Synergistic effect of apolipoprotein E ε4 and butyrylcholinesterase K-variant on progression from mild cognitive impairment to Alzheimer's disease

Roger Lane, Howard H. Feldman, Joanne Meyer, Yunsheng He, Steven H. Ferris, Agneta Nordberg, Taher Darreh-Shori, Hilkka Soininen, Tuula Pirttilä, Martin Farlow, Nikolaos Sfikas, Clive Ballard, Nigel H. Greig

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

OBJECTIVE: To evaluate the synergistic effects of the apolipoprotein E (APOE) ε4 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 ε4 and ≥1 BCHE-K allele. The presence of APOE ε4 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 ε4 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 ε4 and BCHE-K alleles and lowest in BCHE-K carriers without the APOE ε4 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 ε4 alleles.

Original languageEnglish
Pages (from-to)289-298
Number of pages10
JournalPharmacogenetics and Genomics
Volume18
Issue number4
DOIs
StatePublished - Apr 2008

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Apolipoprotein E4
Butyrylcholinesterase
Alzheimer Disease
Alleles
Rivastigmine
Placebos
Cognitive Dysfunction
Incidence
Brain
Genetic Testing
Apolipoproteins E

Keywords

  • Apolipoprotein E
  • Butyrylcholinesterase
  • Mild cognitive impairment

ASJC Scopus subject areas

  • Genetics
  • Pharmacology

Cite this

Synergistic effect of apolipoprotein E ε4 and butyrylcholinesterase K-variant on progression from mild cognitive impairment to Alzheimer's disease. / Lane, Roger; Feldman, Howard H.; Meyer, Joanne; He, Yunsheng; Ferris, Steven H.; Nordberg, Agneta; Darreh-Shori, Taher; Soininen, Hilkka; Pirttilä, Tuula; Farlow, Martin; Sfikas, Nikolaos; Ballard, Clive; Greig, Nigel H.

In: Pharmacogenetics and Genomics, Vol. 18, No. 4, 04.2008, p. 289-298.

Research output: Contribution to journalArticle

Lane, R, Feldman, HH, Meyer, J, He, Y, Ferris, SH, Nordberg, A, Darreh-Shori, T, Soininen, H, Pirttilä, T, Farlow, M, Sfikas, N, Ballard, C & Greig, NH 2008, 'Synergistic effect of apolipoprotein E ε4 and butyrylcholinesterase K-variant on progression from mild cognitive impairment to Alzheimer's disease', Pharmacogenetics and Genomics, vol. 18, no. 4, pp. 289-298. https://doi.org/10.1097/FPC.0b013e3282f63f29
Lane, Roger ; Feldman, Howard H. ; Meyer, Joanne ; He, Yunsheng ; Ferris, Steven H. ; Nordberg, Agneta ; Darreh-Shori, Taher ; Soininen, Hilkka ; Pirttilä, Tuula ; Farlow, Martin ; Sfikas, Nikolaos ; Ballard, Clive ; Greig, Nigel H. / Synergistic effect of apolipoprotein E ε4 and butyrylcholinesterase K-variant on progression from mild cognitive impairment to Alzheimer's disease. In: Pharmacogenetics and Genomics. 2008 ; Vol. 18, No. 4. pp. 289-298.
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abstract = "OBJECTIVE: To evaluate the synergistic effects of the apolipoprotein E (APOE) ε4 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 ε4 and ≥1 BCHE-K allele. The presence of APOE ε4 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 ε4 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 ε4 and BCHE-K alleles and lowest in BCHE-K carriers without the APOE ε4 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 ε4 alleles.",
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T1 - Synergistic effect of apolipoprotein E ε4 and butyrylcholinesterase K-variant on progression from mild cognitive impairment to Alzheimer's disease

AU - Lane, Roger

AU - Feldman, Howard H.

AU - Meyer, Joanne

AU - He, Yunsheng

AU - Ferris, Steven H.

AU - Nordberg, Agneta

AU - Darreh-Shori, Taher

AU - Soininen, Hilkka

AU - Pirttilä, Tuula

AU - Farlow, Martin

AU - Sfikas, Nikolaos

AU - Ballard, Clive

AU - Greig, Nigel H.

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N2 - OBJECTIVE: To evaluate the synergistic effects of the apolipoprotein E (APOE) ε4 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 ε4 and ≥1 BCHE-K allele. The presence of APOE ε4 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 ε4 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 ε4 and BCHE-K alleles and lowest in BCHE-K carriers without the APOE ε4 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 ε4 alleles.

AB - OBJECTIVE: To evaluate the synergistic effects of the apolipoprotein E (APOE) ε4 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 ε4 and ≥1 BCHE-K allele. The presence of APOE ε4 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 ε4 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 ε4 and BCHE-K alleles and lowest in BCHE-K carriers without the APOE ε4 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 ε4 alleles.

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