mild cognitive impairment (MCI); benign senile forgetfulness; age-associated memory impairment (AAMI)

Introduction

Questionable dementia or possible Alzheimer's disease (AD). MCI corresponds to a clinical dementia rating (CDR) of 0.5.

Classification

• amnestic: memory impairment
• nonamnestic: memory intact
  • cognitive impairment in other domain

Etiology

• higher medical burden increases risk for MCI
• COPD increases risk for MCI
  • RR for non-amnestic MCI is 1.86
• chronic hypertension
  • SPRINT group reports reduction in mild cognitive impairment, but not dementia using SPRINT goals* (14.6 vs 18.3 per 1000 person-years)
  • treatment reduces risk 20.2% vs 21.1% within 4 years
• diabetes mellitus may increase risk & may accelerate progression of MCI to dementia
• frailty increases risk
• parasympatholytics increase risk
• ApoE4 positivity

* systolic BP < 120 mm Hg

Epidemiology

• 13% of adults > 60 years of age report memory problems or confusion during preceding year
• 6.7% age 60-64 years, 25.2% age 80-84 years

Pathology

• some neuropathologic data support the view that MCI is early Alzheimer's disease (AD)
• late-life cognitive impairment generally results from a combination of vascular & neurofibrillary pathology
• most patients with MCI have mixed AD pathology
  • concurrent cerebrovascular disease in 60-70%
  • < 25% with pure AD pathology

Clinical manifestations

• mild dysfunction from age-related cognitive impairment
  • activities of daily living intact (basic & instrumental)
    • driving is not an activity of daily living
• 6-12 month history of worsening memory complaints
  • difficulty remembering recent conversations
  • difficulty remembering appointments
• retrieval difficulty that improves with recognition & cueing
• disproportionate declines in visuospatial memory
• difficulty with working memory
• decline in other cognitive domains may occur in the absence of memory impairment, i.e. verbal fluency & visuospatial deficits
• MCI can occur across multiple domains, including executive function
• difficulty managing money may be an early sign of cognitive impairment in the elderly
• functional impairment not severe enough to require help with activities of daily living (ADL)
• psychological well-being may decline prior to onset of MCI
  • purpose in life & personal growth most notable declines
• positive relationships with others decline after diagnosis of MCI

Laboratory

• dementia workup maybe appropriate (see dementia)
• CSF for beta-amyloid & tau & apoE4 genotype with some predictive value for progression to Alzheimer's disease
• tau in CSF + amyloid-beta 42 in CSF in addition to brain MRI proposed to predict progression of mild cognitive impairment to Alzheimer's disease
• decline in function better predictor than biomarkers
  • tau in CSF & amyloid-beta 42 in CSF best biomarkers

* no clinical markers or diagnostic tests can predict the likelihood of progression to dementia

Diagnostic procedures

• evidence of cognitive impairment on cognitive testing
  • difficulty in recall of 3 items
  • difficulty drawing intersecting pentagons
• neuropsychologic testing may be helpful
  • combination of 4 office-based tests with 80% predictive value for progression to dementia
  • mood disorder (depression or anxiety) may predict progression to dementia
  • delayed verbal memory along with MRI findings are best predictors of progression to Alzheimer's disease
• insufficient evident to support routine cognitive testing in elderly with MCI

* prediction model for conversion of normal cognition to MCI

• baseline age & education
• neuropsychological assessment
  • Digit Symbol Substitution Test
    • from the Wechsler Adult Intelligence Scale
  • Revised & the Verbal Paired Associates
  • Immediate recall from the Wechsler Memory Scale
• phosphorylated tau in CSF & amyloid-beta in CSF
• right hippocampal volume & right entorhinal cortex thickness measurements from brain MRI
• apoE genotype

Radiology

• neuroimaging indicated to exclude structural lesions
• MRI: thickness of left middle temporal lobe cortex predicts progression to Alzheimer's disease
• positron emission tomography (PET scan)
  • FDG-PET scan
  • amyloid PET: both amyloid-positive & amyloid-negative results associated with changes in diagnosis & treatment
  • not routinely indicated

Complications

• annual conversion rate to Alzheimer's disease is 5-15%*
  • 15% conversion to dementia in 4.5 years
  • 15% conversion to dementia within 2 years in patients > 65 years
    • reversion to normal cognition uncommon
• people with MCI & the apoE4 allele progress to Alzheimer's disease more rapidly
• multidomain MCI, antidepressant use, & depressive symptoms associated with clinical progression to dementia
• vulnerability to scams in older patients is associated with cognitive impairment & Alzheimer dementia

* ref gives very different estimates

• disease interaction(s) of mild cognitive impairment with depression
• disease interaction(s) of diabetes mellitus with mild cognitive impairment & Alzheimer's disease
• disease interaction(s) of mild cognitive impairment (MCI) with depression in the elderly

Differential diagnosis

• age-associated memory impairment
  • no significant functional impairment
• early dementia
  • greater severity of memory difficulty
  • greater problems responding to memory cues
  • needs assistance with activities of daily living (bADL or iADL)

Management

• no effective pharmacotherapy to prevent MCI or slow transition to dementia
  • no indication for cholinesterase inhibitors to prevent or treat MCI
    • oral Chinese herbal medicine plus donepezil appears more effective than donepezil alone in improving the cognitive function of MCI*
  • SSRI may delay onset on dementia in depressed patients with MCI (for up to 3 years)
  • vitamin D 400 IU/day may slow progression of MCI
    • vitamin D supplementation of no benefit
  • omega-3 fatty acid of no benefit
  • improved glycemic control may slow progression to dementia in patients with diabetes mellitus
  • aducanumab-avwa (Aduhelm) FDA approved using accelerated approval pathway
• discontinue anticholinergic agents & benzodiazepines, if possible
• nicotine patch may have benefit(s), but editorialist advises against use
• cognitive rehabilitation somewhat effective in some patients
• ensure adequate nutrition
• exercise of benefit
• aerobic exercise of benefit
  • improves executive control processes for older women at high risk of cognitive decline
  • improves executive functioning in elderly with MCI
  • also see exercise for seniors
• memory training programs
  • no evidence that games or puzzles designed to stimulate memory will affect cognitive ability. (GRS11)
  • computerized cognitive training
    • studies yield conflicting results
    • computerized drill & practice & virtual-reality interventions with some effect that quickly diminish when activity discontinued
  • cognitive training may be of some benefit
• aerobic-resistance exercises with sequential computerized cognitive training may improve cognition
  • magnitude of benefit is small
• consistent engagement in mentally stimulating activities may reduce risk for MCI in late life
  • apoE4 allele may attenuate this MCI risk reduction
• multidomain interventions (combined cognitive & physical training for < 1 year) associated with improvements in global cognition, memory, executive function, & verbal fluency vs single interventions in older adults with MCI
• older adults with MCI were more likely to regain normal cognition if they engaged in positive thinking about aging
• caution patients about driving
• control of cardiovascular risk factors may slow progression to Alzheimer's disease
• requires no further evaluation
• quality measures
  • annual cognitive health assessment for patients >= 65 years
  • cognitive & functional assessment for patients with MCI or memory loss
  • MCI diagnosis disclosure & counseling on treatment options
  • assessment & treatment of factors contributing to MCI
  • avoidance of anticholinergic medications for patients with MCI
  • education of care partners of patients with MCI

* benefit of donepezil for MCI is questionable

* no difference in cognitive function scores between donepezil & placebo but lower incidence of progression to dementia (NNT = 20)

* benefit to risk for recommending donepezil for MCI is unfavorable

Clinical trials

• Ornish Intensive Lifestyle changes improved cognition in patients with mild cognitive impairment or early dementia

More general terms

• sign/symptom

More specific terms

• motoric cognitive risk syndrome

Additional terms

• Alzheimer's disease (AD)
• clinical dementia rating scale (CDR)
• neuropsychiatric features of aging