Adding gabapentin to existing calcium channel blocker therapy increased dementia risk by 144% (hazard ratio 2.44) compared to pregabalin in 7,141 hypertensive adults. Remarkably, reversing the order—starting calcium channel blockers after gabapentin—showed no elevated risk, suggesting drug sequence timing fundamentally alters safety outcomes. This challenges the assumption that medication combinations have uniform effects regardless of introduction order. The finding has immediate clinical relevance given how commonly older adults accumulate medications over time, often adding gabapentin for neuropathic pain to regimens already containing calcium channel blockers for hypertension. However, significant limitations temper these results: this is a preprint awaiting peer review, the reverse-sequence group was much smaller (685 vs 7,141 patients), and observational data cannot establish causation. The biological mechanism remains unclear—perhaps chronic calcium channel blocker exposure primes neurons for gabapentin-related cognitive effects. While this represents potentially paradigm-shifting evidence for sequence-dependent drug interactions, replication in larger cohorts and mechanistic studies are essential before changing clinical practice.