Vaccines such as the old tuberculosis (TB) Bacille Calmette–Guérin (BCG) can apparently defer dementia onset with an efficacy better than all drugs known to date. Understanding how and why is of immense importance because it could represent a sea-change in how we manage patients with mild cognitive impairment through to dementia. There is growing evidence that infection and/or inflammation is likely to contribute to the development of dementias such as Alzheimer's disease, our aim is to provide neuroscientists and neurologists with a historical and molecular background to how vaccines, adjuvants, and their component molecules can elicit broad-spectrum protective effects against diverse agents. Early studies in which poxvirus, herpes virus, and TB infections can afford cross-protection against unrelated pathogens, is a concept known as 'trained immunity'. A prime example is the attenuated vaccine, BCG, which was introduced to protect against the causative agent of TB, Mycobacterium tuberculosis. From the development of BCG in the 1920s through to the discovery, by Freund and McDermott in the 1940s, it was shown that extracts of mycobacteria can themselves exert potent immunostimulating (adjuvant) activity. The Freund's complete adjuvant (FCA) was then based on mycobacteria and remains the most potent immunopotentiator reported to date. Whether the beneficial effects of BCG require long-term persistence of live bacteria, or can depend on specific mycobacterial molecules that mediate immuno-potentiation is queried.