HIV-associated neurocognitive disorders (HANDs) persist even with virologic suppression on combination antiretroviral therapy (cART), and the underlying pathophysiological mechanisms are not well understood. We performed structural magnetic resonance imaging and MR spectroscopy (MRS) in HIV+ individuals without major neurocognitive comorbidities. Study participants were classified as neurocognitively unimpaired (NU), asymptomatic (ANI), mild neurocognitive disorder (MND), or HIV­associated dementia (HAD). Using structural MRI, we measured volumes of cortical and subcortical gray matter and total and abnormal white matter (aWM). Using single-voxel MRS, we estimated metabolites in frontal gray matter (FGM) and frontal white matter (FWM) and basal ganglia (BG) regions. Adjusted odds ratios were used to compare HAND to NU. Among 253 participants, 40% met HAND criteria (21% ANI, 15% MND, and 4% HAD). Higher risk of HAND was associated with more aWM. Both HAD and MND also had smaller gray and white matter volumes than NU. Among individuals with undetectable plasma HIV RNA, structural volumetric findings were similar to the overall sample. MND had lower FWM creatine and higher FGM choline relative to NU, whereas HAD and ANI had lower BG N­acetyl aspartate relative to NU. In the virologically suppressed subgroup, however, ANI and MND had higher FGM choline compared to NU. Overall, HAND showed specific alterations (more aWM and inflammation; less gray matter volume and lower NAA). Some MR measures differentiated less severe subtypes of HAND from HAD. These MR alterations may represent legacy effects or accumulating changes, possibly related to medical comorbidities, antiretroviral therapy, or chronic effects of HIV brain infection.

Background: Aging and HIV have adverse effects on the central nervous system, including increased inflammation and neural injury and confer risk of neurocognitive impairment (NCI). Previous research suggests the nonacute neurocognitive effects of cannabis in the general population are adverse or null. However, in the context of aging and HIV, cannabis use may exert beneficial effects due to its anti-inflammatory properties. In the current study, we examined the independent and interactive effects of HIV and cannabis on NCI and the potential moderation of these effects by age. Methods: Participants included 679 people living with HIV (PLHIV) and 273 people living without HIV (HIV−) (18–79 years old) who completed neurocognitive, neuromedical, and substance use assessments. NCI was defined as a demographically corrected global deficit score ≥ 0.5. Logistic regression models examined the effects of age, HIV, cannabis (history of cannabis substance use disorder and cannabis use in past year), and their 2-way and 3-way interactions on NCI. Results: In logistic regression models, only a significant interaction of HIV X cannabis was detected (P = 0.02). Among PLHIV, cannabis was associated with a lower proportion of NCI (odds ratio = 0.53, 95% confidence interval = 0.33–0.85) but not among HIV− individuals (P = 0.40). These effects did not vary by age. Conclusions: Findings suggest cannabis exposure is linked to a lower odds of NCI in the context of HIV. A possible mechanism of this result is the anti-inflammatory effect of cannabis, which may be particularly important for PLHIV. Further investigations are needed to refine the effects of dose, timing, and cannabis compound on this relationship, which could inform guidelines for cannabis use among populations vulnerable to cognitive decline.

Background: There is a sparsity of data describing the periodontal microbiome in elderly individuals. We analyzed the association of subgingival bacterial profiles and clinical periodontal status in a cohort of participants in the Washington Heights-Inwood Columbia Aging Project (WHICAP). Methods: Dentate individuals underwent a full-mouth periodontal examination at six sites/tooth. Up to four subgingival plaque samples per person, each obtained from the mesio-lingual site of the most posterior tooth in each quadrant, were harvested and pooled. Periodontal status was classified according to the Centers for Disease Control/American Academy of Periodontology (CDC/AAP) criteria as well as based on the percentage of teeth/person with pockets ≥4 mm deep. Bacterial DNA was isolated and was processed and analyzed using Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS). Differential abundance across the periodontal phenotypes was calculated using the R package DESeq2. α-and β-diversity metrics were calculated using DADA2based clustering. Results: The mean age of the 739 participants was 74.5 years, and 32% were male. Several taxa including Sneathia amnii-like sp., Peptoniphilaceae [G-1] bacterium HMT 113, Porphyromonas gingivalis, Fretibacterium fastidiosum, Filifactor alocis, and Saccharibacteria (TM7) [G-1] bacterium HMT 346 were more abundant with increasing severity of periodontitis. In contrast, species such as Veillonella parvula, Veillonella dispar, Rothia dentocariosa, and Lautropia mirabilis were more abundant in health. Microbial diversity increased in parallel with the severity and extent of periodontitis. Conclusions: The observed subgingival bacterial patterns in these elderly individuals corroborated corresponding findings in younger cohorts and were consistent with the concept that periodontitis is associated with perturbations in the resident microbiome.

Objective: The causes of neurocognitive and everyday functioning impairment among aging people living with HIV (PLWH) are multifactorial. Exposure to stress and trauma can result in neurocognitive deficits via activation of neurological and other biological mechanisms. Methods: PLWH (n=122) and persons without HIV (n=95), 35–65 years of age, completed four questionnaires that were used to generate a trauma, economic hardship (food insecurity and low socioeconomic status), and stress composite variable (TES). Participants also completed a comprehensive neuropsychological battery and standardized self-reports of activities of daily living (ADLs). We examined the independent and interactive effects of TES and HIV status on neurocognitive performance and ADL declines. Results: PLWH had more traumatic events, more food insecurity, lower socioeconomic status, and higher perceived stress compared to HIV- individuals (all ps<.0001). Among PLWH, a higher composite TES score was associated with worse executive functioning (p=.02), worse learning (p=.02), worse working memory (p=.02), and more ADL declines (p<.0001), even after controlling for relevant demographic, psychiatric, substance use, and HIV disease covariates. On their own, individual TES components did not predict these outcomes. Conversely, no significant relationships were observed between TES and cognitive domains nor ADL declines among HIV- individuals. Conclusions: A composite score of trauma, economic hardship, and stress was significantly associated with worse neurocognitive performance and functional declines among PLWH. These adverse experiences may contribute to neurocognitive and daily functioning difficulties commonly observed among PLWH. Longitudinal studies are needed to elucidate the relationships between economic/psychosocial adversity and cognitive/functional outcomes over time, and examine potential mediators, such as inflammatory biomarkers.