INTRODUCTION of Minimal Cognitive Impairment

Background

Mild degrees of cognitive impairment, particularly when self-reported by patients, pose a substantial challenge to the clinician. The physician may be dealing with a patient with a mild or transient condition, a drug-induced adverse effect, or a depressive disorder; the patient may be in the early stages of a condition that will eventually lead to a dementia; or the complaint may be due to a psychological condition rather than an organic brain disorder. Because a variety of conditions may result in such a complaint, an individualized workup for such conditions and a consensus on a therapeutic approach should be sought.

In recent years, the term minimal cognitive impairment (MCI) is commonly used to refer to a stage of cognitive impairment (and specifically a subtype with memory loss [ie, amnestic MCI]) prior to attaining clinical criteria for dementia in Alzheimer disease (AD) and related disorders. However, no completely reliable means, other than long-term follow-up and eventual autopsy, exist to distinguish between patients experiencing MCI due to preclinical AD and patients experiencing MCI due to less frequently occurring conditions (Petersen, 2001). In this context, MCI is regarded as a high-risk condition that precedes AD in a large proportion of cases. It should be emphasized, however, that considerable controversy still exists considering the formulation of the concept of MCI and the practical implementation of the diagnosis. Furthermore, there is no consensus whatsoever as to treatments for this controversial condition.

In fact, the relatively recent formulation of MCI follows previous attempts to characterize cognitive decline associated with aging, including benign senescent forgetfulness, age-associated memory impairment, and age-associated cognitive decline (Crook, 1986; Kral, 1962; Levy, 1994). Therefore, this relatively new concept is perhaps best considered as a stage in the difficult process of understanding and characterizing mild defects in cognition that do not fit clearly within the scope of established neurological and psychiatric disorders.

In general, many of the previous terms imply extremes in a hypothetical process of normal aging as opposed to representing a precursor to pathological aging and dementia (eg, the "malignant" senescent forgetfulness [Kral, 1962]). Thus, in contrast with many previous terms, individuals with MCI have a condition that appears to some as different from normal aging in that long-term follow-up indicates that they tend to progress as a group to AD at an accelerated rate (Petersen, 1995; Petersen, 1999). Other terms with connotations similar to MCI include isolated memory impairment, incipient dementia, and dementia prodrome, although these latter terms are not nearly as widely accepted as MCI and they should not be considered as exact synonyms of MCI.

Pathophysiology

The pathophysiology of MCI is unknown. However, if one adopts the view that it most commonly results from AD, one hypothesis is that the disorder is associated with a gradual build-up of senile plaques and neurofibrillary tangles in areas of the cerebral cortex targeted by AD (entorhinal and perirhinal cortex) before the density of these lesions reaches the threshold necessary for the histopathologic diagnosis of AD (Morris, 2001). Similarly, the development of certain neurotransmitter deficiencies, and especially a cortical cholinergic deficiency, in the most common amnestic form of MCI is hypothesized. In the few studies undertaken to date, most patients with MCI have neuropathologic changes akin to AD, while a few individuals who are clinically similar do not have significant numbers of AD-like lesions (Mufson, 1999; Price, 1999; Troncoso, 1996). However, much larger numbers of patients with MCI must be studied before definitive statements can be made about the pathobiology of MCI.

Frequency in
United States

Annual prevalence estimates for MCI range from 17-34% among elderly populations (Barker, 1995; Larrabee, 1994; Petersen, 2001). However, note that only a relatively small amount of work has been conducted in the epidemiology of MCI because it is a comparatively recently characterized entity. In addition, most individuals evaluated in memory disorders facilities already meet the clinical criteria for dementia, justifying the perception that MCI is comparatively underrepresented in such populations.

Mortality/Morbidity

Amnestic MCI is said to progress to AD at a rate of 10-15% per year, as compared with healthy elderly individuals who develop AD at a rate of 1-2% per year. In addition, in a study from the Mayo Alzheimer's Disease Center, which monitored patients for over 10 years, the rate of conversion into AD was as high as 80% after 6 years of follow-up (Petersen, 1995). This is significant from the perspective that AD is often cast as the fourth leading cause of death in the United States.

Race

Virtually nothing is known about cultural and racial factors influencing the clinical manifestations of MCI.