Lipoic acid as a novel treatment for mild cognitive impairment and early-stage Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative brain disorder that gradually destroys a patient’s memory and ability to learn, make judgments, communicate within the social environment, and carry out daily activities. In the course of the disease, short-term memory is affected first, caused by neuronal dysfunction and degeneration in the hippocampus and amygdala. As the disease progresses further, neurons also degenerate and die in other cortical regions of the brain.¹ At this stage, sufferers often experience dramatic changes in personality and behavior, such as anxiety, suspiciousness and agitation, as well as delusions and hallucinations.² AD prevalence rates are 1% for individuals between 65 and 69 years old, 3% for those between 70 and 74 years old, 6% for those between 75 and 79 years old, 12% for those between 80 and 84 years old, and 25% for those aged 85 years and older. AD is further characterized by two major neuropathological hallmarks: The deposition of neuritic, β-amyloid (Aβ) peptide-containing senile plaques in hippocampal and cerebral cortical regions of AD patients is accompanied by the presence of intracellular neurofibrillary tangles that occupy much of the cytoplasm of pyramidal neurons. Inflammation, as evidenced by the activation of microglia and astroglia, is another hallmark of AD. Inflammation, including superoxide production (“oxidative burst”), is an important source of oxidative stress in AD patients.^3,4 The inflammatory process occurs mainly around the amyloid plaques and is characterized by proinflammatory substances released from activated microglia and astroglia.⁵ Glia-produced cytokines, including interleukin-1β (IL-1β), IL-6, macrophage colony-stimulating factor, and tumor necrosis factor-α (TNF-α),⁶ are prominent molecules in the inflammatory process. Besides morphological alterations, AD is also associated with a markedly impaired cerebral glucose metabolism, as detected by reduced cortical ¹⁸F-labeled desoxyglucose utilization in positron emission tomography of AD patients.⁷.