Current and future treatments of memory complaints and Alzheimer’s disease

In the early 1980s, my colleagues and I developed tacrine as the first pragmatic treatment for Alzheimer’s disease (AD) [1]. Tacrine was synthesized by Adrian Albert as part of the Australian World War II effort to find an intravenous antiseptic [2]. Use of tacrine to treat AD was unanticipated by the scientific community and there was considerable controversy [3–5]. Yet 7 years later, in 1993, tacrine (Cognex) was the first US FDA-approved treatment for AD. The theory behind tacrine was the cholinergic hypothesis [6]. According to this theory, drugs that enhanced cholinergic neuronal function would improve memory. This might be by cholinesterase inhibition (CI), stimulation of the nicotinic receptor or enhancement of acetylcholine production. The intent of tacrine was to assist failing cholinergic neurons. Symptomatic treatment. Prevention or reversal of the disease process was never intended with CI therapy. It was understood that the deficits of the cholinergic system seen in AD were the result of the disease, not the cause.