Synergistic effect of apolipoprotein E epsilon 4 and butyrylcholinesterase K-variant on progression from mild cognitive impairment to Alzheimer's disease

TY - JOUR

T1 - Synergistic effect of apolipoprotein E epsilon 4 and butyrylcholinesterase K-variant on progression from mild cognitive impairment to Alzheimer's disease

AU - Lane, R

AU - Feldman, H H

AU - Meyer, J

AU - He, Y

AU - Ferris, S H

AU - Nordberg, A

AU - rreh-Shori, T

AU - Soininen, H

AU - Pirttila, T

AU - Farlow, M R

AU - Sfikas, N

AU - Ballard, C

AU - Greig, N H

PY - 2008

Y1 - 2008

N2 - Objective To evaluate the synergistic effects of the apolipoprotein E (APOE) epsilon 4 and butyrylcholinesterase K-variant (BCHE-K) alleles on progression to Alzheimer's disease (AD) in individuals with mild cognitive impairment (MCI). Methods This was a post-hoc exploratory analysis from a 3-4-year, randomized, placebo-controlled study of rivastigmine in participants with MCI (InDDEx study). Participants who consented to genetic testing were included in the current analyses. The incidence of progression to AD, cognitive decline and changes in MRI brain volumes were investigated in participants from the placebo arm of the InDDEx study. Results Of the 1018 participants in the overall study, 464 were successfully genotyped for both APOE and butyrylcholinesterase. Of these, 68 (14.7%) carried >= 1 APOE epsilon 4 and >= 1 BCHE-K allele. The presence of APOE epsilon 4 was associated with a significantly higher incidence of progression to AD whereas the presence of BCHE-K had no independent effect on progression. A synergistic effect of the combined presence of APOE epsilon 4 and BCHE-K on the time to clinical diagnosis of AD and on MRI brain volumes was seen. Progression to AD and hippocampal volumetric loss was greatest in participants who carried both APOE epsilon 4 and BCHE-K alleles and lowest in BCHE-K carriers without the APOE epsilon 4 allele. Conclusion In MCI, the risk of cognitive decline, hippocampal volumetric loss and progression to AD seems to be the greatest in individuals who carry at least one copy of both the BCHE-K and APOE epsilon 4 alleles. Pharmacogenetics and Genomics 18:289-298 (c) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

AB - Objective To evaluate the synergistic effects of the apolipoprotein E (APOE) epsilon 4 and butyrylcholinesterase K-variant (BCHE-K) alleles on progression to Alzheimer's disease (AD) in individuals with mild cognitive impairment (MCI). Methods This was a post-hoc exploratory analysis from a 3-4-year, randomized, placebo-controlled study of rivastigmine in participants with MCI (InDDEx study). Participants who consented to genetic testing were included in the current analyses. The incidence of progression to AD, cognitive decline and changes in MRI brain volumes were investigated in participants from the placebo arm of the InDDEx study. Results Of the 1018 participants in the overall study, 464 were successfully genotyped for both APOE and butyrylcholinesterase. Of these, 68 (14.7%) carried >= 1 APOE epsilon 4 and >= 1 BCHE-K allele. The presence of APOE epsilon 4 was associated with a significantly higher incidence of progression to AD whereas the presence of BCHE-K had no independent effect on progression. A synergistic effect of the combined presence of APOE epsilon 4 and BCHE-K on the time to clinical diagnosis of AD and on MRI brain volumes was seen. Progression to AD and hippocampal volumetric loss was greatest in participants who carried both APOE epsilon 4 and BCHE-K alleles and lowest in BCHE-K carriers without the APOE epsilon 4 allele. Conclusion In MCI, the risk of cognitive decline, hippocampal volumetric loss and progression to AD seems to be the greatest in individuals who carry at least one copy of both the BCHE-K and APOE epsilon 4 alleles. Pharmacogenetics and Genomics 18:289-298 (c) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

M3 - Article

VL - 18

SP - 289

EP - 298

JO - PHARMACOGENETICS AND GENOMICS

JF - PHARMACOGENETICS AND GENOMICS

IS - 4

ER -