BACKGROUND: Patients with Alzheimer's disease and dementia commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to BPSD development in Alzheimer's disease has been demonstrated. Several studies have investigated whether the exon 4 epsilon2/epsilon3/epsilon4 haplotype of the apolipoprotein E (APOE) gene is associated with BPSD, with variable results. OBJECTIVE: We investigated the exon 4 polymorphisms and extended this study to include promoter polymorphisms and the resultant haplotypes across the gene. METHODS: Our large independent cohort of 388 patients with longitudinal measures of BPSD assessed by the Neuropsychiatric Inventory was used to analyse whether any of these variants were associated with the presence of BPSD. RESULTS: We revealed several significant relationships before correction for multiple testing. The exon 4 haplotype was associated with hallucinations and anxiety, A-491T with irritability, T-427C with agitation/aggression and appetite disturbances, and T-219C with depression. Haplotype analyses of all variants did not reveal any statistically significant findings. CONCLUSIONS: Our data and a review of previous studies showed a diversity of relationships, suggesting that these findings might be due to chance and so collectively do not support a role for the APOE gene in BPSD.
BACKGROUND:Patients with Alzheimer's disease and dementia commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to BPSD development in Alzheimer's disease has been demonstrated. Several studies have investigated whether the exon 4 epsilon2/epsilon3/epsilon4 haplotype of the apolipoprotein E (APOE) gene is associated with BPSD, with variable results. OBJECTIVE: We investigated the exon 4 polymorphisms and extended this study to include promoter polymorphisms and the resultant haplotypes across the gene. METHODS: Our large independent cohort of 388 patients with longitudinal measures of BPSD assessed by the Neuropsychiatric Inventory was used to analyse whether any of these variants were associated with the presence of BPSD. RESULTS: We revealed several significant relationships before correction for multiple testing. The exon 4 haplotype was associated with hallucinations and anxiety, A-491T with irritability, T-427C with agitation/aggression and appetite disturbances, and T-219C with depression. Haplotype analyses of all variants did not reveal any statistically significant findings. CONCLUSIONS: Our data and a review of previous studies showed a diversity of relationships, suggesting that these findings might be due to chance and so collectively do not support a role for the APOE gene in BPSD.
Authors: C Courtney; D Farrell; R Gray; R Hills; L Lynch; E Sellwood; S Edwards; W Hardyman; J Raftery; P Crome; C Lendon; H Shaw; P Bentham Journal: Lancet Date: 2004-06-26 Impact factor: 79.321
Authors: G Ramachandran; K Marder; M Tang; P W Schofield; M R Chun; D P Devanand; Y Stern; R Mayeux Journal: Neurology Date: 1996-07 Impact factor: 9.910
Authors: C G Lyketsos; L Baker; A Warren; C Steele; J Brandt; M Steinberg; S Kopunek; A Baker Journal: J Neuropsychiatry Clin Neurosci Date: 1997 Impact factor: 2.198
Authors: T Gabryelewicz; D Religa; M Styczynska; B Peplonska; A Pfeffer; B Wasiak; E Luczywek; M Golebiowski; W Androsiuk; K Czyzewski; I Przekop; M Barcikowska Journal: Dement Geriatr Cogn Disord Date: 2002 Impact factor: 2.959
Authors: G W Small; S T Chen; S Komo; L Ercoli; K Miller; P Siddarth; A Kaplan; D Dorsey; H Lavretsky; S Saxena; S Y Bookheimer Journal: Int J Geriatr Psychiatry Date: 2001-11 Impact factor: 3.485
Authors: M Lehtovirta; H Soininen; S Helisalmi; A Mannermaa; E L Helkala; P Hartikainen; T Hänninen; M Ryynänen; P J Riekkinen Journal: Neurology Date: 1996-02 Impact factor: 9.910
Authors: C Arbus; V Gardette; C E Cantet; S Andrieu; F Nourhashémi; L Schmitt; B Vellas Journal: J Nutr Health Aging Date: 2011-08 Impact factor: 4.075
Authors: Zahinoor Ismail; Minh-Quan Nguyen; Corinne E Fischer; Tom A Schweizer; Benoit H Mulsant; David Mamo Journal: Curr Psychiatry Rep Date: 2011-06 Impact factor: 5.285
Authors: Mohit P Chopra; Reid D Landes; Richard A Jones; Zach L Feldman; Cornelia Beck; Sue T Griffin Journal: Int J Geriatr Psychiatry Date: 2009-06 Impact factor: 3.485
Authors: Nathan Pankratz; Karen S Marder; Cheryl A Halter; Alice Rudolph; Cliff W Shults; William C Nichols; Tatiana Foroud Journal: Mov Disord Date: 2008-11-15 Impact factor: 10.338