eMedicine Specialties > Neurology > Behavioral Neurology and Dementia

Mild Cognitive Impairment

Author: Heather S Anderson, MD, Assistant Professor, Staff Neurologist, Department of Neurology, Alzheimer and Memory Center, University of Kansas Medical Center
Coauthor(s): Rodrigo O Kuljis, MD, Esther Lichtenstein Professor of Psychiatry and Neurology, Director, Division of Cognitive and Behavioral Neurology, Department of Neurology, University of Miami School of Medicine
Contributor Information and Disclosures

Updated: Nov 24, 2008

Introduction

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 a complaint of cognitive impairment, an individualized workup for such conditions and a consensus on a therapeutic approach should be sought.

Normal expected age-related memory functions

• Memory functions that remain relatively stable with increasing age
  • Semantic memory - Facts and general knowledge about the world; remains stable with age, especially if the information is used frequently¹ (However, retrieval of highly specific information, such as names, typically declines.)
  • Procedural memory – Acquisition and later performance of cognitive and motor skills¹
• Memory functions that decrease with age
  • Working memory - Holding and manipulating information in the mind such as reorganizing a short list of words into alphabetical order¹ ; verbal and visuospatial working speed, memory, and learning, with visuospatial cognition more affected by aging than verbal cognition²
  • Episodic memory – Personal events and experiences¹
  • Processing speed³
  • Prospective memory – The ability to remember to perform an action in the future such as remembering an appointment or to take a medication¹

To demonstrate that cognitive function is worse than expected for age, neuropsychological testing is necessary so that a patient’s performance can be compared with that of an age-matched (and ideally education-matched) control group.
 
Mild cognitive impairment (MCI) represents a stage of cognitive impairment that exceeds the normal expected age-related changes, but functional activities are largely preserved and so MCI does not meet the criteria for dementia.⁴ Different subtypes of MCI are recognized. One common classification distinguishes between amnestic and nonamnestic forms of MCI. The amnestic form, where memory impairment predominates, is often a precursor for clinical Alzheimer’s disease. A variety of types of cognitive impairments may occur in nonamnestic forms of MCI, with the most common impairment probably being executive function. This form of nonamnestic MCI may be associated with cerebrovascular disease or may be a precursor for some frontotemporal dementias. A substantial number of patients with MCI may be judged as having normal cognition on follow-up visit.

Ultimately, long-term follow-up and eventual autopsy are necessary to distinguish between patients experiencing MCI due to preclinical Alzheimer’s disease and patients experiencing MCI due to less frequently occurring conditions. However, some factors can be helpful in predicting the likelihood of progression. The severity of memory impairment is predictive of progression to Alzheimer’s disease; those patients with more severe memory impairment are more likely to progress. Patients with nonamnestic MCI (ie, impairment in language, executive function, or visuospatial skills, in addition to memory) have been found to have higher rates of mortality compared with patients with memory-only (amnestic) MCI.⁵ Whole brain and hippocampal volume on MRI imaging has been shown to be predictive of progression from MCI to Alzheimer's disease⁶ , as has apolipoprotein E (ApoE) status⁷ ; however, ApoE testing is not recommended for routine clinical use. 

No medications have been FDA approved for the treatment of MCI.

Previous attempts have been made to characterize cognitive decline associated with aging, including benign senescent forgetfulness, age-associated memory impairment, and age-associated cognitive decline.^8,9,10 The term MCI is intended to represent an intermediate stage between normal aging and the development of pathological aging and dementia (eg, the malignant senescent forgetfulness⁹ ). 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.

Pathophysiology

The pathophysiology of mild cognitive impairment is multifactorial. Most cases of the amnestic form of MCI result from the pathological changes of Alzheimer’s disease that are not yet severe enough to cause clinical dementia.¹¹ At least in specialty research populations, autopsies in amnestic MCI have found the neuropathology to be typical of Alzheimer’s disease.¹² Nonamnestic MCI may be associated with cerebrovascular disease, frontotemporal dementias, or no specific pathology.

Frequency

United States

Annual prevalence estimates for mild cognitive impairment range from 3-4% in the eighth decade¹³ in the general population and 19.2% for ages 65-74 years, 27.6% for ages 75-84 years, and 38% for ages 85 years and older¹⁴ among community-dwelling African Americans.

See Medscape’s CME activity Mild Cognitive Impairment Affects 22% of Those 71 Years of Age and Older.

Mortality/Morbidity

Subtypes of mild cognitive impairment progress to Alzheimer's disease at different rates. A study by Roundtree et al showed that the conversion rate to Alzheimer's disease for amnestic MCI was 56%, for amnestic-subthreshold MCI was 50%, and for nonamnestic MCI was 52%.¹⁵ For all MCI subtypes, the 4-year conversion to dementia was 56% (14% annually) and to Alzheimer's disease was 46% (11% annually).¹⁵ This was compared with healthy elderly individuals who develop Alzheimer's disease at a rate of 1-2% per year. Boyle et al reported that patients with MCI are almost 7 times more likely to develop Alzheimer's disease compared with older individuals without cognitive impairment.¹⁶  Of patients with MCI, 80% are said to progress to dementia after approximately 6 years. This is significant from the perspective that Alzheimer's disease 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 mild cognitive impairment.

Sex

Many studies indicate that the risk of Alzheimer’s disease is significantly higher in women than in men, and it is therefore presumed that the likelihood of developing mild cognitive impairment is greater in women than in men.

Age

The prevalence of mild cognitive impairment increases with age. The prevalence is 10% in those aged 70-79 years and 25% in those aged 80-89 years.¹⁷

Clinical

History

Patients with mild cognitive impairment (MCI) often present with vague and subjective symptoms of declining cognitive performance, which may be difficult to distinguish from the decline in such performance affecting healthy older individuals. The most common symptom is said to be memory loss, consistent with the prevalent view that the amnestic form of memory loss is the most common type of MCI. However, some authorities affirm that the most common form of MCI affects multiple spheres of cognition. Less common presentations include language disturbance (eg, word-finding difficulty), attentional deficit (eg, difficulty following or focusing on conversations), and deterioration in visuospatial skills (eg, disorientation in familiar surroundings in the absence of motor and sensory conditions that would account for the complaint).

Dissociating purely cognitive symptoms from those attributable to various degrees of sensory deprivation (eg, hearing loss, loss of visual acuity) that tend to coexist in the same patient population is often difficult and may be compounded by motor deficits that also beset the same individuals. In any case, the defining element of MCI, as postulated by Petersen, is a single sphere of slowly progressive cognitive impairment not attributable to motor or sensory deficits, to which other areas of involvement may eventually be added, before social or occupational impairment supervenes (because this marks the onset of dementia).⁴ Virtually nothing is known about the average duration of these manifestations before they are usually (if ever) brought to medical attention.

Physical

No feature of the general physical examination is characteristic of mild cognitive impairment (MCI). However, a physical examination should be performed as part of the general evaluation in an effort to determine whether conditions capable of causing MCI are present (eg, signs of thyroid disease, cobalamin deficiency, or venereal disease) and whether sensory and motor deficits are present that could explain or compound the symptoms. Mental status examination is also important to document the degree of cognitive dysfunction. 

See Medscape’s CME activity Everyday Cognition Questionnaire Helps Assess Cognitive Function in Older Adults.

Causes

Mild cognitive impairment is heterogeneous both in its clinical manifestations and in its etiology. Amnestic MCI often results from Alzheimer’s disease pathology, and most patients with amnestic MCI progress to clinical Alzheimer’s disease within 6 years. Nonamnestic forms of MCI may be due to cerebrovascular disease, Lewy body dementia, or Parkinson's disease, frontotemporal dementias, atypical Alzheimer's disease, or no specific underlying pathology. Mood disorders, medical illness, and medications may affect cognition such that a patient will meet criteria for MCI (usually nonamnestic MCI). Many such patients have normal neuropsychological testing when reevaluated a year later.

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