Post-stroke cognitive impairment and the risk of stroke recurrence and death in patients with insulin resistance.

OBJECTIVE: Post-stroke cognitive impairment (PSCI) is associated with etiology, severity, and functional outcome of stroke. The risks of recurrent stroke and death in patients with PSCI and insulin resistance (IR) is unknown. The goal of this study was to determine whether global and domain-specific cognitive impairment after stroke in patients with IR was associated with recurrent stroke and death. MATERIALS AND METHODS: We studied patients with recent stroke or transient ischemic attack (TIA) and IR with a baseline Modified Mini-Mental State Examination (3MS) cognitive exam at median of 79 days after stroke. We considered a baseline score of ≤ 88 on the 3MS to indicate global cognitive impairment, and domain-specific summary scores in the lowest quartile to indicate language, attention, orientation, memory and visuospatial impairments. The primary endpoint was fatal or non-fatal recurrent stroke, and the secondary endpoints were all-cause mortality, and fatal or non-fatal myocardial infarction (MI). RESULTS: Among studied n = 3,338 patients 13.6% had global cognitive impairment. During the median 4.96 years of follow-up, 7.4% patients experienced recurrent stroke, 3.5% MI, and 7.3% died. In the fully adjusted model, impairment in language (HR 1.35; 95% CI 1.01-1.81) and orientation (HR 1.41; 95% CI: 1.06-1.87) were associated with a higher risk of recurrent stroke, while attention impairment was associated with all-cause mortality (HR 1.34; 95% CI: 1.01-1.78). DISCUSSION/CONCLUSION: In patients with recent stroke/TIA and IR, post-stroke language and orientation impairments independently predicted recurrent stroke, while attention deficit was associated with increased risk of all-cause mortality.

A cytoskeletal protein complex is essential for division of intracellular amastigotes of Leishmania mexicana.

Previous studies in Leishmania mexicana have identified the cytoskeletal protein KHARON as being important for both flagellar trafficking of the glucose transporter GT1 and for successful cytokinesis and survival of infectious amastigote forms inside mammalian macrophages. KHARON is located in three distinct regions of the cytoskeleton: the base of the flagellum, the subpellicular microtubules, and the mitotic spindle. To deconvolve the different functions for KHARON, we have identified two partner proteins, KHAP1 and KHAP2, which associate with KHARON. KHAP1 is located only in the subpellicular microtubules, whereas KHAP2 is located at the subpellicular microtubules and the base of the flagellum. Both KHAP1 and KHAP2 null mutants are unable to execute cytokinesis but are able to traffic GT1 to the flagellum. These results confirm that KHARON assembles into distinct functional complexes and that the subpellicular complex is essential for cytokinesis and viability of disease-causing amastigotes but not for flagellar membrane trafficking.

Effect of pioglitazone on vascular events in post-stroke cognitive impairment: Post hoc analysis of the IRIS trial.

BACKGROUND: In stroke patients with insulin resistance (IR), post-stroke cognitive impairment (PSCI) is associated with higher risk of recurrent stroke, but the effect of pioglitazone on that risk has not been explored. The goal of this study was to compare the secondary stroke prevention effect of pioglitazone against placebo in patients with versus without PSCI. METHODS: We studied patients enrolled in the Insulin Resistance Intervention after Stroke (IRIS) trial with a post-stroke modified Mini-Mental State Examination (3MS) cognitive assessment (mean time of assessment: 79 days post-stroke). We considered a baseline score of ⩽ 88 on the 3MS to indicate global PSCI, and domain-specific summary scores in the lowest quartile to indicate attention, language, memory, orientation, and visuospatial impairments. RESULTS: In n = 3338 patients with IR, the effect of pioglitazone versus placebo on secondary stroke significantly differed by initial post-stroke global (interaction p = 0.0127) and memory impairment status (interaction p = 0.0003). Hazard ratios (HRs) were time-dependent such that, among those with either global or memory impairment, pioglitazone has an increasingly stronger protective effect at later timepoints. There was no statistically significant effect of pioglitazone among those without either global or memory impairment. The effect of pioglitazone versus placebo on myocardial infarction (MI) also significantly differed by global impairment status (interaction p = 0.030). Pioglitazone was protective among those with global impairment (HR = 0.23 [95% CI: 0.08, 0.71]) but not among those without (HR = 0.88 [95% CI: 0.59, 1.31]). CONCLUSION: These data indicate that pioglitazone treatment may be more effective at reducing risk of recurrent stroke and MI in stroke patients with PSCI. Simple cognitive testing 2-3 months post-stroke may identify patients for whom treatment would be most beneficial.