%0 Journal Article %J Neurology %D 2011 %T Report of the task force on designing clinical trials in early (predementia) AD. %A Aisen, P S %A Andrieu, S %A Sampaio, C %A Carrillo, M %A Khachaturian, Z S %A Dubois, B %A Feldman, H H %A Petersen, R C %A Siemers, E %A Doody, R S %A Hendrix, S B %A Grundman, M %A Schneider, L S %A Schindler, R J %A Salmon, E %A Potter, W Z %A Thomas, R G %A Salmon, D %A Donohue, M %A Bednar, M M %A Touchon, J %A Vellas, B %K Advisory Committees %K Alzheimer Disease %K Amyloidogenic Proteins %K Biomarkers %K Clinical Trials as Topic %K Cognition %K Consensus %K Disease Progression %K Drug Industry %K Early Diagnosis %K Europe %K Humans %K Indans %K International Cooperation %K Nootropic Agents %K Outcome Assessment (Health Care) %K Patient Selection %K Piperidines %K Positron-Emission Tomography %K Research Design %K Treatment Outcome %K United States %K United States Food and Drug Administration %K Vitamin E %X

BACKGROUND: A large number of promising candidate disease-modifying treatments for Alzheimer disease (AD) continue to advance into phase II and phase III testing. However, most completed trials have failed to demonstrate efficacy, and there is growing concern that methodologic difficulties may contribute to these clinical trial failures. The optimal time to intervene with such treatments is probably in the years prior to the onset of dementia, before the neuropathology has progressed to the advanced stage corresponding to clinical dementia.

METHOD: An international task force of individuals from academia, industry, nonprofit foundations, and regulatory agencies was convened to discuss optimal trial design in early (predementia) AD.

RESULTS: General consensus was reached on key principles involving the scope of the AD diagnosis, the selection of subjects for trials, outcome measures, and analytical methods.

CONCLUSION: A consensus has been achieved in support of the testing of candidate treatments in the early (predementia) AD population.

%B Neurology %V 76 %P 280-6 %8 2011 Jan 18 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/21178097?dopt=Abstract %R 10.1212/WNL.0b013e318207b1b9 %0 Journal Article %J Neurology %D 2010 %T Alzheimer's Disease Neuroimaging Initiative (ADNI): clinical characterization. %A Petersen, R C %A Aisen, P S %A Beckett, L A %A Donohue, M C %A Gamst, A C %A Harvey, D J %A Jack, C R %A Jagust, W J %A Shaw, L M %A Toga, A W %A Trojanowski, J Q %A Weiner, M W %K Aged %K Aged, 80 and over %K Alzheimer Disease %K Biomarkers %K Cross-Sectional Studies %K Diagnostic Imaging %K Female %K Follow-Up Studies %K Humans %K Longitudinal Studies %K Male %K Middle Aged %X

BACKGROUND: Neuroimaging measures and chemical biomarkers may be important indices of clinical progression in normal aging and mild cognitive impairment (MCI) and need to be evaluated longitudinally.

OBJECTIVE: To characterize cross-sectionally and longitudinally clinical measures in normal controls, subjects with MCI, and subjects with mild Alzheimer disease (AD) to enable the assessment of the utility of neuroimaging and chemical biomarker measures.

METHODS: A total of 819 subjects (229 cognitively normal, 398 with MCI, and 192 with AD) were enrolled at baseline and followed for 12 months using standard cognitive and functional measures typical of clinical trials.

RESULTS: The subjects with MCI were more memory impaired than the cognitively normal subjects but not as impaired as the subjects with AD. Nonmemory cognitive measures were only minimally impaired in the subjects with MCI. The subjects with MCI progressed to dementia in 12 months at a rate of 16.5% per year. Approximately 50% of the subjects with MCI were on antidementia therapies. There was minimal movement on the Alzheimer's Disease Assessment Scale-Cognitive Subscale for the normal control subjects, slight movement for the subjects with MCI of 1.1, and a modest change for the subjects with AD of 4.3. Baseline CSF measures of Abeta-42 separated the 3 groups as expected and successfully predicted the 12-month change in cognitive measures.

CONCLUSION: The Alzheimer's Disease Neuroimaging Initiative has successfully recruited cohorts of cognitively normal subjects, subjects with mild cognitive impairment (MCI), and subjects with Alzheimer disease with anticipated baseline characteristics. The 12-month progression rate of MCI was as predicted, and the CSF measures heralded progression of clinical measures over 12 months.

%B Neurology %V 74 %P 201-9 %8 2010 Jan 19 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/20042704?dopt=Abstract %R 10.1212/WNL.0b013e3181cb3e25