Abstract:
INTRODUCTION:Depression and psychosis are two of the most severe neuropsychiatric symptoms (NPS) in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Both NPS have negative effects on cognitive performance and life expectancy. The current study aimed to investigate and compare monoaminergic etiologies between both neurodegenerative conditions, given the lack of an efficient pharmacological treatment until present. METHODS:Eleven behaviorally relevant brain regions of the left frozen hemisphere of 10 neuropathologically confirmed AD patients with/without depression (AD + D/-D; 5 were psychotic within AD + D), 10 confirmed DLB patients, all of whom were depressed (DLB + D; 5 psychotic patients), and, finally, 10 confirmed control subjects were regionally dissected. All patients were retrospectively assessed before death using the Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) and Cornell Scale for Depression in Dementia amongst others. The concentrations of dopamine (DA), serotonin (5-HT), (nor)adrenaline and respective metabolites, i.e. 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), 5-hydroxy-3-indoleacetic acid (5-HIAA), and, 3-methoxy-4-hydroxyphenylglycol (MHPG), were determined using reversed-phase high-performance liquid chromatography with electrochemical detection. RESULTS:DLB subjects had the overall lowest monoamine and metabolite concentrations regarding 33 out of 41 significant monoaminergic group alterations. Moreover, MHPG levels were significantly decreased in almost 8 out of 11 brain regions of DLB- compared to AD patients. We also observed the lowest 5-HT and 5-HIAA levels, and 5-HIAA/5-HT turnover ratios in DLB + D compared to AD + D subjects. Additionally, a 4- and 7-fold increase of DOPAC/DA and HVA/DA turnover ratios, and, a 10-fold decrease of thalamic DA levels in DLB + D compared to AD + D patients and control subjects was noticed. Regarding psychosis, hippocampal DA levels in the overall DLB group significantly correlated with Behave-AD AB scores. In the total AD group, DA levels and HVA/DA ratios in the amygdala significantly correlated with Behave-AD AB scores instead. CONCLUSIONS:Monoaminergic neurotransmitter alterations contribute differently to the pathophysiology of depression and psychosis in DLB as opposed to AD, with a severely decreased serotonergic neurotransmission as the main monoaminergic etiology of depression in DLB. Similarly, psychosis in DLB might, in part, be etiologically explained by dopaminergic alterations in the hippocampus, whereas in AD, the amygdala might be involved.
journal_name
Alzheimers Res Therjournal_title
Alzheimer's research & therapyauthors
Vermeiren Y,Van Dam D,Aerts T,Engelborghs S,Martin JJ,De Deyn PPdoi
10.1186/s13195-014-0090-1subject
Has Abstractpub_date
2015-02-11 00:00:00pages
7issue
1issn
1758-9193pii
90journal_volume
7pub_type
杂志文章abstract:BACKGROUND:Amyloid pathology, which is one of the characteristics of Alzheimer's disease (AD), results from altered metabolism of the beta-amyloid (Aβ) peptide in terms of synthesis, clearance, or aggregation. A decrease in cerebrospinal fluid (CSF) level Aβ1-42 is evident in AD, and the CSF ratio Aβ42/Aβ40 has recentl...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-020-00696-1
更新日期:2020-10-02 00:00:00
abstract:INTRODUCTION:The long-term efficacy and safety of donepezil 10 mg in patients with dementia with Lewy bodies (DLB) were investigated in a 52-week Phase 3 trial. METHODS:This 52-week study consisted of 16-week randomized placebo-controlled (RCT) and 36-week open-label extension phases. Of 142 DLB patients enrolled in t...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-014-0081-2
更新日期:2015-02-03 00:00:00
abstract:INTRODUCTION:Subcortical hyperintensities (SHs) are radiological entities commonly observed on magnetic resonance imaging (MRI) of patients with Alzheimer's disease (AD) and normal elderly controls. Although the presence of SH is believed to indicate some form of subcortical vasculopathy, pathological heterogeneity, me...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt279
更新日期:2014-08-11 00:00:00
abstract:BACKGROUND:Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by neuropathologic changes involving beta-amyloid (Aβ), tau, neuronal loss, and other associated biological events. While levels of cerebrospinal fluid (CSF) Aβ and tau peptides have enhanced the antemortem detection of AD-specifi...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/s13195-018-0426-3
更新日期:2018-09-25 00:00:00
abstract:BACKGROUND:Subjective cognitive decline (SCD) is a potential risk factor for dementia. We aimed to investigate the association between SCD and subsequent dementia in a nationwide population-based cohort in South Korea. METHODS:This cohort included 579,710 66-year-old adults who were followed for a total of 3,870,293 p...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-020-00618-1
更新日期:2020-05-06 00:00:00
abstract:BACKGROUND:Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia in the elderly population. In this study, we used the APP/PS1 transgenic mouse model to explore the feasibility of using diffusion kurtosis imaging (DKI) as a tool for the early detection of microstruct...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-017-0329-8
更新日期:2018-01-09 00:00:00
abstract:BACKGROUND:Metabolic alterations, related to cerebral glucose metabolism, brain insulin resistance, and age-induced mitochondrial dysfunction, play an important role in Alzheimer's disease (AD) on both the systemic and central nervous system level. To study the extent and significance of these alterations in AD, quanti...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-019-0551-7
更新日期:2019-11-28 00:00:00
abstract:BACKGROUND:Imaging agents capable of quantifying the brain's tau aggregates will allow a more precise staging of Alzheimer's disease (AD). The aim of the present study was to examine the in vitro properties as well as the in vivo kinetics, using gold standard methods, of the novel positron emission tomography (PET) tau...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-018-0402-y
更新日期:2018-07-31 00:00:00
abstract:INTRODUCTION:Amyloid-β (Aβ) has been investigated as a diagnostic biomarker and therapeutic drug target. Recent studies found that cerebrospinal fluid (CSF) Aβ fluctuates over time, including as a diurnal pattern, and increases in absolute concentration with serial collection. It is currently unknown what effect differ...
journal_title:Alzheimer's research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/s13195-015-0136-z
更新日期:2015-07-29 00:00:00
abstract:BACKGROUND:Accumulating evidence implicates the neuroendocrine immunomodulation (NIM) network in the physiopathological mechanism of Alzheimer's disease (AD). Notably, we previously revealed that the NIM network is dysregulated in the PrP-hAβPPswe/PS1ΔE9 (APP/PS1) transgenic mouse model of AD. METHODS:After treatment ...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-016-0226-6
更新日期:2016-12-13 00:00:00
abstract::Dementia with Lewy bodies (DLB) has become the second most common neurodegenerative dementia due to demographic ageing. Differential diagnosis is still troublesome especially in early stages of the disease, since there is a great clinical and neuropathological overlap primarily with Alzheimer's disease and Parkinson's...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13195-014-0072-3
更新日期:2014-10-16 00:00:00
abstract:BACKGROUND:The age gap between participants in trials and patients who could benefit from the drugs studied has been widely documented across different clinical areas. Patients with dementia included in clinical research are systematically younger than those in the general population. We examined the age gap between pa...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13195-016-0201-2
更新日期:2016-08-12 00:00:00
abstract:INTRODUCTION:There have been recent reports about a decline in dementia incidence, but only little is known about trends in the mortality of patients with dementia. Only the simultaneous analysis of both trends can inform whether the reported decline in dementia has led to a compression of dementia into higher ages. M...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-015-0146-x
更新日期:2015-11-05 00:00:00
abstract:BACKGROUND:Recent Genome Wide Association Studies (GWAS) have identified novel rare coding variants in immune genes associated with late onset Alzheimer's disease (LOAD). Amongst these, a polymorphism in phospholipase C-gamma 2 (PLCG2) P522R has been reported to be protective against LOAD. PLC enzymes are key elements ...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-019-0469-0
更新日期:2019-02-02 00:00:00
abstract:INTRODUCTION:The Third National Alzheimer Plan (2008-2012) was a major public health initiative in France that included €200 million of funding for research in Alzheimer disease and related disorders (AD). The aim of this study was to document trends in French academic output in AD following the implementation of the p...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-015-0144-z
更新日期:2015-09-26 00:00:00
abstract:BACKGROUND:In patients with amyloid-positive mild cognitive impairment (MCI), neurodegenerative biomarkers such as medial temporal lobe atrophy (MTA) are useful to predict disease progression to dementia. Although posterior atrophy (PA) is a well-known neurodegenerative biomarker of Alzheimer's disease, little is known...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-017-0326-y
更新日期:2017-12-16 00:00:00
abstract:INTRODUCTION:There has been a significant increase in the use of testosterone in aging men, but little investigation into its impact on men with Alzheimer's disease (AD). The findings of the few studies that have been done are inconsistent. In the present study, we investigated the relationship between total testostero...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-015-0107-4
更新日期:2015-05-01 00:00:00
abstract:BACKGROUND:Results from recent clinical studies suggest that cerebrospinal fluid (CSF) biomarkers that are indicative of Alzheimer's disease (AD) can be replicated in blood, e.g. amyloid-beta peptides (Aβ42 and Aβ40) and neurofilament light chain (NFL). Such data proposes that blood is a rich source of potential biomar...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-019-0545-5
更新日期:2019-11-28 00:00:00
abstract::The oligomer cascade hypothesis, which states that oligomers are the initiating pathologic agents in Alzheimer's disease, has all but supplanted the amyloid cascade hypothesis, which suggested that fibers were the key etiologic agents in Alzheimer's disease. We review here the results of in vivo, in vitro and in silic...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/alzrt226
更新日期:2013-11-29 00:00:00
abstract:BACKGROUND:Optical coherence tomography (OCT) of the retina is a fast and easily accessible tool for the quantification of retinal structural measurements. Multiple studies show that patients with Alzheimer's disease (AD) exhibit thinning in several retinal layers compared to age-matched controls. Subjective cognitive ...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-020-00602-9
更新日期:2020-03-31 00:00:00
abstract::Symptomatic treatments for Alzheimer's disease should retain a place in the advanced stages of disease since their actions on these symptoms, even if not modifying the course of disease, are critical for improving patients' comfort and reducing the burden felt by caregivers, especially those facing behavioral disorder...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt228
更新日期:2013-12-11 00:00:00
abstract:BACKGROUND:The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a multicenter randomized controlled trial that reported beneficial effects on cognition for a 2-year multimodal intervention (diet, exercise, cognitive training, vascular risk monitoring) versus control (gene...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/s13195-019-0506-z
更新日期:2019-06-04 00:00:00
abstract:BACKGROUND:A growing number of pharmacological and nonpharmacological trials have been performed to test the efficacy of approved or experimental treatments in Alzheimer disease (AD) and mild cognitive impairment (MCI). In this context, functional magnetic resonance imaging (fMRI) may be a good candidate to detect brai...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13195-018-0347-1
更新日期:2018-02-20 00:00:00
abstract:BACKGROUND:Association between kidney dysfunction and dementia has been studied in western cohorts, but with inconsistent conclusions which may be due to the different measurements of kidney function. We aim to verify the hypothesis that lower levels of kidney function would be associated with increased risk of inciden...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-020-00729-9
更新日期:2021-01-11 00:00:00
abstract:BACKGROUND:Animal models of Alzheimer's disease (AD) are essential to understanding the disease progression and to development of early biomarkers. Because AD has been described as a disconnection syndrome, magnetic resonance imaging (MRI)-based connectomics provides a highly translational approach to characterizing th...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-018-0346-2
更新日期:2018-02-07 00:00:00
abstract:BACKGROUND:Development of new treatments for Alzheimer's disease (AD) has broadened into early interventions in individuals with modest cognitive impairment and a slow decline. The 11-item version of the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) was originally developed to measure cognition in ...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-016-0170-5
更新日期:2016-02-12 00:00:00
abstract:INTRODUCTION:Peripheral biomarkers to diagnose Alzheimer's disease (AD) have not been established. Given parallels between neuron and platelet biology, we hypothesized platelet membrane-associated protein changes may differentiate patients clinically defined with probable AD from noncognitive impaired controls. METHOD...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt186
更新日期:2013-06-13 00:00:00
abstract::Therapeutic products that depend on the use of an in vitro diagnostic biomarker test to confirm their effectiveness are increasingly being developed. Use of biomarkers is particularly meaningful in the context of selecting the patient population where the therapeutic treatment is believed to be efficacious (patient en...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/alzrt142
更新日期:2012-10-17 00:00:00
abstract:BACKGROUND:Several monoclonal antibodies for the treatment of Alzheimer's disease (AD) have been in development over the last decade. BAN2401 is a monoclonal antibody that selectively binds soluble amyloid β (Aβ) protofibrils. METHODS:Here we describe the first clinical study with BAN2401. Safety and tolerability were...
journal_title:Alzheimer's research & therapy
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1186/s13195-016-0181-2
更新日期:2016-04-06 00:00:00
abstract:BACKGROUND:Whether age at onset influences Alzheimer's disease (AD) progression and the effectiveness of cholinesterase inhibitor (ChEI) therapy is not clear. We aimed to compare longitudinal cognitive and global outcomes in ChEI-treated patients with early-onset Alzheimer's disease (EOAD) versus late-onset Alzheimer's...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,多中心研究
doi:10.1186/s13195-017-0294-2
更新日期:2017-08-31 00:00:00