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Diabetes, Lung Disease, Depression, Cannabis Tied to 12-Year Cognitive Drop With HIV
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CROI 2021, Conference on Retroviruses and Opportunistic Infections, March 6-10, 2021
Mark Mascolini
Through 12 years of follow-up, nearly one quarter of a US group taking antiretroviral therapy (ART) had test evidence of cognitive decline [1]. This 400-person CHARTER study analysis linked diabetes, chronic lung disease, major depressive disorder, and lifetime cannabis use to waning cognitive function. But most study participants did not have severe cognitive decline.
Much work confirms higher rates of cognitive decline in people with HIV than in the general population. But no study has traced cognitive changes over more than a decade. US CHARTER study researchers mounted this analysis of 397 people with good antiretroviral control of HIV, testing cognitive function 12 years after their initial assessment and seeking factors associated with declining cognitive function.
Cohort members had comprehensive neuromedical and neurocognitive assessments at an initial study visit and again about 12 years later. These assessments included a neuropsychological test battery that covered 7 cognitive domains. Participants also had standard physical exams, blood sampling, and tracking of medical history, prescribed medications, and substance use. The researchers calculated a regression-based change score (RBCS) with normative data from people with and without HIV. This metric compares cognitive performance to a reference group of 296 adults (172 with HIV and 124 without HIV) who made 3 to 6 visits. The researchers defined cognitive decline as a change worse than the 5th percentile of normative data. They used multivariable regression to identify factors associated with RBCS-defined cognitive decline.
The 397 participants averaged 43.6 years of age at the first visit and 56.3 years at the 12-year visit. Respective durations of HIV infection were 9.9 and 22.6 years, and of ART 4.9 and 15.3 years. While 24.4% of the study group were women, 46.6% were black, and 10.8% Hispanic. Three quarters of the group took ART at the first visit and 97% at the second visit. At the second visit, median CD4 count stood at 591, 92% had a plasma viral load at or below 200 copies, and 94% has a cerebrospinal fluid viral load at or below 50 copies.
Median follow-up stood at 12.4 years. Median global deficit score barely changed from 0.39 to 0.38 from the initial visit to the 12-year visit. Among people taking ART, nearly one quarter, 23.4%, had global cognitive decline. At the first visit and 12-year visit, proportions with current major depressive disorder were 12.8% and 7.0%, with diabetes 6.5% and 20.2%, with chronic lung disease 9.3% and 19.9%, with hypertension 18.9% and 48.6%, with hyperlipidemia 9.8% and 38.0%, with lifetime alcohol use disorder 53.1% and 57.9%, with lifetime cannabis use disorder 27.4% and 31.7%, with lifetime cocaine use disorder 40.3% and 42.3%, and with lifetime opioid use disorder 14.6% and 16.4%.
In the first multivariable model, four variables were significantly associated with global cognitive decline (worse RBCS):
- Diabetes mellitus: beta = -0.111, P = 0.008
- Chronic lung disease: beta = -0.103, P = 0.012
- Current major depressive disorder: beta = - 0.146, P = 0.018
- Lifetime cannabis use disorder: beta = -0.081, P = 0.033
In another model the interaction between current major depressive disorder and diabetes was associated with global cognitive change (beta = -0.163, P = 0.015). Another model linked hypertension to worse cognitive function (beta = -0.119, P = 0.011) and antihypertensive use to better cognitive function (beta = 0.308, P = 0.0003).
The 12-year cognitive decline charted in nearly one quarter of these people with HIV compares with a decline in an estimated 5% of people without HIV. The CHARTER team stressed that "the magnitude of decline was not severe in most participants." The study confirmed one well-known aging-related risk factor for waning cognitive function-diabetes-but it also uncovered less frequently reported factors: chronic lung disease, major depressive disorder, and lifetime cannabis use disorder. The research team cautioned that survivor bias or other biases may affect these 12-year findings.
Reference
1. Letendre S, Ellis RJ, Tang B, et al. 12-Year cognitive decline is associated with lung disease, diabetes, and depression. CROI 2021, Conference on Retroviruses and Opportunistic Infections, March 6-10, 2021. Abstract 101.
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