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 disease (LOAD) in clinical practice. METHODS:This 3-year, prospective, observational, multicentre study included 1017 participants with mild to moderate AD; 143 had EOAD (age at onset < 65 years) and 874 had LOAD (age at onset ≥ 65 years). At baseline and semi-annually, patients were assessed using cognitive, global and activities of daily living (ADL) scales, and the dose of ChEI was recorded. Potential predictors of decline were analysed using mixed-effects models. RESULTS:Six-month response to ChEI therapy and long-term prognosis in cognitive and global performance were similar between the age-at-onset groups. However, deterioration was significantly faster when using the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) over 3 years in participants with EOAD than in those with LOAD; hence, prediction models for the mean ADAS-Cog trajectories are presented. The younger cohort had a larger proportion of homozygote apolipoprotein E (APOE) ε4 allele carriers than the older cohort; however, APOE genotype was not a significant predictor of cognitive impairment in the multivariate models. A slower rate of cognitive progression was related to initiation of ChEIs at an earlier stage of AD, higher ChEI dose and fewer years of education in both groups. In LOAD, male sex, better instrumental ADL ability and no antipsychotic drug use were additional protective characteristics. The older patients received a lower ChEI dose than the younger individuals during most of the study period. CONCLUSIONS:Although the participants with EOAD showed a faster decline in ADAS-Cog, had a longer duration of AD before diagnosis, and had a higher frequency of two APOE ε4 alleles than those with LOAD, the cognitive and global responses to ChEI treatment and the longitudinal outcomes after 3 years were similar between the age-at-onset groups. A higher mean dose of ChEI and better cognitive status at the start of therapy were independent protective factors in both groups, stressing the importance of early treatment in adequate doses for all patients with AD.
journal_name
Alzheimers Res Therjournal_title
Alzheimer's research & therapyauthors
Wattmo C,Wallin ÅKdoi
10.1186/s13195-017-0294-2subject
Has Abstractpub_date
2017-08-31 00:00:00pages
70issue
1issn
1758-9193pii
10.1186/s13195-017-0294-2journal_volume
9pub_type
杂志文章,多中心研究abstract:INTRODUCTION:Alzheimer's disease (AD) is increasing in frequency as the global population ages. Five drugs are approved for treatment of AD, including four cholinesterase inhibitors and an N-methyl-D-aspartate (NMDA)-receptor antagonist. We have an urgent need to find new therapies for AD. METHODS:We examined Clinical...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt269
更新日期:2014-07-03 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::Parkinson's disease, the most common movement disorder, results in an insidious reduction for patients in quality of life and ability to function. A hallmark of Parkinson's disease is the brain accumulation of neuronal cytoplasmic inclusions comprised of the protein α-synuclein. The presence of α-synuclein brain aggre...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/alzrt151
更新日期:2012-12-17 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::The long-term consequences of repetitive head impacts have been described since the early 20th century. Terms such as punch drunk and dementia pugilistica were first used to describe the clinical syndromes experienced by boxers. A more generic designation, chronic traumatic encephalopathy (CTE), has been employed sinc...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13195-014-0068-z
更新日期:2014-09-24 00:00:00
abstract:BACKGROUND:[18F]FDG-PET hypometabolism patterns are indicative of different neurodegenerative conditions, even from the earliest disease phase. This makes [18F]FDG-PET a valuable tool in the diagnostic workup of neurodegenerative diseases. The utility of [18F]FDG-PET in dementia with Lewy bodies (DLB) needs further val...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-019-0473-4
更新日期:2019-02-23 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:INTRODUCTION:Weight loss has been described in 20% to 45% of patients with Alzheimer's disease (AD) and has been associated with adverse outcomes. Various mechanisms for weight loss in AD patients have been proposed, though none has been proven. This study aimed to elucidate a mechanism of weight loss in AD patients by...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-015-0098-1
更新日期:2015-04-06 00:00:00
abstract:INTRODUCTION:There are no empiric data to support guidelines for duration of therapy with antidementia drugs. This study examined whether persistent use of antidementia drugs slows clinical progression of Alzheimer disease (AD) assessed by repeated measures on serial tests of cognition and function. METHODS:Six hundre...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt7
更新日期:2009-10-21 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:INTRODUCTION:The goal was to identify which neurochemicals differ in professional athletes with repetitive brain trauma (RBT) when compared to healthy controls using a relatively new technology, in vivo Localized COrrelated SpectroscopY (L-COSY). METHODS:To achieve this, L-COSY was used to examine five former professi...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-015-0094-5
更新日期:2015-03-15 00:00:00
abstract::Autosomal-dominant Alzheimer's disease has provided significant understanding of the pathophysiology of Alzheimer's disease. The present review summarizes clinical, pathological, imaging, biochemical, and molecular studies of autosomal-dominant Alzheimer's disease, highlighting the similarities and differences between...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt59
更新日期:2011-01-06 00:00:00
abstract:BACKGROUND:Theory of mind (ToM) refers to the ability to attribute mental states, thoughts (cognitive component) or feelings (affective component) to others. This function has been studied in many neurodegenerative diseases; however, to our knowledge, no studies investigating ToM in dementia with Lewy bodies (DLB) have...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-016-0179-9
更新日期:2016-03-16 00:00:00
abstract::The strongest known risk factors for late-onset Alzheimer disease (LOAD) remain a positive family history and the APOE epsilon4 allele. van Exel and colleagues used these known risk factors to identify high- and low-risk samples of middle-aged persons in whom they compared levels of inflammatory and vascular risk fact...
journal_title:Alzheimer's research & therapy
pub_type: 社论
doi:10.1186/alzrt29
更新日期:2010-04-12 00:00:00
abstract::Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting older people worldwide. It is a progressive disorder mainly characterized by the presence of amyloid-beta (Aβ) plaques and neurofibrillary tangles within the brain parenchyma. It is now well accepted that neuroinflammation constitutes an ...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-015-0125-2
更新日期:2015-04-15 00:00:00
abstract:INTRODUCTION:Chromosome 9 open reading frame 72 (C9orf72) is an evolutionarily conserved protein with unknown function, expressed at high levels in the brain. An expanded hexanucleotide GGGGCC repeat located in the first intron of the C9orf72 gene represents the most common genetic cause of familial frontotemporal deme...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt136
更新日期:2012-08-16 00:00:00
abstract:BACKGROUND:Amyloid-β 1-42 (Aβ1-42) peptide is a well-established cerebrospinal fluid (CSF) biomarker for Alzheimer's disease (AD). Reduced levels of Aβ1-42 are indicative of AD, but significant variation in the absolute concentrations of this analyte has been described for both healthy and diseased populations. Preanal...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-018-0445-0
更新日期:2018-11-28 00:00:00
abstract:BACKGROUND:Intracerebral inoculation of extracts from post-mortem human Alzheimer's disease brains into mice produces a prion-like spreading effect of amyloid-β. The differences observed between these extracts and the synthetic peptide, in terms of amyloid-β internalization and seed and cell-to-cell transmission of cyt...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-019-0513-0
更新日期:2019-06-29 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:BACKGROUND:Given the growing older population worldwide, and the associated increase in age-related diseases, such as Alzheimer's disease (AD), investigating non-invasive methods to ameliorate or even prevent cognitive decline in prodromal AD is highly relevant. Previous studies suggest transcranial direct current stim...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-020-00692-5
更新日期:2020-11-07 00:00:00
abstract:BACKGROUND:The concept of dependence has been proposed as a unified representation of disease severity to quantify and stage disease progression in a manner more informative to patients, caregivers, and healthcare providers. METHODS:This paper provides a review of the Dependence Scale (DS) as a quantitative measure of...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13195-018-0414-7
更新日期:2018-08-13 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:BACKGROUND:Down syndrome (DS), caused by chromosome 21 trisomy, is associated with an ultra-high risk of dementia due to Alzheimer's disease (AD), driven by amyloid precursor protein (APP) gene triplication. Understanding relevant molecular differences between those with DS, those with sporadic AD (sAD) without DS, and...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-019-0477-0
更新日期:2019-03-21 00:00:00
abstract::In May 2012, the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia brought together in Montreal experts from around Canada to update Canadian recommendations for the diagnosis and management of patients with neurodegenerative conditions associated with deterioration of cognition. Multiple...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/alzrt199
更新日期:2013-07-08 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: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:Widespread implementation of Alzheimer's disease biomarkers in routine clinical practice requires the establishment of standard operating procedures for pre-analytical handling of cerebrospinal fluid (CSF). METHODS:Here, CSF collection and storage protocols were optimized for measurements of β-amyloid (Aβ)....
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-019-0517-9
更新日期:2019-07-19 00:00:00
abstract:BACKGROUND:The retina and brain share many neuronal and vasculature characteristics. We investigated the retinal microvasculature in Alzheimer's disease (AD) and mild cognitive impairment (MCI) using optical coherence tomography angiography (OCTA). METHODS:In this cross-sectional study, 24 AD participants, 37 MCI part...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-020-00724-0
更新日期:2020-12-04 00:00:00
abstract:BACKGROUND:The pathophysiology of neurodegeneration is complex. Its diagnosis requires an early identification of sequential changes in several hallmarks in the brains of affected subjects. The presence of brain pathology can be visualized in the cerebrospinal fluid (CSF) by protein profiling. It is clear that the fiel...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-017-0265-7
更新日期:2017-06-06 00:00:00
abstract:BACKGROUND:Mild cognitive impairment (MCI) has an uncertain etiology and prognosis and may be challenging for clinicians to discuss with patients and families. Amyloid imaging may aid specialists in determining MCI etiology and prognosis, but creates novel challenges related to disease labeling. METHODS:We convened a ...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13195-017-0261-y
更新日期:2017-05-04 00:00:00