Different Patterns of Cerebral Injury in Dementia With or Without Diabetes

Abstract

The association between diabetes mellitus (DM) and increased risk for dementia in the elderly is well documented. Multiple possible mechanisms for this association have been proposed, including direct effects of hyperglycemia, insulin resistance, and insulin-induced amyloid-β peptide (Aβ) amyloidosis in the brain as well as indirect ischemic effects of DM-promoted cerebrovascular disease.¹ Numerous clinical and autopsy studies have attempted to clarify the mechanism(s) through which DM increases dementia risk. Indeed, DM increases risk for strokes and lacunar infarction^2,3; however, findings from prior studies have been inconsistent with respect to the association of DM with clinical dementia from either Alzheimer disease (AD) or vascular dementia.⁴ Autopsy studies have been partially illuminating. Heitner and Dickson³ failed to demonstrate an association between DM and the histopathologic features of AD—neuritic plaques and neurofibrillary tangles—in a study of 49 cases of diabetes and 52 age- and sex-matched nondiabetic control subjects. A recent, large autopsy series reported a negative association between the histopathologic features of AD and a diagnosis of DM.⁵ Other investigators report no association,^6,7 while others have reported an association of DM with microvascular infarcts (MVIs), but not with macroscopic infarcts or the histopathologic features of AD.⁸ Microvascular infarcts are thought to mostly represent damage secondary to intrinsic microvascular disease, but they may also derive from emboli. Although relatively few in number, these studies support the view that the cerebral dysfunction associated with DM is at least partially mediated by cerebrovascular disease, especially small-vessel disease.⁹