Long American study explores trends in dementia among people with and without HIV

• Researchers analyzed the health of nearly 25,000 people with and 500,000 people without HIV
• Over 23 years the risk of people with HIV developing dementia fell significantly
• The study highlights the need to integrate cognitive health and dementia screening into HIV care

In the early 1980s, when the HIV pandemic was first recognized, doctors and patients became aware that some people with the disease were developing HIV-related brain problems with thinking clearly, reasoning and memory. In severe cases, dementia and a loss of personality occurred. These problems were happening because HIV-infected cells of the immune system had traveled to the brain, where they released new copies of HIV, viral proteins and harmful chemical messengers. The combination of HIV, its proteins and these chemical messengers results in inflammation within the brain and over time can degrade the health and functioning of this vital organ. In cases of severe HIV-related immune deficiency (AIDS), the brain could become susceptible to serious infections by other viruses, bacteria, fungi and parasites. These other germs could create an additional layer of harm to the brain.

A change due to effective HIV treatment

Beginning in 1996, the widespread availability of effective HIV treatment (antiretroviral therapy; ART) in Canada and other high-income countries led to a greater proportion of people with suppressed levels of HIV in their body. A suppressed viral load results in a better-functioning immune system and improved overall health. Thanks to ART, today dementia related to HIV has become comparatively rare in Canada and other high-income countries, particularly in people who are in care and whose viral load is suppressed.

Another beneficial effect of ART is that many people who take this therapy as directed and maintain a suppressed level of HIV will have a near-normal life expectancy. This means that people with HIV will live long enough to be affected by issues of aging that affect people without HIV. Cognitive decline and dementia are two such issues. 

An American study on dementia

Researchers with Kaiser Permanente, a healthcare delivery system in the U.S., analyzed and compared health-related information collected between the years 2000 and 2023 from about 25,000 people with HIV and nearly 500,000 people without HIV. Specifically, the researchers focused on diagnoses of dementia in the medical records of participants.

The researchers found that, overall, diagnoses of dementia decreased over time in both populations. However, new cases of dementia were more common among people with HIV. This may inadvertently alarm some readers, but it is noteworthy that the proportions of HIV-positive people with dementia were relatively low.

Declining cognitive functioning and dementia can degrade quality of life and become disabling. Therefore, the study scientists called for “sustained attention to cognitive health and the integration of dementia-related services in HIV care.”

Study details

Researchers analyzed health-related databases compiled by Kaiser Permanente from the following jurisdictions: 

• California
• Maryland
• Virginia
• Washington, D.C.

Data from each HIV-positive person was matched with data from 20 HIV-negative people of the same age, gender, ethno-racial group, year they enrolled in Kaiser, and so on. This matching made the profile of participants as similar as possible, with the obvious exception of HIV status.

The distribution of participants was as follows:

• HIV positive – 24,762 people
• HIV negative – 494,963 people

The average profile of people with HIV upon study entry was as follows:

• 87% cisgender male, 13% cisgender female
• age – 51 years
• CD4+ count – 48% of participants had a CD4+ count of 500 cells/mm³ or higher
• 82% were taking ART and 70% of ART users were virally suppressed
• major ethno-racial groups: White – 46%; Black – 23%; Hispanic – 20%; Asian – 4%
• high cholesterol levels – 45%
• history of smoking – 37%
• high blood pressure – 33%
• depression – 26%
• obesity – 21%
• substance use disorder – 14%
• diabetes – 13% 
• cardiovascular disease – 6%
• stroke – 3%

Results

During the study period, overall dementia diagnoses were distributed as follows:

• people without HIV – 9,428 cases of dementia (2%)
• people with HIV – 819 cases of dementia (3%)

What’s more important were the trends in time. Over the course of the study, the risk of new dementia diagnoses decreased in both groups of participants. Among people with HIV, the risk of dementia fell almost fivefold. 

However, despite this decrease, new cases of dementia were more likely to occur among people with HIV. This trend occurred despite the scientists considering factors such as the following:

• sociodemographic
• other health conditions
• substance use
• frequency of visits to healthcare providers

The trends found among people with HIV occurred regardless of ethno-racial group or sex assigned at birth.

Researchers performed a sensitivity analysis whereby they excluded participants in the following categories of people with HIV:

• detectable viral load upon entering the study
• a history of low CD4+ cell counts in the past

Despite these adjustments, the overall trends that were found with the larger group of people with HIV in the study remained when people with the above factors were removed from analysis.

Type of dementia

Unfortunately, the researchers were unable to provide detailed information on the specific forms of dementia in most people in the study. As mentioned earlier, in the history of the HIV pandemic, HIV itself could be a contributing cause of dementia, though reports suggest that this is rare today among ART users in high-income countries whose viral load is suppressed. The researchers noted that as most participants eventually would have been taking ART in the study and been virally suppressed, it is unlikely that HIV-related cognitive problems would have contributed to most cases of dementia in their study (Jennifer Lam PhD, Kaiser Permanente, personal communication).

The researchers also noted that in the present study, cases of Alzheimer’s dementia were lower among people with HIV (2%) compared to people without HIV (9%). They offered no explanation for this. 

Other studies suggest that people with HIV who use nucleoside analogues as part of their HIV treatment have a reduced risk for developing Alzheimer’s dementia. However, these studies are observational in design and cannot prove that taking nucleoside analogues reduces the risk for developing Alzheimer’s disease. 

Note that the present study was retrospective in design; that is, it used data captured in the past for one purpose and analyzed it in the present for another purpose. It is possible that this study design may have drawn incorrect conclusions. However, several other studies have found similar trends. Notably, the present study did not collect information on exercise. This issue may be useful in future analyses of cardiovascular risk and brain health. 

Why did the risk of dementia decline over time?

The study scientists argued that several factors played a role in the declining risk of dementia among people with HIV in the study, including the following:

• more effective ART
• better management of comorbidities that can contribute to age-related dementia (such as prescription of medicines to reduce high cholesterol, high blood pressure and high blood sugar as well as monitoring of these issues)
• smoking cessation

Virological control is important

Keeping HIV suppressed is vital for overall health. However, the study team noted that “maintaining consistent HIV viral suppression can be challenging, particularly in older populations where cognitive decline may impair ART adherence.” Thus, as ART users age, healthcare providers may need to monitor adherence to ART and intervene with assistance when necessary.

Bear in mind

The importance of the present report from Kaiser Permanente is that the study period covered 23 years and contained information on more than half a million people. 

The good news is that this study showed that the risk of developing dementia among people with HIV is declining and approaching that seen in a similar population of people without HIV. However, the overall risk of dementia is still higher among people with HIV. As a result, the study scientists recommend that “dementia screening and care will need to remain a continued focus in HIV primary care for years to come.” 

The study team also suggested that its findings “highlight the need to integrate HIV-specific considerations into broader aging care strategies. Given that people with HIV often experience social isolation and have fewer informal caregiving options, adapting existing HIV and dementia care infrastructure to meet increasing demands could support more inclusive care and positively impact the wellbeing of people aging with HIV.”

A note about residual risk of dementia

A separate analysis also by the Kaiser Permanente researchers focused on 21,354 people with HIV (and no participants without HIV). In that analysis, having a low CD4+ count (less than 200 cells/mm³) in the past was associated with a subsequent increased risk of dementia. In this analysis, researchers found that the subsequent risk of dementia in participants whose CD4+ cell counts rose to 500 cells/mm³ or more within two years of initiating ART was greatly reduced, though not eliminated.

The researchers argued that having a low CD4+ count in the past very likely reflects a delay in HIV diagnosis and initiation of ART. They added that it is possible that having such a low CD4+ count results in injury to the brain. Initiation of ART likely helps the brain largely recover, however, some degree of injury may persist. Other studies have also found a similar trend among people with low CD4+ cell counts prior to initiation of ART.

This separate analysis underscores the importance of early diagnosis of HIV and prompt initiation of ART.

In British Columbia

Scientists in British Columbia have also studied the risk of dementia in about 5,000 people with HIV over 15 years. They found that about 2% of participants developed dementia, a figure similar to that found in the larger American study reported in this CATIE News bulletin. The B.C. scientists noted that immune suppression (a history of CD4+ counts less than 50 cells/mm³) and inflammation increased a person’s subsequent risk for dementia. They called for “the enhanced integration of care services provided for HIV, mental health, substance use disorder and other risk-inducing comorbidities as a means of lowering the risk of dementia within this population.”

Dementia is not destiny

As people age, it is important for them to engage in activities that are good for the brain. Such activities can significantly delay the onset of cognitive decline or sometimes slow the decline once it has started. 

General tips for overall health that also help brain health include the following:

• regular visits to your healthcare provider to monitor general health so conditions that could affect the brain (cardiovascular disease, high blood pressure, high cholesterol, high blood sugar) are caught early and treated
• regular exercise (your healthcare provider can tell you what type is best)
• vaccination against shingles (some studies have found that this vaccine can reduce the risk of dementia)
• eating influenced by the Mediterranean diet, the DASH (Dietary Approaches to Stop Hypertension) diet or a combination of the two called MIND (the Mediterranean-DASH Intervention for Neurodegenerative Delay), as studies have found that these diets can delay cognitive decline
• maintaining a healthy weight; if necessary, speak with your healthcare provider about how to achieve this goal
• engaging in stress reduction exercises when necessary
• talking to your healthcare provider about being screened for mental health issues when necessary
• getting help for reducing the use of alcohol, tobacco and other substances when necessary
• speaking to your healthcare provider about investigating problems with memory, talking or reasoning if you are experiencing them
• joining clubs or social groups to foster interaction with other people

Keeping the brain active

Neuropsychologist Andrea Zammit (Rush University Medical Center, Chicago) has been studying the risk of Alzheimer’s disease and other dementias in people without HIV. Her latest study included almost 2,000 people with an average age of 80 who did not have dementia when they were enrolled. After an average monitoring period of eight years, 551 people developed Alzheimer’s disease and 719 others developed mild cognitive impairment. 

Zammit and her colleagues found that engaging in intellectually stimulating activities could have the following benefits:

• help reduce the risk of Alzheimer’s disease by nearly 40%
• help reduce the risk of developing mild cognitive impairment by 36%
• delay the onset of Alzheimer’s dementia and mild cognitive decline by up to seven years

Such activities could include reading books, engaging in creative writing, taking courses at a college or university, or learning a new language. 

Other activities that stimulate the brain include learning to play a new musical instrument, trying to solve crossword puzzles and playing Sudoku.

Looking after one’s health requires work but making brain-stimulating activities fun and a regular part of life can pay off in the long term.

—Sean R. Hosein

Resources

Brain Health – A Practical Guide to a healthy body for people living with HIV — CATIE

HIV and cardiovascular disease – CATIE

Six-month study finds exercise and stretching beneficial for brain and body in people with HIV – CATIE News

Dementia Education Program – McGill University

A Dementia Strategy for Canada: Together We Achieve - 2024 Annual Report — Public Health Agency of Canada

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