Abstract
In this chapter, an initial exploration of the definition and symptoms of neurodegenerative disorders will be conducted along with an in-depth analysis of their underlying neurobiological basis, shedding light on their manifestation in the brain. The central focus will then shift towards comprehending and addressing the specific social cognitive deficits associated with different types of NDs and examining the challenges posed in the realm of social cognition. Strategies and interventions specifically designed for social cognitive rehabilitation will be investigated. The chapter will encompass a discussion on the caregiver burden and effective coping strategies to alleviate the stresses faced. The primary objective of this chapter is to provide readers with a comprehensive understanding of the intricate nature of social cognitive deficits in neurodegenerative disorders and equip them with practical tools aimed at enhancing social cognition and improving the quality of life for individuals affected by these complex conditions.
TopNeural Basis Of Neurodegenerative Disorders
Neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS), are characterized by the gradual loss of neurons and a decline in central nervous system (CNS) functions. The pathophysiology of these diseases involves the malfunction of neuroglial cells, which have a critical role in maintaining neuronal balance and safeguarding the nervous system (Joshi & Ahuja, 2023).
Prion proteins (PrP) are infectious agents consisting of proteins that induce neurodegenerative diseases by altering the shape of cellular prion proteins (PrPC) (Shinagawa et al., 2015). In these conditions, the deterioration of glial homeostatic and protective functions leads to the demise of neurons over time. In certain cases, abnormal glial cells can instigate neuronal death, as seen in amyotrophic lateral sclerosis. Lifestyle adjustments can target neuroglial cells and enhance their ability to protect neurons, potentially slowing down neurodegeneration and prolonging cognitive well-being (Verkhratsky & Butt, 2023).
Alzheimer's Disease (AD) is characterized by the aggregation of amyloid-beta and tau proteins, leading to synaptic dysfunction and neuronal death. This leads to atrophy of the hippocampus and cerebral cortex. These pathological changes result in widespread neuronal loss and disruption of neural circuits involved in memory and cognition (Blennow et al., 2015; Jack Jr et al., 2018). In AD, neuroinflammation is a notable feature, with immune cells in the brain becoming activated, leading to significant inflammation. The disease is also characterised by dysregulation of various neurotransmitters, including acetylcholine, glutamate, and gamma-aminobutyric acid (GABA), contributing to cognitive disturbances. Synaptic dysfunction is a hallmark, resulting in the loss of synapses and impaired synaptic plasticity. The disruption of neuronal networks further compounds the effects of the disease, leading to impaired communication between different brain regions. Additionally, genetic factors, particularly mutations in genes such as APP, PSEN1, and PSEN2, play a substantial role in the development and progression of Alzheimer's disease (Alexandersen et al., 2022).
Frontotemporal dementia (FTD) is a multifaceted neurodegenerative disorder marked by the accumulation of proteins, notably tau and TDP-43, leading to synaptic dysfunction and eventual neuronal degeneration. It primarily affects the frontal and temporal lobes, influencing key areas responsible for personality, behaviour, and language functions, including the orbitofrontal cortex, anterior cingulate cortex, and temporal pole. FTD encompasses diverse pathological substrates, such as Pick's disease and frontal lobe degeneration, each showcasing distinct cellular mechanisms. For instance, FTD cases with Pick's disease histology demonstrate pronounced cortical gliosis and robust microglial activity in both grey and white matter. Conversely, instances of frontal lobe degeneration, another FTD variant, point towards a disorder predominantly affecting white matter, with minimal gliosis and microglial activity confined mainly to the white matter.
Key Terms in this Chapter
Lewy Bodies: Aberrant protein aggregations specifically in the brain called Lewy bodies form inside nerve cells. Alpha-synuclein is the main protein that makes them up. A number of neurodegenerative diseases, such as Parkinson's disease, dementia with Lewy bodies, and certain instances of Alzheimer's disease, are characterized by Lewy bodies. Lewy body buildup is linked to brain cell degeneration and is thought to play a role in the onset and progression of the cognitive and motor symptoms that are present in these illnesses.
Autophagosomal-Lysosomal Pathway: A cellular mechanism that speeds up the breakdown and recycling of broken proteins, organelles, and other parts of cells. It entails the production of autophagosomes, which are double-membrane structures that engulf the targeted cellular constituents. Following their fusion, these autophagosomes give rise to lysosomes, which are organelles found in cells that have a variety of enzymes that can degrade the items they have ingested into their constituent parts. By eliminating superfluous or defective cellular components, the cell can preserve equilibrium through this pathway, improving cellular health and avoiding the buildup of potentially hazardous compounds. This procedure is essential for many cellular processes, such as the elimination of misfolded proteins, control over cell metabolism, and reaction to nutrition supply and stress. It is also essential for preserving cellular homeostasis and may have consequences for a number of illnesses, like: neurodegenerative disorders and cancers.
Cellular Prion Proteins: Membrane-bound glycoprotein that is primarily present in neurons is called cellular prion proteins, or PrPC. They are highly expressed in the central nervous system and are encoded by the PRNP gene. Numerous physiological processes, such as neuroprotection, synaptic plasticity, and cell signalling, are influenced by PrPC. PrPC is essential for preserving neuronal homeostasis in healthy circumstances. Nevertheless, under some conditions, PrPC may misfold into an aberrant conformation, resulting in the production of infectious prions. These are linked to prion illnesses including Creutzfeldt-Jakob disease and its variation.
Neuroinflammation: The inflammation within the brain and spinal cord is referred to as the central nervous system (CNS). It is an intricate immunological reaction brought on by a number of things, including infections, wounds, and autoimmune diseases. The process of neuroinflammation entails the activation of various immune cells in the central nervous system (CNS), including astrocytes and microglia, which release inflammatory mediators and pro-inflammatory cytokines and chemokines. Although the body uses inflammation as a natural defence against hazardous stimuli, excessive or persistent neuroinflammation can injure and malfunction nervous system cells, including neurons. Since neuroinflammation is linked to a number of neurological conditions, such as stroke, multiple sclerosis, and neurodegenerative illnesses, therapeutic approaches try to lessen the negative effects of inflammation on the CNS.
Ubiquitin-Proteasomal System: A crucial cellular mechanism that directs the targeted degradation of particular proteins inside the cell. It regulates the course of the cell cycle, apoptosis, a mechanism of regulated cell death, and the removal of misfolded or damaged proteins, among other cellular processes. The targeted protein is marked for breakdown in this process by the attachment of ubiquitin, a tiny regulatory protein. The proteasome, a sizable protein complex in charge of protein degradation in cells, then recognizes and degrades the tagged protein. The ubiquitin-proteasomal system plays a crucial role in the immunological response, neurological illnesses, cancer, and other critical biological processes. It is also necessary for preserving the proper balance of proteins inside the cell.