Longitudinal decline in mild-to-moderate Alzheimer's disease: Analyses of placebo data from clinical trials.
Alzheimer's & Dementia 12(5):598 (2016)
Accurate estimates of cognitive and clinical decline rates are essential to the design of clinical trials in Alzheimer's disease (AD) dementia.
To investigate the trajectories of individuals enrolled in therapeutic trials in mild-to-moderate AD, we analyzed the placebo arm data from 20 clinical ...
A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease.
Neurology 85(16):1383 (2015)
A randomized, placebo-controlled, double-blind, multicenter 52-week phase 2 trial of resveratrol in individuals with mild to moderate Alzheimer disease (AD) examined its safety and tolerability and effects on biomarker (plasma Aβ40 and Aβ42, CSF Aβ40, Aβ42, tau, and phospho-tau 181) and volumetr...
Longitudinal plasma amyloid beta in Alzheimer's disease clinical trials.
Alzheimer's & Dementia 11(9):1069 (2015)
Little is known about the utility of plasma amyloid beta (Aβ) in clinical trials of Alzheimer's disease (AD).
We analyzed longitudinal plasma samples from two large multicenter clinical trials: (1) donezepil and vitamin E in mild cognitive impairment (n = 405, 24 months) and (2) simvastatin in m...
Peripheral and central effects of γ-secretase inhibition by semagacestat in Alzheimer's disease.
Alzheimer's Research & Therapy 7(1):36 (2015)
The negative efficacy study examining the γ-secretase inhibitor semagacestat in mild to moderate Alzheimer's disease (AD) included a number of biomarkers of the disease as well as safety outcomes. We analyzed these data to explore relationships between drug exposure and pharmacodynamic effects a...
The preclinical Alzheimer cognitive composite: measuring amyloid-related decline.
JAMA Neurology 71(8):961 (2014)
As Alzheimer disease (AD) research moves to intervene in presymptomatic phases of the disease, we must develop outcome measures sensitive to the earliest disease-related changes.
To demonstrate the feasibility of a cognitive composite outcome for clinically normal elderly participants with evide...
Clinical trial of an inhibitor of RAGE-Aβ interactions in Alzheimer disease.
Neurology 82(17):1536 (2014)
To examine safety, tolerability, and efficacy of PF-04494700, an inhibitor of the receptor for advanced glycation end products (RAGE), in mild to moderate Alzheimer disease (AD).
Double-blind, placebo-controlled trial at 40 academic centers (United States). Subjects with AD and Mini-Mental State...
Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease.
New England Journal of Medicine 370(4):311 (2014)
Alzheimer's disease is characterized by amyloid-beta plaques, neurofibrillary tangles, gliosis, and neuronal loss. Solanezumab, a humanized monoclonal antibody, preferentially binds soluble forms of amyloid and in preclinical studies promoted its clearance from the brain.
In two phase 3, double-...
A phase 3 trial of semagacestat for treatment of Alzheimer's disease.
New England Journal of Medicine 369(4):341 (2013)
Alzheimer's disease is characterized by the presence of cortical amyloid-beta (Aβ) protein plaques, which result from the sequential action of β-secretase and γ-secretase on amyloid precursor protein. Semagacestat is a small-molecule γ-secretase inhibitor that was developed as a potential treatm...
Age and apolipoprotein E genotype influence rate of cognitive decline in nondemented elderly.
Neuropsychology 27(4):391 (2013)
This study examined the impact of age and apolipoprotein E (APOE) genotype on the rate of cognitive decline in nondemented elderly participants in a simulated Alzheimer's disease (AD) primary prevention treatment trial carried out by the Alzheimer's Disease Cooperative Study.
Cognitive tests wer...
Establishing the psychometric underpinning of cognition measures for clinical trials of Alzheimer's disease and its precursors: a new approach.
Alzheimer's & Dementia 9(1 Suppl):S56 (2013)
The Alzheimer's disease (AD) Cognitive Behavior Section (ADAS-Cog) is the most commonly used cognitive test in clinical trials of AD. Recent trials have focused on people earlier in the course of disease; however, there are concerns about using the ADAS-Cog at this crucial stage. Using data from...
Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures.
Archives of Neurology 69(7):836 (2012)
To evaluate whether antioxidant supplements presumed to target specific cellular compartments affected cerebrospinal fluid (CSF) biomarkers.
Double-blind, placebo-controlled clinical trial.
Academic medical centers.
Subjects with mild to moderate Alzheimer disease.
Random assignment to treatment...
Association of common genetic variants in GPCPD1 with scaling of visual cortical surface area in humans.
PNAS 109(10):3985 (2012)
Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area ...
Incidence of new-onset seizures in mild to moderate Alzheimer disease.
Archives of Neurology 69(3):368 (2012)
To estimate the incidence rate and predictors of seizures in patients with mild to moderate Alzheimer disease (AD).
Cohort study of patients with mild to moderate AD in clinical trials. Risk factors for potential seizures were evaluated by stratified descriptive statistics and univariable and mu...
Dietary self-monitoring and its impact on weight loss in overweight children.
International Journal of Pediatric Obesity 6(3-4):197 (2011)
To examine whether dietary self-monitoring is related to weight loss in overweight children and whether perceived social support or dietary self-efficacy affects this relation. Design. Longitudinal, behavioral intervention study.
The study population included 153 children, aged 7-12 years, with ...
Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease.
Archives of General Psychiatry 68(8):853 (2011)
Agitation and psychosis are common in Alzheimer disease and cause considerable morbidity. We attempted to delay or to prevent agitation and psychosis with the use of divalproex sodium (valproate).
To determine whether treatment with valproate could delay or prevent emergence of agitation or psyc...
Adding delayed recall to the Alzheimer Disease Assessment Scale is useful in studies of mild cognitive impairment but not Alzheimer disease.
Alzheimer Disease and Associated Disorders 25(2):122 (2011)
To determine if the addition of delayed recall (DR) assessment adds sensitivity to the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog) in clinical trials in mild cognitive impairment (MCI) and Alzheimer Disease (AD).
Memory, particularly DR, is the most sensitive test for...
Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial.
JAMA 304(17):1903 (2010)
Docosahexaenoic acid (DHA) is the most abundant long-chain polyunsaturated fatty acid in the brain. Epidemiological studies suggest that consumption of DHA is associated with a reduced incidence of Alzheimer disease. Animal studies demonstrate that oral intake of DHA reduces Alzheimer-like brain...
Clinical Core of the Alzheimer's Disease Neuroimaging Initiative: progress and plans.
Alzheimer's & Dementia 6(3):239 (2010)
The Clinical Core of the Alzheimer's Disease Neuroimaging Initiative (ADNI) has provided clinical, operational, and data management support to ADNI since its inception. This article reviews the activities and accomplishments of the core in support of ADNI aims. These include the enrollment and f...
MRI substudy participation in Alzheimer disease (AD) clinical trials: baseline comparability of a substudy sample to entire study population.
Alzheimer Disease and Associated Disorders 23(4):333 (2009)
To determine if a self-selected group of participants who enroll in an imaging substudy of Alzheimer disease (AD) clinical trials is representative of the overall study sample.
Baseline data from 2 ongoing AD clinical trials with 402 and 313 randomized participants were analyzed. Magnetic resona...
Plasma urate and progression of mild cognitive impairment.
Neurodegenerative Diseases 6(1-2):23 (2009)
Impaired antioxidant defenses are implicated in neurodegenerative disease. The plasma levels of urate, a water-soluble antioxidant, are reduced in Alzheimer's disease (AD).
We aimed to test the hypotheses that high plasma urate at baseline is associated with: (1) a reduced rate of conversion fro...