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Broad range of risk factors associated with mild cognitive impairment in HIV-positive men on ART
Michael Carter, 2016-02-03 10:30:00
A broad range of
factors are associated with cognitive impairment in middle-aged HIV-positive
men, according to Dutch research published in the online edition of AIDS. The observational,
cross-sectional, case-controlled study involved antiretroviral-treated participants
with sustained viral suppression. Reduced cognitive function was associated
with cannabis use, depression, metabolic factors and previous HIV-related
cognitive performance probably results from a multifactorial process,” comment
Mild cognitive impairment can become evident in the form of changes such as reduced attention span, slower information processing, reduced fluency in the use of language, and a reduced ability to plan and organise everyday life or to solve problems. These changes are considered by specialists to exceed the declines in memory and mental sharpness that usually accompany ageing.
In some cases mild cognitive impairment may be an early warning sign of Alzheimer's disease and people who develop mild cognitive impairment are at increased risk of going on to develop Alzheimer's disease. However, mild cognitive impairment can have numerous causes, including cardiovascular disease, drug use, medication side effects, vitamin and thyroid deficiency, and depression or anxiety, many of which are treatable.
A high prevalence
of mild cognitive impairment has been reported among people with HIV,
even when they are doing well on antiretroviral therapy. Rates as high as 59%
have been reported in some studies, but it seems that criteria used to diagnose
the condition have been oversensitive and that diagnoses have included a large
number of false positives.In particular studies may define people as having mild cognitive impairment as a result of having reductions in some, but not all, cognitive functions.
In order to
establish a more accurate understanding of the prevalence of mild cognitive
impairment among people with HIV in the era of modern antiretroviral era,
investigators in Amsterdam have used a form of analysis called multivariate
normative comparison (MNC). This technique controls for false positives while
still able to capture cases of impairment, by comparing outcomes of all an individual's cognitive function tests to the distribution of average results in the age-matched reference population.
The team of
investigators who pioneered this analysis now wanted to gain a clearer
understanding of the factors associated with mild cognitive impairment in
middle-aged people with HIV who were responding well to antiretrovirals.
They hypothesised that a number of factors would be involved with the
condition, including drug/alcohol use, mental health problems, metabolic and
cardiovascular risk factors and factors related to HIV infection and its
enrolled in the AGEhIV study of age-associated illness in people
with HIV were recruited to a cognitive substudy between 2011 and 2013.
Recruitment criteria included current HIV therapy with viral suppression for at
least twelve months. Exclusion criteria included serious neurological disease,
ongoing psychiatric disorders, current injecting drug use, daily use of
illicit substances (with the exception of cannabis), traumatic brain injury and
past/current HIV-related neurological disease.
A total of 103 HIV-positive men were recruited to the study and they were matched with 74 HIV-negative
controls. Median age in both groups was 54 years. The HIV-positive men had
had an undetectable viral load for a median of eight years. Just over a third
(35%) had experienced a previous AIDS-defining illness and average
nadir CD4 cell count was approximately 170 cells/mm3, but current
average counts were 625 cells/mm3.
The patients and
controls were well matched. However, smoking was more prevalent among the
HIV-positive participants, who also had lower body mass index and a higher hip-to-waist-ratio
when compared to HIV-negative individuals.
A wide battery of
tests was used to assess the neurocognitive function of both the HIV-positive men and
controls. Their results showed that 17% of the HIV-positive men and 5% of the
controls had mild impairment.
with impairment in the HIV-positive group included cannabis use, a history
of cardiovascular disease (borderline significance), impaired renal function
(borderline significance), above normal hip-to-waist ratio, the presence of depressive
symptoms and a low nadir CD4 count. In further analysis, cannabis use (p < 0.001), history
of cardiovascular disease (p = 0.014), impaired renal function (p = 0.017) and diabetes (p = 0.097 - borderline) remained
independently associated with cognitive impairment.
The authors note
that many of these associations have been identified in previous studies and
are biologically plausible. They acknowledge because the study was
cross-sectional, it was “merely able to demonstrate associations rather than
causality.” The study population was
male, Caucasian and had a very low prevalence of viral hepatitis co-infection,
possibly meaning that the findings may not apply to other populations.
indicate that reduced cognitive performance in HIV-1 infected men with
sustained suppressed viraemia on cART [combination antiretroviral therapy] is
likely to be a multifactorial process, in which not only HIV-1 associated
factors such as having experienced more severe immune deficiency, but also
cardiovascular/metabolic factors, cannabis use, and depressive symptoms are key
contributors,” conclude the authors. “These are likely to gain increased
importance as the population of people living with HIV continues to age.”