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Synergistic effect of apolipoprotein E epsilon4 and butyrylcholinesterase K-variant on progression from mild cognitive impairment to Alzheimer's disease.
Pharmacogenet Genomics 2008; 18(4):289-98PG

Abstract

OBJECTIVE

To evaluate the synergistic effects of the apolipoprotein E (APOE) epsilon4 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 > or =1 APOE epsilon4 and > or =1 BCHE-K allele. The presence of APOE epsilon4 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 epsilon4 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 epsilon4 and BCHE-K alleles and lowest in BCHE-K carriers without the APOE epsilon4 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 epsilon4 alleles.

Authors+Show Affiliations

Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936-1080, USA. roger.lane@novartis.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18334913

Citation

Lane, Roger, et al. "Synergistic Effect of Apolipoprotein E Epsilon4 and Butyrylcholinesterase K-variant On Progression From Mild Cognitive Impairment to Alzheimer's Disease." Pharmacogenetics and Genomics, vol. 18, no. 4, 2008, pp. 289-98.
Lane R, Feldman HH, Meyer J, et al. Synergistic effect of apolipoprotein E epsilon4 and butyrylcholinesterase K-variant on progression from mild cognitive impairment to Alzheimer's disease. Pharmacogenet Genomics. 2008;18(4):289-98.
Lane, R., Feldman, H. H., Meyer, J., He, Y., Ferris, S. H., Nordberg, A., ... Greig, N. H. (2008). Synergistic effect of apolipoprotein E epsilon4 and butyrylcholinesterase K-variant on progression from mild cognitive impairment to Alzheimer's disease. Pharmacogenetics and Genomics, 18(4), pp. 289-98. doi:10.1097/FPC.0b013e3282f63f29.
Lane R, et al. Synergistic Effect of Apolipoprotein E Epsilon4 and Butyrylcholinesterase K-variant On Progression From Mild Cognitive Impairment to Alzheimer's Disease. Pharmacogenet Genomics. 2008;18(4):289-98. PubMed PMID: 18334913.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synergistic effect of apolipoprotein E epsilon4 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 R, AU - Sfikas,Nikolaos, AU - Ballard,Clive, AU - Greig,Nigel H, PY - 2008/3/13/pubmed PY - 2008/5/2/medline PY - 2008/3/13/entrez SP - 289 EP - 98 JF - Pharmacogenetics and genomics JO - Pharmacogenet. Genomics VL - 18 IS - 4 N2 - OBJECTIVE: To evaluate the synergistic effects of the apolipoprotein E (APOE) epsilon4 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 > or =1 APOE epsilon4 and > or =1 BCHE-K allele. The presence of APOE epsilon4 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 epsilon4 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 epsilon4 and BCHE-K alleles and lowest in BCHE-K carriers without the APOE epsilon4 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 epsilon4 alleles. SN - 1744-6872 UR - https://www.unboundmedicine.com/medline/citation/18334913/Synergistic_effect_of_apolipoprotein_E_epsilon4_and_butyrylcholinesterase_K_variant_on_progression_from_mild_cognitive_impairment_to_Alzheimer's_disease_ L2 - http://Insights.ovid.com/pubmed?pmid=18334913 DB - PRIME DP - Unbound Medicine ER -