AIDS dementia complex
Encyclopedia
AIDS dementia complex is a common neurological disorder associated with HIV
infection
and AIDS
. It is a metabolic encephalopathy
induced by HIV
infection and fueled by immune activation of brain
macrophage
s and microglia
. These cells are actively infected with HIV and secrete neurotoxin
s of both host and viral origin. The essential features of ADC are disabling cognitive impairment accompanied by motor dysfunction, speech problems and behavioral change. Cognitive impairment is characterised by mental slowness, trouble with memory
and poor concentration
. Motor symptoms include a loss of fine motor control leading to clumsiness, poor balance and tremors. Behavioral changes may include apathy
, lethargy and diminished emotional responses and spontaneity. Histopathologically
, it is identified by the infiltration of monocyte
s and macrophage
s into the central nervous system
(CNS), gliosis
, pallor of myelin sheaths, abnormalities of dendritic
processes and neuron
al loss.
ADC typically occurs after years of HIV infection and is associated with low CD4+ T cell levels and high plasma viral loads. It is sometimes seen as the first sign of the onset of AIDS. Prevalence is between 10-24% in Western countries and has only been seen in 1-2% of India based infections. With the advent of highly active antiretroviral therapy (HAART), the incidence
of ADC has declined in developed countries
, however its prevalence
is increasing. HAART may prevent or delay the onset of ADC in people with HIV infection, and may also improve mental function in people who already have ADC.
Dementia
only exists when neurocognitive impairment in the patient is severe enough to interfere markedly with day-to-day function. That is, the patient is typically unable to work and may not be able to take care of him or herself. Before this, the patient is said to have a mild neurocognitive disorder.
While the progression of dysfunction is variable, it is regarded as a serious complication and, untreated, can progress to a fatal outcome. Diagnosis is made by neurologist
s who carefully rule out alternative diagnoses. This routinely requires a careful neurological examination, brain scans (MRI or CT scan) and a lumbar puncture
to evaluate the cerebrospinal fluid
. No single test is available to confirm the diagnosis, but the constellation of history, laboratory findings, and examination can reliably establish the diagnosis when performed by experienced clinicians. The amount of virus in the brain does not correlate well with the degree of dementia
, suggesting that secondary mechanisms are also important in the manifestation of ADC.
. It is one of the few conditions caused directly by HIV itself, but it is not quite as simple as that because the central nervous system can be damaged by a number of other causes:
Many researchers believe that HIV damages the vital brain cells, neurons, indirectly. According to one theory, HIV either infects or activates cells that nurture and maintain the brain, known as macrophages and microglia
. These cells then produce toxins that can set off a series of reactions that instruct neurons to kill themselves. The infected macrophages and microglia also appear to produce additional factors chemokine
s and cytokine
s - that can affect neurons as well as other brain cells known as astrocyte
s. The affected astrocytes, which normally nurture and protect neurons, also may now end up harming neurons. HIV protein gp120
inhibits the stem cells in the brain from producing new nerve cells. In the neuronal cells, the HIV gp120 induces mitochondrial-death proteins like caspases which may influence the upregulation of the death receptor Fas leading to apoptosis. Researchers hope that new drugs under investigation will interfere with the detrimental cycle and prevent neuron death.
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
and AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
. It is a metabolic encephalopathy
Encephalopathy
Encephalopathy means disorder or disease of the brain. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of global brain dysfunction; this syndrome can be caused by many different illnesses.-Terminology:...
induced by HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
infection and fueled by immune activation of brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
s and microglia
Microglia
Microglia are a type of glial cell that are the resident macrophages of the brain and spinal cord, and thus act as the first and main form of active immune defense in the central nervous system . Microglia constitute 20% of the total glial cell population within the brain...
. These cells are actively infected with HIV and secrete neurotoxin
Neurotoxin
A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...
s of both host and viral origin. The essential features of ADC are disabling cognitive impairment accompanied by motor dysfunction, speech problems and behavioral change. Cognitive impairment is characterised by mental slowness, trouble with memory
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
and poor concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...
. Motor symptoms include a loss of fine motor control leading to clumsiness, poor balance and tremors. Behavioral changes may include apathy
Apathy
Apathy is a state of indifference, or the suppression of emotions such as concern, excitement, motivation and passion. An apathetic individual has an absence of interest in or concern about emotional, social, spiritual, philosophical or physical life.They may lack a sense of purpose or meaning in...
, lethargy and diminished emotional responses and spontaneity. Histopathologically
Histopathology
Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...
, it is identified by the infiltration of monocyte
Monocyte
Monocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...
s and macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
s into the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(CNS), gliosis
Gliosis
Gliosis is a proliferation of astrocytes in damaged areas of the central nervous system . This proliferation usually leads to the formation of a glial scar....
, pallor of myelin sheaths, abnormalities of dendritic
Dendritic cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...
processes and neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
al loss.
ADC typically occurs after years of HIV infection and is associated with low CD4+ T cell levels and high plasma viral loads. It is sometimes seen as the first sign of the onset of AIDS. Prevalence is between 10-24% in Western countries and has only been seen in 1-2% of India based infections. With the advent of highly active antiretroviral therapy (HAART), the incidence
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...
of ADC has declined in developed countries
Developed country
A developed country is a country that has a high level of development according to some criteria. Which criteria, and which countries are classified as being developed, is a contentious issue...
, however its prevalence
Prevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
is increasing. HAART may prevent or delay the onset of ADC in people with HIV infection, and may also improve mental function in people who already have ADC.
Dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
only exists when neurocognitive impairment in the patient is severe enough to interfere markedly with day-to-day function. That is, the patient is typically unable to work and may not be able to take care of him or herself. Before this, the patient is said to have a mild neurocognitive disorder.
Diagnostic criteria
- Marked acquired impairment of at least two ability domains of cognitive function (e.g. memory, attention): typically, the impairment is in multiple domains, especially in learning, information processing and concentration/attention. The cognitive impairment is ascertained by medical historyMedical historyThe medical history or anamnesis of a patient is information gained by a physician by asking specific questions, either of the patient or of other people who know the person and can give suitable information , with the aim of obtaining information useful in formulating a diagnosis and providing...
, mental status examination or neuropsychological testing. - Cognitive impairments identified in 1. interfere markedly with day-to-day functioning.
- Cognitive impairments identified in 1. are present for at least one month.
- Cognitive impairments identified in 1. do not meet the criteria for deliriumDeliriumDelirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...
, or if delirium is present, dementia was diagnosed when delirium was not present. - No evidence of another, pre-existing aetiology that could explain the dementia (e.g. another CNS infection, CNS neoplasm, cerebrovascular disease, pre-existing neurological disease, severe substance abuse compatible with CNS disorder.
While the progression of dysfunction is variable, it is regarded as a serious complication and, untreated, can progress to a fatal outcome. Diagnosis is made by neurologist
Neurologist
A neurologist is a physician who specializes in neurology, and is trained to investigate, or diagnose and treat neurological disorders.Neurology is the medical specialty related to the human nervous system. The nervous system encompasses the brain, spinal cord, and peripheral nerves. A specialist...
s who carefully rule out alternative diagnoses. This routinely requires a careful neurological examination, brain scans (MRI or CT scan) and a lumbar puncture
Lumbar puncture
A lumbar puncture is a diagnostic and at times therapeutic procedure that is performed in order to collect a sample of cerebrospinal fluid for biochemical, microbiological, and cytological analysis, or very rarely as a treatment to relieve increased intracranial pressure.-Indications:The...
to evaluate the cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
. No single test is available to confirm the diagnosis, but the constellation of history, laboratory findings, and examination can reliably establish the diagnosis when performed by experienced clinicians. The amount of virus in the brain does not correlate well with the degree of dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
, suggesting that secondary mechanisms are also important in the manifestation of ADC.
Research
AIDS Dementia Complex (ADC) is not a true opportunistic infectionOpportunistic infection
An opportunistic infection is an infection caused by pathogens, particularly opportunistic pathogens—those that take advantage of certain situations—such as bacterial, viral, fungal or protozoan infections that usually do not cause disease in a healthy host, one with a healthy immune system...
. It is one of the few conditions caused directly by HIV itself, but it is not quite as simple as that because the central nervous system can be damaged by a number of other causes:
- opportunistic infections - there are many
- Primary cerebral lymphomaAIDS-related lymphomaAIDS-related lymphoma describes lymphomas occurring in patients with acquired immunodeficiency syndrome .A lymphoma is a type of cancer arising from lymphoid cells...
or metastasisMetastasisMetastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
of other AIDS-related cancers - direct effects of HIV in the brain
- toxic effects of drug treatments
- malnutritionMalnutritionMalnutrition is the condition that results from taking an unbalanced diet in which certain nutrients are lacking, in excess , or in the wrong proportions....
Many researchers believe that HIV damages the vital brain cells, neurons, indirectly. According to one theory, HIV either infects or activates cells that nurture and maintain the brain, known as macrophages and microglia
Microglia
Microglia are a type of glial cell that are the resident macrophages of the brain and spinal cord, and thus act as the first and main form of active immune defense in the central nervous system . Microglia constitute 20% of the total glial cell population within the brain...
. These cells then produce toxins that can set off a series of reactions that instruct neurons to kill themselves. The infected macrophages and microglia also appear to produce additional factors chemokine
Chemokine
Chemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines...
s and cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s - that can affect neurons as well as other brain cells known as astrocyte
Astrocyte
Astrocytes , also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord...
s. The affected astrocytes, which normally nurture and protect neurons, also may now end up harming neurons. HIV protein gp120
Gp120
Envelope glycoprotein GP120 is a glycoprotein exposed on the surface of the HIV envelope. The 120 in its name comes from its molecular weight of 120 kilodaltons...
inhibits the stem cells in the brain from producing new nerve cells. In the neuronal cells, the HIV gp120 induces mitochondrial-death proteins like caspases which may influence the upregulation of the death receptor Fas leading to apoptosis. Researchers hope that new drugs under investigation will interfere with the detrimental cycle and prevent neuron death.
ADC stage characteristics
- Stage 0 (Normal) Normal Mental and Motor FunctionMotor skillA motor skill is a learned sequence of movements that combine to produce a smooth, efficient action in order to master a particular task. The development of motor skill occurs in the motor cortex, the region of the cerebral cortex that controls voluntary muscle groups.- Development of motor skills...
- Stage 0.5 (Subclinical) Minimal symptoms of cognitive or motor dysfunction characteristic of ADC, or mild signs (snout responseSnout reflexThe Snout reflex is a pouting or pursing of the lips that is elicited by light tapping of the closed lips near the midline. The contraction of the muscles causes the mouth to resemble a snout....
, slowed extremity movements), but without impairment of work or capacity to perform activities of daily living (ADL). Gait and strength are normal. - Stage 1 (Mild) Evidence of functional intellectual or motor impairment characteristic of ADC, but able to perform all but the more demanding aspects of work or ADL. Can walk without assistance.
- Stage 2 (Moderate) Cannot work or maintain the more demanding aspects of daily life, but able to perform basic activities of self care. Ambulatory, but may require a single prop.
- Stage 3 (Severe) Major intellectual incapacity - cannot follow news or personal events, cannot sustain complex conversation, considerable slowing of all output. And/or motor disability - cannot walk unassisted, requiring walker or personal support, usually with slowing and clumsiness of arms as well.
- Stage 4 (End Stage) Nearly vegetative. Intellectual and social comprehension and responses are at a rudimentary level. Nearly or absolutely mute. Paraparetic or paraplegic with urinary incontinenceUrinary incontinenceUrinary incontinence is any involuntary leakage of urine. It is a common and distressing problem, which may have a profound impact on quality of life. Urinary incontinence almost always results from an underlying treatable medical condition but is under-reported to medical practitioners...
and fecal incontinenceFecal incontinenceFecal incontinence is the loss of regular control of the bowels. Involuntary excretion and leaking are common occurrences for those affected. Subjects relating to defecation are often socially unacceptable, thus those affected may be beset by feelings of shame and humiliation...
.