What is HIV Neurocognitive Disorders?
People infected with human immunodeficiency virus (HIV, a virus that attacks the body’s immune system) may experience various types of mental health problems. These problems are categorized as neuropsychiatric illnesses, which includes issues related to thinking abilities, mood changes, and anxiety-related symptoms. In the past, especially before the introduction of antiretroviral treatment (medication that suppresses the HIV virus), many HIV-infected people suffered untreated mental health problems. This led to high levels of illness and death among these individuals. Most of these mental health disorders were caused by untreated infections that individuals got from AIDS (Acquired Immunodeficiency Syndrome, the last stage of an HIV infection), like toxoplasmosis (an infection caused by a parasite) and encephalitis (brain inflammation). A significant decline in such cases of mental health problems occurred with the advent of HAART (highly active antiretroviral therapy). HAART is a combined drug treatment for HIV that was developed around 1996. Since then, the occurrence of HIV-related mental health disorders has started to decrease.
In 2007, the United States National Institutes of Health introduced a system to identify these kinds of mental health issues. This system, known as the “Frascati criteria,” has been designed for better clinical assessments and research, even though it hasn’t been accepted globally. According to the Frascati criteria:
– Asymptomatic neurocognitive impairment: Identified when an individual scores significantly lower than the average in two or more cognitive-related (thinking-related) tests. These individuals do not show any obvious signs of function impairment.
– Mild neurocognitive disorder: Identified when an individual not only scores significantly lower than the average in two or more cognitive-related tests but also shows mild impairment in their daily functioning.
– HIV-associated dementia: Identified when an individual scores significantly lower than the average in two or more cognitive-related tests and has difficulties with their daily activities.
Please note these categorizations can only be made after eliminating the possibilities of any other conditions causing these impairments. This includes ruling out opportunistic infections (infections that occur more frequently and are severe in individuals with weakened immune systems), cancer, strokes, substance abuse, or severe brain disorders.
What Causes HIV Neurocognitive Disorders?
HIV, the virus that causes AIDS, can cross from the bloodstream into the brain during the early stage of infection. However, it is during a later phase, characterized by ongoing inflammation, that changes in thinking or memory may occur. HIV affects various cells in the brain, including types of white blood cells called monocytes and macrophages, as well as brain tissue itself.
HIV can reproduce itself within a type of brain cell called microglia. These cells act like the brain’s immune system. This virus reproduction can cause shifts in the brain linked to symptoms of thinking and memory disorders. However, it’s essential to understand that not everyone with HIV will develop these disorders. Several risk factors can influence the likelihood of these disorders developing, as outlined below.
The first risk factor is a low “nadir CD4 count.” CD4 cells are a type of white blood cell that HIV targets and destroys. The nadir CD4 count is the lowest point that someone’s CD4 count drops to during their HIV disease. Some studies have suggested that the more severe the HIV disease (marked by a lower nadir CD4 count), the greater the risk of developing thinking and memory disorders. Moreover, research has suggested that these cognitive problems may persist and not be entirely reversible in these patients. Interestingly, these studies noted that even when HIV treatment improved laboratory values, the associated brain injury did not seem to get better.
Being older can also be a risk factor. People with HIV who are 50 or older are more likely to experience cognitive disorders, although it is unclear if this is due to HIV infection, aging itself, or a combination of both.
Next, other health conditions, like heart disease and obesity, can increase the risk of dementia in people living with HIV compared to the general population. People with both HIV and heart disease, for example, are more likely to develop cognitive disorders, regardless of their HIV viral load or CD4 cell counts.
Additionally, having both HIV and hepatitis C might increase the risk of thinking and memory disorders, although studies have reported mixed findings. Some suggests a higher risk exists, while others find no additional risk. A history of a type of infection called toxoplasmosis has also been associated with an increased risk of such disorders, especially in people with ongoing (latent) toxoplasmosis infections.
Interestingly, despite efforts to identify genetic risk factors for these thinking and memory disorders in people with HIV, no specific genetic mutations have been found. A large study involving more than 1200 patients found no link between any genetic variations and these disorders.
Risk Factors and Frequency for HIV Neurocognitive Disorders
HIV-associated dementia was initially seen as a common issue among those infected with HIV, impacting around 40% of these individuals. This group of disorders, originally labeled as “AIDS dementia complex,” were also found in about 50% of HIV patients in the United States in early research. However, with the usage of antiretroviral therapy, the prevalence of these cognitive impairments has lessened, especially in those who consistently stay on treatment. According to the CASCADE cohort, incidents of these disorders dropped from 6.49 to 0.66 per 1000 person-years.
Despite the decrease in severe neurocognitive difficulties, mild cognitive impairment remains common even when the virus is suppressed. In the era after the introduction of HAART, asymptomatic neurocognitive impairment is the most frequently occurring disorder of this kind, affecting about a third of patients. Mild neurocognitive disorder has a 12% prevalence rate, while HIV-associated dementia is found in just 2% of cases. Recent discussions question the reasons behind these lingering neurocognitive problems in the post-HAART period. Some research indicates increased neurocognitive disorder risk in HIV patients, while other studies find no significant difference in disorder prevalence between HIV patients with proper viral suppression and CD4 cell counts, and individuals of the same age without HIV.
Signs and Symptoms of HIV Neurocognitive Disorders
People suffering from HIV-associated neurocognitive disorders (HAND) usually show changes in thinking and behavior. Early signs include problems with thinking clearly, remembering things, and making decisions. Over time, people might also become slow, sad, easily upset, and show signs of shaking hands and overactive reflexes. As the condition gets worse, people can show all the signs of serious dementia, spinal cord disease, nerve disease, and even symptoms seen in Parkinson’s disease. What symptoms a person shows and how fast they get worse can depend on how serious their HIV is and whether they are getting treatment for it.
If serious dementia is present, people usually have trouble with attention, feel depressed, and their physical movement is slow. They also have trouble remembering things, making decisions, and might not care about things they used to enjoy. If the cognitive decline is mild, the person might mainly have trouble with attention and working memory, with possibly some decision-making problems. These problems might not be obvious at first and might only be noticed once they start to affect a person’s reading or their ability to focus on a conversation or activity. Physical problems are usually not seen in mild cases unless dementia is also present.
“CNS Viral Escape Syndrome” is a rare condition that shows up in people getting HIV treatment and have sudden severe neurological problems. This condition happens when the HIV is under control everywhere else in the body but is still active in the brain. Not everyone who has HIV active in the brain will develop this condition. If this condition is suspected, it’s important to check the HIV RNA levels in the cerebrospinal fluid (the fluid around the brain and spinal cord) to decide if a change in treatment is needed.
“Immune Reconstitution Inflammatory Syndrome (IRIS)” is another rare cause of new cognitive symptoms in people with HIV. This condition can cause severe brain inflammation, abnormalities in the brain’s white and gray matter (seen on scans), and a high number of CD8 cells (a type of immune cell) in the brain’s fluid.
Testing for HIV Neurocognitive Disorders
Doctors often use a series of mental exercises known as neuropsychological tests to check a patient’s level of cognitive function. These tests look at several areas like memory, attention and multitasking, mental flexibility, problem-solving, verbal ability, and motor skills (fine movements coordinated by your brain). Some examples of these tests include the trail making test to see how well you can plan and organize, a digit span test to measure mental speed and memory, and the Stroop test to examine how quickly you can process information.
Another way doctors can assess your cognitive health is by using imaging techniques, like MRI or CT scans. These tools can provide detailed pictures of your brain, helping doctors visualize any changes in the brain’s structure. Back when HIV treatments were not as advanced, brain scans often showed signs of brain shrinkage. Nowadays, we can use more advanced types of imaging like FLAIR, which can show specific areas in the brain that might be shrinking. Modern 3D imaging can even map out the exact pattern of brain shrinkage, comparing it to a healthy brain, and relating it to a person’s cognitive impairment.
A simple but useful test for initial screening is the International HIV Dementia Scale. This test checks a person’s memory, motor speed (how quickly they can move), and psychomotor speed (how quickly they can combine thinking and movement). The test goes as follows:
First, the patient is asked to remember and repeat four words, then try to remember them for later. Their motor speed is then tested by asking them to tap their first two fingers together as fast as they can for five seconds. The tester will count the number of taps. Lastly, the psychomotor speed is checked by asking the patient to perform a series of tasks, like clenching their fist and then placing their hand on a table in different positions. The patient is then asked to recall the four words they practiced earlier.
Another commonly used test is the modified HIV scale, which checks instant memory and delayed recall, as well as basic problem-solving skills and motor speed. Memory is tested by asking patients to remember and then recall four words a few minutes later. Problem-solving skills are tested by asking the patient to copy a cube drawing, while motor speed is checked by asking the patient to write the alphabet in capital letters.
Recent research suggests that three simple questions can also serve as a good initial check for cognitive problems in patients with HIV: do they experience memory loss, do they find it hard to pay attention, and do they feel slower when reasoning or doing complicated tasks? That said, examining the patient’s medical history and noting when cognitive decline started is still the best route to properly assess them.
Treatment Options for HIV Neurocognitive Disorders
Treatment for cognitive issues related to HIV includes medications known as antiretroviral drugs. These drugs help improve mental functioning and are effective in lowering the virus amount in the body and increasing the count of defensive cells (CD4 cells). Some experts believe that for these drugs to reduce the virus effectively, they must penetrate the blood-brain barrier, meaning they have to reach a particular region of our brain fluid.
A study was conducted to find which drugs can penetrate the brain effectively. Each drug was scored ranging from 0, meaning low penetration, to 1, indicating high penetration. This ranking was based on the drug concentration in brain fluid, its chemical properties, and the drug’s effectiveness in clinical trials. However, the relationship between the drug’s ability to cross the brain barrier and its effectiveness is complex. Research has shown that while some drugs with high penetration may improve brain function, others can be harmful to the brain.
Despite these findings, it’s important to understand that no specific combination of drugs works better than others when dealing with HIV-related cognitive disorders. Some professionals suggest drugs with a high penetration score based on brain fluid drug reactions could be more beneficial, but supporting scientific evidence for this approach is limited.
In general, medical professionals recommend avoiding a particular drug, efavirenz, in patients with HIV-related cognitive issues because of its potential for serious mental health side effects. Mood-related medications like antidepressants may be beneficial for patients who also experience mood disorders. Antipsychotic medications might be useful for patients with symptoms like fatigue, apathy, or mania, although this remains understudied.
It’s essential to remember that some of these mental health medications, like carbamazepine, can interact negatively with specific antiretroviral drugs. Finally, some medicines are generally regarded as being helpful for the brain, including memantine, pentoxifylline, selegiline, nimodipine, and peptide T; however, the effectiveness of these drugs is still unclear.
What else can HIV Neurocognitive Disorders be?
When it comes to identifying other conditions that could potentially be mistaken for HIV-associated dementia, doctors look at several possibilities. These conditions could include underlying cognitive disorders, depressive disorders presenting similar signs and symptoms, issues related to substance intoxication or withdrawal, metabolic disorders, infections that can affect the brain, brain tumors, brain injuries, or side effects from HIV medications.
Here are some of the conditions that doctors would consider:
Central Nervous System Diseases:
- Lymphoma in the nervous system
- Toxoplasmosis affecting the nervous system
- Vasculitis of the nervous system
- Cryptococcal meningitis
- Cytomegalovirus encephalitis
- Spread of cancer to the nervous system
- Neurosyphilis
- Progressive multifocal leukoencephalopathy
- Tuberculous meningitis
Substance Withdrawal or Intoxication:
- Alcohol
- Chronic cannabis
- Opioids
Metabolic and Endocrine Diseases:
- Addison’s disease
- Vitamin B12 deficiency
- Thyroid disease
Psychiatric Illnesses:
- Delirium
- Mood disorders including major depression and dysthymia
What to expect with HIV Neurocognitive Disorders
As per the MIND exchange working group, no studies have been done to look at the long-term outcomes of a condition called HIV-associated neurocognitive disorder (HAND). This refers to cognitive, motor and neurological impairments in people with HIV. However, certain indicators related to HIV such as low CD4 count (this is a type of white blood cell that fights infection) and high viral load (the amount of HIV in the blood), poor performance in mental tests, and existing mood disorders might suggest a poor long-term outcome or prognosis.
Possible Complications When Diagnosed with HIV Neurocognitive Disorders
HIV dementia can lead to other problems. These can include mood and anxiety disorders. Studies have found that if a person is under chronic stress, it weakens their immune system and raises the risk of getting other diseases as well. As people live longer with HIV now, other types of dementia like primary neurocognitive illness are also becoming a common issue.
Complications from HIV Dementia:
- Mood disorders
- Anxiety disorders
- Weakened immune system
- Increased risk of other diseases
- Other forms of dementia, including primary neurocognitive illness
Preventing HIV Neurocognitive Disorders
Teaching patients about a disease usually focuses on recognizing early signs and starting treatment as soon as possible. Treating HIV with a type of therapy known as HAART (Highly Active Antiretroviral Therapy) can delay, or even prevent, the development of dementia caused by the disease. Patients with higher levels of the virus and lower counts of immune cells known as CD4 cells have a greater chance of developing HIV-related dementia. This makes starting HAART therapy early very important to prevent serious decline in mental abilities in HIV patients.
The idea of routinely testing HIV patients without symptoms for signs of mental impairment is a bit controversial. Some people argue against it because of cost concerns and limited resources in many settings to test patients without symptoms. However, some research suggests that testing these patients could lead to an early diagnosis. This could allow the treatment to be changed to HAART medications that are better at reaching the central nervous system, potentially improving the patient’s overall health outcome.