Diabetes mellitus (DM) is an important risk factor for Alzheimer's disease (AD). Most diabetic patients have insulin resistance (IR) that is associated with compensatory hyperinsulinemia, one of the mechanisms suggested for increased AD risk in patients with DM. Alpha-lipoic acid (ALA) is a disulfide molecule with antioxidant properties that has positive effects on glucose metabolism and IR. This study evaluated the effect of ALA treatment (600？mg/day) on cognitive performances in AD patients with and without DM. One hundred and twenty-six patients with AD were divided into two groups, according to DM presence (group A) or absence (group B). Cognitive functions were assessed by MMSE, Alzheimer's Disease Assessment Scale-cognitive (ADAS-Cog), Clinician's Interview-Based Impression of Severity (CIBIC), Clinical Dementia Rating (CDR), and Alzheimer's Disease Functional and Change Scale (ADFACS). IR was assessed by HOMA index. At the end of the study, MMSE scores showed a significant improvement in 43% patients of group A (26 subjects) and 23% of group B (15 subjects), compared to baseline ( ). Also ADAS-Cog, CIBIC, and ADFACS scores showed a significant improvement in group A versus group B. IR was higher in group A. Our study suggests that ALA therapy could be effective in slowing cognitive decline in patients with AD and IR. 1. Introduction Alzheimer’s disease (AD) is a neurological disorder characterized by profound memory loss and progressive dementia. The cause of sporadic AD remains poorly understood. In addition to genetic susceptibility genes, such as ApoE4 allele, a number of risk factors has been identified including many lifestyle and dietary choices [1]. Type 2 diabetes mellitus (T2-DM2) is an important risk factor for AD and vascular dementia [2, 3]. Recent longitudinal studies have shown that AD is related to glucose metabolism disorders [4, 5]. An explanation seems to be that vascular complications of diabetes may cause neurodegenerative disease [6]. On the other hand, in addition to its peripheral metabolic effects, insulin may also have important outcome on brain functions. A recent commentary offers two models on the relationship between T2-DM and AD: “central insulin resistance” and inflammation. Both mechanisms influence insulin sensitivity in the brain, finally leading to β-amyloid accumulation and, consequently, to AD [7]. Moreover, most diabetic patients have insulin resistance (IR) that is associated with compensatory hyperinsulinemia, one of the mechanisms suggested to explain the increased AD risk in diabetic patients [8, 9].
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