<i>Background:</i> Although the overall effects of cholinesterase inhibitors (CEIs) are limited, there could be a subpopulation of patients who experience unequivocal benefit. This study aimed to describe a clinical profile based on a combination of specific neuropsychological test scores and clinical symptoms associated with a favourable response to rivastigmine. <i>Methods:</i> A prospective cohort study was conducted in 53 patients who started rivastigmine treatment. Neuropsychological evaluation was performed at baseline and 6 months of treatment. Patients were labelled responders and non-responders based on change scores after 6 months in 3 clinical domains: cognition, activities of daily living and behaviour. <i>Results:</i> After 6 months 19 responders and 15 non-responders were identified. Variability in reaction time and Continuous Performance Test (CPT) scores differed significantly at baseline between groups. A previously defined cluster of 4 items of the Neuropsychiatric Inventory was correlated with therapeutic response. <i>Conclusion:</i> These findings suggest that patients who respond well to CEI therapy can be identified by deficits in attention, combined with a cluster of behavioural symptoms, including hallucinations, apathy, anxiety and psychomotor disturbances. This may constitute the clinical profile of cholinergic deficiency. Further prospective studies in larger populations are warranted to investigate whether this profile can be used to select patients who will benefit from CEIs.