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2 Very Recent Studies Linking Inflammation to Causing Cognitive Impairment / inflammation-telomerase connection
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Systemic inflammation during midlife and cognitive change over 20 years - (02/15/19)
So what causes inflammation: we know HIV & it causes immune activation which ears to inflammation despite suppressed HIV with ART; comorbidities; number of comorbidities; trauma history; sleep disorders; mediterranean diet & exercise ca reduce inflammation; STDs including history of HCV; history of IDU/drug use; lifestyles/behavior; smoking.....
AND - Cumulative Inflammatory Load Is Associated with Short Leukocyte Telomere Length in the Health, Aging and Body Composition Study: [there has been quite a lot of discussion IN HIV around that HIV shortens telomerase length & certain ARTs contribute to this.Jules] In sum, older adults with high levels of inflammatory activity may be at increased risk for accelerated leukocyte telomere shortening, and those with short LTL may have increased risk for diseases with an inflammatory etiology.. Leukocyte telomere length (LTL) is an emerging marker of biological age.. Chronic inflammatory activity is commonly proposed as a promoter of biological aging in general, and of leukocyte telomere shortening in particular. In addition, senescent cells with critically short telomeres produce pro-inflammatory factors. However, in spite of the proposed causal links between inflammatory activity and LTL, there is little clinical evidence in support of their covariation and interaction. Short LTL, a potential index of biological age, is associated with increased risk for age-related diseases as well as early all-cause and disease-specific mortality [3], [4], [5], [6]. The present research study is to date the largest to demonstrate an association between elevated inflammatory activity and short LTL. Moreover, the present study is the first to indicate that the combination of high IL-6 and TNF-α is associated with increased odds for short LTL, over and above the odds associated with having high levels of only one of these markers. Of note, having high levels of both IL-6 and TNF-α conferred almost twice the odds of being in the bottom tertile for LTL compared with having lower levels of both markers. In contrast, having high levels of CRP, as indexed by CRP levels either in the top tertile for the sample or above the established clinical cutoff, was not associated with increased odds for short LTL. Importantly, all of our results held when controlling for the contribution of numerous established risk factors for short LTL and potential confounds. Together with the observed causal relationships between inflammatory activity and LTL in animal and in vitro studies, these data provide preliminary evidence that adjunct anti-inflammatory therapies could potentially prevent accelerated leukocyte telomere shortening or protect against the negative effects of short LTL in older adults. Equally plausible, however, is the emerging hypothesis that participants with short LTL in our study had the greatest proportion of accumulated senescent bodily cells overall, including fibroblasts and epithelial cells, which could plausibly contribute to the observed higher levels of IL-6 and TNF-α in this group [28], [38]. Given that TNF-α and IL-6 may inhibit programmed cell death in specific cell types [39], [40], high levels of these cytokines could even contribute to the maintenance of senescent cells in the system and hence the continued production of pro-inflammatory factors. However, the cross-sectional design of our study precludes drawing conclusions about the causal direction in the relationship between inflammatory activity and LTL. n previous research, the cumulative load of high IL-6, high TNF-α and high CRP was found to confer the greatest risk for cardiovascular events in the Health ABC cohort.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0019687#s3
Inflammation Relates to Poorer Complex Motor Performance Among Adults Living With HIV on Suppressive Antiretroviral Therapy / HIV-positive participants had worse complex motor performance than HIV-negative participants
http://www.natap.org/2018/HIV/010219_06.htm
Although neurologic findings commonly associated with HIV infection have been suggested to largely remit with initiation of cART, our cross-sectional study observed worse complex motor skills across the adult age continuum of HIV-positive, relative to HIV-negative, adults. Inflammation burden was higher among HIV-positive adults, compared with the HIV-negative comparison group. Consistent with our hypothesis, HIV infection was observed to have both direct and indirect effects through inflammation on complex motor performance, such that inflammation burden accounted for 15.1% of the effect of HIV infection on motor performance when controlling for relevant covariates. These results indicate that inflammatory processes may contribute to worse complex motor skills in the context of cART-treated HIV.
HIV-positive participants had worse complex motor performance ......we found the rate of impairment to be significantly higher in the HIV-positive group (20.0%) than in the HIV-negative group (6.4%; P = 0.008, odds ratio = 3.67). Participants with impaired complex motor performance, on average, had a higher composite inflammation burden score [mean = 2.4 (SD 1.2)] than participants without impairment [mean = 1.6 (SD 1.2), P = 0.003; Hedges g = 0.66]. .....Path analysis results indicated that HIV serostatus was significantly associated with higher composite inflammation burden score.....HIV serostatus was also associated with poorer complex motor performance......When HIV serostatus was entered simultaneously with the composite inflammation burden score, effects of HIV disease were at a trend level for statistical significance (see model of complex motor performance in Table 4). The indirect effect of HIV disease through inflammation burden was statistically significant accounting for 15.1% of the effect of HIV on complex motor performance.......A greater proportion of the HIV-positive group had global neurocognitive impairment (41.1%) compared with the HIV-negative group (25.5%; P = 0.02; odds ratio = 2.04). Composite inflammation burden scores were higher among participants with global neurocognitive impairment [mean = 2.0 (SD 1.4)] compared to those without impairment [mean = 1.5 (SD 1.2), P = 0.02; Hedges g = 0.38]. Finally, we examined whether other neurocognitive domains (ie, recall, executive functions, learning, verbal, working memory, and speed of information processing) would show similar associations with the composite inflammation burden score. After controlling for FDR using the BH method, only the complex motor domain showed a statistically significant association with the composite inflammation burden score.
The sample consisted of 90 ART-treated virally suppressed HIV-positive and 94 HIV-negative adults, aged 36-65 years, with balanced recruiting in each age decade (36-45, 46-55, and 56-65). Biomarkers of inflammation (d-dimer, IL-6, MCP-1/CCL2, sCD14, and TNF-α) were measured, and a composite inflammation burden score was calculated. Complex motor performance was evaluated using the Grooved Pegboard Test. Among the HIV-positive participants, 60% had an AIDS diagnosis, median estimated duration of HIV infection was 18.5 years, median current CD4+ T-cell count was 629 cells/mm3, and median nadir CD4+ T-cell count was 183 cells/mm3. HIV disease characteristics did not differ by age decade (P's > 0.05; Table 2), with the exception of duration of HIV infection and duration of exposure to ART, which were longer for each increasing age decade (P's < 0.01). Of the 5 individual inflammation biomarkers, the HIV serostatus groups differed on levels of MCP-1, sCD14, and TNF-a, which were higher in the HIV-positive group (P's < 0.05; Table 3). The HIV-positive group had a higher average composite inflammation burden score than the HIV-negative group (P < 0.001; Hedges g = 0.78). On average, participants were non-Hispanic white (62.5%) men (78.3%) with some college education [mean 14.6 (SD 2.3) years of formal education]. Compared to the HIV-negative group, the HIV-positive group had fewer years of education, a greater proportion of males, and a greater proportion of individuals with medical comorbidities, MDD, and lifetime substance use disorders (P's < 0.05; Table 1).
In summary, HIV has a deleterious impact on complex motor skills, which may be partially explained by inflammatory processes. Complex motor skills refer to a combination of cognitive and perceptual motor abilities, including perception, planning, continuous tracking, and sequential movements.
The interaction between aging and HIV disease stage suggest that complex motor skills may be particularly susceptible to aging-related progression of neurocognitive impairment among HIV-positive adults.
HIV caused a decrease in activity during cue processing in the ventral striatum, with normal cortical functioning during reward outcome processing. Our results therefore suggest that HIV not only has an impact on fronto-striatal systems involved in executive functioning, but also has a direct impact on the function of the ventral-striatal reward system. 2nd study
Inflammation is one putative factor that may contribute to central nervous system (CNS) injury, including deficits in complex motor skills. Biomarkers of inflammation, such as cytokines and monocytes, are elevated in the context of HIV infection. HIV, viral products, and activated immune cells are able to cross the blood-brain barrier and contribute to inflammation in the CNS.10 Neuroimaging studies have shown that peripheral inflammatory biomarkers are able to alter neural activity in the basal ganglia, including dopaminergic activity, which is reflected by psychomotor slowing in HIV-negative adults.11 Among HIV-positive persons, global neurocognitive impairment is associated with elevation of various peripheral biomarkers of inflammation and coagulation (eg, cytokines,12 monocytes,13,14 and d-dimer15).
Taken together, deficits in complex motor performance are commonly observed among HIV-positive persons, and elevation in peripheral biomarkers of inflammation may be a contributing factor. Thus, we hypothesize that HIV will have negative direct and indirect effects through inflammation on complex motor performance."
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