Effect of statins on Alzheimer's disease biomarkers in cerebrospinal fluid.

Background: Treatment with HMG-CoA reductase inhibitors ("statins") has been variably associated with a reduced risk of Alzheimer's disease (AD) in epidemiologic studies and reduced amyloid-beta (Abeta) deposition in animal models of AD. Putative neuroprotective effects of statins may vary in relation to their ability to penetrate into the central nervous system (CNS).

Methods: We measured levels of cerebrospinal fluid (CSF) AD biomarkers following 14 weeks of treatment with simvastatin (a CNS permeant statin; n=10) at 40 mg/day or pravastatin (a CNS impermeant statin; n=13) at 80 mg/day in hypercholesterolemic subjects without dementia.

Statins of different brain penetrability differentially affect CSF PLTP activity.

Background/aims: Phospholipid transfer protein (PLTP) and apolipoprotein E (apoE) are key proteins involved in lipoprotein metabolism in the peripheral circulation and in the brain. Several epidemiological studies suggested that use of 3-hydroxyl-3-methylglutaryl-coenzyme A reductase inhibitors (statins) reduces risk of Alzheimer's disease (AD). However, the effects of statins of differing blood-brain barrier (BBB) penetrability on brain-derived molecules in cognitively normal individuals are largely unknown.

Lewy body pathology in late-onset familial Alzheimer's disease: a clinicopathological case series.

Background: Lewy body pathology (LBP) is a common finding in Alzheimer's disease (AD), but the pathophysiology for this coexistent pathology remains unclear.

Methods: We ascertained late-onset dementia (mean age > 60 years old) families with at least 3 autopsies. We then conducted systematic alpha-synuclein (SNCA) immunostaining to determine the frequency and distribution of LBP in families with late-onset AD.

Safety and acceptability of the research lumbar puncture.

Three hundred forty-two subjects underwent 428 research lumbar punctures for studies of cerebrospinal fluid (CSF) biomarkers. Subjects were 67 Alzheimer disease or mild cognitive impairment (AD/MCI) patients and 275 cognitively normal adults aged 21 to 88. Lumbar puncture was performed in the lateral decubitus or sitting position using the Sprotte 24 g atraumatic spinal needle.

Propranolol for disruptive behaviors in nursing home residents with probable or possible Alzheimer disease: a placebo-controlled study.

Objective: Enhanced behavioral responsiveness to central nervous system (CNS) norepinephrine (NE) in Alzheimer disease (AD) may contribute to the pathophysiology of disruptive behaviors such as aggression, uncooperativeness with necessary care, irritability, and pressured pacing. We evaluated the efficacy of the beta-adrenergic antagonist propranolol for treatment-resistant disruptive behaviors and overall behavioral status in nursing home residents with probable or possible AD.

Methods: Thirty-one subjects (age 85 +/- 8 [SD]) with probable or possible AD and persistent disruptive behaviors that interfered with necessary care were randomized to propranolol (n = 17) or placebo (n = 14) in a double-blind study.

Effect of vascular lesions on cognition in Alzheimer's disease: a community-based study.

Objectives: To investigate whether clinical and neuropathological differences exist between Alzheimer's disease (AD) cases with and without vascular lesions neuropathologically diagnosed using Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria.

Design: Descriptive observational study.

Setting: A community-based registry that identified incident dementia cases.