Derived Phytoestrogen 1039
Dietary Isoflavone Supplementation and Cognitive Aging 1039
Potential Mechanisms for S-Equol and Cognitive Function 1041
Activation of Antioxidant Defense System 1041
Activation of Mitochondrial COX Activity 1041
Enhancement of Glucose Metabolism and Mitochondrial Function 1042
Genomic Imprinting and Cognitive Function 1042
Conclusions 1043
Summary Points 1043
References 1043
95 Ginkgo biloba and Usage in Dementia: From Eastern Tradition to Western Science 1046
List of Abbreviations 1046
Introduction 1046
The Ginkgo Tree 1046
Ginkgo Seeds as a Traditional Nutrient 1047
Ginkgo Seeds in TCM 1047
Ginkgo Leaf Extracts as Pharmaceuticals 1047
Ginkgo Leaf Products as Dietary Supplements 1047
GLEs as Herbal Medicinal Products in the Treatment of Alzheimer’s Disease and Vascular Dementia 1047
Pharmaceutical Quality 1047
Mechanism of Action 1049
Clinical Trials 1049
Applications to Other Areas of Cognitive Decline 1052
Practical Issues 1053
Summary Points 1053
References 1053
96 Krill Oil Supplementation and Cognitive Function 1056
List of Abbreviations 1056
Introduction 1056
Preclinical Studies on Cognitive Function and Depression with Supplemental n-3 PLs from Krill 1058
Effects on Brain Activity After Krill Oil Supplementation in Humans 1060
Applications to Other Areas of Cognitive Decline 1060
Practical Issues 1061
Summary 1061
References 1061
97 Murraya koenigii Leaves and Their Use in Dementia 1064
List of Abbreviations 1064
Introduction 1064
Murraya koenigii 1065
Effect of M. koenigii on Memory 1065
Effect of M. koenigii on Brain Cholinergic System 1065
M. koenigii as an Antioxidant 1067
Effect of M. koenigii on Neuroinflammation 1068
Effect of M. koenigii on Cholesterol Level and Aß Deposition 1069
Effect of M. koenigii on Blood Glucose Level 1069
Applications to Other Areas of Cognitive Decline 1071
Practical Issues 1071
Summary Points 1071
References 1072
98 Ocimum sanctum Linn. (Holy Basil) to Improve Cognition 1074
List of Abbreviations 1074
Introduction 1074
Ocimum sanctum 1075
Experimental and Clinical Studies on OS 1076
Antioxidant Activity 1076
Antiinflammatory Activity 1076
Immunomodulatory Activity 1076
Adaptogenic Activity/Antistress Activity 1076
Lipid-Lowering Activity 1076
Cholinesterase Inhibitory Activity 1076
Application to Other Areas of Dementia 1077
Experimental Models 1077
Practical Issues 1078
Behavioral Evidence 1078
Passive Avoidance Task 1078
Biochemical Evidence 1079
Estimation of Brain AChE Activity 1079
Summary Points 1080
Acknowledgment 1082
References 1082
99 Polydatin Use in Vascular Dementia 1084
List of Abbreviations 1084
Introduction 1084
PD and VaD 1086
PD and AD 1089
Applications to Other Areas of Cognitive Decline 1090
Practical Issues 1090
Summary Points 1090
Acknowledgments 1090
References 1090
100 A Naturally Occurring ß-Secretase Modulator, Tannic Acid, Improves Behavioral Impairment and Mitigates Alzheime ... 1094
List of Abbreviations 1094
Introduction 1095
Properties of TA 1096
Improvement in Alzheimer-Like Behavioral Impairment After TA Treatment 1097
TA Mitigates Cerebral Amyloidosis and Reduces Aß Production 1098
Modulation of Amyloidogenic APP Metabolism by TA 1099
Amelioration of Glial Inflammation Following TA Treatment 1100
Practical Issues 1100
Application to Other Dementias 1101
Conclusion 1101
Summary Points 1102
Acknowledgments 1102
References 1102
VI. Practical Issues and Nutritional Health in Dementia and Cognitive Decline 1106
101 The Importance of Nutritional Assessment in Institutionalized Elderly with Dementia: Malnutrition, Early Detection 1108
List of Abbreviations 1108
Introduction 1108
Nutritional Screening (NS) 1109
Mini Nutritional Assessment (MNA) 1109
Full MNA 1110
MNA-SF 1110
Nutrition Screening Initiative (NSI) 1111
Subjective Global Assessment (SGA) 1111
Malnutrition Universal Screening Tool (MUST) 1111
Nutritional Risk Screening (NRS-2002) 1111
Comprehensive Nutritional Assessment (CNA) 1112
Medical–Nutritional History 1112
Psychosocial Backgrounds 1112
Personal Medical History 1112
Mental and Functional Capacity 1112
Dietary History 1113
Physical Examination 1113
Anthropometric Assessment and Body Composition Analysis 1114
Laboratory Tests 1116
Other Studies 1116
Applications to Other Areas of Cognitive Decline 1119
Summary Points 1119
References 1119
102 Obesity and Neurodegeneration: A Focus on Dietary Influence 1122
List of Abbreviations 1122
Introduction 1122
Nutritional Factors and the Risk of Neurodegenerative Disorders 1122
Role of Diet in the Development of Neurodegeneration 1123
Dietary Fat and Cholesterol 1123
Dietary Carbohydrates 1124
Caloric Intake Restriction as a Preventative Strategy 1124
Dietary Patterns 1125
Obesity–Neurodegeneration Relationship 1126
Applications of Dietary Manipulation to Other Areas of Cognitive Decline 1126
Practical Issues 1127
Summary Points 1129
References 1129
103 Eating Abnormalities in Neurodegenerative Dementias 1132
List of Abbreviations 1132
Introduction 1132
Phenomenology of Eating Abnormalities 1133
Eating Abnormalities in AD 1134
Eating Abnormalities in FTD 1135
Eating Abnormalities in DLB 1137
Conclusions 1137
Summary Points 1138
References 1138
104 Nutrition and Amyotrophic Lateral Sclerosis 1140
List of Abbreviations 1140
Introduction 1140
Amyotrophic Lateral Sclerosis 1140
Nutrition and Etiology of Disease 1141
Nutritional Evaluation 1142
Nutritional Support 1143
Oral Proceedings 1143
Enteral Nutrition 1144
Applications to Other Areas of Cognitive Decline 1146
Practical Issues 1146
Summary Points 1146
Acknowledgments 1146
References 1146
105 Oral Health Care in People with Huntington’s Disease 1150
List of Abbreviations 1150
Introduction 1150
HD and Oral Health 1150
Nutritional Factors 1151
Percutaneous Endoscopic Gastrostomy 1151
Medication 1152
Oral Hygiene 1152
Access to and Provision of Dental Care 1153
Additional Dental Considerations 1153
A Guideline for Care 1154
Relation to Oral Health Care 1154
Assessment 1154
Preventive Care 1154
Treatment 1155
Applications to Other Areas of Dementia and Cognitive Decline 1155
Practical Issues 1155
Summary Points 1156
Acknowledgment 1157
References 1157
106 Swallowing in Progressive Supranuclear Palsy and Implications for Nutrition 1160
List of Abbreviations 1160
Introduction and Application to Other Dementias 1160
Swallowing and Nutrition 1160
Nature of Swallowing Impairment 1162
Therapy of Swallowing Impairment and Implications for Nutrition 1164
Swallowing Treatment by SLTs 1164
Pharmacological Treatment 1164
Enteral Nutrition 1165
Practical Issues 1165
Summary Points 1165
References 1165
107 Percutaneous Endoscopic Gastrostomy in Dementia 1168
Abbreviation 1168
Introduction 1168
Indications and Contraindications for PEG in Dementia 1168
Procedure for PEG in Dementia 1169
Complications for PEG in Dementia 1169
Functional Status and Quality of Life for PEG in Dementia 1170
Ethical Issues for PEG in Dementia 1171
Conclusion 1172
References 1172
108 Mealtime Challenges and Swallowing Difficulties in Elderly Dementia Patients 1174
Introduction 1174
Mealtime Challenges in Dementia 1174
Swallowing Difficulties: Applications to Different Types of Dementias 1175
Occurrence and Pathophysiological Changes in Swallowing 1175
Types of Dysphagias 1175
Oropharyngeal Dysphagia 1175
Esophageal Dysphagia 1175
Presentation of Mealtime Challenges and Swallowing Difficulties 1176
Weight Loss 1176
Dysphagia 1176
Aspiration Pneumonia 1177
Evaluation of Mealtime Challenges and Swallowing Difficulties 1177
Nutrition Assessment 1177
Bedside Swallowing Assessment for Dementia Patients 1177
Videofluoroscopic Swallow Study 1178
Fiberoptic Endoscopic Evaluation of Swallowing 1178
Practical Issues: Management of Mealtime Challenges and Swallowing Difficulties 1179
Approaches to Address Mealtime Challenges and Behaviors 1179
Approaches to Reduce Aspiration Risk 1179
Alternate Routes of Feeding and Comfort Care Considerations in Dementia 1179
Summary Points 1182
References 1182
109 The Mini-Mental State Examination and Other Neuropsychological Assessment Tools for Detecting Cognitive Decline 1184
List of Abbreviations 1184
Introduction 1184
Choice of Cognitive Test 1184
Cognitive Test Procedures 1185
Diet and Nutrition 1185
Aging 1185
Cognitive Tests 1186
Mini-Mental State Examination 1186
Administration, Scoring, and Interpretation of the MMSE 1192
Brief Screening Tests 1192
The Montreal Cognitive Assessment 1192
Elderly Cognitive Assessment Questionnaire 1192
Abbreviated Mental Test Score 1195
Repeatable Battery for the Assessment of Neuropsychological Status 1195
Comprehensive Batteries for Detecting Cognitive Impairment 1196
Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV) 1196
Wechsler Memory Scale Fourth Edition 1197
Applications to Other Dementias 1197
Practical Issues 1197
Summary Points 1197
References 1198
110 The Mini-Nutritional Assessment and Cognitive Impairment in Older People 1200
List of Abbreviations 1200
Introduction 1200
MNA Procedure 1201
MNA and Dementia 1201
Applications to Other Areas of Cognitive Decline: MNA and Preclinical Phase of Dementia 1206
MNA and Prognostic Evaluation 1206
Practical Issue: Guide of MNA Procedure 1208
Well-Nourished Subjects 1208
Subjects At Risk of Malnutrition 1208
Malnourished Subjects 1208
MNA Limitations 1208
Conclusions 1208
Summary Points 1209
References 1209
111 Ethics and Decision Making in Dementia 1212
List of Abbreviations 1212
Introduction 1212
Why Do We Need to Consider Ethics? 1212
Factors to Consider 1213
Shared Decision Making 1213
Psychosocial 1213
Feeding Tubes: Saints or Sinners? 1213
Culture 1214
Patients Can Say No 1214
Defensive Practice 1215
Frameworks 1215
Values, Morals, and Ethics—Where Is the Bias Coming From? 1216
Medical Ethical Principles 1216
Evidence-Based Practice 1217
The Seedhouse Ethical Grid 1217
Conclusion 1219
Applications to Other Areas of Cognitive Decline 1219
Practical Issues 1220
Summary Points 1220
References 1220
112 Palliative Care in Dementia 1222
List of Abbreviations 1222
Introduction 1222
Advanced Dementia 1222
How to Address Comorbidity in Advanced Dementia 1224
Intercurrent Infections 1224
Nutritional Problems 1225
Does It Prevent Aspiration Pneumonia? 1226
Does It Prevent Malnutrition and Its Consequences? 1226
Does It Increase Survival? 1226
Does It Prevent or Improve the Progress of PU? 1227
Does It Reduce the Incidence of Infections? 1227
Does It Improve Performance Status? 1227
Does It Provide Comfort (to Prevent Hunger and Thirst) and Improve Quality of Life? 1227
What Alternatives to AN Are Available? 1227
Control of Symptoms 1228
Planning of Care and Care for the Family 1228
Applications to Other DementiaS or Areas of Cognitive Decline 1229
Practical Issues 1229
Summary Points 1229
References 1230
Index 1232