Fatigue Affects Cognitive Processing Speed in the Aging HIV Population

Liz Scherer

May 31, 2022

Successful aging is something that most of us strive for. But with aging comes a pervasive condition called fatigue that, in many older adults, interferes with everyday functioning, mental health, social support, and overall quality of life.

The relationship between fatigue and cognitive and functional impairment is one of particular interest in people living with HIV (PWH), a patient population that is disproportionately affected but whose lifespan now matches that of the general population.

Dr Raeanne Moore

"In persons with HIV, prevalence rates of fatigue range from 30% to upwards of 88%," Raeanne Moore, PhD, an associate professor of psychiatry at the University of California San Diego (UCSD) Health and coauthor of a study examining the fatigue-cognition conundrum in PWH, told Medscape Medical News.

Moore and lead investigator Laura Campbell, a graduate student researcher in clinical psychology at UCSD Health, were determined to tease out this relationship.

Laura Campbell

"Even though fatigue and changes in cognition are some of the most highly reported symptoms in people with HIV, there's not a lot of information on the relationship, particularly in older people with HIV," Campbell explained.

HIV-related neurocognitive disorders also commonly interfere with both independence and quality of life in this population.

Speed Processing Most Affected

The investigators asked a cohort of 105 adults, 69 of whom were PWH and 36 HIV-negative, to complete a series of tests assessing cognitive domains, performance-based functional capacity, and ability to engage independently in daily tasks, and to self-report on measures of fatigue, depression, anxiety, sleep quality, and social functioning over a 4-week period. Participants were between the ages of 50 and 74.

Study findings, which were published in the journal AIDS, confirmed that not only was fatigue significantly greater in PWH (especially in the 94.2% on antiretroviral therapy) compared with their HIV-negative peers (P < .001) but also significantly associated with worse global cognition (P = .003). This relationship remained strong even after accounting for current depression, anxiety, and sleep quality (P = .005).

Fatigue in PWH was largely driven by cognitive measures related to processing speed. 

"When we think of processing speed, we really think about how quickly and accurately someone can complete a task that is presented to them," Campbell explained. "Our processing speed tasks have both a motor and non-motor component, and typically, in people with depressive or sleep disorders, we do see psychomotor slowing or...very slow processing speed," she said. 

The same appears to be true for HIV. 

Significant fatigue-related cognitive deficits were observed in tests involving a speed or timed component and remained after adjusting for the other disorders. Test examples included Category Fluency, Letter Fluency, and Stroop Color-Word Test-Interference Trial (all P < .05). 

Fatigue also affected self-reported everyday functioning among participants with HIV, even after adjusting for covariates, with findings indicating a greater odds ratio (OR, 1.66) for every 10-point increase in fatigue (P = .039) for impaired ability to independently carry out daily tasks (such as taking medications or managing finances).

Biological Underpinnings, Clinical Interventions

Although the biological underpinnings of fatigue in HIV are still unclear, Campbell points to three theories: 1) modulation by thalamo-striato-cortical circuitry that involve the basal ganglia, 2) inflammation (which is often elevated in PWH), and 3) mitochondrial dysfunction. However, without a better understanding of the underlying mechanisms, it might be difficult to design specific treatments or treatment strategies.

Still even without specific approved pharmacological treatments for fatigue in older PWH, it's important to address it as well as cognition during routine clinical visits.

Judith Lee

"The association between fatigue and cognition and everyday function is really meaningful for our patients; it impacts their daily life every single day," said Judith Lee, NP, an adult gerontology nurse practitioner at the University of Maryland Institute of Human Virology's THRIVE (Together, Healing, Reaching, Inspiring to achieve Victory over illness and Embrace life) Program in Baltimore. Lee was not involved in the study.

"In our practice, we always ask patients if they are experiencing fatigue as part of their review of systems," she said, noting that, after ruling out other causes such as Vitamin D deficiency or hypothyroidism, "we've had patients get referred to outside sites for neuropsych testing."

But Lee acknowledged that, without more research, fatigue in HIV is "a difficult fix."

It's possible that behavioral strategies may help. "Even though at this point [there are] no biological treatments for fatigue that we know are effective, there are some behavioral strategies that are helpful that have been applied to other populations," Moore said.

Having patients identify their own patterns of fatigue throughout the day and reserving cognitively stimulating activities or tasks for those times of day when patients feel most rested can be beneficial, as can taking 10-minute breaks every hour for a snack or a walk.

"There's also a number of things that can keep the brain healthy or support brain health in general," Campbell added; "things like physical activity, healthy nutrition, and good regular sleep."

Currently, PWH who are 50 years or older make up almost 50% of the overall HIV population in the United States. By 2030, that number is estimated to increase by roughly 25%, further underscoring the need to not only learn more about the impact of fatigue on cognition in this group but also leverage those learnings so that PWH can achieve high physical and psychological functioning that defines successful aging.

AIDS. 2022 May 1;36(6):763-772. Abstract

Moore is a consultant with NeuroUX and cofounder of KeyWise Inc. Campbell and Lee report no relevant financial relationships. The study was supported by NIH.

Liz Scherer is an independent journalist specializing in infectious and emerging diseases, cannabinoid therapeutics, neurology, oncology, and women’s health. You can find her on Twitter @lizscherer

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