Aim/hypothesis. Type 2 diabetes increases the risk not only of vascular dementia but also of Alzheimer's disease. The question remains whether diabetes increases the risk of Alzheimer's disease by diabetic vasculopathy or whether diabetes influences directly the development of Alzheimer neuropathology. In vivo, hippocampal and amygdalar atrophy on brain MRI are good, early markers of the degree of Alzheimer neuropathology. We investigated the association between diabetes mellitus, insulin resistance and the degree of hippocampal and amygdalar atrophy on magnetic resonance imaging (MRI) accounting for vascular pathology. Methods. Data was obtained in a population-based study of elderly subjects without dementia between 60 to 90 years of age. The presence of diabetes mellitus and, in non-diabetic subjects, insulin resistance was assessed for 506 participants in whom hippocampal and amygdalar volumes on MRI were measured. We assessed the degree of vascular morbidity by rating carotid atherosclerosis, and brain white matter lesions and infarcts on MRI.Results. Subjects with diabetes mellitus had more hippocampal and amygdalar atrophy on MRI compared to subjects without diabetes mellitus. Furthermore, increasing insulin resistance was associated with more amygdalar atrophy on MRI. The associations were not due to vascular morbidity being more pronounced in persons with diabetes mellitus. Conclusions/interpretation. Type 2 diabetes is associated with hippocampal and amygdalar atrophy, regardless of vascular pathology. This could suggest that Type 2 diabetes directly influences the development of Alzheimer neuropathology. [Diabetologia (2003[Diabetologia ( ) 46:1604[Diabetologia ( -1610

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Blood pressure and indicators of small-vessel disease in the brain may be associated with atrophy of structures affected by Alzheimer pathology.

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