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LDL Phenotype in Subjects with Mild Cognitive Impairment and Alzheimer's Disease


Background: Centenarians with normal cognitive function have a “longevity phenotype” characterized by large low-density lipoproteins (LDL) and high-density lipoproteins (HDL) and low incidence of metabolic syndrome, hypertension, and cognitive impairment. Alzheimer's disease (AD) is associated with a number of cardiovascular risk factors, but it is not known if they have or lack the “longevity phenotype”. Objective: The study was designed to determine LDL size and body fat content and distribution in subjects with mild cognitive impairment (MCI) and AD. Results: Fifty-eight persons with MCI or AD (cases) and 42 control subjects of similar age had measurement of LDL size and lipoprotein lipids after a 12 h fast and analysis of body composition by dual x-ray absorptiometry. Cases had small LDL size more often than controls (73% versus 66%) associated with significantly higher triglycerides, lower HDL cholesterol, and higher triglyceride/HDL cholesterol ratio (p ≤ 0.02). Cases with large LDL had a better lipoprotein profile than those with small LDL. Cases and controls had similar percent body fat, fat index, and lean mass index. Forty-seven percent of cases and 39% of controls were obese. Conclusion: The prevalence of small LDL phenotype in MCI and AD cases contrasts with the “longevity phenotype” reported for centenarians with preserved cognitive function. The small LDL phenotype is an atherogenic lipoprotein profile found in metabolic syndrome, type 2 diabetes, and insulin resistance. It is now also reported in persons with MCI and AD.