Many Factors -- From Marijuana to Heart Disease -- Tied to Mental Slowing With HIV

September 2016

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Several diseases and behaviors are linked to decreased mental function in older HIV-positive men compared with older men without HIV, according to results of a careful comparison.1 Disease factors included cardiovascular disease, diabetes, and poor kidney function. Other factors were smoking marijuana and a wide waist. The study also linked a lower CD4 count before starting antiretroviral therapy to decreased cognitive performance.

Cognitive impairment can be defined as problems in memory, language, thinking, or judgment. These problems continue to affect many HIV-positive people who reach and maintain an undetectable viral load with antiretroviral therapy. Experts have different opinions on how to define cognitive impairment in people with HIV. Researchers in the Netherlands who conducted this new study believe one widely used method for identifying cognitive impairment in people with HIV is too broad because it classifies too many people with normal cognitive function as impaired.2 The Netherlands team worked with a new method (called multivariate normative comparison, or MNC) that appears to pinpoint cognitively impaired HIV-positive people more precisely.3

The new study focused on HIV-positive and negative members of the AGEhIV study group in Amsterdam. The researchers aimed to identify factors linked to decreased cognitive function in these people.

How the Study Worked

The AGEhIV Cohort Study analyzes age-related diseases and conditions in HIV-positive people 45 years old or older and a highly similar group of HIV-negative people. Researchers select HIV-negative people from an Amsterdam sexual health clinic to create a group that matches the HIV-positive group in age, sex, sexual risk behavior, and other behaviors.4 At an initial visit and then every 2 years, all HIV-positive and negative AGEhIV members complete a series of tests to detect age-related conditions.


The cognitive performance study focused on HIV-positive men with a viral load below 40 copies for at least 12 months on antiretroviral therapy and a highly comparable set of HIV-negative men. Everyone in both groups was at least 45 years old. The study did not accept people who had evidence of previous or current severe problems that might cause cognitive (mental) problems, including stroke, multiple sclerosis, serious brain injury, major depression, or HIV-associated dementia. The study also excluded men who drank a lot of alcohol, injected illegal drugs, or used illegal drugs daily. Men who smoked marijuana daily could enter the study.

All study participants with and without HIV infection completed a set of standard tests that measure six areas of cognitive function -- attention, information processing speed, memory, motor function (movement and coordination), executive function (ability to get things done), and fluency (ability to name as many things as possible in a category -- like animals or fruits -- in a set time).

The AGEhIV researchers used the method they had studied earlier (MNC)3 to compare the combined results of these cognitive tests (cognitive impairment) in men with versus without HIV. The research team compared cognitive function in the HIV-positive and negative groups in two ways: (1) a yes/no measure (either you have cognitive impairment or you don't), and (2) a continuous measure (the degree to which each HIV-positive person differed from the whole HIV-negative group).

What the Study Found

The study involved 103 men with HIV and 74 men without HIV. As planned, the groups with and without HIV were similar in many ways. Both groups had a median (midpoint) age of 54 years, about 90% in each group were gay or bisexual, and more than 85% in each group were Dutch. Men with HIV had taken antiretroviral therapy for a median of 11.6 years and had a viral load below 200 copies for a median of 8.3 years. The group's lowest-ever median CD4 count stood at 170 and their current CD4 count at 625.

About 15% of both groups smoked marijuana daily. About 5% in both groups had mild to moderate symptoms of depression, and no one had severe depressive symptoms. Waist-to-hip ratio was above normal in 85% of men with HIV versus 70% of men without HIV.* About two thirds in each group had someone in their immediate family with cardiovascular disease, but cardiovascular disease rates in the men themselves were low (partly because many men were middle-aged) and did not differ much between groups. About 5% of men in each group had diabetes. A lower proportion of men with than without HIV (81% versus 94%) had normal kidney function.**

Seventeen of 103 men with HIV (17%) had cognitive impairment (reduced mental capacity), compared with 4 of 74 men without HIV (5%).

Comparing the degree to which cognitive performance in each HIV-positive person differed from the whole HIV-negative group, the researchers identified seven factors independently associated with worse cognitive function in the HIV group (Figure 1):

  • Daily to monthly marijuana use
  • Cardiovascular disease in the past
  • Impaired kidney function
  • Diabetes
  • Above normal waist-to-hip ratio (wide waist)
  • Symptoms of depression
  • Lower nadir (lowest-ever) CD4 count

Factors Linked to Worse Cognitive Function With HIV

Factors Linked to Worse Cognitive Function With HIV

Figure 1. A careful comparison of 103 middle-aged and older men with HIV and 74 similar men without HIV pinpointed seven factors related to worse cognitive function (mental ability) in the HIV group. Many of these individual factors may also be related to each other, as suggested by the lines (1) between depression symptoms and regular marijuana and (2) between the four conditions making up the bottom of the circle, which are traditional risk factors for cognitive decline. Because HIV or antiretroviral therapy may have a negative impact on these four traditional risk factors, these factors may influence the impact of HIV or antiretrovirals on cognition. (Cardio = cardiovascular). (Credit: Teresa B. Southwell)

A separate analysis identified four factors that independently predicted whether or not an HIV-positive man had cognitive impairment:

  • Marijuana use (raised odds of cognitive impairment about 28 times)
  • Cardiovascular disease in the past (raised odds of cognitive impairment about 18 times)
  • Poor kidney function (raised odds of cognitive impairment about 9 times)
  • Diabetes (raised odds of cognitive impairment about 6 times)
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High Rates of Age-Related Disease With HIV -- But No Sign of Accelerated Aging

This article was provided by The Center for AIDS Information & Advocacy. It is a part of the publication HIV Treatment ALERTS!. Visit CFA's website to find out more about their activities and publications.

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