Alzheimer's Research & Therapy

http://link.springer.com/journal/13195

List of Papers (Total 573)

Genome-wide analysis of genetic predisposition to Alzheimer’s disease and related sex disparities

BackgroundAlzheimer’s disease (AD) is the most common cause of dementia in the elderly and the sixth leading cause of death in the United States. AD is mainly considered a complex disorder with polygenic inheritance. Despite discovering many susceptibility loci, a major proportion of AD genetic variance remains to be explained.MethodsWe investigated the genetic architecture of AD...

Exome sequencing in an Italian family with Alzheimer’s disease points to a role for seizure-related gene 6 (SEZ6) rare variant R615H

BackgroundThe typical familial form of Alzheimer’s disease (FAD) accounts for about 5% of total Alzheimer’s disease (AD) cases. Presenilins (PSEN1 and PSEN2) and amyloid-β (A4) precursor protein (APP) genes carry all reported FAD-linked mutations. However, other genetic loci may be involved in AD. For instance, seizure-related gene 6 (SEZ6) has been reported in brain development...

The impact of education on cortical thickness in amyloid-negative subcortical vascular dementia: cognitive reserve hypothesis

BackgroundThe protective effect of education has been well established in Alzheimer’s disease, whereas its role in patients with isolated cerebrovascular diseases remains unclear. We examined the correlation of education with cortical thickness and cerebral small vessel disease markers in patients with pure subcortical vascular mild cognitive impairment (svMCI) and patients with...

Study partners: essential collaborators in discovering treatments for Alzheimer’s disease

BackgroundGlobal leaders have set an ambitious goal of developing interventions to effectively treat or prevent Alzheimer’s disease by 2025.Case presentationAchieving this goal will require clinical trials to test promising interventions, yet Alzheimer’s researchers are confronting a clinical trial recruitment crisis. One reason for this is that Alzheimer’s disease trials must...

Cardiorespiratory fitness attenuates age-associated aggregation of white matter hyperintensities in an at-risk cohort

BackgroundAge is the cardinal risk factor for Alzheimer’s disease (AD), and white matter hyperintensities (WMH), which are more prevalent with increasing age, may contribute to AD. Higher cardiorespiratory fitness (CRF) has been shown to be associated with cognitive health and decreased burden of AD-related brain alterations in older adults. Accordingly, the aim of this study was...

Sex ratio in dementia with Lewy bodies balanced between Alzheimer’s disease and Parkinson’s disease dementia: a cross-sectional study

BackgroundGender distribution varies across neurodegenerative disorders, with, traditionally, a higher female frequency reported in Alzheimer’s disease (AD) and a higher male frequency in Parkinson’s disease (PD). Conflicting results on gender distribution are reported concerning dementia with Lewy bodies (DLB), usually considered as an intermediate disease between AD and PD. The...

Clinical dementia severity associated with ventricular size is differentially moderated by cognitive reserve in men and women

BackgroundInterindividual differences in cognitive reserve (CR) are associated with complex and dynamic clinical phenotypes observed in cognitive impairment and dementia. We tested whether (1) CR early in life (E-CR; measured by education and IQ), (2) CR later in life (L-CR; measured by occupation), and (3) CR panel (CR-P) with the additive effects of E-CR and L-CR, act as...

Cerebrovascular disease influences functional and structural network connectivity in patients with amnestic mild cognitive impairment and Alzheimer’s disease

BackgroundPatients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) show functional and structural connectivity alterations in the default mode network (DMN) while cerebrovascular disease (CeVD) shows functional and structural connectivity changes in the executive control network (ECN). Such disruptions are associated with memory and executive function...

Subjective Cognitive Impairment Cohort (SCIENCe): study design and first results

BackgroundWe aimed to describe the Subjective Cognitive Impairment Cohort (SCIENCe) study design, to cross-sectionally describe participant characteristics, and to evaluate the SCD-plus criteria.MethodsThe SCIENCe is a prospective cohort study of subjective cognitive decline (SCD) patients. Participants undergo extensive assessment, including cerebrospinal fluid collection and...

Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease

BackgroundA growing body of evidence suggests that the plasma concentration of the neurofilament light chain (NfL) might be considered a plasma biomarker for the screening of neurodegeneration in Alzheimer’s disease (AD).MethodsWith a single molecule array method (Simoa, Quanterix), plasma NfL concentrations were measured in 99 subjects with AD at the stage of mild cognitive...

Single-word comprehension deficits in the nonfluent variant of primary progressive aphasia

BackgroundA subset of patients with the nonfluent variant of primary progressive aphasia (PPA) exhibit concomitant single-word comprehension problems, constituting a ‘mixed variant’ phenotype. This phenotype is rare and currently not fully characterized. The aim of this study was twofold: to assess the prevalence and nature of single-word comprehension problems in the nonfluent...

Modifiable dementia risk score to study heterogeneity in treatment effect of a dementia prevention trial: a post hoc analysis in the preDIVA trial using the LIBRA index

BackgroundSelecting high-risk participants for dementia prevention trials based on a modifiable dementia risk score may be advantageous, as it increases the opportunity for intervention. We studied whether a multi-domain intervention can prevent all-cause dementia and cognitive decline in older people across three different levels of a modifiable dementia risk score...

Cognition comes of age: comments on the new FDA draft guidance for early Alzheimer’s disease

BackgroundThe FDA have recently published draft guidance for the development of treatments for early Alzheimer’s disease. Key features of this guidance are the advocacy of sensitive cognitive measures and a taxonomy of disease severity. Whilst desirable patterns of cognitive-functional improvement are included, specific measures, and the magnitude of required effects, are not...

Alzheimer’s disease master regulators analysis: search for potential molecular targets and drug repositioning candidates

BackgroundAlzheimer’s disease (AD) is a multifactorial and complex neuropathology that involves impairment of many intricate molecular mechanisms. Despite recent advances, AD pathophysiological characterization remains incomplete, which hampers the development of effective treatments. In fact, currently, there are no effective pharmacological treatments for AD. Integrative...

Vascular Endothelial Growth Factor remains unchanged in cerebrospinal fluid of patients with Alzheimer’s disease and vascular dementia

BackgroundIncreasing evidence suggests that cerebral vascular dysfunction is associated with the early stages of Alzheimer’s disease (AD). Vascular endothelial growth factor (VEGF) is one of the key players involved in the development and maintenance of the vasculature. Here, we hypothesized that VEGF levels in cerebrospinal fluid (CSF) may be altered in AD patients with vascular...

Infrequent false positive [18F]flutemetamol PET signal is resolved by combined histological assessment of neuritic and diffuse plaques

BackgroundThe performance of [18F]flutemetamol amyloid PET against histopathological standards of truth was the subject of our recent article in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring (2017;9:25–34).Main bodyThis viewpoint article addresses infrequently observed discordance between visual [18F]flutemetamol PET image readings and histopathology based...

Hepatitis B core VLP-based mis-disordered tau vaccine elicits strong immune response and alleviates cognitive deficits and neuropathology progression in Tau.P301S mouse model of Alzheimer’s disease and frontotemporal dementia

BackgroundTruncated mis-disordered tau protein plays an important role in the pathogenesis of Alzheimer’s disease (AD) and frontotemporal dementia (FTD). Tau294–305, an epitope in the truncated tau, is essential for pathological tau-tau interaction and aggregation. A tau294–305-targeted approach may have beneficial effects in the treatment of AD and FTD.MethodsIn this study, we...

Immunotherapy to improve cognition and reduce pathological species in an Alzheimer’s disease mouse model

BackgroundAlzheimer’s disease (AD) is characterized by physiologically endogenous proteins amyloid beta (Aβ) and tau undergoing a conformational change and accumulating as soluble oligomers and insoluble aggregates. Tau and Aβ soluble oligomers, which contain extensive β-sheet secondary structure, are thought to be the most toxic forms. The objective of this study was to...

Efficient clearance of Aβ protofibrils in AβPP-transgenic mice treated with a brain-penetrating bifunctional antibody

BackgroundAmyloid-β (Aβ) immunotherapy is one of the most promising disease-modifying strategies for Alzheimer’s disease (AD). Despite recent progress targeting aggregated forms of Aβ, low antibody brain penetrance remains a challenge. In the present study, we used transferrin receptor (TfR)-mediated transcytosis to facilitate brain uptake of our previously developed A...

Effects of lifetime cumulative ginseng intake on cognitive function in late life

BackgroundWe investigated the effects of lifetime cumulative ginseng intake on cognitive function in a community-dwelling population-based prospective cohort of Korean elders.MethodsCommunity-dwelling elders (N = 6422; mean age = 70.2 ± 6.9 years, education = 8.0 ± 5.3 years, female = 56.8%) from the Korean Longitudinal Study on Cognitive Aging and Dementia were included. Among...

Meaning in life: resilience beyond reserve

BackgroundThe contribution of psychological factors to brain health and resilience remains poorly investigated. Furthermore, their possible interaction with ‘classical’ cognitive reserve (CR) estimates in predicting perceived mental health and cognitive status has not been specifically addressed.MethodsWe obtained data from 1081 adults responding to questionnaires on the three...

Cross-sectional associations of plasma vitamin D with cerebral β-amyloid in older adults at risk of dementia

BackgroundVitamin D deficiency is associated with an increased risk of Alzheimer’s disease and increased beta-amyloid (Aβ) in animals. Hence we sought to investigate the relationship between plasma 25-hydroxyvitamin D (25(OH)D) and cerebral Aβ in older adults with subjective memory complaints.MethodsThis is a secondary analysis of the Multidomain Alzheimer Preventive Trial...

A language-based sum score for the course and therapeutic intervention in primary progressive aphasia

BackgroundWith 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 literature, but cognitive scores are still lacking. This study...