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Research Article

Cholesterol 24-hydroxylase (CYP46A1) polymorphisms are associated with faster cognitive deterioration in Chinese older persons: a two-year follow up study

  1. Brenda Yan Fu1,3,*,
  2. Suk Ling Ma2,3,
  3. Nelson Leung Sang Tang2,3,
  4. Cindy Woon Chi Tam1,
  5. Victor Wing Cheong Lui1,
  6. Helen Fung Kum Chiu1,
  7. Linda Chiu Wa Lam1

Article first published online: 11 FEB 2009

DOI: 10.1002/gps.2196

Issue

International Journal of Geriatric Psychiatry

International Journal of Geriatric Psychiatry

Volume 24, Issue 9, pages 921–926, September 2009

Additional Information

How to Cite

Fu, B. Y., Ma, S. L., Tang, N. L. S., Tam, C. W. C., Lui, V. W. C., Chiu, H. F. K. and Lam, L. C. W. (2009), Cholesterol 24-hydroxylase (CYP46A1) polymorphisms are associated with faster cognitive deterioration in Chinese older persons: a two-year follow up study. Int. J. Geriat. Psychiatry, 24: 921–926. doi: 10.1002/gps.2196

Author Information

  1. 1

    Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR, China

  2. 2

    Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China

  3. 3

    Department of Chemical Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China

*Department of Psychiatry, a/f Multi-Centre, Tai Po Hospital, Tai Po, NT, Hong Kong SAR, China.

Publication History

  1. Issue published online: 14 AUG 2009
  2. Article first published online: 11 FEB 2009
  3. Manuscript Accepted: 7 NOV 2008
  4. Manuscript Received: 18 JAN 2008

Funded by

  • RGC Research Grant Direct Allocation from the Chinese University of Hong Kong. Grant Number: CRE-2003.1.072
  • Mr Lai Seung Hung and Mrs Lai Chan Pui Ngong Dementia in Hong Kong Research Fund

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Keywords:

  • CYP46A1;
  • gene polymorphism;
  • Alzheimer's disease;
  • cognitive function

Abstract

Objectives

We previously found that the polymorphisms of cholesterol 24-hydroxylase (CYP46A1) gene were associated with the risk of Alzheimer's disease (AD) in Chinese. However, its effect in predicting progression of cognitive decline remains unknown.

Methods

Two hundred and eighty-one Chinese subjects (121 cognitively intact, 101 with mild cognitive impairment and 59 with mildly dementia) were followed-up with a mean (SD) duration of 25.22(5.74) months. Association between the CYP46A1 gene polymorphisms and 2-year cognitive deterioration were evaluated.

Results

At follow-up, 225(80.0%) subjects were reassessed. Sixty-three subjects were diagnosed as AD, 68 were MCI and 94 were cognitively intact. Among them, 158 had improved or remained stable while 67 deteriorated. The ‘deteriorated’ group was older than ‘improved or stable’ group (t-test, t = −2.87, p < 0.001). IVS2-150 polymorphism was associated with a higher risk of cognitive deterioration. Subjects with T allele were more likely to deteriorate compared with those without T allele (Pearson χ2 = 8.98, df 2, p = 0.011). IVS3-128 CC genotype was higher in ‘improved or stable’ group (Likelihood Ratio = 6.55, df 2, p = 0.038), suggesting a protective role for this allele. The two other polymorphisms, IVS1-192 and IVS4-122, did not show any significant association with cognitive function.

Conclusion

CYP46A1 gene may act to modulate the course of cognitive deterioration in late life. Copyright © 2009 John Wiley & Sons, Ltd.

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