title: Apolipoprotein E genotype is not associated with cognitive impairment in older adults with bipolar disorder.
abstract: OBJECTIVE
  Cognitive decline is part of the long-term outcome for many individuals with bipolar disorder (BD). The ε4 allele (APOE*4) of apolipoprotein E (APOE) is a well-established risk factor for dementia in Alzheimer's disease (AD). However, its contribution to the risk of cognitive deterioration in BD has not yet been determined. Our aim was to analyze the APOE genotype association with cognitive status in a sample of older adults with BD and compare this to the association in individuals with AD, individuals with mild cognitive impairment (MCI), and healthy controls.
  
  
  METHODS
  Participants (n = 475) were allocated to four groups: individuals with BD (n = 77), those with AD (n = 211), those with MCI (n = 43), and healthy controls (n = 144) according to clinical and neuropsychological assessment. APOE was genotyped by real-time polymerase chain reaction. Tukey's honest significant difference test and Pearson's chi-squared test were used to compare diagnostic groups.
  
  
  RESULTS
  Subjects with BD were similar to controls with respect to the distribution of the APOE genotype (p = 0.636) and allele frequencies (p = 0.481). Significant differences were found when comparing the AD group to the BD group or to controls (APOE genotype: p < 0.0002; allele frequencies: p < 0.001). APOE*4 was significantly increased in the AD group when compared to the BD group (p = 0.031) and controls (p < 0.0001). The cognitively impaired BD subgroup (Mini-Mental State Examination below the cutoff score and/or neuropsychological assessment compatible with MCI) had a statistically significant higher frequency of APOE*2 compared to the AD group (p = 0.003).
  
  
  CONCLUSIONS
  APOE*4 is not associated with the diagnosis of BD and does not impact the occurrence of dementia in BD. Given the distinct clinical and biological features of cognitive impairment in BD, we hypothesized that dementia in BD is unrelated to AD pathological mechanisms.
authors.affiliation: Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo (USP), São Paulo, SP, Brazil.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Daniel Shikanai
authors.initials: DS
authors.lastname: Kerr
authors.affiliation: Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo (USP), São Paulo, SP, Brazil.|Biosciences Institute, UNESP-Universidade Estadual Paulista, São Paulo, SP, Brazil.
authors.forename: Florindo
authors.initials: F
authors.lastname: Stella
authors.affiliation: Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo (USP), São Paulo, SP, Brazil.
authors.forename: Márcia
authors.initials: M
authors.lastname: Radanovic
authors.affiliation: Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo (USP), São Paulo, SP, Brazil.
authors.forename: Ivan
authors.initials: I
authors.lastname: Aprahamian
authors.affiliation: Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Paulo Henrique Ferreira
authors.initials: PH
authors.lastname: Bertollucci
authors.affiliation: Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo (USP), São Paulo, SP, Brazil.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Orestes Vicente
authors.initials: OV
authors.lastname: Forlenza
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D001714:Bipolar Disorder / Q000150:complications / Q000235:genetics*; D003072:Cognition Disorders / Q000150:complications / Q000235:genetics*; D060825:Cognitive Dysfunction / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E
keywords: APOE*4; Alzheimer's disease; apolipoprotein E; bipolar disorder; cognitive decline; mild cognitive impairment