Background/Aims: Late-onset Alzheimer's disease (LOAD) comprises sporadic LOAD and familial LOAD. We wanted to determine whether total plasma homocysteine (Hcy), cardiovascular risk factors and volumetric analyses of cerebral magnetic resonance imaging (MRI) were differently associated with mild cognitive impairment (MCI) in subjects from families with aggregation of LOAD (probable familial LOAD) and MCI in subjects from families without LOAD (probable sporadic LOAD). Methods: A total of 103 subjects with MCI without known stroke or other apparent causative diseases were included as cases together with 58 controls. The cases were stratified into 3 groups according to the number of biological relatives with probable LOAD on one side of the family. Cerebral MRI was obtained from all. The case groups were compared to the control group in sex-specific analyses of covariance. Results: Hcy was significantly elevated in all cases compared to controls, except for women with probable familial LOAD. These women also had significantly smaller hippocampal volume and significantly larger lateral ventricles, unlike the women in the other case groups. Conclusions: Our findings suggest that research on Hcy, cardiovascular risk factors and other potential risk factors for LOAD might benefit from distinguishing between sporadic and familial LOAD.

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