Do MCI criteria in drug trials accurately identify subjects with predementia Alzheimer's disease?
BACKGROUND
Drugs effective in Alzheimer-type dementia have been tested in subjects with mild cognitive impairment (MCI) because these are supposed to have Alzheimer's disease in the predementia stage.


OBJECTIVE
To investigate whether MCI criteria used in these drug trials can accurately diagnose subjects with predementia Alzheimer's disease.


METHODS
MCI criteria of the Gal-Int 11 study, InDDEx study, ADCS memory impairment study, ampakine CX 516 study, piracetam study, and Merck rofecoxib study were applied retrospectively in a cohort of 150 non-demented subjects from a memory clinic. Forty two had progressed to Alzheimer type dementia during a five year follow up period and were considered to have predementia Alzheimer's disease at baseline. Outcome measures were the odds ratio, sensitivity, specificity, and positive and negative predictive value.


RESULTS
The odds ratio of the MCI criteria for predementia Alzheimer's disease varied between 0.84 and 11. Sensitivity varied between 0.46 and 0.83 and positive predictive value between 0.43 and 0.76. None of the criteria combined a high sensitivity with a high positive predictive value. Exclusion criteria for depression led to an increase in positive predictive value and specificity at the cost of sensitivity. In subjects older than 65 years the positive predictive value was higher than in younger subjects.


CONCLUSIONS
The diagnostic accuracy of MCI criteria used in trials for predementia Alzheimer's disease is low to moderate. Their use may lead to inclusion of many patients who do not have predementia Alzheimer's disease or to exclusion of many who do. Subjects with moderately severe depression should not be excluded from trials in order not to reduce the sensitivity.
Visser
P J
PJ
Department of Psychiatry, University Hospital Maastricht and Alzheimer Centre Limburg, Maastricht, Netherlands. pj.visser@np.unimaas.nl
Scheltens
P
P
Verhey
F R J
FR
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005702:Galantamine / Q000627:therapeutic use*; D006801:Humans; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D008569:Memory Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D010889:Piracetam / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013450:Sulfones / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002800:Cholinesterase Inhibitors; D007783:Lactones; D018696:Neuroprotective Agents; D013450:Sulfones; D005702:Galantamine; C116926:rofecoxib; D010889:Piracetam