Alzheimer's Research & Therapy

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

List of Papers (Total 562)

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...

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Cognition comes of age: comments on the new FDA draft guidance for early Alzheimer’s disease

BackgroundThe FDA have recently published draft guidance for the development of treatments for early Alzheimer’s disease.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...

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...

Naming is not explaining: future directions for the “cognitive reserve” and “brain maintenance” theories

Contemporary imaging measures of the human brain explain less than half of the differences in cognitive functioning and change among older adults. Researchers have advanced several theories and concepts to guide research that aims to better explain these individual differences in cognitive aging. Taking the fundamental measurement model in the empirical sciences as a starting...

Cerebrospinal fluid in the differential diagnosis of Alzheimer’s disease: clinical utility of an extended panel of biomarkers in a specialist cognitive clinic

BackgroundCerebrospinal fluid (CSF) biomarkers are increasingly being used to support a diagnosis of Alzheimer’s disease (AD). Their clinical utility for differentiating AD from non-AD neurodegenerative dementias, such as dementia with Lewy bodies (DLB) or frontotemporal dementia (FTD), is less well established. We aimed to determine the diagnostic utility of an extended panel of...

White paper by the Society for CSF Analysis and Clinical Neurochemistry: Overcoming barriers in biomarker development and clinical translation

Body fluid biomarkers have great potential for different clinical purposes, including diagnosis, prognosis, patient stratification and treatment effect monitoring. This is exemplified by current use of several excellent biomarkers, such as the Alzheimer’s disease cerebrospinal fluid (CSF) biomarkers, anti-neuromyelitis optica antibodies and blood neurofilament light. We still...