Challenges of epidemiological studies of mild cognitive impairment.

The concept of intermediate stages of cognitive impairment is receiving a great deal of attention in the literature. The study by Meguro and colleagues on the Tajiri Project in Japan reported in the current issue of Alzheimer’s Disease and Associated Disorders is an example of the international attention being paid to this topic. The Tajiri Project not only highlights the importance of clarifying certain issues surrounding subject selection and implementation of clinical criteria but also demonstrates some of the challenges in interpreting the literature. The study raises important issues in assessing the epidemiology of MCI. The primary challenge faced by these investigators and others trying to estimate the incidence and prevalence of MCI from ongoing studies concerns the application of the criteria to existing data sets. Out of necessity, investigators must retrofit clinical MCI criteria to epidemiological data collected for other purposes. Therefore, the investigators can only approximate the operationalization of the MCI criteria to suit their database. The typical criteria for what is now called amnestic MCI are as follows: 1) memory complaint, preferably corroborated by an informant, 2) objective memory impairment relative to appropriate reference group, 3) essentially normal general cognition, 4) largely preserved activities of daily living, and 5) not demented. Difficulties arise in trying to apply these criteria to epidemiological data collected in the field. The Tajiri Project represents an example of this challenge. The primary cognitive data available to the investigators are derived from the Cognitive Assessment Screening Instrument (CASI). The CASI is a screening tool that out of necessity is brief and does not involve detailed assessments of any cognitive domain. For example, to implement criterion # 2 for MCI concerning an objective memory impairment, the investigators had to use the memory assessment tasks available to them, a three word recall task and immediate recall of five figures. In addition, the authors used a cutoff score of 1.5 standard deviations (SD) below appropriate comparison norms as suggested by the “Mayo criteria. ” In fact, the Mayo criteria are implemented using clinical judgment and not cutoff scores. The subjects described in the Mayo series who met criteria for amnestic MCI had a mean performance on a variety of memory instruments of approximately 1.5 SD below appropriate comparison norms. However, it is important to note that many subjects had memory impairments less severe than 1.5 SD below the mean, and some may have been impaired on one memory test, eg, the Auditory Verbal Learning Test, but not another test, eg, The Wechsler Memory Scale-Revised Logical Memory II. No single memory instrument or cutoff score was used in making this determination. Clinical judgment was used to fulfill the criterion of an objective memory impairment using performance on several different memory instruments of moderate difficulty. The Tajiri Project used only recall of three items after interference (like the memory item from the Mini-Mental State Examination) and immediate recall of five figures. Neither of these tests is believed to be adequate assessments of memory function as required for the diagnosis of amnestic MCI. The three-word memory instrument is insensitive to early changes of cognition and immediate recall of five figures is also inadequate since it does not employ a delayed recall procedure. Consequently, by the time subjects are impaired at the level of 1.5 SDs below appropriate education groups on these less challenging instruments, they are likely significantly impaired in other cognitive domains as well and are probably