Provision of recommended treatment for stimulant use disorder in United States substance use treatment facilities.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β accumulation, tau pathology, and neuronal loss. Aging and the apolipoprotein E () ε4 allele remain the strongest risk factors for AD, but additional variables, including sex and vascular risk factors, modulate disease severity. More than 55 million people are living with dementia worldwide, with AD accounting for 60–70% of cases. Current treatment approaches primarily focus on slowing disease progression and alleviating symptoms. While current anti-amyloid therapy approaches offer promise, identifying early biomarkers and modifiable risk factors remains a priority for reducing dementia burden. Multiple lines of evidence suggest that alterations in the gut microbiota may precede or co-occur with AD pathology. Gut microbes produce a wide array of metabolites that modulate host physiology and may influence neurodegenerative processes. Many gut microbial metabolites enter the bloodstream, where they can influence central nervous system (CNS) function indirectly via peripheral signaling or directly by crossing the blood-brain barrier (BBB). Previous studies have identified several bacterial metabolites associated with AD, implicating gut bacterial metabolism as a potential contributor to neurodegeneration. Imidazole propionate (ImP) is a metabolite produced during anaerobic metabolism of histidine by bacteria expressing the enzyme urocanate reductase (UrdA), which catalyzes the reduction of urocanate during anaerobic respiration. Elevated blood levels of ImP have been linked with multiple dementia risk factors, including type II diabetes (T2D), hypertension, atherosclerosis, and chronic kidney disease, suggesting potential detrimental effects on host health. However, the impact of ImP on brain function and AD pathophysiology remains largely unexplored.