Danielle de Jong

No effect of one-year treatment with indomethacin on Alzheimer's disease progression: a randomized controlled trial.

Background The objective of this study was to determine whether treatment with the nonselective nonsteroidal anti-inflammatory drug (NSAID) indomethacin slows cognitive decline in patients with Alzheimers disease (AD). Methodology/Principal Findings This double-blind, randomized, placebo-controlled trial was conducted between May 2000 and September 2005 in two hospitals in the Netherlands. 51 patients with mild to moderate AD were enrolled into the study. Patients received 100 mg indomethacin or placebo daily for 12 months. Additionally, all patients received omeprazole. The primary outcome measure was the change from baseline after one year of treatment on the cognitive subscale of the AD Assessment Scale (ADAS-cog). Secondary outcome measures included the Mini-Mental State Examination, the Clinicians Interview Based Impression of Change with caregiver input, the noncognitive subscale of the ADAS, the Neuropsychiatric Inventory, and the Interview for Deterioration in Daily life in Dementia. Considerable recruitment problems of participants were encountered, leading to an underpowered study. In the placebo group, 19 out of 25 patients completed the study, and 19 out of 26 patients in the indomethacin group. The deterioration on the ADAS-cog was less in the indomethacin group (7.8±7.6), than in the placebo group (9.3±10.0). This difference (1.5 points; CI −4.5–7.5) was not statistically significant, and neither were any of the secondary outcome measures. Conclusions/Significance The results of this study are inconclusive with respect to the hypothesis that indomethacin slows the progression of AD. Trial Registration ClinicalTrials.gov NCT00432081

Current state and future directions of neurochemical biomarkers for Alzheimer's disease.

In this comprehensive review, we summarize the current state-of-the-art of neurochemical biomarkers for Alzheimers disease. Predominantly, these biomarkers comprise cerebrospinal fluid biomarkers directly related to the pathophysiology of this disorder (such as amyloid beta protein, tau protein). We particularly pay attention to the innovations in this area that have been made in technological aspects during the past 5 years (e.g., multiplex analysis of biomarkers, proteomics), to the discovery of novel, potential biomarkers (e.g., amyloid beta oligomers, isoprostanes), and to the extension of this research towards identification of biomarkers in plasma.

Cerebrospinal fluid analysis differentiates multiple system atrophy from Parkinson's disease

We investigated whether cerebrospinal fluid (CSF) analysis discriminates between idiopathic Parkinsons disease (PD; n = 35) and multiple system atrophy (MSA; n = 30). The median CSF concentration of the neurotransmitter metabolites 5‐hydroxyindolacetic acid (5‐HIAA) and 3‐methoxy‐4‐hydroxyphenylethyleneglycol (MHPG) was reduced significantly (49‐70%) in MSA compared to PD. In contrast, several brain‐specific proteins (tau, neuron‐specific enolase, myelin basic protein) were elevated (130–230%) in MSA compared with those in PD. A combination of CSF tau and MHPG discriminated PD from MSA (adjusted odds ratios: tau, 27.2; MHPG, 0.14). Our data suggest that the more progressive and widespread neurodegenerative nature of MSA, as compared with PD, is reflected in the composition of CSF. We propose that CSF analysis may become part of the diagnostic work‐up of patients with parkinsonian syndromes.

Cerebral Amyloid Angiopathy with Severe Secondary Vascular Pathology: A Histopathological Study

Cerebral amyloid angiopathy (CAA) is a common neuropathological finding and is characterized by deposition of fibrillar amyloid in cortical and leptomeningeal vessels. In this study we describe the macroscopic and microscopic neuropathological findings of 5 patients with severe CAA-associated secondary vascular changes, including smooth muscle cell degeneration, hyalinization, ‘double-barreling’ phenomenon, macrophage infiltration, and aneurysmal dilatation of the vessel wall. In 3 of the 5 patients these vascular changes were associated with multiple small hemorrhages, whereas in 2 patients areas of ischemic necrosis were observed. However, none of these patients suffered from large (lobar) hemorrhagic accidents. Nevertheless, severe CAA, particularly when associated with secondary vascular pathology, may lead to vascular dementia-like ischemic changes. Hence, the distinction between patients with severe CAA and secondary vascular abnormalities from those suffering from vascular dementia can be difficult. We speculate that CAA, particularly when associated with secondary vascular pathology, although not resulting in large hemorrhages, may contribute to cognitive decline. The functional impact of CAA and CAA-related secondary vascular changes on cognitive performance warrants further exploration.