Neurobiology of Aging
Volume 31, Issue 5 , Pages 741-746, May 2010

The PPAR-gamma Pro12Ala polymorphism and risk of cognitive impairment in a longitudinal study

  • Nancy A. West

      Affiliations

    • Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA
    • Present address: Department of Preventive Medicine and Biometrics, University of Colorado School of Medicine, Denver, CO 80246, USA.
    • ,
  • Mary N. Haan

      Affiliations

    • Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 734 615 9606; fax: +1 734 936 2079.
    • ,
  • Hal Morgenstern

      Affiliations

    • Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA
    • Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA

Received 17 December 2007; received in revised form 22 May 2008; accepted 7 June 2008. published online 21 July 2008.

Abstract 

The Pro12Ala polymorphism in the PPAR-γ gene has been associated with reduced incidence of type 2 diabetes. Although diabetes has been implicated as a risk factor for dementia, the association of Pro12Ala with cognitive impairment is unclear. Dementia and cognitive impairment without dementia (CIND) were determined during six annual follow-up evaluations in a cohort of 929 older Latinos. Among those with diabetes at baseline, there was an increased rate of dementia/CIND for Ala carriers compared to non-carriers (adjusted hazard ratio (HR)=2.5, 95% confidence interval (CI): 1.3–4.9) but not among non-diabetic participants (adjusted HR=0.94; 95% CI: 0.49–1.8). Among males, there was also an increased rate for Ala carriers (adjusted HR=2.7, 95% CI: 1.4–5.2) but not among female carriers (adjusted HR=0.88; 95% CI: 0.47–1.6). The rate of dementia/CIND was highest in diabetic male Ala carriers (adjusted HR=4.2; 95% CI: 1.5–11) compared to non-diabetic male carriers (adjusted HR=2.9; 95% CI: 1.1–7.4), diabetic female carriers (HR=1.6; 95% CI: 0.66–4.1), and non-diabetic female carriers (HR=0.52; 95% CI: 0.21–1.3). These data suggest that although the Ala variant is associated with a reduced risk of type 2 diabetes, it may increase the risk of cognitive impairment in individuals once diabetes has developed. Male Ala carriers may also have a greater risk of dementia/CIND.

Keywords: Pro12Ala genotype, Cognitive impairment, Dementia

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PII: S0197-4580(08)00211-X

doi:10.1016/j.neurobiolaging.2008.06.005

Neurobiology of Aging
Volume 31, Issue 5 , Pages 741-746, May 2010

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