Decreased Levels of Circulating Adiponectin in Mild Cognitive Impairment and Alzheimer’s Disease

Abstract

Adiponectin, an adipocytokine released by the adipose tissue and has important roles in the metabolic regulation and inflammatory control, may play an important roles in the physiopathology of psychiatric and neurodegenerative disorders. The aim of the present work was to evaluate adiponectin serum levels in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) as compared to cognitively healthy elders and to correlate these levels with clinical and cognitive parameters. We further evaluated whether circulating adiponectin levels could predict progression from MCI to Alzheimer's disease upon follow-up. We recruited 157 subjects (41 with AD, 65 with MCI and 51 elderly controls) in the baseline assessment. Follow-up data were available for 54 subjects with MCI and 43 controls in whom we ascertained the conversion to AD and the progression of cognitive impairment. Adiponectin was assayed by sandwich ELISA. Serum levels of adiponectin were significantly lower in MCI and AD as compared to controls (p < 0.001). After controlling for age, educational level and APOE genotype, adiponectin levels remained significantly reduced in these groups (p < 0.001). Circulating adiponectin levels did not predict cognitive decline in the elderly controls (i.e., progression from normal cognition to MCI) or progression to Alzheimer's disease in subjects with MCI. We conclude that lower levels of adiponectin were associated with cognitive dysfunction, though it did not predict additional cognitive decline and conversion to dementia in this cohort of elderly subjects. Decreased adiponectin may be a surrogate marker of the pathological process in AD, linking clinical comorbidities, inflammation and cognitive dysfunction.

Possible Involvement of Adiponectin, the Anti-Diabetes Molecule, in the Pathogenesis of Alzheimer’s Disease

“…Consistent with previous studies [7][8][9][10], serum APN levels in MCI and AD were significantly higher than in controls. A large-scale study in 2012 showed that increased plasma APN was an independent risk factor for development of all-cause dementia and AD in women [7].…”

“…Previous clinical studies have shown that lifestyle-related diseases such as hypertension, type II diabetes, dyslipidemia, and obesity may enhance the risks for AD and other neurodegenerative diseases [7][8][9][10]. However, only one study has examined APN in this context, with Une et al finding increased serum APN in patients with mild cognitive impairment (MCI) and AD compared to age-matched normal controls (NC) and increased CSF APN in MCI compared to NC [8].…”

Importance of adiponectin activity in the pathogenesis of Alzheimer's disease

“…(Table 1). 36 The reasons for the discrepancies among these studies are unclear, but the APN level may be affected by multiple factors. Given that many AD patients have concomitant metabolic disorders,1 it is possible that plasma APN may fluctuate during coprogression of the disease 37.…”

Obesity as a risk factor for Alzheimer’s disease: the role of adipocytokines

“…In our point of view, it could also translate a protective effort against a neurotoxic insult. More recently, Teixeira et al (2013) demonstrated that circulating adiponectin levels were reduced in MCI and AD patients but did not predict progression to dementia. On other hand, Bigalke et al (2011) and Warren et al (2012) failed to demonstrate a correlation between plasmatic levels of this adipocytokine and AD.…”