Variations in metabolic risk factors for dementia do not affect APOE‐mediated cognitive or functional decline in patients with Alzheimer’s disease from São Paulo, Brazil

Abstract

AbstractBackgroundMidlife cerebrovascular risk, low education and copies of APOE‐ε4 are risk factors for Alzheimer’s disease (AD), whereas metabolic derangements have been associated with dementia onset. This prospective study aimed to explore the impacts of variations in metabolic risk factors on progression of AD in São Paulo, Brazil.MethodsOutpatients with late‐onset AD according to National Institute on Aging – Alzheimer’s Association criteria were assessed for APOE haplotypes (rs7412 & rs429358 genotyped by way of TaqMan® Real‐Time Polymerase Chain Reaction technology) and variations in one year of the following potential metabolic predictors: fasting glycemia, TSH, free T4, vitamin B12, and folic acid. Metabolic variations were assessed in accordance with concurrent variations in the Clinical Dementia Rating Sum‐of‐Boxes, the Index of Independence in Activities of Daily Living, Lawton’s Scale for Instrumental Activities of Daily Living, and the Mini‐Mental State Examination in multiple linear regression models for all patients, and after stratification according to APOE‐ε4 carrier status, with the threshold of significance set at p<0.05.ResultsOf 122 patients, there were 81 women (66.4%) and 41 men (33.6%), 69 APOE‐ε4 carriers (56.5%) and 53 APOE‐ε4 non‐carriers (43.5%). The mean estimated age at AD onset was 73.13±7.1 years‐old. Overall, 120 patients used a cholinesterase inhibitor (98.4%), and 90 patients used Memantine (73.8%). All test scores were significantly different at the end of one year (p<0.01), except for the Mini‐Mental State Examination (p = 0.13). None of the potential metabolic predictors varied significantly after one year (p>0.16), and no variations in metabolic risk factors were concurrently associated with variations in the Clinical Dementia Rating Sum‐of‐Boxes (p>0.17), the Index of Independence in Activities of Daily Living (p>0.09), Lawton’s Scale for Instrumental Activities of Daily Living (p>0.22), or the Mini‐Mental State Examination (p>0.40), neither for APOE‐ε4 carriers (p>0.28), nor for APOE‐ε4 non‐carriers (p>0.07).ConclusionsLifetime metabolic risk factors may affect onset of AD, but concurrent variations in metabolic parameters seem to have no associations with cognitive or functional decline in such patients, regardless of APOE‐ε4 carrier status. (Supported by FAPESP grant #2015/10109‐5)