The aim of this critical review is to address that the study of cognition and
antipsychotics is not always driven by logic and that research into real pro-cognitive
drug treatments must be guided by a better understanding of the biochemical mechanisms underlying cognitive processes and deficits. Many studies have established that typical
neuroleptic drugs do not improve
cognitive impairment. Atypical
antipsychotics improve cognition, but the pattern of improvement differs from
drug to
drug. Diminished
cholinergic activity has been associated with memory impairments. Why atypical drugs improve aspects of cognition might lie in their ability to increase
dopamine and
acetylcholine in the prefrontal cortex. An optimum amount of
dopamine activity in the prefrontal cortex is critical for cognitive functioning. Another mechanism is related to procedural learning, and would explain the quality of the practice during repeated evaluations with atypical
antipsychotics due to a more balanced blockage of D2 receptors. Laboratory studies have shown that
clozapine,
ziprasidone,
olanzapine, and
risperidone all selectively increase
acetylcholine release in the prefrontal cortex, whereas this is not true for
haloperidol and
thioridazine. A few studies have suggested that
cholinomimetics or AChE inhibitors can improve memory functions not only in
Alzheimer's disease but also in other pathologies. Some studies support the role of decreased
cholinergic activity in the cognitive deficits while others demonstrate that decreased
choline acetyltransferase activity is related to deterioration in cognitive performance in
schizophrenia. Overall, results suggest the hypothesis that the
cholinergic system is involved in the
cognitive dysfunctions observed in
schizophrenia and that increased
cholinergic activity may improve these impairments. Furthermore, a dysfunction of glutamatergic neurotransmission could play a key role in cognitive deficits associated with
schizophrenia. Further meta-analysis of various clinical trials in this field is required to account for matters on the grounds of evidence-based medicine.