“Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology”: Links And Excerpts

In this post, I link to and excerpt from Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology [PubMed Abstract] [Full-Text HTML] [Full-TextPDF]. Neurology. 2018 Jan 16;90(3):126-135. doi: 10.1212/WNL.0000000000004826. Epub 2017 Dec 27.

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Objective: To update the 2001 American Academy of Neurology (AAN) guideline on mild cognitive impairment (MCI).

Methods: The guideline panel systematically reviewed MCI prevalence, prognosis, and treatment articles according to AAN evidence classification criteria, and based recommendations on evidence and modified Delphi consensus.

Results: MCI prevalence was 6.7% for ages 60-64, 8.4% for 65-69, 10.1% for 70-74, 14.8% for 75-79, and 25.2% for 80-84. Cumulative dementia incidence was 14.9% in individuals with MCI older than age 65 years followed for 2 years. No high-quality evidence exists to support pharmacologic treatments for MCI. In patients with MCI, exercise training (6 months) is likely to improve cognitive measures and cognitive training may improve cognitive measures.

Major recommendations: Clinicians should assess for MCI with validated tools in appropriate scenarios (Level B). Clinicians should evaluate patients with MCI for modifiable risk factors, assess for functional impairment, and assess for and treat behavioral/neuropsychiatric symptoms (Level B). Clinicians should monitor cognitive status of patients with MCI over time (Level B). Cognitively impairing medications should be discontinued where possible and behavioral symptoms treated (Level B). Clinicians may choose not to offer cholinesterase inhibitors (Level B); if offering, they must first discuss lack of evidence (Level A). Clinicians should recommend regular exercise (Level B). Clinicians may recommend cognitive training (Level C). Clinicians should discuss diagnosis, prognosis, long-term planning, and the lack of effective medicine options (Level B), and may discuss biomarker research with patients with MCI and families (Level C).

Practice recommendations

Section A: Recommendations for assessing for MCI

Recommendation A1


For patients for whom the patient or a close contact voices concern about memory or impaired cognition, clinicians should assess for MCI and not assume the concerns are related to normal aging (Level B).

Recommendation A2


In the United States, the Medicare Annual Wellness Visit requires an assessment to detect cognitive impairment.e31 Subjective cognitive complaints alone can result in overdiagnosis or underdiagnosis of MCI and thus are insufficient to screen for MCI.e29 Clinicians assessing for cognitive impairment should use a brief, validated cognitive assessment instrument in addition to eliciting patient and informant history regarding cognitive concerns.


When performing a Medicare Annual Wellness Visit, clinicians should not rely on historical report of subjective memory concerns alone when assessing for cognitive impairment (Level B).

Recommendation A4


In the presence of cognitive impairment, clinicians need to distinguish between a diagnosis of MCI and one of dementia, although the boundary is not always clear. Diagnosing dementia prematurely can lead to negative consequences for patients and families. Only a proportion of patients with MCI will proceed to dementia. In patients with cognitive impairment, clinicians must carefully assess for evidence of functional impairment limiting independence in daily activities (e.g., by taking a careful history from the patient and a close contact), a requirement for all dementia diagnoses, to help distinguish between MCI and dementia. With a specific inquiry about functional impairment, clinicians may also identify dementia in patients when patients and family are less forthcoming about functional problems.


For patients with MCI, clinicians should assess for the presence of functional impairment related to cognition before giving a diagnosis of dementia (Level B).

Recommendation A5


For patients suspected to have MCI, clinicians who lack the necessary experience should refer these patients to a specialist with experience in cognition (Level B).

Recommendation A6


Although MCI is a high-risk state for progression to dementia, some patients with MCI remain stable and some improve. Some cases of MCI are associated with reversible causes of cognitive impairment, including medication side effects, sleep apnea, depression, and other medical conditions.e33 Patients with MCI should undergo a medical evaluation for MCI risk factors that may be treatable.


For patients diagnosed with MCI, clinicians should perform a medical evaluation for MCI risk factors that are potentially modifiable (Level B).

Recommendation A7


Because patients with MCI can improve, remain stable, or progress cognitively, identifying biomarkers that can stratify risk is expected to be particularly important for prognosis. The use of biomarkers in patients with MCI is a rapidly evolving field,e34–e36 but to date, there are no biomarkers clearly shown to predict progression in patients with MCI.e37

Recommendation A7a

For patients and families asking about biomarkers in MCI, clinicians should counsel that there are no accepted biomarkers available at this time (Level B).

Recommendation A7b

For interested patients, clinicians may discuss the option of biomarker research or refer patients, or both, if feasible, to centers or organizations that can connect patients to this research (e.g., subspecialty centers, Trial Match, ClinicalTrials.gov) (Level C).

Recommendation A8


Because patients with MCI can improve, remain stable, or progress cognitively over time, patients must be monitored serially for changes in status that could change diagnosis and thus management approach (e.g., treatment, counseling). Although MCI has no approved pharmacologic management, there are US Food and Drug Administration (FDA)–approved agents for treatment of Alzheimer dementia,e38–e42 further emphasizing the importance of assessing for a change in cognitive status over time.


For patients diagnosed with MCI, clinicians should perform serial assessments over time to monitor for changes in cognitive status (Level B).

Section B: Recommendations for management of MCI

Recommendation B1


Some patients with MCI improve or remain stable rather than progress. In addition, some cases of MCI are associated with reversible causes of cognitive impairment, including medication side effects, general medical conditions, sleep disturbance, and depression.e33 Because these risk factors are treatable and have implications of their own, weaning patients from use of cognitively impairing medications where feasible and treating risk factors that may contribute to cognitive impairment should be the first steps in managing MCI, particularly because symptomatic treatment options are limited for impaired cognition.


For patients diagnosed with MCI, clinicians should wean patients from medications that can contribute to cognitive impairment (where feasible and medically appropriate) and treat modifiable risk factors that may be contributing (Level B).


Recommendation B2


There are no FDA-approved medications for the treatment of MCI. Moreover, there are no high-quality, long-term studies identifying pharmacologic or dietary agents that either improve cognition or delay progression in patients with MCI.


For patients diagnosed with MCI, clinicians should counsel the patients and families that there are no pharmacologic or dietary agents currently shown to have symptomatic cognitive benefit in MCI and that no medications are FDA-approved for this purpose (Level B).

Recommendation B3


Studies of cholinesterase inhibitors showed no benefit on cognitive outcomes or reduction in progression from MCI to dementia, although some studies could not exclude an important effect. In addition to lacking efficacy, side effects of cholinesterase inhibitors are common, including gastrointestinal symptoms and cardiac concerns.e43

Recommendation B3a

For patients diagnosed with MCI, clinicians may choose not to offer cholinesterase inhibitors (Level B).

Recommendation B3b

If clinicians choose to offer cholinesterase inhibitors, they must first discuss with patients the fact that this is an off-label prescription not currently backed by empirical evidence (Level A).

Recommendation B4


Clinical trials provide an opportunity for interested patients to participate in identifying or testing new treatment options, which is of particular importance when no pharmacologic options are available.


For patients diagnosed with MCI who are interested in pharmacologic treatment, clinicians may inform these patients of centers or organizations that can connect patients to clinical trials (e.g., subspecialty centers, Trial Match, ClinicalTrials.gov) (Level C).

Recommendation B5


Although long-term studies are unavailable, 6-month studies suggest a possible benefit of twice-weekly exercise for cognition in MCI. Exercise also has general health benefits and generally limited risk.


For patients diagnosed with MCI, clinicians should recommend regular exercise (twice/week) as part of an overall approach to management (Level B).

Recommendation B6


Because the concept of MCI may be poorly understood or distressing to patients and families, it is important to educate patients and families regarding the diagnosis of MCI and how it may progress to dementia but also how individuals with MCI can remain stable or improve. Because MCI may progress to dementia, and particularly because of the lack of effective pharmacologic therapy or any proven methods to reduce the risk of progression of MCI to dementia, it is particularly important to educate patients with MCI regarding their diagnosis and prognosis at the MCI stage while they can still understand the discussion and participate in planning, even though they may or may not progress. Because of the possibility of progression to a dementia state where patients may no longer be able to participate in decision making, patients with MCI should be encouraged to participate in long-term planning, including topics such as advance directives, living wills, power of attorney designations, and finances, which are important irrespective of progression.


For patients diagnosed with MCI, clinicians should discuss diagnosis and uncertainties regarding prognosis. Clinicians should counsel patients and families to discuss long-term planning topics such as advance directives, driving safety, finances, and estate planning (Level B).

Recommendation B7


Although there are no treatments for cognitive symptoms in MCI, clinicians need to evaluate for and treat other symptoms that can contribute to quality of life in MCI. Behavioral/psychiatric symptoms are common in MCIe44–e46 and may be associated with greater functional impairmente47 and an increased risk of progression from MCI to dementia.e48,e49


Clinicians should assess for behavioral and neuropsychiatric symptoms in MCI and treat with both pharmacologic and nonpharmacologic approaches when indicated (Level B).

Recommendation B8


In patients with MCI, cognitive interventions may be beneficial in improving measures of cognitive function. It is good practice to offer nonmedication approaches to care.


In patients with MCI, clinicians may recommend cognitive interventions (Level C).

Suggestions for future research

The guideline panel recommends (1) the use of consistent diagnostic criteria for MCI and dementia in clinical trials, to improve the ability to apply and combine results; (2) the inclusion of patient cohorts with specific biomarker data in treatment studies targeted at specific pathologies (e.g., MCI due to AD); (3) the use of outcome measures that are direct measures of clinically meaningful patient outcomes (i.e., development of dementia, reduction of ability to undertake activities of daily living or IADL, patient or caregiver [or both] quality of life measures) or surrogate markers that have previously been shown to have a strong correlation with such measures; (4) standardized reporting of trial design in publications using CONSORT criteriae50; (5) study of MCI thought to be secondary to AD and MCI related to other pathologies (e.g., vascular MCI, MCI related to Lewy body pathology); and (6) further study of early lifestyle and comorbidity modifications and the effects of such changes on the progression of MCI to different dementia subtypes.

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