Amyloid-associated depression - A prodromal depression of Alzheimer disease?

Department of Psychiatry, Tufts-New England Medical Center, Campus Box 1007, 750 Washington St, Boston, MA 02111, USA.
Archives of general psychiatry (Impact Factor: 14.48). 05/2008; 65(5):542-50. DOI: 10.1001/archpsyc.65.5.542
Source: PubMed


A high ratio of plasma amyloid-beta peptide 40 (Abeta(40)) to Abeta(42), determined by both high Abeta(40) and low Abeta(42) levels, increases the risk of Alzheimer disease. In a previous study, we reported that depression is also associated with low plasma Abeta(42) levels in the elderly population.
To characterize plasma Abeta(40):Abeta(42) ratio and cognitive function in elderly individuals with and without depression.
Cross-sectional study.
Homecare agencies.
A total of 995 homebound elderly individuals of whom 348 were defined as depressed by a Center for Epidemiological Studies Depression score of 16 or greater.
Cognitive domains of memory, language, executive, and visuospatial functions according to levels of plasma Abeta(40) and Abeta(42) peptides.
Subjects with depression had lower plasma Abeta(42) levels (median, 14.1 vs 19.2 pg/mL; P = .006) and a higher plasma Abeta(40):Abeta(42) ratio (median, 8.9 vs 6.4; P < .001) than did those without depression in the absence of cardiovascular disease and antidepressant use. The interaction between depression and plasma Abeta(40):Abeta(42) ratio was associated with lower memory score (beta = -1.9, SE = 0.7, P = .006) after adjusting for potentially confounders. Relative to those without depression, "amyloid-associated depression," defined by presence of depression and a high plasma Abeta(40):Abeta(42) ratio, was associated with greater impairment in memory, visuospatial ability, and executive function; in contrast, nonamyloid depression was not associated with memory impairment but with other cognitive disabilities.
Amyloid-associated depression may define a subtype of depression representing a prodromal manifestation of Alzheimer disease.

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    • "Other studies evaluated the plasma levels of Ab peptides. Most studies found a significant reduction of plasma Ab 42 and increased Ab 40 :Ab 42 ratio in LLD; although non-significant results have also been reported (Sun et al., 2008; Baba et al., 2012; Benitez et al., 2009; Kita et al., 2009). The current knowledge about the dynamics of Ab peptides in the CSF and plasma of LLD patients are limited by the small sample size of individual studies that are generally underpowered to detect small, but significant, group differences. "
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    ABSTRACT: This study aimed to evaluate differences in plasma and cerebrospinal fluid (CSF) levels of Ab peptides in older adults with late-life depression compared to non-depressed older controls. We conducted a systematic review and meta-analysis of the literature using PubMed, Web of science and Scopus databases with no search limits for publication dates or languages. Two independent reviewers extracted data and assessed quality. Six hundred references were retrieved, and we included 12 studies in the meta-analysis after eligibility screening. Older adults with late-life depression (LLD) had a higher plasma Ab 40 :A b42 ratio compared to non-depressed participants (SMD ¼ 1.10, CI 95% [0.28; 1.96], p ¼ 0.01), and marginally significant reduction of CSF Ab 42 levels (SMD ¼ À1.12, CI 95% [À2.47; 0.22], p ¼ 0.1). The present results evidence that older adults with depression have significant differences in Ab metabolism, in the same direction observed in individuals with AD. These differences in the Ab metabolism may help identify a subgroup of subjects with LLD at higher risk of developing AD.
    Journal of Psychiatric Research 08/2015; 69. DOI:10.1016/j.jpsychires.2015.07.024 · 3.96 Impact Factor
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    • "Notably, AD patients with a history of depression have shown higher burdens of brain A␤ load than those without a history of depression [120]. The metabolism of A␤ may be affected in depression, whether early or late onset [121] [122] [123] [124] [125] [126]. In geriatric subjects, depression is associated with poor cognitive performance, increased likelihood of MCI and AD, and more rapid cognitive decline [127]. "
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    • "Finally, studies indicate that there is a relationship between plasma Ab levels in patients with depression and cognitive impairment. In a cross-sectional study, a type of amyloid-associated depression (depression with a high ratio of plasma Ab peptide 40 [Ab 40 ] to Ab 42 ) was associated with impairment on several cognitive domains, including memory, visuospatial abilities, and executive function [84]. Thus, amyloid-associated depression may represent a preclinical or prodromal depression of AD. "
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