Differential qualitative responses to rivastigmine in APOE ɛ4 carriers and noncarriers

Abstract

This retrospective analysis of two double-blind, placebo-controlled studies in patients with mild to moderately severe AD investigated the efficacy of rivastigmine 6-12 mg/day on cognitive outcomes in patients with or without the apolipoprotein (APOE) e4 allele. APOE data were collected from patients who consented to pharmacogenetic testing. Treatment differences within each subgroup were compared, using the Observed Case (OC) population. The APOE e4 and non-APOE e4 subgroups comprised 246 and 121 patients, respectively. Overall, APOE e4 noncarriers showed greater decline than carriers (Po0.05). However, at 26 weeks, placebo-treated APOE e4 patients declined 3.04 points below baseline on the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), and rivastigmine-treated patients improved by 1.67 points. Non-APOE e4 placebo-treated patients declined by 4.59 points and rivastigmine-treated patients declined by 0.48 points. Thus, non-APOE e4 carriers showed a less favorable course under either placebo or rivastigmine, but both genotype-defined subgroups showed quantitatively similar responses to therapy (both Po0.05 vs placebo).

Lipid homeostasis and apolipoprotein E in the development and progression of Alzheimer's disease

“…These anti-dementia agents differ with respect to their ability to inhibit BuChE in addition to AChE and whether the inhibition of target enzymes is sustained (214). Rivastigmine and galantamine appeared to achieve similar quantitative responses in both carriers and noncarriers of APOE 4 in retrospective analyses of placebo-controlled trials in patients with mild to moderate AD (215,216). However, the response of patients with two APOE 4 alleles may vary among ChE-Is (217,218).…”

Apolipoprotein E ε4 Allele Differentiates the Clinical Response to Donepezil in Alzheimer’s Disease

“…Therefore, rivastigmine treatment in AD showed some differences in relation to the different APOE status [18] .…”

“…A very recent study carried out evaluating the response to rivastigmine in ApoE 4 carriers and non-carriers with AD showed that ApoE 4 non-carriers had a less favourable course treated with either placebo or rivastigmine [18] . Preserved cognitive functions after 12 months of rivastigmine treatment in AD have been reported in another recent study where, at variance with the previous one, the pattern of no change of neuropsychological test results was unchanged after considering the possible infl uence of APOE status [19] .…”

Clinical implications of neuropharmacogenetics

“…A large number of pharmacogenetic studies or analyses have been performed looking at the different responses of the three currently used cholinesterase inhibitors donepezil, rivastigmine, and galantamine. Controlled randomised clinical trials found no association between APOE genotypes and the clinical response to donepezil [7], galantamine [8; 9], or rivastigmine [10]. Most subsequent open-label label studies or cohorts of patients have confirmed these results [11][12][13][14][15][16][17][18][19][20][21], although some of them reported a better response to cholinesterase inhibitors for APOE-4 allele carriers [22; 23], but also the reverse result [24; 25].…”