JAMA neurology
-
Randomized Controlled Trial Multicenter Study
Efficacy and Safety of Lanabecestat for Treatment of Early and Mild Alzheimer Disease: The AMARANTH and DAYBREAK-ALZ Randomized Clinical Trials.
Alzheimer disease (AD) is a neurodegenerative disorder characterized by cognitive deterioration and impaired activities of daily living. Current treatments provide only minor symptomatic improvements with limited benefit duration. Lanabecestat, a brain-permeable inhibitor of human beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1/β-secretase), was developed to modify the clinical course of AD by slowing disease progression. ⋯ Treatment with lanabecestat was well tolerated and did not slow cognitive or functional decline.
-
Midlife vascular risk burden is associated with late-life dementia. Less is known about if and how risk exposure in early adulthood influences late-life brain health. ⋯ Higher vascular risk is associated with smaller whole-brain volume and greater white matter-hyperintensity volume at age 69 to 71 years, with the strongest association seen with early adulthood vascular risk. There was no evidence that higher vascular risk influences amyloid deposition, at least up to age 71 years. Reducing vascular risk with appropriate interventions should be considered from early adulthood to maximize late-life brain health.
-
Neuroprotective and remyelinating therapies are required for multiple sclerosis (MS), and acute optic neuritis (AON) is a potential condition to evaluate such treatments. ⋯ Acute optic neuritis is a suitable condition to test neuroprotective and remyelinating therapies after acute inflammation, providing sensitive markers to assess the effects on both processes and prospective visual recovery within a manageable timeframe and with a relatively small sample size.