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.
MEDICATIONS HAVE LITTLE ROLE IN MANAGEMENT
No drug has yet been approved by the US Food and Drug Administration for treating MCI.
The acetylcholinesterase inhibitors donepezil (Aricept), galantamine (Razadyne), and rivastigmine (Exelon) have undergone clinical trials for treatment of MCI but have not been definitely shown to significantly reduce the risk of progression to dementia.24
On the other hand, Diniz et al25 performed a meta-analysis of the use of cholinesterase inhibitors in patients with MCI as a means of delaying the progression to Alzheimer disease.25 They calculated that 15.4% of patients who received these drugs progressed to dementia, compared with 20.4% of those who received placebo, for a relative risk of 0.75 (95% confidence interval 0.66–0.87, P < .001). They concluded that the use of these drugs in patients with MCI “may attenuate the risk of progression” to Alzheimer disease and dementia.
In addition to not being approved for this indication and showing mixed evidence of efficacy, these drugs have well-known side effects such as diarrhea, nausea, vomiting, anorexia, and rhinitis, as well as significant but lesser-known side effects such as syncope, bradycardia, gastrointestinal bleeding, and vivid dreams.26
Nevertheless, some patients with MCI, particularly those at high risk with amnestic MCI, may still want to try these medications. In these cases, the risks and possible benefits (or lack of them) should be reviewed thoroughly with the patient and family, and the discussion should be documented before starting therapy. The lowest starting dose of acetylcholinesterase inhibitor should be used to determine tolerability; generally, the dose is increased after 4 weeks to a maintenance dosage, with particular consideration of side effects.
Other agents have also been evaluated for MCI but have shown no evidence of benefit. Nonsteroidal anti-inflammatory drugs have not been found to either improve symptoms or delay progression to dementia. Ginkgo biloba has shown unclear benefit in achieving important treatment goals for MCI,27 and it increases the risk of bleeding in the elderly. Vitamin E was evaluated in one study and did not slow progression to dementia.28
STAYING HEALTHY AND ACTIVE MAY HELP
We recommend optimizing vascular risk factors such as diabetes, blood pressure, smoking, and lipid levels in managing MCI, given that uncontrolled vascular risk factors may lead to progression to dementia. However, we can point to no research to support this recommendation.
Cognitive rehabilitation involves training in deficient domains and developing strategies to compensate for deficits. Different interventions are used, including computerized simulation exercises, memory aids, organizational techniques, personal digital assistants, crossword puzzles, mind games, and other mentally engaging activities.29
Increasing physical activity is another aspect of treatment. Some studies have shown that it improves cognitive performance in MCI, at least in the short term.30,31
Optimizing mood and emotions is also important. If present, depression should be identified and optimally treated. Social activity can be useful and leads to less emotional stress and to better coping mechanisms.
A multidisciplinary approach may help patients and may also help relieve the burden on the caregiver. Periodic reassessment of cognitive and functional symptoms may be warranted.
Maintaining disease-specific registries of patients who have MCI may be useful to longitudinally follow patients and ensure that they get the care they need.
PROGNOSIS VARIES
MCI is a heterogeneous condition that often does not predictably progress to dementia. Patients and families should be told that having MCI does not mean that the patient will necessarily get dementia.
Several studies have shown that the annual risk of progression to dementia for patients with MCI is 5% to 10% in community-dwelling populations and up to 15% in specialty-clinic patients.24,32 In comparison, the incidence of dementia in the general elderly population is 1% to 3% per year.
On the other hand, a number of studies show that MCI improves significantly in up to 15% to 40% of patients and sometimes reverts to a normal cognitive state.33,34 But prospective studies of patients with clinically diagnosed MCI usually find a low rate of reversion to a normal state.35,36 Many are short-term follow-up studies of different populations, making generalizations difficult.14
Patients with impairment in instrumental activities of daily living may be more likely to have nonreversible MCI and may be at higher risk of progressing to dementia.37
PATIENT AND FAMILY EDUCATION AND FOLLOW-UP CONSIDERATIONS
Caregiver education and stress management are important components of managing patients with MCI. Formally assessing caregiver stress is useful. Steps to prevent caregiver burnout include making use of respite care, counseling, education, and community resources such as adult day care and those offered by the Alzheimer’s Association.
Clinicians should follow patients with MCI closely to evaluate progression, address specific concerns, minimize risks, emphasize healthy habits, manage concurrent illnesses, and evaluate management.
Functional status, as demonstrated by activities of daily living, is the most important determinant of progression of MCI to dementia and should be evaluated at each visit. Repeat cognitive testing should be done on patients who have significant loss of functional status. Changes in work habits also warrant further attention.
Patients diagnosed with MCI or those who have persistent cognitive concerns should be considered for neuropsychological evaluation after 1 year to assess specific deficits and progression of cognitive impairment.
Finally, consideration should be given to current clinical research, and referrals should be made to research centers that focus on MCI management and treatment.
