Mild cognitive impairment: Hope for stability, plan for progression
ABSTRACTMild cognitive impairment (MCI) is a common heterogeneous syndrome that in some cases is transitional between normal age-related cognitive changes and dementia. Identifying it early may lead to prompt recognition of reversible causes and allows for timely future planning. This article describes definitions of MCI and its evaluation, differential diagnosis, and management.
KEY POINTS
- MCI that primarily involves memory or multiple domains has a higher risk of progressing to dementia.
- Depression and the effects of anticholinergic medication can mimic MCI, and these should be looked for in patients presenting with cognitive loss.
- Impaired functional status as reflected in activities of daily living is an important sign of progression from MCI to dementia.
- Acetylcholinesterase inhibitors are not approved for treating MCI, have shown little efficacy in altering progression to dementia, and have multiple side effects.
- Enhancing physical and mental health and developing strategies to compensate for deficits are key management approaches.
EARLY RECOGNITION ALLOWS PROMPT EVALUATION AND PLANNING
Pathologic cognitive decline is best detected early, for many reasons. Early recognition and intervention may help delay further decline. Establishing a diagnosis can also lessen family and caregiver stress and misunderstanding. Education of caregivers is important so that they can prepare for likely behavioral changes and plan for future care. Advance care planning, including advance directives, power of attorney, and designation of proxy for decision-making, is extremely important and is best considered before cognitive impairment becomes severe.
The diagnosis of MCI also provides the opportunity to assess safety concerns related to driving, working, medication compliance, the home environment, and firearms. Because patients with MCI are still highly functional, these issues need not be fully evaluated and should be handled on a case-by-case basis, depending on concerns raised. For example, if depression is an active concern, firearms safety should be addressed.
MEMORY LOSS MAY NOT BE THE PRIMARY CONCERN
MCI is categorized into two types based on whether memory loss is the primary cognitive deficit.
The amnestic type predominantly involves memory problems and is more common. Generally, several years elapse between initial memory concerns and a clinical diagnosis of MCI. Patients with amnestic MCI that progresses to dementia are more likely to develop Alzheimer disease.2,15
Nonamnestic types involve domains of cognition other than memory, such as executive function, attention, visuospatial ability, and language. Nonamnestic MCI can be subcategorized through extensive neuropsychological evaluation as involving single or multiple impaired domains.16,17 Such categorization is particularly important in determining prognosis, as patients with involvement of multiple domains are at higher risk of progressing to dementia.
Patients with nonamnestic MCI who progress to dementia are more likely to have non-Alzheimer types of dementia, such as Lewy body dementia and frontotemporal dementias.10
HISTORY SHOULD FOCUS ON FUNCTION, MEDICATIONS, AND DEPRESSION
Cognitive impairment should be clinically evaluated within the context of cognition, function, and behavior. Clinicians should focus on the time course of cognitive concerns, the specifics of the concerns, and their impact on day-to-day living and functioning. In assessing functional capacity, it is important to determine the level of assistance the patient needs to perform specific activities of daily living and instrumental activities of daily living (ie, the more advanced skills needed to live independently) (Table 2).
A thorough history includes consideration of baseline education, intellect, and previous learning disabilities; sensory impairments with emphasis on sight and hearing impairments; uncontrolled pain; head trauma; sleep disorders; concurrent medical and psychosocial illnesses such as depression and anxiety; substance abuse; and polypharmacy.
Depression, delirium, and the use of anticholinergic drugs are particularly important to evaluate, as these can result in cognitive deficits associated with MCI. The cognitive deficits may resolve with treatment or with stopping the drug.
Behavioral concerns such as wandering, agitation, and anger and sleep concerns, eating habits, and social etiquette are also important to evaluate.
PHYSICAL EVALUATION: RULE OUT REVERSIBLE CONDITIONS
The differential diagnosis of MCI includes delirium, depression, dementia, possibly reversible conditions affecting cognition (vitamin B12 deficiency, hypothyroidism, effects of anticholinergic drugs), and uncommonly, central nervous system conditions (normal pressure hydrocephalus, subdural hematoma, tumor, stroke), and others (Table 3).18
A thorough physical examination should include neurologic, cardiovascular, hearing, and vision examinations, as well as an evaluation of functional status.
Laboratory studies. Although evidence is lacking to support a laboratory diagnostic workup for MCI, a selective evaluation including a comprehensive metabolic profile, complete blood count, thyroid studies, and a vitamin B12 level can be useful. Occasionally, a treatable cause of impaired cognition such as vitamin B12 deficiency or thyroid disease can be identified and resolved. A further comprehensive laboratory evaluation should be obtained if a patient progresses to dementia.
Imaging can be used in conjunction with other supportive evidence but should not be used solely to establish a diagnosis of MCI. Magnetic resonance imaging (MRI) can detect metastatic disease, normal pressure hydrocephalus, and subdural hematoma, in addition to traumatic, inflammatory, infectious, and vascular causes of cognitive impairment. MRI can also determine focal areas of atrophy; temporal lobe atrophy is a risk factor for progression to dementia.
Other studies. Structural MRI using techniques to evaluate the hippocampus, functional imaging, genetic testing for ApoE4 alleles, and biomarkers in cerebrospinal fluid are currently under evaluation to identify those at risk of progression to dementia. Recently published guidelines by the Alzheimer’s Association and the National Institute on Aging indicate that pathophysiologic findings in MCI that may predict future Alzheimer disease are meant to guide research and are not part of clinical practice at this time.19
COGNITIVE AND NEUROLOGIC TESTING IDENTIFIES DEFICITS
A number of global measures of cognition can be used in the office in clinical practice to help in evaluating significant cognitive concerns and to determine areas and severity of deficits at presentation. These include the Mini-Mental State Examination, the Montreal Cognitive Assessment, the Saint Louis University Mental Status, and many others (Table 4).20
Caveats about interpreting the results: each of these tests has different sensitivities and specificities for detecting MCI. Also, we need to take into account the patient’s level of education, as highly educated people tend to do better on these tests.21–23 It is important to note that some patients with MCI have normal results or only minimally abnormal results on these tests.
Neuropsychological testing is reserved for patients needing further evaluation, eg, those with atypical or complex cases, and those in whom the specific domains of cognition involved need to be identified. It can also provide additional insight into the contribution of depression to cognitive deficits. Neuropsychological testing is usually very time-intensive and requires patients to be able to perform complicated cognitive tasks. Not all patients are good candidates for this testing; sensory and motor impairments must be considered to determine if patients can adequately participate in testing. The cost of neuropsychological testing for MCI may not be covered by insurance and should be discussed with patients before referral. Specific concerns about cognitive problems that need further evaluation should be stated in the referral.
No one test should be used to make a diagnosis of MCI or dementia; clinical judgment is also necessary. The need for referral to a neurologist, geriatrician, or psychiatrist depends on the nature of the cognitive and behavioral concerns, the complexity of making a diagnosis, the need for further assessment of functional ability, and the need for evaluation of risk of progression to dementia.
