Deletion/Insertion Polymorphism of the Angiotensin‐Converting Enzyme Gene and White Matter Hyperintensities in Dementia: A Pilot Study

OBJECTIVES: To examine the association between the angiotensin‐converting enzyme (ACE) deletion/insertion (D/I) polymorphism and white matter hyperintensities (WMHs) in patients with dementia. DESIGN: Observational pilot study with adjustment for potential confounders using analysis of covariance. SETTING: Secondary care old‐age psychiatry services in greater Manchester, United Kingdom. PARTICIPANTS: Ninety‐seven patients with dementia: 49 with Alzheimer's disease (AD, National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria) and 48 with vascular dementia (VaD, National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria). MEASUREMENTS: The ACE D/I polymorphism, WMHs (deep WMHs (DWMHs) and periventricular hyperintensities (PVHs)) on T2‐weighted magnetic resonance imaging, and potential cardiovascular confounders. RESULTS: The D/D polymorphism of the ACE genotype was associated with severity of DWMH ( P= .005) but not PVH ( P= .34), corrected for age, cardiovascular risk factors, and type of dementia. Post hoc analyses were limited by statistical power but suggested an interaction with the apolipoprotein E ɛ4 allele. CONCLUSION: The results support previous observations that genetic factors influence the development of WMHs in dementia. The involvement of the ACE D/I polymorphism in the pathogenesis of DWMHs in dementia (AD and VaD), by a mechanism that is independent of its association with cardiovascular risk factors, should be confirmed in a large population‐based sample.