title: Apolipoprotein E ε4 genotype and the temporal relationship between depression and dementia.
abstract: To investigate how apolipoprotein E (APOE) affects the temporal relationship between depression and dementia, we conducted a nested case-control study with longitudinal depression and dementia evaluations from several population studies by using 804 dementia cases and 1600 matched controls, totaling 1519 unique individuals. Depression within 10 years of onset of dementia was strongly associated with dementia diagnosis regardless of APOE status (incidence rate ratio [IRR] 5.25, 95% confidence interval [95% CI] 3.32-8.31 for ε4 carriers, IRR 4.40, 95%CI 3.23-5.99 for noncarriers). However, we found a significant interaction between depression more than 10 years before the onset of dementia and APOE (p = 0.01), with depression more distal to dementia being a risk factor only in ε4 carriers (IRR 3.39, 95% CI 1.69-6.78 for carriers, IRR 1.01, 95% CI 0.60-1.70 for noncarriers). Thus, depression with onset close in time to dementia onset is associated with disease irrespective of APOE genotype, whereas depression more distal to dementia onset is a risk factor only in ε4-carriers. This is the first study to show the interaction between APOE and depression to be dependent on timing of depression onset.
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors: Ida K
authors: IK
authors: Karlsson
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors: Anna M
authors: AM
authors: Bennet
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors: Alexander
authors: A
authors: Ploner
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors: Therese M-L
authors: TM
authors: Andersson
authors: Department of Psychology, University of California-Riverside, Riverside, CA, USA.
authors: Chandra A
authors: CA
authors: Reynolds
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychology, University of Southern California, Los Angeles, CA, USA.
authors: Margaret
authors: M
authors: Gatz
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychology, University of Southern California, Los Angeles, CA, USA. Electronic address: Nancy.Pedersen@ki.se.
authors: Nancy L
authors: NL
authors: Pedersen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053327:Apolipoprotein E4 / Q000235:genetics*; D016022:Case-Control Studies; D003704:Dementia / Q000235:genetics*; D003863:Depression / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D012307:Risk Factors; D013997:Time Factors
chemical_list: D053327:Apolipoprotein E4
keywords: Alzheimer disease; Apolipoprotein E; Dementia; Depression