Chronic Inflammatory Conditions and Conversion to Mild Cognitive Impairment/Alzheimer’s Disease

Objectives: Alzheimer’s Disease (AD), the most common neurodegenerative disorder of the elderly, is characterized by neural loss and consequently cognitive decline. Although the specific factors involved in the pathogenesis of AD are not fully understood, inflammation is believed to play a significant role. Increased proinflammatory cytokines and inflammation-reactive proteins characterize inflammation in the brain. These molecules stimulate glial cells to further produce proinflammatory molecules, thus perpetuating a vicious circle. The corollary hypothesis is that processes that increase brain inflammation, such as peripheral inflammatory conditions, could amplify the brain inflammatory state and contribute to AD.

This study tested the hypothesis that cognitively normal subjects (NL) that declined to mild cognitive impairment (MCI) or AD have an increased inflammatory burden compared to subjects that remained NL.
Methods: Study subjects were derived from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). A nested-case control study was used. Cases and controls were defined as NL subjects that converted to MCI/AD or remained NL within 3 years. The exposures were the subjects’ chronic inflammatory conditions (INF-CD) defined by summing the reported chronic inflammatory medical conditions over their lifetime. Logistic regression determined the relationship between INF-CD at baseline and conversion to MCI/AD.
Results: Patients with two or more systemic chronic inflammatory conditions had increased likelihood of converting to AD or MCI over a three year period, even after accounting for potential confounders [OR=5.02; 95%CI (1.85-13.61)].
Conclusions: This study suggests that inflammatory conditions may affect AD progression. Since periodontal disease is a chronic inflammation, it may also contribute to AD and further studies are needed.