Depression often precedes the onset of Alzheimer's disease (AD) before the appearance of cognitive symptoms. Plasma Amyloid-beta peptide 42 (Abeta42) declines before and soon after the onset of AD, yet the relationship between plasma Abeta42 and depression is unclear.
We used 515 homebound elders aged 60 and older in a population-based, cross-sectional study to investigate associations between plasma Abeta levels and depression with and without cardiovascular co-morbidities. Depression was evaluated by using the Center for Epidemiological Studies Depression (CES-D) scale. Plasma Abeta40 and Abeta42 were measured.
The elderly with depression had lower plasma Abeta42 (median: 15.3 vs. 18.9, p = 0.008) than those without depression. The CES-D score was inversely associated with plasma Abeta42 (p = 0.001) in subjects with no cardiovascular disease (CVD); however, in the presence of CVD, this association did not exist. Low plasma Abeta42 (OR = 0.41, p = 0.007) and the presence of CVD (OR = 1.84, p = 0.005) were independently associated with depression after adjusting for the confounders of age, stroke and apolipoprotein E4.
Depressive symptoms are associated with low plasma Abeta42 independently of CVD. Prospective studies are needed to determine whether depression associated with low plasma Abeta42 is a separate depression subtype that could predict the onset of AD.
"Notably, AD patients with a history of depression have shown higher burdens of brain A␤ load than those without a history of depression . The metabolism of A␤ may be affected in depression, whether early or late onset      . In geriatric subjects, depression is associated with poor cognitive performance, increased likelihood of MCI and AD, and more rapid cognitive decline . "
[Show abstract][Hide abstract] ABSTRACT: Cholinesterase enzymes metabolize acetylcholine (ACh). Inhibition of acetylcholinesterase (AChE) in damaged but functional cholinergic synapses in the brains of dementia patients increases intrasynaptic ACh. This enhances cholinergic neurotransmission and improves cognition. There is a window of opportunity for this symptomatic treatment effect that opens and closes during the course of dementia depending on when significant synaptic damage occurs. Cholinesterases also metabolize extrasynaptic ACh with butyrylcholinesterase (BuChE) apparently playing the major dynamic role in extracellular ACh homeostasis. Extracellular ACh plays a key regulatory role in controlling the reactivity and functional states of non-excitable cells, such as neuroglia. Current inhibitors of cholinesterases (ChEIs) have similar effects on intrasynaptic ACh, but differ markedly in abilities to upregulate extracellular AChE, inhibit BuChE, and influence the fibrilization of amyloid-β peptides. Importantly, ChEIs can have detrimental disease modifying effects in particular individuals characterized by age, gender, and genotype. In contrast, preliminary evidence suggests that the right dose of the right ChEI in the right patient might significantly slow the progression of neurodegenerative processes. For a particular patient, understanding the condition of cholinergic synapses and the reactivity and functional status of neuroglia could allow administration of appropriate ChEI therapy for symptomatic and disease modifying benefits.
"The findings of these cross-sectional studies were inconsistent. While high Ab 1-42 levels in people with depression were found in some studies, an association between low Ab 1-42 levels and depression was observed in others (Moon et al., 2011; Pomara et al., 2006; Qiu et al., 2007; Sun et al., 2011, 2009, 2007, 2008). Moreover, to what extent prodromal dementia contributes to the cross-sectional associations is unknown. "
[Show abstract][Hide abstract] ABSTRACT: Plasma amyloid β (Aβ) levels have been associated with an increased risk of Alzheimer's disease (AD). As depression is common before the onset of AD, a few clinical studies tested the cross-sectional association of Aβ levels with depression in elderly and showed incongruous findings. Hence, we tested the longitudinal association between Aβ levels and depressive symptoms in community-dwelling elderly. The study is embedded in a population-based cohort of 980 participants aged 60 years or older from the Rotterdam Study with Aβ levels. Participants were evaluated for depressive symptoms with the Centre for Epidemiological Studies-Depression scale at baseline and repeatedly over the mean follow-up of 11 years. We first performed cross-sectional analyses. Then, we tested the longitudinal association between Aβ levels and depressive symptoms after excluding participants with dementia during follow-up. In cross-sectional analyses, persons with high Aβ(1-40) levels had more clinically relevant depressive symptoms. However, this association was accounted for by persons with clinically relevant depressive symptoms who developed dementia within the next 11 years. In longitudinal analyses, persons with low levels of Aβ(1-40) and Aβ(1-42) without dementia had a higher risk of clinically relevant depressive symptoms during the follow-up. These findings suggest that the cross-sectional association between high plasma Aβ levels and clinically relevant depressive symptoms in the elderly is due to prodromal dementia. In contrast, the longitudinal association between low plasma Aβ levels and depressive symptoms could not be explained by dementia during follow-up suggesting that Aβ peptides may play a distinct role on depression etiology.
Journal of Psychiatric Research 01/2013; 47(4). DOI:10.1016/j.jpsychires.2012.12.008 · 3.96 Impact Factor
"The results of the present study showed that a group of bipolar patients present lower plasma levels of Aβ42 and higher Aβ40/Aβ42 ratio respect to a control group. These data are consistent with previous findings in depressed patients showing lower plasma levels of Aβ42, no changes in Aβ40 and a greater Aβ40/Aβ42 ratio respect to healthy subjects (Qiu et al., 2007; Sun et al., 2007; Sun et al., 2008). Moreover, the study by Sun et al. (Sun et al., 2008) highlighted how the so-called " amyloid-associated " depression (higher Aβ40/Aβ42 ratio) correlates with a more severe deficit in memory, visual-spatial skills and in the executive functions. "
[Show abstract][Hide abstract] ABSTRACT: Patients with mood disorders present a great risk for dementia and generally for cognitive decline. Low levels of β-amyloid peptide 1-42 (Aβ42) and high Aβ40/Aβ42 ratio have been associated with this risk and have been reported also in geriatric patients suffering from depression. The aim of the present study was to compare the plasma levels of Aβ40 and Aβ42 in patients with bipolar depression and healthy subjects, and to correlate them with the characteristics of clinical course.
Levels of Aβ40 and Aβ42 were measured by using specific ELISA kits in 16 patients with bipolar depression and in 16 control subjects with a negative history for somatic, psychiatric, neurological and substance abuse disorders.
Patients presented significantly lower plasma Aβ42 levels and higher Aβ40/Aβ42 ratio, as compared with control subjects. Moreover, a significant negative correlation was found between Aβ42 plasma levels and the duration of the illness, while a positive correlation was detected between the Aβ40/Aβ42 ratio and the number of affective episodes.
The major limitations of the study are the small sample size, the scanty characterization of the illness episodes and the fact that all the patients were under psychopharmacological treatment.
Although further research is necessary to establish firm conclusions, the present data would suggest that changes in plasma levels of different Aβ peptides might represent a useful tool to identify the risk for cognitive decline in bipolar patients.
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