Plasma leptin levels are not predictive of dementia in patients with mild cognitive impairment

Background: animal studies suggest a neuroprotective role for leptin, but human studies have shown mixed results. We examined whether plasma leptin levels in individuals with mild cognitive impairment (MCI) were related to cognitive function at baseline and whether higher leptin levels were associated with reduced risk of dementia. Methods: we categorised 352 MCI participants into sex-specific tertiles based on log-transformed fasting plasma leptin levels. In sex-stratified analyses, we investigated whether cognitive ability differed by leptin tertile. We also examined whether the risk of dementia over a 3-year follow-up period differed by leptin level. Analyses controlled for numerous potential confounding variables, including body mass index, hypertension and levels of blood insulin and C-reactive protein. Results: baseline cognitive ability did not differ as a function of leptin level, nor were higher leptin levels associated with reduced hazard of developing dementia. Controlling for related co-variates did not reveal any significant associations between leptin and dementia risk. Conclusion: in this cohort of older adults with MCI, plasma leptin level was not associated with cognitive function at baseline, nor did it predict risk of dementia. Other biological measures, such as volumetric MRI and cerebrospinal fluid protein levels, have demonstrated robust dementia prediction in this cohort. Thus, the current negative findings suggest that plasma leptin, on its own, is unlikely to become a useful clinical biomarker for Alzheimer's disease. Efforts to develop other blood-based biomarkers are needed.