Brain and Mental Health in Ageing

Preface
Contents
Contributors
Part I Concepts, Definitions and Historical Perspectives
1 Defining, Re-defining, and Understanding the Brain and Mental Health During Ageing
	1.1 Introduction: Organ and Norgan
	1.2 What is a Healthy Brain and What Happens to It During Ageing?
		1.2.1 Healthy Brain Ageing
		1.2.2 Pathological Brain Ageing
	1.3 What is a Healthy Mental State and What Happens to It During Ageing?
	1.4 Brain-Mind Interaction
	1.5 Conclusions and Perspectives
	References
2 Social, Historical and Anthropological Aspects of Research on the Brain and Mental Health in Ageing
	2.1 Mental and Physical Health in Ageing Through Harmonization
		2.1.1 The Science of Gerontology Born of the Pursuit of Harmony
		2.1.2 Concepts of Harmonization in the History of Ageing Care and General Medicine
		2.1.3 The Emergence of the Concepts of Homeostasis and Stress Response
		2.1.4 Contemporary Concepts of Biological System Stability
	2.2 Loss of Regulation and Integration of the Organism and Environment—Determinants of Ageing-Related Mental and Physical Decline
		2.2.1 The Integrative Elevation Theory of Ageing
		2.2.2 Therapeutic Integration and Harmonization
		2.2.3 Striving for “Biosocial Synthesis”
	2.3 The Revitalizing Power of the Mind
		2.3.1 What Constitutes Vitality in Old Age?
		2.3.2 Concepts of Vitality in Ancient Medical Traditions
		2.3.3 Vitalist Concepts in the History of Modern Ageing Research
	2.4 Conclusion
	References
3 Understanding Hormesis for Optimizing Brain Health
	3.1 Hormesis: Conceptual and Historical Background
	3.2 Key Questions for Hormesis and Brain Health
		3.2.1 When Does Hormesis Start to Become a Factor in Brain Health?
		3.2.2 Is There a Single Best Hormetic Agent for Brain Health?
		3.2.3 Does Low Bioavailability of Agents Preclude/Affect Enhancing Brain Health?
		3.2.4 Is It Ever Too Late in Life to Start Efforts to Attempt to Enhance Brain Health?
		3.2.5 Are Mixtures of Hormetic Agents Better Than a Single Agent for Brain Health Protection?
		3.2.6 Does the 30–60% Maximum Hormetic Response Change with Age and/or Health Status?
		3.2.7 Can Brain Health Be Enhanced by Light Therapy?
		3.2.8 Do Statins Have a Significant Role in Brain Health?
	References
Part II Biological Modulators of the Ageing Brain
4 Dietary Constituents for Mental Health Promotion and Healthy Ageing
	4.1 Introduction
	4.2 Polyunsaturated Fatty Acids
	4.3 Vitamins
	4.4 Magnesium
	4.5 Phenolics
	4.6 Conclusion
	References
5 Physical Activity and Dietary Interventions for Mental Health in Ageing and Longevity
	5.1 Introduction
	5.2 Physical Activity
		5.2.1 Neuroprotective Effects of Physical activity
		5.2.2 Brain Plasticity
		5.2.3 Cognitive Restructuring
		5.2.4 Mood Enhancement
		5.2.5 Improved Sleep
		5.2.6 Stress Reduction
		5.2.7 Social Interaction
	5.3 Dietary Interventions
		5.3.1 Nutrient-Rich Diet
		5.3.2 Gut-Brain Connection
		5.3.3 Potential Benefits of Healthy Dietary Habits
	5.4 Conclusions
	References
6 Immunity, Immunosenescence, Brain and Cognitive/Mental Health
	6.1 Introduction
	6.2 Systemic Immune System
	6.3 Brain Immune System
	6.4 Immunosenescence and Immunity in Ageing
	6.5 Immune Changes in the Ageing Brain
	6.6 Importance of Age-Related Changes for Age-Associated Disease Development
		6.6.1 Alzheimer’s Disease
		6.6.2 Parkinson’s Disease
		6.6.3 Amyotrophic Lateral Sclerosis
		6.6.4 Multiple Sclerosis
		6.6.5 Mental Health Disorders
	6.7 Conclusion
	References
7 Neurovirology and Brain Health—A Microglial Perspective
	7.1 Introduction
	7.2 Microglia in Virus-Induced Neurodegeneration
	7.3 Neurovirology and Brain Ageing from a Microglial Perspective
		7.3.1 Human Immunodeficiency Virus
		7.3.2 West Nile Virus
		7.3.3 Borna Disease Virus
		7.3.4 Epstein-Barr Virus
		7.3.5 SARS-CoV-2
	7.4 Neurovirology Mediated Brain Ageing: a Pathological Context
		7.4.1 Alzheimer’s Disease
		7.4.2 Parkinson\'s Disease
		7.4.3 Multiple Sclerosis
	7.5 Conclusion
	References
8 Gut Microbiota-Brain Axis in Healthy Ageing
	8.1 Introduction
		8.1.1 Gut Microbiome and Association Links with Biological Ageing and Health-Span
		8.1.2 Gut Microbiome and Its Link with Age-Associated Neurodegenerative Disorders
	8.2 Induction of Regulatory Responses by the Gut Microbiota on Brain-Health During Ageing
		8.2.1 The Hypothalamic–Pituitary–Adrenal (HPA) Axis and Mental Well-Being in Ageing
		8.2.2 The Gut-Brain-Endocrine Axis and Its Association with Cognitive Ageing
		8.2.3 Exploring Brain Health in Ageing Via Immune Pathways
		8.2.4 Nurturing Cognitive Vitality Through Vagal and Microglial Dynamics
	8.3 Microbiome-Based Intervention Strategies to Rejuvenate the Gut-Brain Connections for Improved Mental Health in Ageing
		8.3.1 Prebiotics, Probiotics and Synbiotics
		8.3.2 Dietary Interventions
		8.3.3 Fecal Microbiota Transplantation (FMT)
		8.3.4 Other Interventions
	8.4 Conclusion
	References
9 Connexin-Mediated Neuroglial Gap Junction Communication: Unravelling Its Significance in Brain Health and Ageing
	9.1 Introduction
	9.2 Neuroglial Cell to Cell Communication in Maintaining Brain Health
	9.3 Gap Junction-Mediated Neuroglial Communication for the Sustenance of Brain Health in Normal Physiological Condition
		9.3.1 Connexins: An Essential Component of Functional Gap Junctions
		9.3.2 Differential Connexin Expression of Neuroglial Cells in Healthy Brain
	9.4 Gap Junction Mediated Intercellular Communication Between Different Neuroglial Cells and Its Implications in Brain Health
		9.4.1 Astro-Oligodendroglial Communication
		9.4.2 Astro-Neuron Communication
		9.4.3 Astro-Microglial Communication
	9.5 Correlation Between Connexin-Mediated Gap Junction Communication and Neuroinflammation-Induced Neurodegeneration and Brain Ageing
	9.6 Major Risk Factors Associated with Brain Ageing
		9.6.1 Connexins in Virus-Induced Neuroinflammation: A Factor Leading to Ageing and Chronic Neurodegenerative Disorders
		9.6.2 Alteration of Glial Cell Communication in Ageing-Associated Neurodegenerative Disease
	9.7 Conclusions
	References
10 Maintenance of Mitochondrial Dynamics for Healthy Brain Ageing
	10.1 Introduction
	10.2 Brain Ageing and Mitochondria
	10.3 Brain Mitochondrial dynamics and its Alterations with Age
	10.4 Mitochondrial dysfunction and Brain diseases
		10.4.1 Charcot-Marie-Tooth (CMT) Disease
		10.4.2 Autosomal Dominant Optic Atrophy (ADOA)
		10.4.3 Parkinson’s Disease (PD)
		10.4.4 Alzheimer’s Disease (AD)
		10.4.5 Huntington’s Disease (HD)
		10.4.6 Other Neurocognitive Disorders (NCDs)
	10.5 Maintenance of Mitochondrial dynamics and it’s Function for Healthy Brain Ageing
		10.5.1 Physical Exercise
		10.5.2 Compounds that Regulate Events of Mitochondrial dynamics
		10.5.3 Genetic Modifications that Alter Mitochondrial dynamics and it’s Function
	10.6 Challenges and Future Directions
	10.7 Conclusion
	References
Part III Brain Health Maintenance, Promotion and Recovery in Ageing
11 Phytochemicals and Vitagenes for a Healthy Brain
	11.1 Introduction
	11.2 Phytochemicals as Neurohormetins
	11.3 Mitochondrial Antiaging Medicine and the Supercomplexe Gain of Function Theory
	11.4 C. elegans Models for Investigating Cognitive Function in Health and Disease
	11.5 Nrf-2 Activators with Potential Therapeutic Potential in Ageing and Age-Related Diseases
		11.5.1 Medical Mushrooms
		11.5.2 Bioactive Phytochemicals
	11.6 Future Directions
		11.6.1 Organoid Models for Investigating Cognitive Function in Health and Disease
	11.7 Declaration of Competing Interest
	References
12 Infection, Neuroinflammation and Interventions for Healthy Brain and Longevity
	12.1 Introduction
	12.2 The Amyloid Cascade Hypothesis
	12.3 The Infection Hypothesis of AD
		12.3.1 What Microbes Are the Most Involved in AD Development?
		12.3.2 How These Microbes May Influence the Brain for the Development of AD?
		12.3.3 The Final Common Way for Microbes to Lead and Maintain AD
		12.3.4 What is the Role of Aβ in the Context of the Infection Hypothesis of AD?
	12.4 Parkinson’s Disease
	12.5 What Are the Implications of the Infection Hypothesis of Neurodegenerative Diseases for the Maintenance of Healthy Brain and Longevity?
	12.6 Conclusion
	References
13 Nutraceuticals as an Intervention for Healthy Brain Ageing
	13.1 Introduction
	13.2 Molecular Mechanisms and Biomarkers of Brain Ageing and neurodegeneration
		13.2.1 Mitochondrial dysfunction and ROS
		13.2.2 Accumulation of Damaged Biomolecules
		13.2.3 Impaired Repair Mechanism
		13.2.4 Intracellular Ca2+ Imbalance
		13.2.5 Impaired Cellular Signaling
		13.2.6 Inflammation
	13.3 Nutraceuticals as an intervention for a Decline in Brain Ageing
		13.3.1 Curcumin
		13.3.2 Resveratrol
		13.3.3 Epigallocatechin Gallate
		13.3.4 Quercetin
		13.3.5 Berberine
		13.3.6 Fisetin
	13.4 Conclusion
	References
14 Pharmacological Interventions for Maintaining Brain Health in Ageing
	14.1 Introduction
	14.2 Senotherapeutic Drugs Targeting Cellular Senescence in Ageing Brain
		14.2.1 Dasatinib and Quercetin
		14.2.2 Polyphenolic Flavonoids
		14.2.3 MTOR Inhibitors
		14.2.4 Flavanoids
		14.2.5 Curcumin and Its Derivatives
	14.3 Peroxisome Proliferator-Activated Receptor(PPAR) Agonists as Neuroprotective Agents in Ageing Brain
		14.3.1 The Marketed PPAR Agonists
		14.3.2 Flavonoids
		14.3.3 Fatty Acids
		14.3.4 Cannabinoids-(CBs)
		14.3.5 Miscellaneous Phytoconstituents
	14.4 Gut Microbiome Therapy to Treat Disorders of Ageing Brain
	14.5 Currently Available Therapeutics and Drugs in Pipeline for Disorders of ageing Brain
	14.6 Conclusion
	References
15 Sleep and Circadian Rhythms as Modulators of Mental Health in Ageing
	15.1 Introduction
	15.2 Ageing Influences CTS and Sleep
	15.3 Sleep and CTS Influences Mental Health with Ageing
	15.4 Therapeutic Intervention
	15.5 Conclusion and Future Perspectives
	References
Part IV Mental Health Maintenance, Promotion and Recovery in Ageing
16 The Impact of Psychopathology and Psychological Well-Being on Cognitive Health
	16.1 Significance of Cognitive Health
	16.2 Psychopathology and Cognitive Functioning
		16.2.1 Depression
		16.2.2 Stress
		16.2.3 Social Isolation
	16.3 Psychological Well-Being and Cognitive Functioning
		16.3.1 Social Connectedness
		16.3.2 Psychological Well-Being
		16.3.3 Subjective Ageing
	16.4 Clinical Implications
	16.5 Conclusion
	References
17 The Neuroscience of Positive Emotions and Gratitude in Healthy Ageing and Longevity
	17.1 Introduction
	17.2 Stress is at the Root of Many Diseases
	17.3 Emotional Guidance Scale
	17.4 Positive Emotion, gratitude, and Brain health
	17.5 The Emotion of gratitude Alters Brain Chemistry
	17.6 Attitude of gratitude Can Reduce Food Intake and Help Prevent Obesity
	17.7 Love and Compassion Are a Direct Offshoot of gratitude
	17.8 Gratitude Practice Makes ‘Letting Go’ Easier
	17.9 Gratitude Practice Leads One to Seek Forgiveness and Forgive Others
	17.10 Conclusions and Perspectives
		17.10.1 F7 Policy and Public Health Initiatives
	References
18 Cognitive Profiles Across Normal and Unhealthy Ageing
	18.1 Introduction
	18.2 Cognitive Ageing
	18.3 Neuropathologies Contributing to Unhealthy Cognitive Ageing
		18.3.1 Mild Cognitive Impairment
		18.3.2 Dementia
		18.3.3 Differential Diagnoses of Dementia
	18.4 Normal and Unhealthy Profiles Across Cognitive Domains
		18.4.1 Memory
		18.4.2 Attention and Information Processing
		18.4.3 Executive Functioning
		18.4.4 Language
	18.5 Successful Ageing and Cognitive Reserve
	References
19 Sleep and Mental Health in the Ageing Population
	19.1 Introduction
	19.2 Age-Related Changes in Sleep
	19.3 Sleep and Quality of Life in Older Adults
	19.4 Sleep and Retirement
	19.5 Sleep and Mental Disorders
		19.5.1 Sleep and Depression
		19.5.2 Sleep and Anxiety
		19.5.3 Sleep and Suicide Risk
		19.5.4 Age-Related Mechanisms Linking Sleep and Mental Disorders
	19.6 Sleep and Neurodegeneration
		19.6.1 Sleep and Neurodegenerative Disorders
		19.6.2 Circadian Disruption and Neurodegenerative Disorders
		19.6.3 Evidence for Specific Treatment Strategies in Neurodegenerative disorders:
	19.7 Interventions for Sleep and Circadian Disturbances in Older Adults
		19.7.1 Hypnotics
		19.7.2 Melatonin
		19.7.3 Bright Light Therapy
		19.7.4 Cognitive-Behavioral Therapy for Insomnia
		19.7.5 Recommendations
	19.8 A Model for Healthy Sleep in Advanced Age
	19.9 Conclusion
	References
20 Brain Health of Women Beyond Middle Age: Hormonal and Non-hormonal Perspectives
	20.1 Introduction
	20.2 Brain health of Women Beyond Middle Age: Hormonal Perspective
		20.2.1 Estrogen and Its Receptors Distribution in the Brain
		20.2.2 Brain Ageing and estrogen Receptors
	20.3 Estrogen Decline Associated Neuropsychological and neurodegenerative Complications
		20.3.1 Mood disorders
		20.3.2 Cognitive Impairments
		20.3.3 Alzheimer’s Disease
		20.3.4 Parkinson’s Disease
	20.4 Brain health of Women Beyond Middle Age: Non-Hormonal Perspective
	20.5 Midlife Transition and Lifestyle factors
		20.5.1 Physical activity and Brain health
		20.5.2 Dietary Patterns, Herbal Supplementation and Brain health
	20.6 Conclusion
	References
21 Psychobiotics: A Restorative Intervention for Lifestyle-Induced Deteriorations of Mental Health
	21.1 Introduction
	21.2 Psychobiotics: a Putative Alternative to Regression of Mental Health
		21.2.1 Promising Psychobiotic Strains
		21.2.2 Psychobiotic Potential of Bacteria: Mechanism of Action
		21.2.3 Role of Prebiotics in Promoting the Growth of Psychobiotic Bacteria
		21.2.4 Role of Bacterial Extracellular Vesicles in Mediating Brain Effects of Psychobiotic Bacteria
		21.2.5 Utilizing Psychobiotic Strains in Fermented Foods and Beverages: The Psychobiotic Diet for Improved Mental Health
	21.3 Lifestyle Factors Affecting Mental Health: Amelioration with Psychobiotics
		21.3.1 Diet
		21.3.2 Consumption of Alcohol
		21.3.3 Sleep
		21.3.4 Physical Exercise
		21.3.5 Social Communication
	21.4 Environmental Factors
		21.4.1 Pesticides
		21.4.2 Heavy Metals
	21.5 Psychobiotics: a Paradigm Shift for Proteostasis
	21.6 Theoretical and Technical Gaps in the Development of Psychobiotics
	21.7 Conclusion and Perspectives
	References
22 Autism and ADHD in Old Age
	22.1 Introduction
	22.2 Diagnosis of Autism in Adults
	22.3 The Spectrum of Autism in Adults
	22.4 Diagnosing ADHD in Adults
	22.5 Psychiatric Conditions
		22.5.1 Autism and Diogenes Syndrome
		22.5.2 ADHD and Diogenes Syndrome
	22.6 Autism and Dementia
	22.7 Autism and Disease in General
	22.8 ADHD and Dementia
	22.9 Gender Dysphoria and Autism
	22.10 Autism and Psychosis
	22.11 Therapies, Interventions (or None)
	22.12 A Final Positive Note
	22.13 Conclusions
	References
23 Epigenetic Regulation of Age-Associated Neuropsychiatric Disorders
	23.1 Introduction
	23.2 Brain Ageing and Psychiatric Health
		23.2.1 Anxiety
		23.2.2 Major Depressive Disorder
		23.2.3 Bipolar Disorder
		23.2.4 Schizophrenia
	23.3 Concluding Remarks
	References
Index