Publications

BACKGROUND

We evaluated cognitive function and factors associated with cognitive impairment in a cohort of older homeless adults. We hypothesized that substance use and a history of traumatic brain injury would be associated with cognitive impairment.

METHODS

We recruited 350 homeless individuals aged ≥50 years using population-based sampling and conducted structured interviews and neuropsychological testing. We evaluated alcohol use with the Alcohol Use Disorder Identification Test, defining high-severity alcohol use as a total score ≥16 or ≥4 on the alcohol dependency sub-scale. We assessed global cognition with the Modified Mini-Mental State Test (3MS) and processing speed and executive function with the Trail Making Test (TMTB), defining impairment as performing 1.5 standard deviations below the standardized mean. We used multivariable logistic regression to examine the association between alcohol use and cognition.

RESULTS

Participants had a median age of 58 years [IQR 54-61], 76.7% were men, and 79.9% were African American. A quarter (25.1%) of participants met criteria for impairment on the 3MS; 32.9% met criteria for impairment on TMTB. In models adjusted for sociodemographic variables and health conditions, high-severity alcohol use was associated with global cognitive impairment (AOR 2.39, CI 1.19-4.79) and executive dysfunction (AOR 3.09, CI 1.61-5.92).

CONCLUSIONS

Older homeless adults displayed a prevalence of cognitive impairment 3-4 times higher than has been observed in general population adults aged 70 and older. Impaired cognition in older homeless adults could impact access to housing programs and the treatment of health conditions, including the treatment of alcohol use disorders.

Interaction between the activating NKG2D receptor on lymphocytes and its ligands MICA, MICB, and ULBP1-6 modulate T and NK cell activity and may contribute to the pathogenesis of Crohn's disease (CD). NKG2D ligands are generally not expressed on the cell surface of normal, non-stressed cells, but expression of MICA and MICB in CD intestine has been reported. In this exploratory study, we further characterize the expression of NKG2D and its ligands, including the less well-described ULBP4-6, in CD, and test if NKG2D ligand interactions are involved in the migration of activated T cells into the affected mucosal compartments. Intestinal tissue from CD patients and healthy controls were analyzed by flow cytometry, mass cytometry, and immunohistochemistry for expression of NKG2D and ligands, and for cytokine release. Furthermore, NKG2D-dependent chemotaxis of activated CD8 T cells across a monolayer of ligand-expressing human intestinal endothelial cells was examined. Activated lymphocytes down-regulated NKG2D expression upon accumulation in inflamed CD intestine. NKG2D expression on CD56 T and γδ T cells from inflamed tissue seemed inversely correlated with CRP levels and cytokine release. B cells, monocytes, mucosal epithelium, and vascular endothelium expressed NKG2D ligands in inflamed CD intestine. The expression of NKG2D ligands was correlated with cytokine release, but was highly variable between patients. Stimulation of vascular intestinal endothelial cells in vitro induced expression of NKG2D ligands, including MICA/B and ULBP2/6. Blockade of NKG2D on CD8 T cells inhibited the migration over ligand-expressing endothelial cells. Intestinal induction of NKG2D ligands and ligand-induced down-regulation of NKG2D in CD suggest that the NKG2D-ligand interaction may be involved in both the activation and recruitment of NKG2D lymphocytes into the inflamed CD intestine.