Designing clinical trials for early (pre-dementia) Alzheimer's disease: determining the appropriate population for treatment.
Treatments that are designed to reduce Alzheimer's disease (AD) pathology may be most useful when given to subjects prior to a diagnosis of AD using current diagnostic criteria. These earlier patients may have early cognitive losses consistent with mild cognitive impairment (MCI) or may be completely asymptomatic. Screening and treatment programs for other disease states have been explored previously; these include cholesterol screening for cardiovascular disease, genetic screening for Huntington ' s disease and screening for some types of cancer. Cancer screening and treatment programs have been developed for colon cancer, breast cancer and prostate cancer. Screening programs for these other disease states are briefly reviewed and are compared to preliminary modeling data describing a hypothetical screening and treatment program for AD. While primary prevention based on screening of asymptomatic individuals using biomarkers has broad appeal, secondary prevention employing treatment of patients with MCI may be more easily implemented.
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. esiemers@lilly.com
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Siemers
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000517:prevention & control / Q000628:therapy; D015415:Biomarkers / Q000032:analysis; D002986:Clinical Trials as Topic; D003072:Cognition Disorders / Q000175:diagnosis*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D008954:Models, Biological; D018579:Patient Selection
D015415:Biomarkers
Gastroenterology. 2008 May;134(5):1570-95
18384785
N Engl J Med. 2009 Mar 26;360(13):1310-9
19297565
Ann Intern Med. 2009 Nov 17;151(10):716-26, W-236
19920272
Lancet Neurol. 2003 Mar;2(3):141-2
12849232
Ann Intern Med. 2008 Feb 5;148(3):ITC2-1-ITC2-16
18252680
JAMA. 2009 Oct 21;302(15):1685-92
19843904
Alzheimers Dement. 2006 Jul;2(3):220-33
19595891
J Gen Intern Med. 2005 Jun;20(6):487-96
15987322
Ann Neurol. 2008 Nov;64(5):492-8
19067364
Lancet Neurol. 2006 Mar;5(3):228-34
16488378
Ann Intern Med. 2007 Apr 3;146(7):511-5
17404353
N Engl J Med. 2009 Mar 26;360(13):1320-8
19297566
Lancet Neurol. 2007 Aug;6(8):734-46
17616482
Lancet. 2005 Oct 8;366(9493):1267-78
16214597
N Engl J Med. 2009 Mar 26;360(13):1351-4
19297564
Neurology. 2001 May 8;56(9):1133-42
11342677
Neurology. 1984 Jul;34(7):939-44
6610841
Neurology. 2007 May 22;68(21):1800-8
17460158
Cancer Epidemiol Biomarkers Prev. 2009 Jul;18(7):1971-8
19567507