title: Amyloid-associated depression and ApoE4 allele: longitudinal follow-up for the development of Alzheimer's disease.
abstract: BACKGROUND
  Amyloid-associated depression is associated with cognitive impairment cross sectionally. This follow-up study was to determine the relationship between amyloid-associated depression and the development of Alzheimer's disease (AD).
  
  
  METHODS
  Two hundred and twenty three subjects who did not have dementia at baseline were given a repeat cognitive evaluation for incident AD. Depression was defined by having a Center for Epidemiological Studies Depression (CES-D) score ≥ 16, and non-amyloid vs. amyloid-associated depression by having a low vs. high plasma amyloid-β peptide 40 (Aβ40)/Aβ42 ratio. Apolipoprotein E (ApoE) genotype was determined, and antidepressant usage was documented.
  
  
  RESULTS
  Fifteen subjects developed AD (7%) after an average follow-up time of 6.2 years. While none of those with non-amyloid depression developed AD, 9% of those with amyloid-associated depression developed AD. Further, among those with amyloid-associated depression, ApoE4 carriers tended to have a higher risk of AD than ApoE4 non-carriers (40% vs. 4%, p = 0.06). In contrast, 8% of those who did not have depression at baseline developed AD, but ApoE4 carriers and non-carriers did not show a difference in the AD risk. After adjusting for age, the interaction between ApoE4 and amyloid-associated depression (β = +0.113, SE = 0.047, P = 0.02) and the interaction between ApoE4 and antidepressant use (β = +0.174, SE = 0.064, P = 0.007) were associated with the AD risk.
  
  
  CONCLUSIONS
  Amyloid-associated depression may be prodromal depression of AD especially in the presence of ApoE4. Future studies with a larger cohort and a longer follow-up are warranted to further confirm this conclusion.
authors.affiliation: Department of Psychiatry, Boston University, Boston, MA, USA.|Department of Pharmacology and Experimental Therapeutics, Boston University, Boston, MA, USA.|Alzheimer's Disease Center, Boston University, Boston, MA, USA.
authors.forename: Wei Qiao
authors.initials: WQ
authors.lastname: Qiu
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Boston University, Boston, MA, USA.
authors.forename: Haihao
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Boston University, Boston, MA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Dean
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Boston University, Boston, MA, USA.|Departments of Anesthesiology, the Second People's Hospital of Shenzhen, China.
authors.forename: Zhiheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Boston University, Boston, MA, USA.
authors.forename: Linh
authors.initials: L
authors.lastname: Vu
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Boston University, Boston, MA, USA.|Departments of Anesthesiology, the Second People's Hospital of Shenzhen, China.
authors.forename: Guanguang
authors.initials: G
authors.lastname: Fan
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Boston University, Boston, MA, USA.|Department of Neurology, the First People's Hospital of Chang Zhou, China.
authors.forename: Huajie
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Public Health and Family Medicine, Tufts University, Boston, MA, USA.
authors.forename: Mkaya
authors.initials: M
authors.lastname: Mwamburi
authors.affiliation: Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Steffens
authors.affiliation: Department of Neurology, Boston University, Boston, MA, USA.
authors.forename: Rhoda
authors.initials: R
authors.lastname: Au
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000097:blood*; D000704:Analysis of Variance; D053327:Apolipoprotein E4 / Q000235:genetics*; D003072:Cognition Disorders / Q000097:blood / Q000523:psychology; D003866:Depressive Disorder / Q000097:blood* / Q000150:complications / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4
keywords: Alzheimer's disease; amyloid-associated depression; apolipoprotein E4 allele (ApoE4)