Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures.

OBJECTIVE: To evaluate whether antioxidant supplements presumed to target specific cellular compartments affected cerebrospinal fluid (CSF) biomarkers. DESIGN: Double-blind, placebo-controlled clinical trial. SETTING: Academic medical centers. PARTICIPANTS: Subjects with mild to moderate Alzheimer disease. INTERVENTION: Random assignment to treatment for 16 weeks with 800 IU/d of vitamin E (α-tocopherol) plus 500 mg/d of vitamin C plus 900 mg/d of α-lipoic acid (E/C/ALA); 400 mg of coenzyme Q 3 times/d; or placebo. MAIN OUTCOME MEASURES: Changes from baseline to 16 weeks in CSF biomarkers related to Alzheimer disease and oxidative stress, cognition (Mini-Mental State Examination), and function (Alzheimer's Disease Cooperative Study Activities of Daily Living Scale). RESULTS: Seventy-eight subjects were randomized; 66 provided serial CSF specimens adequate for biochemical analyses. Study drugs were well tolerated, but accelerated decline in Mini-Mental State Examination scores occurred in the E/C/ALA group, a potential safety concern. Changes in CSF Aß42, tau, and P-tau(181) levels did not differ between the 3 groups. Cerebrospinal fluid F2-isoprostane levels, an oxidative stress biomarker, decreased on average by 19% from baseline to week 16 in the E/C/ALA group but were unchanged in the other groups. CONCLUSIONS: Antioxidants did not influence CSF biomarkers related to amyloid or tau pathology. Lowering of CSF F2-isoprostane levels in the E/C/ALA group suggests reduction of oxidative stress in the brain. However, this treatment raised the caution of faster cognitive decline, which would need careful assessment if longer-term clinical trials are conducted. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00117403.

EEG and MRI data fusion for early diagnosis of Alzheimer's disease.

The prevalence of Alzheimer's disease (AD) is rising alarmingly as the average age of our population increases. There is no treatment to halt or slow the pathology responsible for AD, however, new drugs are promising to reduce the rate of progression. On the other hand, the efficacy of these new medications critically depends on our ability to diagnose AD at the earliest stage. Currently AD is diagnosed through longitudinal clinical evaluations, which are available only at specialized dementia clinics, hence beyond financial and geographic reach of most patients. Automated diagnosis tools that can be made available to community hospitals would therefore be very beneficial. To that end, we have previously shown that the event related potentials obtained from different scalp locations can be effectively used for early diagnosis of AD using an ensemble of classifiers based decision fusion approach. In this study, we expand our data fusion approach to include MRI based measures of regional brain atrophy. Our initial results indicate that ERPs and MRI carry complementary information, and the combination of these heterogeneous data sources using a decision fusion approach can significantly improve diagnostic accuracy.