Understanding Alzheimer’s and HIV in Asia

Alzheimer’s disease—a disorder involving progressive degeneration of the brain affecting cognition (memory, thinking, and behavior)—is the most common form of dementia among the general population, accounting for 60% to 80% of cases. The risk of Alzheimer’s increases exponentially with age, and that risk increases in people living with HIV, for whom 30% to 50% have some form of cognitive impairment. Accurate diagnosis of Alzheimer’s is crucial so that physicians can work with patients to manage symptoms, explore treatment options, and improve quality of life.

Thanks to an amfAR-supported study, researchers have shown that a new method of diagnosing Alzheimer’s—a blood-based biomarker—could be useful in predicting cognitive decline in people living with HIV. Participants were enrolled from cohorts in Bangkok, Thailand, and Kuala Lumpur, Malaysia.

The study is supported through a grant for IeDEA Asia-Pacific, a National Institutes of Health-funded research collaboration co-led by amfAR’s TREAT Asia program and the Kirby Institute of the University of New South Wales in Sydney, Australia.

“Diagnosing Alzheimer’s has traditionally relied on either amyloid PET imaging, a specialized technique of PET imaging, or lumbar punctures for cerebrospinal fluid—both of which are either costly, not widely accessible, or perceived as invasive. A blood-based biomarker test, which has already been extensively studied in the general population, offers a much more accessible and less invasive alternative,” explained Akarin Hiransuthikul, MD, of Chulalongkorn University in Bangkok, Thailand, a CHIMERA Fellow and the study’s principal investigator, about the benefits of testing for phosphorylated Tau 217 (p-tau217) levels.

Dr. Hiransuthikul’s component of the study focused on older Thai adults with suppressed viral loads. In collaboration with Dr. Hiransuthikul, Reena Rajasuriar, PhD, of the University of Malaya in Malaysia and the Peter Doherty Institute, Melbourne University, Australia, and a CHIMERA program mentor, is leading the Malaysian component of the study.

The usefulness of long-term studies of cohorts of aging people living with HIV, said Dr. Rajasuriar, becomes clear when you consider that “changes in these biomarkers occur 10 to 20 years before clinical symptoms of cognitive decline.”

These studies also allow researchers to understand how time plays a factor in the relationship between detection of increased biomarker levels and the subsequent development of cognitive symptoms, Dr. Rajasuriar added.

“Collectively, these studies will be among the first to demonstrate the relationship between Alzheimer’s biomarkers and cognitive decline in people living with HIV from resource-limited settings and allow us to better understand the role of Alzheimer’s pathology in influencing cognitive health in the context of aging with HIV,” she said.

HIV-specific knowledge gaps need to be filled, noted Dr. Rajasuriar. Extensive research has focused on HIV-associated neurocognitive disorder (HAND), but less is known about how Alzheimer’s and vascular dementia contribute to cognitive decline among people with HIV, especially in low- and middle-income countries, she explained.

For example, “it remains uncertain whether HIV directly or indirectly exacerbates susceptibility to [dementia-related] neurodegenerative processes. Compared to the general population, people living with HIV also experience a disproportionately higher burden of risk factors for dementia as they age, including a higher prevalence of cardiovascular risk factors, mental health issues, and persistent immune dysfunction.

“Thus, with 60% of the global HIV population expected to be beyond the age of 40 years by 2030, it is critical to understand the intersecting roles of HAND and Alzheimer’s to inform therapeutic options for people living with HIV facing cognitive decline.”

Dr. Hiransuthikul plans to continue investigating Alzheimer’s and people living with HIV: “Building on prior research that led to the approval of blood-based biomarkers for diagnosing Alzheimer’s in the general population, the next step is to validate these markers against neuroimaging tools in people living with HIV. We also aim to conduct more detailed neuropsychological assessments to further explore the relationship between these biomarkers and cognitive function.”