Evidence-Based Reviews

Mild cognitive impairment: How can you be sure?

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Use evidence-based cognitive and functional tests to differentiate MCI from dementia and normal healthy aging.


 

References

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 is thought to be a transitional state between normal aging and dementia.1 Its estimated prevalence in the general population is 19% among individuals age 85.2

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.
MCI subtypes may have different outcomes for progression to dementia, and all progressive dementias may have their own predementia states.4 Vascular MCI, for instance, is thought to result from cerebrovascular disease and is proposed to describe a prodrome of vascular dementia.5

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

When patients with MCI are followed over time, they progress not only to AD but also to non-AD dementias. For example, patients with Parkinson’s disease (PD) and MCI may be at higher risk of progressing to dementia than cognitively intact PD patients.6 MCI patients with the e4 allele of the apolipoprotein E gene (ApoE e4) are at increased risk to convert from MCI to AD.7

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:

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