Alzheimer's Research & Therapy

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

List of Papers (Total 655)

Safety and tolerability of donepezil 23 mg with or without intermediate dose titration in patients with Alzheimer’s disease taking donepezil 10 mg: a multicenter, randomized, open-label, parallel-design, three-arm, prospective trial

BackgroundHigh-dose donepezil is currently prescribed for patients with Alzheimer’s disease (AD) who showed poor or waning response to a lower dose at the risk of increasing cholinergic side effects. However, the adverse events (AEs) depending on the method of dose escalation have not been clarified yet. This study aimed to find out whether dose titration before escalating to...

Neuroinflammation and amyloid-beta 40 are associated with reduced serotonin transporter (SERT) activity in a transgenic model of familial Alzheimer’s disease

BackgroundDiscrepant and often contradictory results have accumulated regarding the antidepressant and pro-cognitive effects of serotonin transporter (SERT) antagonists in Alzheimer’s disease.MethodsTo address the discrepancy, we measured the activity and density of SERT in the neocortex of 3–24-month-old APPswe/PS1dE9 and wild-type littermate mice, by using [3H]DASB...

Exposure to fluoride aggravates the impairment in learning and memory and neuropathological lesions in mice carrying the APP/PS1 double-transgenic mutation

BackgroundAlzheimer’s disease (AD) is responsible for 60–70% of all cases of dementia. On the other hand, the tap water consumed by hundreds of millions of people has been fluoridated to prevent tooth decay. However, little is known about the influence of fluoride on the expression of APP and subsequent changes in learning and memory and neuropathological injury. Our aim here was...

Personalized risk for clinical progression in cognitively normal subjects—the ABIDE project

BackgroundBiomarkers such as cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) have predictive value for progression to dementia in patients with mild cognitive impairment (MCI). The pre-dementia stage takes far longer, and the interpretation of biomarker findings is particular relevant for individuals who present at a memory clinic, but are deemed cognitively normal...

Risk of suicide and accidental deaths among elderly patients with cognitive impairment

BackgroundThe leading causes of death among the elderly with cognitive impairment are unknown. This study aims to estimate the suicide and accidental death rates on the basis of a clinical case registry of patients diagnosed with cognitive impairment.MethodsThe target sample consisted of 10,169 patients diagnosed with dementia or mild cognitive impairment (MCI), who were...

Risk of dementia in patients with end-stage renal disease under maintenance dialysis—a nationwide population-based study with consideration of competing risk of mortality

BackgroundDementia is prevalent in the end-stage renal disease (ESRD) population. However, it is still not clarified whether ESRD is one of the etiology of dementia or its attributable effect on the cumulative risk of dementia. Meanwhile, the effect of competing risk of mortality should be taken into consideration when performing epidemiologic analyses among populations with high...

Phenocopy syndrome of behavioral variant frontotemporal dementia: a systematic review

BackgroundThe phenocopy syndrome of behavioral variant of frontotemporal dementia (phFTD) refers to patients presenting with neuropsychiatric symptoms mimicking the behavioral variant frontotemporal dementia (bvFTD), but lacking frontotemporal atrophy/hypometabolism on neuroimaging and not evolving to dementia during the follow-up. It is important to recognize phFTD for clinical...

CSF level of β-amyloid peptide predicts mortality in Alzheimer’s disease

ObjectiveAlzheimer’s disease (AD) is the sixth leading cause of death, with an average survival estimated between 5 and 10 years after diagnosis. Despite recent advances in diagnostic criteria of AD, few studies have used biomarker-based diagnostics to determine the prognostic factors of AD. We investigate predictors of death and institutionalization in a population of AD...

Centiloid cut-off values for optimal agreement between PET and CSF core AD biomarkers

BackgroundThe Centiloid scale has been developed to standardize measurements of amyloid PET imaging. Reference cut-off values of this continuous measurement enable the consistent operationalization of decision-making for multicentre research studies and clinical trials. In this study, we aimed at deriving reference Centiloid thresholds that maximize the agreement against core...

Neurexin 3 transmembrane and soluble isoform expression and splicing haplotype are associated with neuron inflammasome and Alzheimer’s disease

BackgroundSynaptic damage precedes neuron death in Alzheimer’s disease (AD). Neurexins, NRXN1, NRXN2, and NRXN3, are presynaptic adhesion molecules that specify neuron synapses and regulate neurotransmitter release. Neurexins and postsynaptic neuroligins interact with amyloid beta oligomer (AβO) deposits in damaged synapses. NRXN3 gene variants have been associated with autism...

Impact of a clinical decision support tool on prediction of progression in early-stage dementia: a prospective validation study

BackgroundIn clinical practice, it is often difficult to predict which patients with cognitive complaints or impairment will progress or remain stable. We assessed the impact of using a clinical decision support system, the PredictND tool, to predict progression in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI) in memory clinics.MethodsIn...

Reversible predictors of reversion from mild cognitive impairment to normal cognition: a 4-year longitudinal study

BackgroundAlthough previous studies have revealed many factors related to mild cognitive impairment (MCI) reversion, information about reversible factors related MCI reversion is limited, impeding the development of intervention strategies. The aim of the present study was to examine whether reversible factors such as lifestyle activities are associated with MCI reversion in...

Lewy Body Dementia Association’s Research Centers of Excellence Program: Inaugural Meeting Proceedings

The first Lewy Body Dementia Association (LBDA) Research Centers of Excellence (RCOE) Investigator’s meeting was held on December 14, 2017, in New Orleans. The program was established to increase patient access to clinical experts on Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), and to create a clinical trials...

Concepts for brain aging: resistance, resilience, reserve, and compensation

A primary goal of research in cognitive impairment and dementia is to understand how some individuals retain sufficient cognitive function for a fulfilling life while many others are robbed of their independence, sometimes their essence, in the last years and decades of life. In this commentary, we propose operational definitions of the types of factors that may help individuals...

Brain glucose metabolism in Lewy body dementia: implications for diagnostic criteria

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 validation by considering large samples of patients and disease...

Longitudinal measurement of serum neurofilament light in presymptomatic familial Alzheimer’s disease

BackgroundTo investigate how serum neurofilament light (NfL) concentration changes through the course of disease in familial Alzheimer’s disease (FAD) and to assess when NfL concentration first increases.MethodsNfL was measured using an ultrasensitive immunoassay in 117 serum samples from 61 individuals from families with PSEN1 or APP mutations in a longitudinal study (mean ± SD...

Striatal amyloid is associated with tauopathy and memory decline in familial Alzheimer’s disease

BackgroundAutosomal dominant Alzheimer’s disease (ADAD) is distinguished from late-onset AD by early striatal amyloid-β deposition. To determine whether striatal Pittsburgh compound B (PiB)-PET measurements of amyloid-β can help predict disease severity in ADAD, we compared relationships of striatal and neocortical PiB-PET to age, tau-PET, and memory performance in the Colombian...

Inferior and medial temporal tau and cortical amyloid are associated with daily functional impairment in Alzheimer’s disease

BackgroundA decline in instrumental activities of daily living (IADL) correlates with the progression from mild cognitive impairment (MCI) to Alzheimer’s disease (AD) dementia and has been associated with frontal and parietal hypometabolism, lower cerebrospinal fluid amyloid β1–42, and inferior temporal cortical thinning. Identifying the underlying biomarkers of functional...

Applicability of in vivo staging of regional amyloid burden in a cognitively normal cohort with subjective memory complaints: the INSIGHT-preAD study

BackgroundCurrent methods of amyloid PET interpretation based on the binary classification of global amyloid signal fail to identify early phases of amyloid deposition. A recent analysis of 18F-florbetapir PET data from the Alzheimer’s disease Neuroimaging Initiative cohort suggested a hierarchical four-stage model of regional amyloid deposition that resembles neuropathologic...

18F-flortaucipir (AV-1451) tau PET in frontotemporal dementia syndromes

BackgroundThe tau positron emission tomography (PET) ligand 18F-flortaucipir binds to paired helical filaments of tau in aging and Alzheimer’s disease (AD), but its utility in detecting tau aggregates in frontotemporal dementia (FTD) is uncertain.MethodsWe performed 18F-flortaucipir imaging in patients with the FTD syndromes (n = 45): nonfluent variant primary progressive aphasia...

Spatial patterns of white matter hyperintensities associated with Alzheimer’s disease risk factors in a cognitively healthy middle-aged cohort

BackgroundWhite matter hyperintensities (WMH) of presumed vascular origin have been associated with an increased risk of Alzheimer’s disease (AD). This study aims to describe the patterns of WMH associated with dementia risk estimates and individual risk factors in a cohort of middle-aged/late middle-aged individuals (mean 58 (interquartile range 51–64) years old).MethodsMagnetic...

Data-driven prognostic features of cognitive trajectories in patients with amnestic mild cognitive impairments

BackgroundAlthough amnestic mild cognitive impairment (aMCI) is generally considered to be a prodromal stage of Alzheimer’s disease, patients with aMCI show heterogeneous patterns of progression. Moreover, there are few studies investigating data-driven cognitive trajectory in aMCI. We therefore classified patients with aMCI based on their cognitive trajectory, measured by...

Consecutive sessions of transcranial direct current stimulation do not remediate visual hallucinations in Lewy body dementia: a randomised controlled trial

BackgroundComplex visual hallucinations are common in Lewy body dementia (LBD) and can cause significant patient and caregiver distress. Current treatments are primarily pharmacological in nature and have limited efficacy and associated side effects. The objective of this study was to assess the effects of consecutive sessions of transcranial direct current stimulation (tDCS) on...

Prevalence and risk of progression of preclinical Alzheimer’s disease stages: a systematic review and meta-analysis

BackgroundAlzheimer’s disease (AD) pathology begins several years before the clinical onset. The long preclinical phase is composed of three stages according to the 2011National Institute on Aging and Alzheimer’s Association (NIA-AA) criteria, followed by mild cognitive impairment (MCI), a featured clinical entity defined as “due to AD”, or “prodromal AD”, when pathophysiological...

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...