Association of Antineuronal Antibody Levels with Cognitive Impairment in Older Cuban Adults

Abstract

ABSTRACT INTRODUCTION Alzheimer disease is the main cause of dementia associated with aging in Cuba and the world. Development of methods for early diagnosis is vital to increasing intervention effectiveness and improving patient quality of life. Recent studies have shown associations between alterations in serum levels of antineuronal antibodies and Alzheimer disease pathology. However, the specific relationship between such antineuronal antibodies and Alzheimer pathogenesis remains unclear because of the great variety of antibodies identified and their heterogeneity among patients and nondemented controls. OBJECTIVE Assess the association between serum levels of antibodies against neuronal antigens (total brain protein, aldolase and amyloid beta protein) and cognitive performance in older Cuban adults. METHODS A cross-sectional pilot study was conducted of adults aged ≥65 years living in Havana’s Playa Municipality and Artemisa Province (southwest of Havana). A sociodemographic and risk factor questionnaire was administered, neuropsychological assessment conducted, and physical and neurological examinations performed. A relative or caregiver was also interviewed. Laboratory tests included: complete blood count, glycemia, lipid panel, and apolipoprotein E genotype. Of 143 individuals studied, 33 were cognitively normal, 52 had mild cognitive impairment, and 58, probable Alzheimer disease. Serum antibody levels were determined by ELISA and compared using covariance analysis with a significance level of 0.05. ELISA specificity, sensitivity and predictive value were assessed by analyzing their respective diagnostic performance curves. RESULTS Patients with probable Alzheimer disease performed least well on the mini mental state examination (cognitively normal 28.8, SD 1.2; mild cognitive impairment 27.4, SD 2.2; probable Alzheimer disease 12.9, SD 6.5; ANOVA p <0.001). The percentage of Apo E4 carriers was seven times greater in the group with probable Alzheimer disease than in the cognitively normal group. Among the antibodies studied, only those against amyloid beta peptide had levels significantly higher in the Alzheimer disease group than in the cognitively normal group (p = 0.007) and the group with mild cognitive impairment (p = 0.002). CONCLUSIONS Results support the presence of an autoimmune component in Alzheimer disease and suggest that serum anti–amyloid-beta could be used for its diagnosis.