Wei Qiao Qiu1,2,3, Haihao Zhu2, Michael Dean2, Zhiheng Liu2,4, Linh Vu2, Guanguang Fan2,4, Huajie Li2,5, Mkaya Mwamburi6, David C Steffens7, Rhoda Au8. 1. Department of Psychiatry, Boston University, Boston, MA, USA. 2. Department of Pharmacology and Experimental Therapeutics, Boston University, Boston, MA, USA. 3. Alzheimer's Disease Center, Boston University, Boston, MA, USA. 4. Departments of Anesthesiology, the Second People's Hospital of Shenzhen, China. 5. Department of Neurology, the First People's Hospital of Chang Zhou, China. 6. Department of Public Health and Family Medicine, Tufts University, Boston, MA, USA. 7. Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, USA. 8. Department of Neurology, Boston University, Boston, MA, USA.
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.
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.
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