What is dementia?

Dementia is a general term used to describe a group of symptoms associated with a decline in cognitive function severe enough to interfere with daily life and activities. It is not a specific disease but rather a set of symptoms that can result from various underlying conditions or diseases affecting the brain. Dementia is characterized by progressive impairment in memory, thinking, communication, judgment, and ability to perform everyday tasks.


The most common type of dementia is Alzheimer’s disease, accounting for approximately 60-80% of cases. Other types of dementia include vascular dementia, Lewy body dementia, frontotemporal dementia, and mixed dementia (a combination of two or more types). Each type of dementia is associated with distinct patterns of cognitive decline, underlying brain changes, and clinical features.


What is the relationship between dementia and oxidative stress?

Oxidative stress is believed to play a significant role in the pathogenesis and progression of various types of dementia. Here’s how dementia and oxidative stress are interconnected:


  • Neurodegenerative Processes: Many types of dementia, including Alzheimer’s disease, Parkinson’s disease dementia, and frontotemporal dementia, are characterized by progressive neurodegeneration—the gradual loss of neurons and synapses in the brain. Oxidative stress is implicated in the neurodegenerative processes underlying dementia, contributing to the accumulation of abnormal protein aggregates (such as beta-amyloid plaques and tau tangles in Alzheimer’s disease) and neuronal dysfunction. Reactive oxygen species (ROS) generated during oxidative stress can damage cellular components, disrupt neuronal signaling, and trigger inflammatory responses, leading to neuronal injury and death.


  • Mitochondrial Dysfunction: Oxidative stress can impair mitochondrial function, the cellular organelles responsible for energy production (ATP synthesis) and regulation of cellular metabolism. Mitochondrial dysfunction is a common feature of neurodegenerative diseases and is believed to contribute to neuronal degeneration and cognitive decline in dementia. Excessive ROS production within mitochondria can damage mitochondrial DNA, proteins, and lipids, leading to impaired ATP production, energy depletion, and increased oxidative stress, creating a vicious cycle of mitochondrial dysfunction and oxidative damage.


  • Inflammation and Glial Activation: Oxidative stress can trigger inflammatory responses in the brain, characterized by the activation of microglia (the brain’s immune cells) and astrocytes (support cells). Chronic neuroinflammation is a prominent feature of dementia and is believed to exacerbate neuronal injury and cognitive decline. Reactive oxygen species generated during oxidative stress can activate inflammatory signaling pathways and promote the release of pro-inflammatory cytokines, chemokines, and reactive nitrogen species (RNS), leading to sustained inflammation, synaptic dysfunction, and neurotoxicity.


  • Blood-Brain Barrier Dysfunction: Oxidative stress can compromise the integrity of the blood-brain barrier (BBB), a specialized barrier that regulates the passage of molecules between the bloodstream and the brain. Disruption of the BBB allows entry of circulating toxins, inflammatory mediators, and immune cells into the brain, exacerbating neuroinflammation and neuronal damage in dementia. Oxidative stress-induced damage to endothelial cells, tight junction proteins, and basement membrane components of the BBB can impair barrier function and promote neurodegeneration.


  • Lipid Peroxidation and Oxidative Damage: Oxidative stress can induce lipid peroxidation, the process by which ROS attack and degrade cell membrane lipids, leading to the formation of toxic lipid peroxidation products (such as 4-hydroxynonenal and malondialdehyde). Lipid peroxidation products can damage neuronal membranes, alter membrane fluidity, and disrupt cellular signaling pathways, contributing to neuronal dysfunction and cognitive impairment in dementia.


Overall, oxidative stress is believed to contribute to the pathogenesis and progression of dementia through its role in neurodegeneration, mitochondrial dysfunction, inflammation, BBB dysfunction, and oxidative damage.