Dementia is one of the public health priorities of the 21 st century. This is due to the simple reason that it mostly affects individuals in old age and hence with an increase in the aging population, cases of dementia are bound to rise. The condition describes a combinations of clinical symptoms that include a decline in memory with progressive loss of other behavioral, thinking, and language capabilities, dementia is a significant public health challenge not just to the individual but for the economic health of nations. The etiology of dementia is wide. Broadly, dementia syndrome is a result of neurodegenerative conditions, nutritional deficiencies, traumatic brain injuries, vascular disorders, infective processes, endocrine and metabolic disorders, drug toxicity and heavy metal poisoning, among others. It is these etiological aspects and risk factors that form one of the bases of dementia classification.
Dementia
Dementia is typically defined as a clinical syndrome of cognitive decline that is sufficiently severe to interfere with social or occupational functioning (Chertkow, Feldman, Claudia, & Fadi, 2013) . Dementia describes a group of symptoms affecting memory with an aspect of cognitive impairment. Individuals with dementia show distorted thinking, trouble communicating, and impaired judgment, with a decline in social abilities that are severe enough to interfere with daily life. It is not a specific disease, but rather a several symptoms and signs. Thus dementia is a term to describe the collection of symptoms that occur when there is a decline in brain function. The WHO has classified dementia as an epidemic, with about 47.47 million people deemed to be living with dementia in 2015 with projections pointing towards one new case of dementia every 4.1 seconds (World Health Organization, 2015) . The etiology of dementia is multifactorial. This paper presents the causes of dementia, as found in the existing literature, which also forms the basis for dementia classification, with an emphasis on the possible pathophysiological mechanisms.
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Dementia is termed as cortical or subcortical. Cortical dementia affects the cerebral cortex. They include Alzheimer’s disease (AD) and Creutzfeldt-Jakob Disease (CJD). The main manifestation is memory loss with language difficulties. Forms of subcortical dementia the effect is on brain parts beneath the cortex. There is an overall slowed thinking process and impairment in doing activities of daily living. However, in most cases, memory and speech are spared hence no forgetfulness. They include HIV Associated dementia, dementia due to Huntington disease and Parkinson's disease. Dementia can also be reversible, for instance, due to nutritional deficiency or progressives such as Alzheimer's disease.
Dementia is caused by damage to or loss of nerve cells and their connections in the brain. In the majority of the cases, there is an accumulation of abnormal proteins in the parts of the brain, mostly the cerebral cortex and part of the midbrain. These abnormal proteins that may be a result of several causes impair the functioning of neurons-transmission of nerve signals and eventually die with some parts of the brain shrinking. In other cases, inflammatory reactions occur that affect the brain in different forms. Dementia could be as a result of one clinical entity or a combination.
The causes of dementia can be broadly classified into several pathophysiologic groups. This includes degenerative neurologic diseases, vascular disorders, traumatic brain injuries, infections of the central nervous system, chronic drug and alcohol use, and certain congenital abnormalities such as hydrocephalus. Simply put, dementia is a result of primary neurologic, neuropsychiatric, and medical conditions (Gale, Acar, & Daffner, 2018) .
Degenerative neurological disorders account for the largest percentage in the etiology of dementia. This includes Alzheimer's disease, which in itself accounts for over 70 percent of all dementia cases. Other degenerative causes include Lewy body dementia, Huntington disease, multiple sclerosis, Parkinson's disease, and other motor neuron disease. A feature of this neurodegenerative condition is that they get worse with time.
Alzheimer's disease is a type of cortical dementia that involves the outer brain layer, the cerebral cortex. It is the most common cause of dementia affecting elderly individuals. With a slow onset of higher function that is followed by memory loss and disorientation over time. It results in severe memory loss leading to loss of words and language. Most cases of Alzheimer's disease have been documented to be sporadic (Chakrabarti, et al., 2015) . However, recent research points to mutations of three genes as a causative factor in early-onset dementia-PSEN1, APP, and PSEN2 (Duong, Tejal, & Chang, 2017) . PSEN1 and PSEN2 code for proteins s182 and stm2, respectively. Both have been shown to lead to raised levels of beta-amyloid. The gene that codes for the apolipoprotein E4 (APOE) has been implicated in late-onset disease. It is present in up to 30% of patients with sporadic Alzheimer’s disease. In the case of late-onset Alzheimer’s disease, SORL 1 gene has been implicated.
However, about 10% show familial tendencies. This means they run in families. Accumulation of beta-amyloid form from amyloid precursor proteins has been shown to exist. The deposition of amyloid-beta proteins results in the formation of senile neuritic plaque, neurofibrillary tangles, and amyloid angiopathy. .With neurofibrillary tangles, the neuronal cell nucleus is deformed or displaced, while other cases contain tau protein that forms tangles within neurons. The neuritic plaques, in most instances, assume a tortuous and dilated morphology and are usually in a different part of the cortex and subcortex depending on the disease staging. In amyloid angiopathy, there is an accumulation of the protein in arterial vascular walls. Because of this, neuronal neurotransmission for nerve signals is impaired. This is even further impaired, considering studies have shown an overall decline in the number of neurotransmitters between nerve cells, especially acetylcholine transmitter (Kumar, Abbas, & Aster) (Mohan, 2010) .
In frontotemporal Dementia (FTD), language and personality changes are the hallmark manifestations with memory impairment coming late. It presents mainly in those between 50 to 70 years. Unlike other forms of dementia, most cases of frontotemporal dementia run in families, meaning they have a genetic component. This kind of dementia is occasioned by a decrease in the size of the frontal and temporal lobe, the lobe in charge of language and behavior, respectively. The brain atrophy that occurs worsens with time. Like Alzheimer's disease, it is irreversible and is affected by the tau protein deposition for those with mutations on the tau gene in chromosome 17. The possible mechanism for brain atrophy may be due to neuronal cell loss and gliosis. FTD may damage the basal ganglia. It has also been referred to as Picks Disease, Frontotemporal lobar degeneration, primary progressive aphasia among a myriad of other clinic-pathological terms (Kumar, Abbas, & Aster) .
Huntington disease has both dementia and movement impairment manifestations. Sides have a genetic component, and it is autosomal dominant. The genetic defect is a CAG trinucleotide mutation in the gene that codes for Huntington protein leading to a repeat expansion defect. The huntingtin protein has been postulated to result in nerve degeneration or inhibition of essential protein synthesis. The disease onset may be anywhere from childhood to adulthood but usually in the 40-60 year age group.
Lew body dementia is another progressive dementia form. In this kind of dementia, there is an association with Parkinsonism-slowness of movement, diminished facial expression, pin rolling tremor, and shuffling gait-in most cases. Other salient features include constant falls, impaired alertness, and even visual hallucinations. Parkinsonism may precede or come after the dementia sets in. Microscopically, there exists a Lewy body in neuronal cells as a cytoplasm component. The Lewy bodies contain a protein labeled alpha-synuclein. The protein distorts the orientation of the nerve cells and impairs neuronal transmission. Usually, it is found in the substantia nigra in patients with idiopathic Parkinsonism disease. They can also be found in the amygdala and cortex. Diffuse Lewy body dementia only has Lewy body, while Lewy body with Alzheimer variant has both the bodies and other pathologic entities such as amyloid protein.
Most old individuals will always have comorbid conditions. This means more than one disease entity occurs. In mixed dementia, both the factors that account for Alzheimer’s disease and Vascular Dementia occur. Thus a patient will have features suggesting both clinically, microscopically, and even in radio imaging assessment.
For the case of vascular disorders, the vessels implicated are in the brain. Such vascular associated factors include global hypoxia that causes ischemic brain injury and multiple brain infarcts. Simply put, dementia comes as a result of decreased brain supply leading to the death of brain hypoxia and cell brain cells death. In hypertensive and diabetic individuals, terminal blood vessels in the subcortex have been shown to narrow and are hardened, possibly through atherosclerosis, leading to small vessel vascular dementia. The same has also been found in smokers. In the case of infarcted stroke, a sudden part of the brain is cut off from blood supply with the blockage occasioned by a blood clot in ischemic stroke. When it occurs over a large brain area, involving multiply infarcts due to multiple small thrombi, multi-infarct dementia ensues.
Experiencing traumatic brain injury in early or midlife is a predictor of dementia later. Affected individuals have a 2 to 4 fold chance of being affected by dementia. Traumatic head injury may be a result of many causes. Among the commonest are car accidents occasioned by drunk driving or over speeding due to psychological disturbances, sporting injuries such as concussions fall from height as in cases of suicidal attempts and even assault involving the head such as in extreme cases of juvenile delinquency. Trauma to the brain leads to the formation of clots in the brain. In chronic subdural hematomas, there is bleeding beneath the dura mater and arachnoid mater of the meninges. The meninges cover the brain and with time, ones the bleeding forms a clot, repeated bleeding and clotting processes exert pressure effect on the brain. The role of traumatic head injury is even more important in this age, where high sports activities and increased road traffic accidents continue to be on the rise.
Dementia pugilistica is a special type of dementia due to chronic repetitive traumatic brain injury. The underlying aspect is chronic traumatic encephalopathy. It is a phenomenon experienced among chronic professional boxers; personality changes precede memory changes. Alzheimer like changes, neuronal loss, subdural hematomas, and cortical atrophy are all possible causes. Although concussions have been shown to result from mild blows to the head with or without loss of consciousness, cases of loss of cognitive abilities although temporarily exist. Overtime, multiple concussions lead to development of neuropsychiatric such as mood and behavioural disturbances all of which have been linked to dementia (Carson, 2016) .
Various forms of infection cause dementia. The infective agent may be a prion, virus, bacteria, or parasites. In most instances, it is the chronic form of the disease process that causes dementia. This is usually a result of damage to brain cells through various inflammatory responses. Infectious diseases such as meningitis, CJD, HIV associated encephalopathy, neurosyphilis, viral encephalitis, and progressive multifocal leuko-encephalopathy have been known to result in dementia. HIV AIDS is a major global pandemic now spanning for over three decades since its discovery. It causes the HIV AIDS dementia complex. HIV is a multisystem illness. It, therefore, spreads through several body systems. It spread to the central nervous system occurs early, but a manifestation of dementia occurs in late-stage disease and is usually due to HIV encephalopathy. With time there is a decline in cognitive ability for an individual, although alertness is maintained. With time, motor and behavioral aspects come into play as the disease is greatly disseminated in the brain. With the inflammatory response, macrophages, microglia, and astrocytes are produced in greater quantities causing cytokine production and other neurotoxic pathways that lead to nerve damage hence dementia (Jameson, et al., 2018) .
Herpes zoster encephalitis, a viral infection of the brain due to varicella-zoster virus (VZV) has also been shown to result in dementia. The presentation entails impaired cognitive and memory functions, slowed information processing and poor motor skills especially to older patients. Although the acute form may have cognitive impairment, the same infection has shown to have brain atrophy, decreased cognitive capabilities, infarctive lesions that predispose to brain hypoperfusion and increased white matter lesions (Bangen, Delano-Wood, & Bondi, 2010) .
CJD belongs to the group of prion diseases. They are acquired through transmission from contaminated organs, iatrogenic, or 85% spontaneously occur in individuals. Prions are abnormal formed proteins with the capacity to transmit their defective components to normal proteins, thus creating the same faulty proteins in neuronal cells. Unfortunately, dementia here progress rapidly, and individual only have a short time to live as no treatment exists (Fabiano, et al., 2015) .
Endocrine disorders have been implicated in the development of dementia. The thyroid gland is an important organ as its hormone regulates many behavioral aspects. Hyperthyroidism has been implicated in increased risk for dementia development, while hypothyroidism at the subclinical level causes reduced risk. Increased levels of free thyroxine (fT4) appear to be the main protein through which hyperthyroidism results in dementia. Of note is past studies that had shown low thyroid levels to have been associated with neurocognitive defects, especially in congenital hypothyroidism that includes other psychiatric conditions, namely depression (Layal, et al., 2016) .
Congenital abnormalities have been associated with dementia. Normal-pressure hydrocephalus has been shown to lead to hydrocephalic dementia. Here the cerebrospinal fluid is a lot, and there is a compressive effect on the brain as a result of enlarged ventricular space. Most have gait disturbances, urinary incontinence, and dementia symptoms, although most will be from neurodegenerative dementias, and only in rare cases will it be from hydrocephalus.
In leukodystrophy related dementia, the myelin sheath, that covers nerves and hence efficient neuronal transmission, is impaired. It is mainly genetic and affects children who present with a gradual decline in cognitive functioning.
Nutritional deficiencies have been studied extensively as a cause of dementia. This is usually attributed to poor nutritional choices, poverty, and other existing medical comorbidities. Various macronutrients, such as the B-complex vitamins, antioxidants, and low-density polyunsaturated fatty acids in addition to vitamin D, play critical roles. They have neuroprotective elements as they slow down neurodegenerative processes. Thus, low levels of these elements cause dementia symptoms. Vitamin B complex has largely been implicated. In pernicious anemia, there is vitamin B12 /cobalamin deficiency. About 40 % of patients with this deficiency have neuropsychiatric manifestations. In the elderly, gastric atrophy worsens the absorption of the mineral. The syndrome causes damage to myelin fibers in the cerebral cortex leading to dementia is the signal transmission is affected due to demyelination. The synergistic pathways of vitamin B12 and folic acid/vitamin B9 also may suggest a role of folate as a causative agent of dementia if deficient (Cardoso, Cominetti, & Cozzolino, 2013) .
Thiamine deficiency damages the midbrain, and dorsomedial part of the thalamus that has been shown to cause memory loss if it is prolonged. This is Wernicke-Korsakoff syndrome, where the patient cannot recall any new information but has long-term memory. Other features entail hallucination and loss of sight and coordination signals.
Pellagra, due to lack of nicotinic acid, has been shown to cause dementia-memory loss, disorientation. Pellagra itself presents as a triad of dementia, dermatitis, and diarrhea.
Vitamin D deficiency may also be associated with dementia because some studies point to a sharp cognitive capabilities decline in demented individuals with deficiency.
Decreased antioxidant activity has been proposed to be a cause of dementia. This is because the brain cells are highly vulnerable to oxidative stress. The aging process is associated with a higher rate of reactive species production with decreased antioxidant mechanisms. Amyloid bet protein increases the production of reactive oxygen species. Selenium, vitamin E are important elements in the antioxidant pathway, and their decreased levels have been shown to lead to cognitive decline in mild dementia.
Chronic alcoholism causes alcohol-related dementia. In the acute phase, alcohol depresses the brain leading to impaired judgment. In chronic alcoholism, there is an associated deficiency of most of the nutritional elements, mainly vitamins due to malnutrition, which leads to dementia with damage to certain brain signal pathways. Korsakoff's syndrome is alcohol-related dementia, where there is a loss of short term memory capabilities.
Tumors through there pressure effects have been shown to cause dementia symptoms, especially if the location is in the frontal or temporal lobe. Although a rare cause of dementia, brain tumors usually will present with other constitutional manifestations such as headache and brain part site-specific symptoms. Management of tumors also through chemotherapy may result in dementia-like symptoms due to the destruction of surrounding brain cells that are healthy.
Increased exposure to heavy metals over time has been shown to correlate to a rise in dementia cases with early-onset. This is especially because of increased anthropogenic activities where some are occupational. Among minerals commonly implicated are cadmium, lead, aluminum, mercury, and even bromides. With aging, metal homeostasis is impaired. Neurotoxic studies point to these heavy metals as contributing to dementia through neurofibrillary tangles formation, amyloid-beta peptide aggregation, all of which channel towards neuronal cell loss (Lee, Park, & Seo, 2018) . Chronic lead poisoning causes apathy and confusion. This is especially in those at occupational risks, such as painters. With mercury exposure chronically, one may manifest with both dementia and peripheral neuropathy. However, a few minerals such as Zinc, Selenium, and calcium are all being studies as possible management entities through supplementation for some dementia forms (Paul & Bush, 2018) .
In conclusion, dementia is not a specific disease. Dementia is a collection of symptoms manifested by at least impairment in two brain functions such as memory impairments. The underlying mechanisms of dementia are not fully understood, however, a number of abnormal proteins such as amyloid beta protein, tau proteins among others have been found to play a role in dementia development. Other factors such as vitamin deficiencies, hypothyroidism, neurodegenerative conditions, vascular abnormalities and trauma to the brain have been identified as causes of dementia. The overall mode appears to be a breakdown in signal transmission by nerves. Further research needs to be undertaken so as to come up with clear links between chromosomal mutations and development of neurodegenerative forms of dementia. This is especially critical as globally there is an overall increase in the aging population.
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