Amyloid-Associated Depression

Sun, Xiaoyan; Steffens, David C.; Au, Rhoda; Folstein, Marshal F.; Summergrad, Paul; Yee, Jacqueline; Rosenberg, Irwin H.; Mwamburi, D. Mkaya; Qiu, Wei Qiao

doi:10.1001/archpsyc.65.5.542

Cited by 148 publications

(76 citation statements)

References 63 publications

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“…Earlier [ 11 C]-PiB-PET findings with small sample size also provided evidence that amyloid load is elevated in late-life depressed MCI subjects [8]. CSF levels of Aß42 were concordantly reduced in MCI suffering from late life depression and correlated with cognitive status [26]. Postmortem analyses have indicated a pronounced deposition of amyloid plaques and tangles in the hippocampus, in brain of AD patients with history of major depression, while subjects with concurrent depressive symptoms at diagnosis of AD exhibited even higher neuropathological changes [27, 28].…”

Section: Discussionmentioning

confidence: 98%

Depressive symptoms accelerate cognitive decline in amyloid-positive MCI patients

Brendel¹,

Pogarell

Xiong

et al. 2015

Eur J Nucl Med Mol Imaging

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Purpose Late-life depression (LLD) even in subsyndromal stages revealed strong associations with Alzheimer’s disease (AD). Furthermore brain amyloidosis depicts an early biomarker in subjects subsequently suffering from AD and is sensitively detectable by amyloid-PET. Therefore we aimed to compare amyloid-load and glucose metabolism in subsyndromally depressed mild cognitive impaired (MCI) subjects. Methods 371 MCI subjects from ADNI underwent [18F]-AV45-, [18F]-FDG-PET, and MRI. Subjects were judged β-amyloid positive (Aß(+); N=206) or negative (Aß(−); N=165) according to [18F]-AV45-PET. Depressive symptoms were assessed by the Neuropsychiatric Inventory Questionnaire (NPI-Q) depression-item. 65 Aß(+) and 41 Aß(−) subjects with depressive symptoms (DEP) were contrasted against their non-depressed (NON-DEP) counterparts. Conversion rates to AD were analysed (mean follow-up time: 21.5±9.1 months) with regard to coexisting depressive symptoms and brain amyloid-load. Results Aß(+) DEP subjects showed large clusters with higher amyloid-load in frontotemporal and insular cortices (p<0.001) and coincident hypermetabolism (p<0.001) in frontal cortices when contrasted against NON-DEP. Faster progression to AD was observed in subjects with either depressive symptoms (p<0.005) or Aß(+) status (p<0.001). Coincident depressive symptoms additionally shortened the conversion time in all Aß(+) subjects (p<0.005) and to a greater extent in a subgroup with high amyloid-load (p<0.001). Conclusions Our results clearly indicate that Aß(+) MCI subjects with depressive symptoms suffer from elevated amyloid-load combined with relative hypermetabolism of connected brain areas when contrasted against cognitively-matched non-depressed individuals. MCI subjects with high amyloid-load and coexistent depressive symptoms represent a high-risk group for faster conversion to AD.

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Section: Discussionmentioning

confidence: 98%

Depressive symptoms accelerate cognitive decline in amyloid-positive MCI patients

Brendel¹,

Pogarell

Xiong

et al. 2015

Eur J Nucl Med Mol Imaging

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“…Two cross-sectional studies reported an elevation of plasma Aβ42 in individuals with late-life major depression (25) or depressive symptoms and signs compared to non- depressed subjects (26). However, other cross-sectional studies found an inverse relationship between plasma Aβ42 and depressive symptomatology (27) (28) (29). Depression with high plasma Aβ40/Aβ42 ratio was accompanied by impairment in memory, visuospatial task performance, and executive function (29).…”

Section: Plasma and Csf Amyloid Studiesmentioning

confidence: 94%

Amyloid Hypothesis: Is There a Role for Antiamyloid Treatment in Late-Life Depression?

Mahgoub

Alexopoulos

2016

The American Journal of Geriatric Psychiatry

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Antidepressants have modest efficacy in late-life depression, perhaps because various neurobiological processes compromise frontolimbic networks required for antidepressant response. We propose that amyloid accumulation is an etiological factor for frontolimbic compromise that predisposes to depression and increases treatment resistance in a subgroup of older adults. In patients without history of depression, amyloid accumulation during the preclinical phase of Alzheimer’s disease may result in the prodromal depression syndrome that precedes cognitive impairment. In patients with early-onset depression, pathophysiological changes during recurrent episodes may promote amyloid accumulation, further compromise neurocircuitry required for antidepressant response and increase treatment resistance during successive depressive episodes. The following findings support the amyloid hypothesis of late-life depression: a) Depression is a risk factor, a prodrome, and a common behavioral manifestation of Alzheimer’s disease; b) Amyloid deposition occurs during a long pre-dementia period when depression is prevalent; c) Patients with lifetime history of depression have significant amyloid accumulation in brain regions related to mood regulation; d) Amyloid deposition leads to neurobiological processes, including vascular damage, neurodeheneration, neuroinflammation, disrupted functional connectivity, that impair networks implicated in depression. The amyloid hypothesis of late-life depression is timely, because availability of ligands allows in vivo assessment of amyloid in the human brain, a number of anti-amyloid agents are relatively safe, and there is evidence that some antidepressants may reduce amyloid production. A model of late-life depression introducing the role of amyloid may guide the design of studies aiming to identify novel antidepressant approaches as well as prevention strategies of Alzheimer’s disease.

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“…According to some authors, the presence of depressive symptoms associated with a high Aβ40/Aβ42 ratio would represent a prodromal manifestation of AD [20]. However, other hypotheses could be suggested, such as the existence of a primarily ‘amyloid-associated' mood disorder (characterized by Aβ disturbances unrelated to prodromal AD) with resistance to treatment and risk for cognitive decline [40,41].…”

Section: Discussionmentioning

confidence: 99%

“…However, a few data are available regarding the relationship between depression and peripheral levels of Aβ peptides. Higher levels of Aβ40, lower levels of Aβ42, and a greater Aβ40/Aβ42 ratio have been reported in elderly patients with depression, as compared with healthy control subjects [18,19,20]. Moreover, the study by Sun et al [20] highlighted how the so-called ‘amyloid-associated' depression (with high Aβ40/Aβ42 ratio) is characterized by a more severe deficit in memory, visual-spatial skills, and executive functions.…”

Section: Introductionmentioning

confidence: 99%

“…Higher levels of Aβ40, lower levels of Aβ42, and a greater Aβ40/Aβ42 ratio have been reported in elderly patients with depression, as compared with healthy control subjects [18,19,20]. Moreover, the study by Sun et al [20] highlighted how the so-called ‘amyloid-associated' depression (with high Aβ40/Aβ42 ratio) is characterized by a more severe deficit in memory, visual-spatial skills, and executive functions. In another study [21], depressed patients showed an enhanced Aβ40/Aβ42 ratio, but no differences in Aβ42 levels, when compared with age-matched control subjects.…”

Section: Introductionmentioning

confidence: 99%

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Plasma Amyloid-β Levels in Drug-Resistant Bipolar Depressed Patients Receiving Electroconvulsive Therapy

et al. 2013

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Aims: Alterations of plasma amyloid-β (Aβ) peptides have been related to a high risk for cognitive impairment and dementia. The present study aimed to measure plasma Aβ peptides (Aβ40, Aβ42) and the Aβ40/Aβ42 ratio in a sample of drug-resistant bipolar depressed patients, as well as to explore the possible correlation between biological parameters and clinical changes along an electroconvulsive therapy (ECT) course. Methods: Aβ40 and Aβ42 were measured by means of an ELISA assay in 25 drug-resistant bipolar depressed patients before (T0) and 1 week after (T1) the end of ECT. The patients were clinically evaluated by means of the Hamilton Rating Scale for Depression, 21-item (HRSD-21), the Mini-Mental State Examination, and the Clinical Global Impressions-Severity of Illness Scale. Results: Plasma Aβ levels and the Aβ40/Aβ42 ratio were similar at T0 and T1. The Aβ40/Aβ42 ratio correlated positively with the HRSD total score at both T0 and T1. At T0, a negative correlation was found between the Aβ40/Aβ42 ratio and the improvement of depressive and cognitive symptoms. Moreover, remitters (n = 9; HRSD ≤10) showed a significantly lower Aβ40/Aβ42 ratio at T0 than nonremitters. Conclusion: The present data suggest that a low Aβ40/Aβ42 ratio might characterize a subgroup of depressed patients who respond to ECT, while higher values of this parameter seem to be typical of more severe cases of patients with cognitive impairment.

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Amyloid-Associated Depression

Abstract: Amyloid-associated depression may define a subtype of depression representing a prodromal manifestation of Alzheimer disease.

Cited by 148 publications

References 63 publications

Depressive symptoms accelerate cognitive decline in amyloid-positive MCI patients

Depressive symptoms accelerate cognitive decline in amyloid-positive MCI patients

Amyloid Hypothesis: Is There a Role for Antiamyloid Treatment in Late-Life Depression?

Plasma Amyloid-β Levels in Drug-Resistant Bipolar Depressed Patients Receiving Electroconvulsive Therapy

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