The risk of dementia in older age is increased by 58% for people living with HIV compared to their HIV-negative peers, according to US research published in the online edition of AIDS. The average age at dementia diagnosis was much younger for people with HIV: 67 years compared to 78 years for people without HIV.
The research – conducted by Dr Jennifer Lam and colleagues at Kaiser Permanente Northern California – is especially interesting because it compared diagnoses of dementia according to HIV status among people in routine care. Previous studies showing an association between living with HIV and cognitive impairment have often relied on cognitive tests which can detect small declines in memory and thinking processes, although such changes may not necessarily have a meaningful impact on people’s lives. In contrast, the present study therefore provides 'real world' information and should help shape research and prevention strategies.
“Age-associated dementia is becoming an increasingly prominent concern for people with HIV and their healthcare providers,” write Dr Lam and her co-authors. “This study contributes evidence that older people with HIV are at significantly elevated risk for dementia despite receiving antiretroviral therapy.”
But it’s also important to emphasise that even though people with HIV had higher rates of dementia, it still remained rare. The rates are well below those seen in the era before modern HIV therapy became available.
Thanks to advances in treatment and care, many people with HIV now have an excellent life expectancy and can expect to live well into old age. An increasing proportion of people with HIV are now aged 50 years and over and diseases associated with ageing are accordingly an important cause of illness and death among HIV-positive individuals. One of these is dementia.
Some risk factors for dementia in older age, such as smoking, drug use and cardiovascular risk, are modifiable. Prompt initiation of HIV treatment helps prevent dementia that is directly caused by the virus (HIV-associated dementia). Moreover, it has been suggested that damage caused by the virus before it is suppressed by HIV treatment contributes to the long-term risk of brain injury, cognitive decline and dementia.
Dr Lam and her colleagues examined dementia diagnoses among individuals receiving routine primary care aged 50 years and over according to their HIV status. Participants were enrolled in Kaiser Permanente, an integrated provider of health insurance and medical care, between 2013 and 2019. All the HIV-positive participants were taking antiretroviral therapy (ART).
When calculating their results, the researchers took into account factors that are known to affect the risk of dementia, including age, sex, race, poverty, cardiovascular disease, diabetes, obesity, high blood pressure, hepatitis C, depression, smoking, drug use and drinking too much alcohol.
For people with HIV, the researchers also took into account viral suppression (a viral load below 200) and whether a person had experienced severe immune suppression before starting HIV therapy (a CD4 cell count below 200).
There were 5381 HIV-positive and 119,022 HIV-negative participants. The two groups were well matched in terms of sex, ethnicity and age: 91% were male, 65% White, 15% Black and 13% Hispanic. The average age at time of recruitment to the study was 57 and 58 years, respectively. In the HIV-positive group, 73% were in their fifties, 23% in their sixties, 4% in their seventies and 0.5% in their eighties.
People with HIV were less likely to be obese, have diabetes or report excess alcohol consumption, but were more likely to be current smokers, have a history of depression, to have used illicit substances and to have hepatitis C.
Analysis of the people with HIV showed that, at baseline, 97% were virally suppressed, two-thirds had a CD4 cell count above 500 and 40% had a history of severe immune suppression.
The mean duration of follow-up was 4.7 years.
During this period, 2.2% of people with HIV and 2% of non-HIV-positive participants were diagnosed with dementia.
Average age at the time of dementia diagnosis was 67 years for people with HIV and 78 years for people without HIV. The vast majority (91%) of people with HIV who were diagnosed with dementia had an undetectable viral load at the time of this diagnosis.
At the age of 60, 2% of HIV-positive and 1% of HIV-negative participants had had a dementia diagnosis. By the age of 70, rates of dementia diagnoses among HIV-positive and HIV-negative participants increased to 7% and 3%, respectively, rising to 26% and 14% by the age of 80. Although there were only around 500 HIV-positive people still in follow up at age 70 and around 100 at age 80, these differences were highly statistically significant (p < 0.001).
After taking into account other factors associated with dementia, the investigators found that people with HIV had a 58% increase in the risk of dementia compared to HIV-negative individuals (hazard ratio (HR) = 1.58; 95% CI, 1.31-1.92).
This finding was little changed when they only included participants with viral suppression at baseline (HR = 1.50; 95% CI, 1.23-1.83) or excluded those with a history of severe immune suppression (HR = 1.77; 95% CI, 1.37-2.29).
“People with HIV remained at 58% increased risk for dementia even after accounting for medical and psychiatric comorbidities and other dementia risk factors and at 40% increased risk for dementia after additionally accounting for competing risk of death,” comment Dr Lam and her colleagues. “This residual elevated risk may be due to non-modifiable risk factors such as HIV-mediated inflammation, HIV-acquisition in the pre-ART era, brain injury from previously untreated HIV infection, or paradoxically, from the neurotoxic effects of ART.”
They note that these results are broadly similar to those of a recent study comparing dementia rates among US military veterans. An important difference is that many of the HIV-positive veterans were not taking HIV treatment and dementia diagnoses were more common than in the present study.
The investigators call for further research into dementia risk factors among people with HIV taking ART. Such research, they suggest, could help identify strategies and priority targets for dementia prevention.
Lam JO et al. Comparison of dementia risk after age 50 between individuals with and without HIV infection. AIDS, online edition ahead of print, 2021.
Correction: This article was amended on 18 and 21 January 2021. An earlier version suggested that the figures for dementia at ages 70 and 80 were based on modelling, rather than observed data.