Mr. R, age 67, presents with what he describes as uncharacteristic “memory loss” that is affecting his ability to run his accounting business. He and his wife relate that he was doing well until approximately 9 months ago, when he started showing difficulties remembering clients’ names and addresses.
His wife became extremely concerned when he made serious accounting errors in a 1-month period that resulted in the loss of a longtime customer. Mr. R has become easily distracted and absentminded as well, and his wife reports he is misplacing things around the house.
Screening for mild cognitive impairment (MCI) is not recommended for asymptomatic, cognitively healthy older persons, but memory complaints in individuals age >50—especially when corroborated by a reliable informant—warrant further assessment. Your challenge is to determine whether subtle cognitive changes in patients such as Mr. R are part of normal aging, caused by medical or mental illnesses, or a harbinger of Alzheimer’s disease (AD) or another dementia.
Although no treatments can yet prevent dementia, substantial new research is defining the MCI diagnosis for clinicians. This article describes:
- the evolving understanding of MCI and its subtypes
- risk factors for converting from MCI to AD
- an evidence-based work-up (including functional, cognitive, and neuropsychological testing)
- neuroprotective strategies for patients with an MCI diagnosis, including evidence on cholinesterase inhibitors, vitamin E, and anti-inflammatory agents.
MCI’s evolving definition
MCI is characterized by subjective and objective cognitive decline greater than expected for an individual’s age and education but less than the functional deficit required for a dementia diagnosis. MCI is proposed to identify persons with early but pathologic cognitive impairment that has a high risk to progress to AD and possibly other dementias.
MCI subtypes. Some experts view MCI as a single entity, whereas others suggest amnestic (aMCI) and nonamnestic (nMCI) subtypes.1,3 Each subtype is further divided into single and multiple cognitive domains. So, for example, the diagnosis would be:
- aMCI-single cognitive domain for memory impairment only
- aMCI-multiple cognitive domains for memory impairment plus nonmemory deficits, such as in language, executive function, or visuospatial function
- nMCI-single or multiple cognitive domains for nonmemory deficits without memory impairment.
Determining a patient’s MCI subtype is still a research activity and calls for comprehensive neuropsychological testing. MCI patients perform at least 1.5 standard deviations below the average for age- and education-matched healthy individuals on objective measures of memory.1
Conversion to dementia
In longitudinal population studies patients with MCI have shown an 11% to 33% risk of developing dementia within 2 years, whereas 44% reverted to normal 1 year later. Reasons for reversibility may include variable definitions of MCI among the longitudinal studies and the possibility that patients who recovered or improved may have had reversible causes of dementia.1
Individuals with aMCI (Table 1)8 progress to AD at a rate of 10% to 15% per year, compared with 1% to 2% per year in normal elderly persons. The Mayo AD research center studies reported a conversion rate of up to 80% from aMCI to AD within 6 years.9
Research focuses on identifying preclinical AD states and potential targets for intervention using disease-modifying therapies. Some experts consider MCI to be the earliest clinical manifestation of AD, at least in a subgroup of patients.
Identifying markers to predict which patients are likely to convert from MCI to dementia also is a major research objective. In addition to ApoE status (Table 2),7,9-15 predictors of conversion may include: