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 participants in recent clinical trials testing interventions for Alzheimer's disease and epidemiological data. METHODS:We systematically searched literature databases (MedLine, EMBASE, the Cochrane Library) and ClinicalTrials.gov from 2000 to July 2015 to retrieve clinical trials testing pharmacologic treatments for Alzheimer's disease, other than cholinesterase inhibitors and memantine. We included ongoing and completed phase II/III randomized clinical trials, irrespective of their publication status. From each study reporting the participants' ages, we extracted size of sample, mean age, and standard deviation, and estimated the proportions of participants in different age classes. The number of patients with Alzheimer's disease by age class in the USA population was used for comparison. RESULTS:We included 165 clinical trials testing almost 100 different compounds, which enrolled or planned to enroll about 74,300 participants. Seventy-nine of these trials, accounting for about 26,800 participants, reported the age of the participants. The weighted mean age was 73.6 years (standard deviation, 8.2). People younger than 80 years were highly represented in clinical trials (78 %), despite the fact that those aged 80 and older form the majority (72 %) of patients with Alzheimer's disease. Only 8 % of clinical trial participants were 85 years or older. CONCLUSIONS:Patients enrolled in clinical trials on Alzheimer's disease are far from being representative of actual distribution of the patients in the general population. Clinical research should not be designed and conducted overlooking the fact that the majority of individuals with Alzheimer's disease are likely to be 80 or older.
journal_name
Alzheimers Res Therjournal_title
Alzheimer's research & therapyauthors
Banzi R,Camaioni P,Tettamanti M,Bertele' V,Lucca Udoi
10.1186/s13195-016-0201-2subject
Has Abstractpub_date
2016-08-12 00:00:00pages
32issn
1758-9193pii
10.1186/s13195-016-0201-2journal_volume
8pub_type
杂志文章,评审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: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::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:BACKGROUND:Synaptic dysfunction contributes to cognitive impairment in Alzheimer's disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients with Alzheimer's dis...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/s13195-017-0286-2
更新日期:2017-07-26 00:00:00
abstract:BACKGROUND:Synapse damage and loss are fundamental to the pathophysiology of Alzheimer's disease (AD) and lead to reduced cognitive function. The goal of this review is to address the challenges of forging new clinical development approaches for AD therapeutics that can demonstrate reduction of synapse damage or loss. ...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13195-020-00588-4
更新日期:2020-03-02 00:00:00
abstract:BACKGROUND:Blood-based biomarkers for Alzheimer's disease (AD) are highly needed in clinic practice. So far, the gold standards for AD diagnosis are brain neuroimaging and beta-amyloid peptide, total tau, and phosphorylated tau in cerebrospinal fluid (CSF); however, they are not attractive for large-scale screening. Bl...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-020-00750-y
更新日期:2021-01-08 00:00:00
abstract::The cerebrospinal fluid (CSF) biochemical markers (biomarkers) Amyloidβ 42 (Aβ42), total Tau (T-tau) and Tau phosphorylated at threonine 181 (P-tau181) have proven diagnostic accuracy for mild cognitive impairment and dementia due to Alzheimer's Disease (AD). In an effort to improve the accuracy of an AD diagnosis, it...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13195-019-0485-0
更新日期:2019-04-22 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: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:Identifying and understanding the functional role of genetic risk factors for Alzheimer disease (AD) has been complicated by the variability of genetic influences across brain regions and confounding with age-related neurodegeneration. METHODS:A gene co-expression network was constructed using data obtained...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-020-00674-7
更新日期:2020-09-02 00:00:00
abstract:BACKGROUND:The application of advanced sequencing technologies and improved mass-spectrometry platforms revealed significant changes in gene expression and lipids in Alzheimer's disease (AD) brain. The results so far have prompted further research using "multi-omics" approaches. These approaches become particularly rel...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-019-0558-0
更新日期:2019-12-30 00:00:00
abstract:BACKGROUND:Cognitive composite scores are used as the primary outcome measures for Alzheimer's disease (AD) prevention trials; however, the extent to which these composite measures correlate with AD pathology has not been fully investigated. Since many on-going AD prevention studies are testing therapies that target ei...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-018-0401-z
更新日期:2018-09-11 00:00:00
abstract:BACKGROUND:Determination of β-amyloid (Aβ) positivity and likelihood of underlying Alzheimer's disease (AD) relies on dichotomous biomarker cut-off values. Individuals with mild cognitive impairment (MCI) and Aβ within the normal range may still have a substantial risk of developing dementia, primarily of Alzheimer typ...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-019-0557-1
更新日期:2019-12-05 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: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::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: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 betwe...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-014-0090-1
更新日期:2015-02-11 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: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:Disturbed amyloid precursor protein (APP) processing is considered to be central to the pathogenesis of Alzheimer's disease (AD). The autosomal dominant form of the disease, familial AD (FAD), may serve as a model for the sporadic form of AD. In FAD the diagnosis of AD is reliable and presymptomatic individu...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-017-0234-1
更新日期:2017-02-16 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: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:Targeting the expression of genes has emerged as a potentially viable therapeutic approach to human disease. In Alzheimer's disease, therapies that silence the expression of tau could be a viable strategy to slow disease progression. METHODS:We produced a novel strain of transgenic mice that could be used t...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-016-0202-1
更新日期:2016-09-05 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: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: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:BACKGROUND:Global leaders have set an ambitious goal of developing interventions to effectively treat or prevent Alzheimer's disease by 2025. CASE PRESENTATION:Achieving this goal will require clinical trials to test promising interventions, yet Alzheimer's researchers are confronting a clinical trial recruitment cris...
journal_title:Alzheimer's research & therapy
pub_type: 社论
doi:10.1186/s13195-018-0425-4
更新日期:2018-09-27 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:BACKGROUND:With upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the lit...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章
doi:10.1186/s13195-018-0345-3
更新日期:2018-04-25 00:00:00
abstract::Lewy body dementia (LBD), including dementia with Lewy bodies and Parkinson's disease dementia, affects over a million people in the USA and has a substantial impact on patients, caregivers, and society. Symptomatic treatments for LBD, which can include cognitive, neuropsychiatric, autonomic, sleep, and motor features...
journal_title:Alzheimer's research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13195-020-00703-5
更新日期:2020-10-29 00:00:00