P4‐055: DECREASED SERUM LEPTIN IN PATIENTS WITH MILD COGNITIVE IMPAIRMENT

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The number of patients with dementia is rising exponentially. So far, no disease-modifying treatments are available (Thies & Bleiler 2013). Therefore, early detection of potentially modifiable risk factors is not only an issue of medical but also social and economic interest (Barnes 2011). The hormone leptin , well-known for its involvement in energy metabolism, is also discussed as a neuroprotective and neurotrophic agent. However, direct associations with age-related cognitive decline and dementia remain controversial (Lieb 2009, Kamogawa 2010). We here aimed to determine whether leptin is reduced in patients with Mild Cognitive Impairment (MCI) as compared to healthy controls. 32 amnestic or amnestic+ MCI patients (men n= 16, women n = 16, aged 67.8 years ± 7 SD, body mass index, BMI, 26 kg/m 2 ± 3 SD) and 32 healthy controls (HC) were pairwise matched for sex, age and BMI. MRI of the brain excluded major alternative pathologies. Cognition was assessed using the Auditory Verbal Learning Test and the trail making test (TMT) A and B (Lezak 2004). In addition, body fat was determined, and fasting serum leptin was assessed in peripheral blood. MCI patients showed significantly poorer learning, consolidation, delayed recall and recognition memory (all p < 0.015), and longer reaction times for completing the TMT (part A, p = 0.02, part B, p = 0.07, B-A, p = 0.17), compared to HC. Serum leptin levels were significantly lower in MCI patients compared to HC (Wilcoxon-signed-rank test, p < 0.001). Adjusting for sex, age and body fat did not attenuate the effect (ANCOVA, all F > 7.1, all p < 0.01). Higher leptin correlated significantly with shorter reaction times in the TMT-B task in female MCI patients (r = -0.54, p = 0.03). In this well-characterized and carefully matched cohort we showed that MCI patients exhibited lower serum leptin levels compared to HC, independent of sex, age and total body fat. Also, higher leptin was associated with better cognitive flexibility. Our findings lend further support to a hypothesized neuroprotective effect of leptin as postulated from animal studies (Paz-Filho 2010).

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