Brief Report Apolipoprotein E genotype is not associated with cognitive impairment in older adults with bipolar disorder Kerr DS, Stella F, Radanovic M, Aprahamian I, Bertollucci PHF, Forlenza OV. Apolipoprotein E genotype is not associated with cognitive impairment in older adults with bipolar disorder. Bipolar Disord 2016: 18: 71–77. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Objectives: Cognitive decline is part of the long-term outcome for many individuals with bipolar disorder (BD). The e4 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. Daniel Shikanai Kerr a,b , Florindo Stella a,c ,M  arcia Radanovic a , Ivan Aprahamian a , Paulo Henrique Ferreira Bertollucci d and Orestes Vicente Forlenza a,b a Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, b Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of S~ ao Paulo, c Biosciences Institute, UNESP–Universidade Estadual Paulista, d Department of Neurology and Neurosurgery, Federal University of S~ ao Paulo (UNIFESP), S~ ao Paulo, SP, Brazil doi: 10.1111/bdi.12367 Key words: Alzheimer’s disease – APOE*4 – apolipoprotein E – bipolar disorder – cognitive decline – mild cognitive impairment Received 25 August 2015, revised 22 October 2015, revised and accepted for publication 4 December 2015 Corresponding author: Daniel Shikanai Kerr Laboratory of Neuroscience LIM-27 IPq- HCFMUSP Rua Dr. Ov  ıdio Pires de Campos 785 CEP 05403-010, S~ ao Paulo, SP Brazil Fax: +55-11-2661-7535 E-mail: dskerr@gmail.com A substantial proportion of subjects with bipolar disorder (BD) present cognitive deterioration in late life (1). In older adults with BD, mild cognitive deficits are exacerbated during abnormal mood states, but may also be present in the euthymic phases (2). These impairments may affect several cognitive domains—namely attention, verbal mem- ory, and executive functions—and are associated with functional decline and progression to demen- tia (3, 4). Neuroimaging studies further suggest 71 Bipolar Disorders 2016: 18: 71–77 © 2016 John Wiley & Sons A/S Published by John Wiley & Sons Ltd. BIPOLAR DISORDERS