10.1177/1056789514562152

Vollständiger Abstract

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BackgroundAlthough both apolipoprotein E (<i>APOE</i>) ε4 and glial cell line-derived neurotrophic factor (GDNF) are implicated in the pathogenesis of Alzheimer's disease (AD), it remains unclear whether they interact to affect cognitive decline among older adults without dementia.ObjectiveThis study aimed to examine the interactive effects of <i>APOE</i> ε4 and GDNF on longitudinal cognitive decline.MethodsA total of 543 individuals (mean age 73 [±7] years; 43% female) with cognitively unimpaired (CU) or mild cognitive impairment (MCI) were included from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Linear mixed-effects models were used to examine the contributions of cerebrospinal fluid (CSF) GDNF levels and <i>APOE</i> ε4 status to longitudinal changes in cognitive measures, including the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating - Sum of Boxes (CDR-SB), the 13-item Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog-13), and the Rey Auditory Verbal Learning Test (RAVLT) total score.ResultsWe found that the 3-way interaction (<i>APOE</i> ε4 × GDNF × time) was significant for MMSE, CDR-SB, and ADAS-Cog-13, and of marginal significance for RAVLT total score, after adjusting for age, sex, and education. Specifically, individuals who were <i>APOE</i> ε4 carriers with low CSF GDNF levels showed the fastest rate of cognitive decline among the four groups (Low/<i>APOE4</i>-, High/<i>APOE4</i>-, Low/<i>APOE4</i>+, and High/<i>APOE4</i>+).Conclusions<i>APOE</i> ε4 appears to interact with CSF GDNF levels to affect longitudinal cognitive decline among older adults without dementia.

Abstract: PubMed · Datensatz