Tag: dementia

Esta publicación esta dedicada a todas las personas que de algun modo lidian a diario con la demencia, ya sea ppr atenderlos como pacientes, o por convivir con algún familiar afectado.

Pathophysiology of Dementia

Dementia is a neurodegenerative disease of the brain that affects millions of people worldwide that is characterized by impairment of people’s cognitive, memory, and daily functioning dimensions.
There are different mechanisms that contribute to the onset and progression of dementia, the most studied of which have been the presence of beta amyloid and tau protein neurofibrils, neuroinflammation and synaptic dysfunction. (Cantone, 2023)
Molecular Mechanism of Dementia
One of the most studied molecular mechanisms in the pathogenesis of the dementia is the presence of the amyloid beta peptide and the tau protein, the former being found extracellularly in the form of plaques, and the latter in the form of tangles intracellularly. The presence of these proteins alters neuronal function and triggers neurotoxicity, which in the long term contributes to synaptic dysfunction and cell apoptosis. (Guo, Zhang, Zeng, & et al, 2020)
Neuroinflammation plays a fundamental role, since microglia, a type of glial cell present in the central nervous system, which is responsible for the defense and phagocytosis of pathogens that attack the brain, is activated in the presence of the mentioned proteins and neuronal damage. This chronic activation of microglia tends to release pro-inflammatory cytokines such as interleukin 1beta and tumor necrosis factor alpha, causing neuroinflammation and compromising the integrity of neurons. (Kuang, et al 2021)
Disorders or alterations of synaptic function contribute to the deterioration of cognitive function that culminates in dementia. (Pei et al, 2022)

Recent research explains the role of mitochondria in neurodegenerative diseases, since cell respiration is carried out in this organelle, the production of ATP and intracellular calcium levels are regulated, they are affected by oxidative stress, oxygen free radicals, the dysregulation of homeostatic mechanisms of calcium ions and the accumulation of toxic or pathogenic proteins. (Anoar, Woodling,& Niccoli,2020)
Epigenetic modifications such as DNA and histone methylation, histone acetylation, RNA micro dysregulation, influence genetic pattern that ensures neuronal survival, synaptic plasticity, and neuroinflammation and contribute to the progression of dementia, also DNA methylation is being studied as a possible biomarker for diagnostics purpose. Other studies suggest that methyl donors and/or drugs that act on methyl metabolism may be therapeutic agents for Alzheimer’s dementia. , (Shadyab, et al 2022)

Type of dementia Symptoms and clinical features
Alzheimer’s Dementia
Associated with amyloid beta protein and tau protein, which cause neuronal damage Memory loss and language, impaired judgment, Loss of ability to perform everyday actions.
Vascular Dementia
There is damage to the blood vessels that run into the brain such as a stroke, or when white matter fibers are damaged. Difficulty solving problems, slowness of Loss of concentration and organization

Lewy body dementia
Lewy bodies are abnormal deposits of the protein alpha synuclein in the brain. They are also seen in Parkinson’s dementia People act out their dreams, have visual hallucinations, sleep speech, have problems with concentration or attention, slow or uncoordinated movements, tremors, rigidity, which is known as Parkinsonism
Frontotemporal Dementia
There is a breakdown of neurons and their connections in the temporal and frontal lobes of the brain

Mixed dementia
There is a combination of causes. Symptoms often overlap depending on the causes

Frontotemporal dementia

These areas are associated with personality, behavior, and language, with the most common symptoms being changes in behavior, personality, thinking, judgment, and language.

The understanding of the molecular pathophysiology is of great relevance since depending on it, it will guide the professionals in charge of these patients in the clinical diagnosis, with the help of the personal and family history, the interaction of the patient with his environment, the physical examination, the use of modern technologies such as MRI, positron emission tomography can detect the alpha amiloyd protein, as well as the use of biomarkers to predict their onset, evolution, prognosis and therapeutic decisions such as the use of drugs that act on methyl metabolism as therapeutic agents for the treatment of Alzheimer’s.
A clinical session assesses memory, language skills, visual perception, attention, problem-solving ability, movement, senses, balance, reflexes, and other areas.
Blood tests can detect, for example, a lack of vitamin B-12 that affects brain function or an underactive thyroid gland. Sometimes, it is analyzed cerebrospinal fluid for review the presence of tau and alpha amyloid proteins that cause neuroinflammation in Alzheimer’s disease and markers of some degenerative diseases.
Conclusion
The study of the molecular mechanisms of dementia allows us to know the presence of the amyloid protein alpha and the protein tau, which cause neuronal damage and are present in Alzheimer’s disease, the synaptic dysfunction that causes cognitive impairment, recently the role of mitochondria in oxidative stress and the accumulation of proteins and cellular pathogens. Current research uses epigenetics to explain the role of DNA methylation in dementias such as Alzheimer’s. The use of biomarkers can be used for early diagnosis and replace histopathological examination in autopsies of patients with dementia, and with comprehensive treatment it will be possible to improve the quality of life by delaying the clinical symptoms and psychiatric condition of these patients. There is still a long way to go in the study of dementia.