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Elevated lipids associated with cognitive decline in middle aged HIV-positive men doing well on ART
Michael Carter, 2016-08-29 08:30:00
cholesterol and a gene associated with Alzheimer’s risk in the general
population are both risk factors for cognitive decline in middle aged
HIV-positive patients with a suppressed viral load, according to US research
published in the online edition of Clinical
The longitudinal observational study involved 273
HIV-positive individuals and 516 matched HIV-negative controls. Higher
cholesterol and LDL cholesterol were associated with faster cognitive decline
in patients with HIV and the presence of the APOE ε4 genotype accelerated
cognitive decline in HIV-positive but not HIV-negative men. Statin use lessened
the effect of elevated cholesterol on cognitive decline in patients with HIV.
“These findings suggest that control of dyslipidemia may reduce the risk
of midlife cognitive decline in aging PLWH [people living with HIV] on ART, and
the APOE ε4 genotype likely influences cognitive trajectories via
mechanisms distinct from its effect on lipid metabolism,” comment the
researchers. “For every 10mg/dl increase in cholesterol or LDL between the ages
50-65, the rate of cognitive decline among HIV+ men increased.”
The proportion of HIV-positive patients aged over 50 years is growing
and the diseases of older age are now a leading cause of illness among
HIV-positive individuals. A large proportion of the older HIV-infected
population have elevated cholesterol and triglycerides, known risk factors for
cognitive decline in the general population.
The APOE ε4 genotype is the
most important genetic risk factor for Alzheimer’s disease and is also a risk
factor for age-related cognitive decline in the general population. However,
its role in cognitive decline and interaction with lipids in HIV-positive
patients has been little studied.
Investigators from the MACS study designed a study to assess the
longitudinal effects of dylipidemia and the APOE ε4 genotype on
cognitive decline in middle-aged HIV-positive men who have sex with men adherent to ART with a
viral load below 400 copies/ml. The study excluded people who were regular users of heroin, cocaine or crack cocaine.
273 people with HIV were matched with 516 HIV-negative controls also being followed in the cohort. Lipid
profiles – total cholesterol, LDL cholesterol, HDL cholesterol and
triglycerides - were measured and participants were tested for the APOE ε4 genotype. Patients and controls underwent a battery of tests at baseline
and during follow-up to assess cognitive function.
Median age at study entry was 51 years and the mean duration of
follow-up was a little over six years. The majority of participants (81%) were
white. Education levels were similar between the HIV-positive and HIV-negative
participants, but individuals with HIV were somewhat more likely to have tests
scores suggesting depressive symptoms (p = 0.08).
Patients with HIV had a median CD4 count at baseline of 514 cells/mm3
and 70% had a viral load below 50 copies/ml.
Baseline cholesterol and LDL cholesterol were similar between both study
groups, however men with HIV had higher triglycerides and lower HDL cholesterol
than HIV-negative men (p < 0.001). Half the HIV-positive group had been
taking statins for at least a year.
HIV-positive men had a faster rate of cognitive decline compared to the
HIV-negative controls (p = 0.003). The impact of cholesterol levels on
cognitive decline appeared to emerge at the age of 50 years.
Higher LDL cholesterol and triglycerides were associated with a steeper
slope in cognitive decline (p < 0.001), however higher HDL cholesterol
lessened the rate of decline in men with HIV (p = 0.02).
Higher cholesterol was associated with a more pronounced decline in
attention and working memory (p < 0.001) and also verbal memory (p = 0.05).
The association between cholesterol level and cognitive decline in
HIV-positive patients remained significant in an analysis that excluded
patients with evidence of cognitive impairment at baseline and also in an analysis
restricted to patients with sustained viral suppression below 50 copies/ml.
In patients with HIV, the cognitive decline associated with elevated
cholesterol was attenuated by statin use (p = 0.0019).
Baseline analysis showed that HIV-positive carriers of the APOE ε4 genotype had significantly higher triglyceride levels (p < 0.001). Once
again, the effect emerged at around the age of 50 years.
The rate of cognitive decline was accelerated among HIV-positive
carriers of ε4 (p = 0.001). On average, cognitive decline began to accelerate around a decade earlier in this group compared to HIV-negative carriers of the gene.
Further analysis suggested that lipids and the ε4 genotype had
independent effects on cognitive decline, so that having high cholesterol levels did not further exacerbate the effect of the ε4 genotype.
“Our findings suggest that clinical management of dyslipidemia with
statins in ART-adherent HIV+ individuals may reduce the risk of midlife cognitive
decline, and a window of opportunity likely occurs between ages 50 -65,”
conclude the investigators. “Given impressive efforts that have improved
survival among HIV+ individuals, this study underscores the importance of lipid
profiles and APOE ε4 allele to
midlife cognitive health in aging HIV+ adults and suggests that clinical
management of dyslipidemia may be an effective adjunctive strategy to reduce
cognitive decline in ART-treated HIV+ individuals.”