> Table of Contents > Mild Cognitive Impairment
Mild Cognitive Impairment
Birju B. Patel, MD, FACP, AGSF
N. Wilson Holland, MD, FACP, AGSF
image BASICS
  • Mild cognitive impairment (MCI) is defined as significant cognitive impairment in the absence of dementia, as measured by standard memory tests:
    • Concern regarding change in cognition
    • Preservation of independence in functional activities (ADLs)
    • Impairment in ≥1 cognitive domains (attention, executive dysfunction, memory, visuospatial, language) (1)
    • Other terms used in the literature relating to MCI: isolated memory impairment; cognitive impairment not dementia (CIND); predementia; mild cognitive disorder; age-associated memory impairment; age-related cognitive decline; benign senescent forgetfulness. Some of these conditions do not progress to dementia (i.e., benign senescent forgetfulness, age-associated memory impairment, age-related cognitive decline). DSM-5 mentions “mild neurocognitive disorder” (NCD) which may be a precursor to Alzheimer disease and has many of the same features as MCI (2).
  • Annual rates of conversion of MCI to dementia are 2-15% in the elderly.
  • Predominant sex: male > female (3)
  • Predominant age:
    • Higher in older persons and in those with less education
    • 12 to 15/1,000 person-years in those age ≥65 years
    • 54/1,000 person-years in those age ≥75 years
  • MCI is more prevalent than dementia in the United States.
  • 3-5% for those age ≥60 years
  • 15% for those age ≥75 years
  • Subtypes of MCI:
    • Single-domain amnestic
    • Multiple-domain amnestic
    • Nonamnestic single-domain
    • Nonamnestic multiple-domain
  • The amnestic subtype is higher risk for progression to Alzheimer disease (4).
  • Vascular, degenerative, traumatic, metabolic, psychiatric, or a combination
Apolipoprotein (APO) E4 genotype: Various pathways exist leading to amyloid accumulation and deposition thought to be associated with dementia.
  • Age
  • Diabetes
  • Hypertension
  • Hyperlipidemia
  • Cerebrovascular disease
  • Smoking
  • Sleep apnea
  • APO E4 genotype
See “Risk Factors” (5).
  • A general exam focusing on clinical clues to identifying vascular disease (e.g., bruits, abnormal BP)
  • Neurologic exam to rule out reversible CNS causes cognitive impairment or other causes of cognitive impairment (e.g., Parkinson disease).
  • Office measures of cognitive function, depression, and functional status
  • Delirium
  • Dementia
  • Depression
  • “Reversible” cognitive impairment
    • Medications (anticholinergics and medications with anticholinergic properties)
    • Hypothyroidism
    • Vitamin B12 deficiency
  • Reversible CNS conditions
  • Give consideration to sleep conditions, especially sleep apnea, that can contribute to cognitive deficits.
Initial Tests (lab, imaging)
  • CBC
  • Comprehensive metabolic profile
  • Thyroid-stimulating hormone
  • Vitamin B12
  • Lipids
  • Consider HIV testing in the appropriate risk setting.
  • Imaging tests are helpful when there are focal neurologic deficits or rapid or atypical presentations:
    • CT scan can detect structural CNS conditions leading to cognitive impairment:
      • Subdural hematoma
      • Normal pressure hydrocephalus
      • Metastatic disease
    • MRI further evaluates vascular, infectious, neoplastic, and inflammatory conditions.
  • Cognitive testing is important (e.g., Montreal Cognitive Assessment [MOCA] and Saint Louis University Mental Status [SLUMS]); MOCA may be more sensitive for detecting and following MCI.
  • Neuropsychological testing for complex and atypical presentations
  • Vascular risk factor reduction and treatment
Follow-Up Tests & Special Considerations
  • Document progression of functional impairment, cognitive decline, concurrent depression, and comorbid conditions.
  • Advanced planning while patient is competent.
  • Early education of caregivers on safety, maintaining structure, managing stress, and future planning
Test Interpretation
  • Little is known about MCI pathology due to a lack of longitudinal studies.
  • Alzheimer dementia pathophysiology:
    • Neurofibrillary tangles in hippocampus
    • Senile plaques (amyloid deposition)
    • Neuronal degeneration
  • Those with MCI have intermediate amounts of pathologic findings of Alzheimer disease with amyloid deposition and neurofibrillary tangles in the mesial temporal lobes compared with those with dementia.
  • Amnestic MCI is associated with white matter hyperintensity volume on MRI, whereas nonamnestic MCI is associated with infarcts.

Atherosclerotic risk factors should be treated aggressively.
The use of cholinesterase inhibitors (ChEIs) in MCI is not associated with any delay in the onset of Alzheimer disease or dementia. Moreover, the safety profile showed that the risks associated with ChEIs are significant. Therefore, ChEIs are not routinely recommended (6)[A],(7)[C].
Consider referral to a memory specialist (i.e., geriatrician, neurologist, geropsychiatrist, neuropsychologist) to evaluate and differentiate subtypes of MCI and specific cognitive deficits.
There may be benefit in terms of improvement in performance on tests for global cognitive functioning with cognitive training and physical exercise (2)[C]
  • No evidence suggests the efficacy of vitamin E in the prevention or treatment of people with MCI. More research is needed to identify the role of vitamin E, if any, in the management of cognitive impairment.
  • Long-term use of ginkgo biloba extract has shown to have no benefit in the treatment of MCI and in terms of progression to dementia. In addition, ginkgo biloba can be associated with increase in bleeding risk including CNS bleeds (8)[B].
  • Delirium is more common in patients hospitalized with all forms of cognitive impairment.
  • Avoid medications that may worsen or precipitate cognitive decline (e.g., anticholinergics, antihistamines).
  • Patients may be extremely sensitive to the hospital environment:
    • Moderate level of stimulation is best.
    • Avoid sensory deprivation. Make sure that patients have access to hearing aids and eyeglasses.
    • Use frequent cueing and have caregivers or family in the room whenever possible with patient.
    • Frequently orient patients to date and time.
Patients should be reevaluated every 6 to 12 months to determine if symptoms are progressing.
Patient Monitoring
Appropriate cognitive and functional testing should be used to evaluate progression, along with clinical history and exam. If a medication is started, patients need to be followed more frequently to evaluate for efficacy, side effects, dose titration, and so forth. Declining executive function may be an early marker to progression of MCI to dementia, and clinicians should monitor and advise patients and families proactively to look for this. Impairments in ADL function is a good clue to progression to dementia from MCI.
Diets that are promoted by the American Heart Association to minimize atherosclerotic risk factors should be emphasized.
  • Encourage lifestyle changes:
    • Physical activity, such as walking 30 minutes daily on most days of the week
    • Mental activity that stimulates language skills and psychomotor coordination should be encouraged. Computer activities, reading books, crafts, crossword puzzles, and games may be linked to decreased risk of development of MCI (9)[C],(10)[B].
  • Cognitive rehabilitation strategies may be beneficial in helping with daily activities relating to memory tasks in MCI.
  • Participation in exercise programs modestly improved some measures of cognition in some studies.
  • Treatment of vascular risk factors (hypertension, diabetes, cerebrovascular disease, and hyperlipidemia) is important in lowering risk of progression to dementia.
  • Conversion rates from MCI to dementia range from 5% to 15% annually.
  • Amnestic subtypes of MCI are most likely to progress to dementia.
  • MCI has prognostic value in that once it is diagnosed, there is a higher risk of progression to dementia (11)[B].
1. Petersen RC. Clinical practice. Mild cognitive impairment. N Engl J Med. 2011;364(23):2227-2234.
2. Petersen RC, Caracciolo B, Brayne C, et al. Mild cognitive impairment: a concept in evolution. J Intern Med. 2014;275(3):214-228.
3. Petersen RC, Roberts RO, Knopman DS, et al. Prevalence of mild cognitive impairment is higher in men. The Mayo Clinic Study of Aging. Neurology. 2010;75(10):889-897.
4. Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):270-279.
5. Li J, Wang YJ, Zhang M, et al. Vascular risk factors promote conversion from mild cognitive impairment to Alzheimer disease. Neurology. 2011;76(17):1485-1491.
6. Russ TC, Morling JR. Cholinesterase inhibitors for mild cognitive impairment. Cochrane Database Syst Rev. 2012;(9):CD009132.
7. Patel BP, Holland NW. Adverse effects of acetylcholinesterase inhibitors clinical geriatrics. Clin Geriatr. 2011;19:27-30.
8. Vellas B, Coley N, Ousset PJ, et al. Long-term use of standardised ginkgo biloba extract for the prevention of Alzheimer's disease (GuidAge): a randomised placebo-controlled trial. Lancet Neurol. 2012;11(10):851-859.
9. Marshall GA, Rentz DM, Frey MT, et al. Executive function and instrumental activities of daily living in mild cognitive impairment and Alzheimer's disease. Alzheimers Dement. 2011;7(3):300-308.
10. Nagamatsu LS, Handy TC, Hsu CL, et al. Resistance training promotes cognitive and functional brain plasticity in seniors with probable mild cognitive impairment. Arch Intern Med. 2012;172(8):666-668.
11. Roberts RO, Knopman DS, Mielke MM, et al. Higher risk of progression to dementia in mild cognitive impairment cases who revert to normal. Neurology. 2014;82(4):317-325.
G31.84 Mild cognitive impairment, so stated
Clinical Pearls
  • Amnestic MCI affects primarily memory and is more likely to progress to Alzheimer dementia.
  • Screen for reversible factors, particularly anticholinergic medications, depression, and sleep disorders.
  • Look closely at vascular risk factors and modify them as best as possible.
  • ChEIs should not be used routinely unless memory complaints are affecting quality of life in patients. Potential side effects of these medications should be thoroughly discussed with patients and their families. A baseline EKG should be done prior to initiation of ChEIs due to risk of bradycardia and syncope.
  • Encourage both physical and mental exercises.