Neuropsychological Contributions to the Diagnosis of Mild Cognitive Impairment Associated With Alzheimer’s Disease

Mild cognitive impairment (MCI) has long been conceptualized as a transitional stage between normal aging and Alzheimer’s disease (AD) and other dementia subtypes, thus providing a potential window for early intervention in at-risk older adults. Nonetheless, effective intervention requires accurate identification of prodromal dementia, and the criteria for MCI have undergone significant evolution over the last 30 years to improve diagnostic sensitivity and specificity. There is increasing recognition of heterogeneous neuropsychological presentations in MCI. When traditional diagnostic criteria for the diagnosis of MCI have been applied a body of research employing statistical algorithms consistently demonstrated the existences of 3 to 4 unique MCI subtypes. Importantly, one subgroup that has emerged across studies involves a sizeable minority of participants that are cognitively normal on comprehensive neuropsychological assessment. These false-positives have highlighted the susceptibility of traditional Petersen/Winblad MCI criteria to diagnostic errors and demonstrated the need for developing of neuropsychological paradigms for MCI classification, and a new set of comprehensive MCI criteria using actuarial methods has been proposed. Accumulating evidence indicates that these comprehensive criteria pose an advantage over conventional criteria in the accurate identification of prodromal dementia and capture the neuropsychological and biological heterogeneity of MCI. Future research should expand on early work examining the association between empirical MCI subtypes and biological, neuroimaging, and genetic markers of AD.