Elevated Dementia Risk Persists Among Older People Living With HIV

Long-term development of dementia remains a concern for older people living with HIV, despite the considerable advances of antiretroviral therapy, according to the results of a large U.S. study published in the journal AIDS. The research found that people living with HIV (PLWH) in the prior decade had a 58% higher risk for dementia compared with demographically similar HIV-negative people.

The findings derive from an observational cohort study conducted by Kaiser Permanente Northern California (KPNC), which examined the electronic records of people who were active KPNC members between July 2013 and December 2017. The cohort included 5,381 PLWH and 119,022 HIV-negative people; it was 91% male (the study was binary in its sex differentiation), 65% white, 15% Black, and 13% Latinx.

All of the PLWH were on antiretroviral therapy and over 50 years of age (the average age at baseline was 57 for PLWH and 58 for HIV-negative people), with no prior diagnosis of dementia. Patient data was included through the end of 2019. The data analysis revealed that by age 80, just over a quarter of PLWH had been diagnosed with dementia, while just under 14% of HIV-negative people had a dementia diagnosis. Even after adjusting for a wide range of factors, the relative risk of dementia among PLWH remained elevated (adjusted hazard ratio = 1.58, 95% CI = 1.31–1.92).

“We found that dementia risk in people with treated HIV was elevated even after accounting for well-known dementia risk factors such as cardiovascular disease, obesity, diabetes, and depression,” as well as sociodemographic factors (e.g., age, sex, socioeconomic status) and lifestyle factors (e.g., smoking, unhealthy alcohol use), Jennifer Lam, Ph.D., M.P.H., a research fellow at KPNC and the lead author of the study, told TheBodyPro. The researchers also adjusted for the frequency of outpatient visits, “because health care utilization can be tied to likelihood of being diagnosed with dementia,” Lam said.

The study participants had been living with HIV for an average of 17 years. Lam noted that people with HIV who were not on antiretroviral therapy were excluded from the study because it’s already well known that untreated HIV is a significant risk factor for dementia and other age-related conditions.

“This residual elevated risk may be due to the effects of long-term HIV infection even when suppressed, HIV-mediated inflammation, previously untreated HIV infection, or some other factor that we were unable to measure in our study,” Lam said. She added that it would take more research to learn what, exactly, about HIV puts people at greater risk of cognitive decline even when viral load is suppressed.

Researchers did not separate subjects by the length of time they had HIV or the number of years they had been on antiretroviral therapy (ART). The length of time on ART would be an important area for future research, as would an exploration of patterns of ART use, type of ART used, and how varying levels of HIV control over time may affect future dementia risk, Lam said.

Another limitation of the study was the small proportion of women who participated (less than 10%). Lam said future research on HIV and dementia should include more women, who are known be at higher risk for dementia, though there is no consensus on the reason.

Broader Implications: HIV, Aging, and Neurocognitive Decline

PLWH who have been taking ART are generally expected to have a normal lifespan, as long as the treatment continues suppressing the virus. But for many, that longer life includes more complications—from the effects of long-term HIV infection, long-term use of antiretrovirals, or both. For example, there is concern that, over time, some antiretrovirals can increase cholesterol and put additional strain on the liver and kidneys.

There is also evidence that as people grow older with HIV, they may suffer more aging-related comorbid illnesses and require substantially more non-ART medications than younger people. And HIV, even with effective treatment to suppress the virus, could impact the biology of aging and result in the onset of age-related comorbidities and syndromes sooner.

Broadly, the new KPNC study adds to a small but growing body of research in the subfield of HIV-associated neurocognitive disorders (HAND) showing that PLWH are at greater risk of various types of cognitive impairment, ranging from mild cognitive impairments (that may not noticeably affect daily activities) to more severe impairments.

However, the Kaiser study appears to be the first to examine clinically apparent dementia incidence among PLWH who have relatively stable HIV disease and who are engaged in primary care.

A related study released last year found that U.S. veterans with HIV had a 50% higher risk of dementia compared with HIV-negative veterans. However, only 61% of people with HIV in that study were on antiretroviral treatment. In the Kaiser study, all PLWH were on treatment, yet they still had elevated dementia risk compared to HIV-negative controls.

Right now, there are no solid answers to a logical clinical question stemming from this research: How can HIV care providers reduce the risk of dementia among their patients, or at least delay its onset? One of the KPNC study’s co-authors, Craig Hou, M.D., the chief of neurology at KPNC, said that the general advice about dementia applies to people aging with HIV. “We encourage people to eat a heart-healthy diet, stay physically active, and engage in ongoing intellectual and mental activity,” he said.