期刊
AMERICAN JOURNAL OF PSYCHIATRY
卷 175, 期 6, 页码 530-537出版社
AMER PSYCHIATRIC PUBLISHING, INC
DOI: 10.1176/appi.ajp.2017.17040442
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资金
- National Institute on Aging [R03 AG045080, R01 AG027435, K24 AG035007]
- Harvard Medical School Department of Psychiatry Dupont-Warren Fellowship and Livingston Award
- Rogers Family Foundation
- Massachusetts Alzheimer's Disease Research Center [P50 AG005134]
- Harvard Aging Brain Study [P01 AGO36694, R01 AG037497]
- Eisai
- Eli Lilly
- Belgian National Science Foundation [SPD28094292]
- Belgian Foundation for Alzheimer Research [P16008]
- GE Healthcare
- Janssen Alzheimer's Immunotherapy
- Lundbeck
- Pfizer
- Biogen
- Janssen Alzheimer Immunotherapy
- Novartis
- Piramal Healthcare
- Siemens
- NATIONAL INSTITUTE OF MENTAL HEALTH [R25MH094612] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [K24AG035007, P01AG036694, P50AG005134, R01AG037497, R01AG027435, K23AG058805, R03AG045080] Funding Source: NIH RePORTER
Objective: To understand the role of depressive symptoms in preclinical Alzheimer's disease, it is essential to define their temporal relationship to Alzheimer's proteinopathies in cognitively normal older adults. The study objective was to examine associations of brain amyloid beta and longitudinal measures of depression and depressive symptom clusters in a cognitively normal sample of older adults. Method: A total of 270 community-dwelling, cognitively normal elderly individuals underwent baseline Pittsburgh compound B (PiB) positron emission tomography (PET) measures of cortical aggregate amyloid beta and annual assessments with the 30-item Geriatric Depression Scale (GDS). The authors evaluated continuous PiB binding as a predictor of GDS scoreor GDS cluster, calculated as total scores and mean scores for three GDS item clusters (apathy-anhedonia, dysphoria, and anxiety-concentration), across time (1-5 years; mean=3.8 years) in separate mixed-effects models with backward elimination. Initial predictors included PiB binding, age, sex, Hollingshead score, American National Adult Reading Test (AMNART) score, apolipoprotein E epsilon 4 status, depression history, and their interactions with time. Results: Higher PiB binding predicted accelerated rates of increase in GDS score over time, adjusting for depression history. Higher PiB binding also predicted steeper rates of increase for anxiety-concentration scores, adjusting for depression history and the AMNART score-by-time interaction. In a post hoc model estimating anxiety scores without concentration disturbance items, the PiB binding-by-time interaction remained significant. Conclusions: Higher amyloid beta burden was associated with increasing anxious-depressive symptoms over time in cognitively normal older individuals. Prior depression history was related to higher but not worsening symptom ratings. These results suggest a direct or indirect association of elevated amyloid beta levels with worsening anxious-depressive symptoms and support the hypothesis that emerging neuropsychiatric symptoms represent an early manifestation of preclinical Alzheimer's disease.
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