Identification of Responders to Rivastigmine: A Prospective Cohort Study

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Effect of APOE and CHRNA7 Genotypes on the Cognitive Response to Cholinesterase Inhibitor Treatment at Different Stages of Alzheimer’s Disease

“…28 Additionally, this group of patients has a higher degree of cholinergic deficits. 25 The presence of APOE ∊ 4 was correlated with the worst response to treatment, compared with non-∊4 alleles, in our sample, in agreement with other studies in the literature. 27,29…”

“…For example, patients with hallucinations and attention deficits have higher cholinergic deficits and also better responses to ChEIs. 25…”

Visual Hallucinations and HLA Class II Antigens in Cortical Dementia

“…Cholinergic deficits due to neuronal loss in the nucleus basalis of Meynert or midbrain, Lewy bodies in the temporal lobes, retinal disorganization, selective atrophy of the lingual gyrus and superior parietal lobe, occipital hypometabolism or dynamic imbalance between occipital and other cortical regions have been proposed based on correlations with functional or histological studies [15][16][17] . In particular, cholinergic dysfunction seems a good candidate since visual hallucinations, together with deficits in attention, are the cognitive symptoms with most improvement under treatment with cholinesterase inhibitors, especially with rivastigmine, in both DLB and PD with dementia [18][19][20] . This may reflect the greater cholinergic deficits in areas of the brain responsible for visual hallucinations.…”

Acute response to cholinergic challenge predicts long‐term response to galantamine treatment in patients with Alzheimer's disease

“…For frontal alpha power, no responders are in the overlapping range. For frontal theta power, two responders (22.2%) and three nonresponders (12.5%) are in the overlapping range test scores at baseline, 11,[64][65][66][67] pre-treatment progression rate, [68][69][70][71] cerebrospinal fluid levels of Aβ42, T-tau and P-tau at baseline, 68,72 carotid intima media thickness, 73 regional cerebral blood flow of the lateral and medial frontal lobes, 74 substantia innominata atrophy, 75,76 performance on baseline alertness tests, 9 baseline behavioural 77 and SPECT profile, 78 pre-treatment blood pressure drop, 62,79 and APOE genotype. [58][59][60][61][80][81][82][83] Some of these factors showed a positive correlation with treatment response.…”

“…7,8 Unfortunately, CEIs lead to a clinical improvement in only 20-40% of the AD patients, depending on the definition of treatment response. 9,10 Since it is difficult to distinguish who will clinically improve in response to treatment and who will not at an early stage of disease, 10,11 many patients are unnecessarily exposed to drug treatment and potentially experience adverse effects. It would be favourable to determine responsiveness to treatment before longterm drug exposure.…”