Cholinergic drug effects on memory and cognition in humans.

Abstract

This chapter summarizes recent attempts to improve normal memory functioning and to alleviate age-related memory deficits by administering drugs that affect transmission at cholinergic synapses. In young adults, a low dose of physostigmine, a short-acting cholinesterase inhibitor, enhanced storage of in formation in long-term memory. Higher doses of physostigmine impaired all aspects of memory. Choline chloride, a precursor to acetylcholine, did not have a substantial effect on memory in a series of four studies with young and elderly adults. It has been difficult to conduct studies of elderly patients suffering from memory loss because of wide individual variations in baseline cognitive abilities and in dose-response curves for cholinergic drugs. A preliminary study utilizing methods that allow for such individual differences indicates that physostigmine can also improve memory in these patients.

Clinical Studies of the Cholinergic Deficit in Alzheimer's Disease

“…Starting at 15 minutes into the infusion and ending approximately five minutes after the end of the infusion, patients were given three trials on a visual recognition memory task. This task measures a patient's ability to store and retrieve information in long‐term memory, an ability that is known to be severely impaired in patients with AD/SDAT 27 and an ability that is known to be sensitive to fluctuations in cholinergic activity 28 . On trial each patient was first shown 12 words or pictures one at a time, then the 12 studied items were randomly mixed together with 12 similar words or pictures that had not been presented to the patient previously.…”

Pharmacotherapy of Memory Loss in the Geriatric Patient

“…19 The work done with cholinergic/anticholinergic drugs supports the important role of cholinergic response in age-related memory impairments and in research in other neurotransmitter systems. Their effects on psychological performance or observed changes depend on a variety of factors, including the drug used, the dose of the drug, the subjects, and the psychological assessment procedures used."…”

“…14 Arecoline, another cholinergic agonist, was found to improve learning in an inverse relationship to baseline memory performance. 19 A study in which arecoline was combined with physostigmine resulted in identical effects in both presenile Alzheimer's patients and normal patients." The ability of physostigmine and arecoline to improve performance is tempered by the adverse side effects, short half-life, and narrow effective dose range."…”

“…It has been postulated that vasopressin induces changes within the brain and CNS that help the electricalimpulses of learning become chemically encoded into LTM.20 Vasopressin experiments have resulted in statistically significant improvement in psychometric tests of concentration, attention, and memory, including storage and retrieval of information. 19.2Q. 42 The exact role of vasopressin is questioned by some researchers since improvement in performance when using vasopressin has occurred in tests requiring both speed and memory.…”

“…In addition, patients with lesions in this region are unable to store new information in LTM. 19 The caudate nucleus portion of the brain also has been implicated in geriatric senility. The inhibiting cholinesterase enzyme has the highest concentration in the caudate nucleus with a resulting decrease in neuronal activity in this area.…”