Most OTC and prescription medicines carry a note along the lines of "the long-term effects of this medication have not been evaluated". When they <i>have</i>, the long-term studies are generally on the order of 2 years, rather than decades. For most medicines, the long-term use risks are probably just hepatic and renal damage, or slow-building tolerance. But we seem to have an increasing list of things which threaten significant indirect dangers over the long term.<p>Anticholinergics, the medicines in the article, have been suspected for quite a while, though proof has been lacking. Acetylcholine is a neurotransmitter, after all, and cholinergics improve brain function in choline-deficient patients. It would almost be surprising if they <i>didn't</i> cause some long-term mental effects.<p>Antihistamines clearly cause short-term sedation and 'brain fog', and are another short-term medicine which many people take regularly for years. I don't know of any equivalent study, but I've heard a number of doctors express concern.<p>Proton-pump inhibitors (i.e. acid reflux meds) are one of the most widely-consumed medications in the US. They've also been linked to dementia in several studies (which are contradicted by several others), and have much less disputed associations with gut bacteria changes that can lead to infection and gastric cancer.<p>Amphetamines (i.e. Adderall) are another obviously-psychoactive medicine studied over short/moderate terms, with primate studies suggesting increased Parkinson's risk at human dosages. This one is a special case, though, because the full risk seems to be incurred after even brief use despite the harms appearing much later.<p>Add to this the stack of worrying-but-vague results showing that many drugs alter gut bacteria, and implicating gut flora in everything from IBS to anxiety to Parkinson's.<p>It increasingly looks like we're running a whole-population study on ourselves, distributing medicines to millions of users with no idea what they do over a lifetime of use. I don't see an obvious cure for this - requiring decades of data before authorizing medications is both unethical and impractical. But long-term drug effects are a disturbingly good explanation for the rising frequency of a whole host of long-term diseases.