Evidence-Based Reviews

Mild cognitive impairment: How can you be sure?

Current Psychiatry. 2008 April;7(4):37-49

References

1. Gauthier S, Reisberg B, Zaudig M, et al. Mild cognitive impairment. Lancet 2006;367:1262-70.

2. Lopez OL, Jagust WJ, DeKosky ST, et al. Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1. Arch Neurol 2003;60:1385-9.

3. Petersen RC. Conceptual review. In: Petersen RC, ed. Mild cognitive impairment: aging to Alzheimer’s disease. New York, NY: Oxford University Press; 2003:1-14.

4. Petersen RC, Morris JC. Mild cognitive impairment as a clinical entity and treatment target. Arch Neurol 2005;62:1160-3.

5. O’Brien JT. Vascular cognitive impairment. Am J Geriatr Psychiatry 2006;14:724-33.

6. Janvin CC, Larsen JP, Aarsland D, et al. Subtypes of mild cognitive impairment in Parkinson’s disease: progression to dementia. Mov Disord 2006;21:1343-9.

7. Farlow MR, He Y, Tekin S, et al. Impact of APOE in mild cognitive impairment. Neurology 2004;63:1898-1901.

8. Winblad B, Palmer K, Kivipelto M, et al. Mild cognitive impairment—beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 2004;256:240-6.

9. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med 2004;256:183-94.

10. Geda YE, Smith GE, Knopman DS, et al. De novo genesis of neuropsychiatric symptoms in mild cognitive impairment (MCI). Int Psychogeriatr 2004;16:51-60.

11. Robert PH, Berr C, Volteau M, et al. Apathy in patients with mild cognitive impairment and the risk of developing dementia of Alzheimer’s disease: a one-year follow-up study. Clin Neurol Neurosurg 2006;108:733-6.

12. Modrego PJ, Ferrandez J. Depression in patients with mild cognitive impairment increases the risk of developing dementia of Alzheimer type. Arch Neurol 2004;61:1290-3.

13. Jack CR, Petersen RC, Xu YC, et al. Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. Neurology 1999;52:1397-1403.

14. Nestor PJ, Fryer TD, Smielewski P, et al. Limbic hypometabolism in Alzheimer’s disease and mild cognitive impairment. Ann Neurol 2003;54:343-51.

15. Sunderland T, Hampel H, Takeda M, et al. Biomarkers in the diagnosis of Alzheimer’s disease: are we ready? J Geriatr Psychiatry Neurol 2006;19:172-9.

16. Lyketsos CG, Lopez O, Jones B, et al. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the Cardiovascular Health Study. JAMA 2002;288:1475-83.

17. Steffens DC, Otey E, Alexoupolos GS, et al. Perspectives on depression, mild cognitive impairment, and cognitive decline. Arch Gen Psychiatry 2006;63:130-8.

18. Gabryelewicz T, Styczynska M, Pfeffer A, et al. Prevalence of major and minor depression in elderly persons with mild cognitive impairment: MADRS factor analysis. Int J Geriatr Psychiatry 2004;19:1168-72.

19. Geda YE, Knopman DS, Mrazek DA, et al. Depression, apolipoprotein E genotype, and the incidence of mild cognitive impairment: a prospective cohort study. Arch Neurol 2006;63:435-40.

20. Devanand DP, Pelton GH, Marston K, et al. Sertraline treatment of elderly patients with depression and cognitive impairment. Int J Geriatr Psychiatry 2003;18:123-30.

21. Mohs RC, Doody RS, Morris JC, et al. A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients. Neurology 2001;57:481-8.

22. Teng EL, Chui HC. The Modified Mini-Mental State (3MS) examination. J Clin Psychiatry 1987;48:314-8.

23. Nasreddine ZS, Phillips NA, Bédirian V, et al. The Montreal Cognitive Assessment (MoCA): a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 2005;53:695-9.

24. Fleisher AS, Sowell BB, Taylor C, et al. Clinical predictors of progression to Alzheimer disease in amnestic mild cognitive impairment. Neurology 2007;68:1588-95.

25. Petersen RC, Thomas RG, Grundman M, et al. for the Alzheimer’s Disease Cooperative Study Group. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med 2005;352:2379-88.

26. Feldman HH, Ferris S, Winblad B, et al. Effect of rivastigmine on delay to diagnosis of Alzheimer’s disease from mild cognitive impairment: the InDDEx study. Lancet Neurol 2007;6:501-12.

27. Petersen RC. Mild cognitive impairment: current research and clinical implications. Semin Neurol 2007;27:22-31.

28. Thal LJ, Ferris SH, Kirby L, et al. A randomized, double-blind study of rofecoxib in patients with mild cognitive impairment. Neuropsychopharmacology 2005;30(6):1204-15.

Clinical Point

After an MCI diagnosis, monitor the patient and repeat the MoCA and modified MMSE every 6 to 12 months

A substantial functional decline precludes an MCI diagnosis, although the degree of functional decline can be difficult to assess in older adults with physical limitations caused by medical comorbidities.

Cognitive assessment. Because most individuals with MCI score in the normal range on the Folstein Mini-Mental State Examination (MMSE), the modified MMSE (3MS)²² may be more sensitive for detecting MCI. The 3MS retains the MMSE’s brevity (≤10 minutes to administer) but incorporates 4 additional items, has more graded scoring responses, and broadens the score range to 0 to 100. The clock-drawing test also is sensitive for MCI, especially in detecting early visuoconstructional dysfunction.

The Montreal Cognitive Assessment (MoCA) is a 10-minute, 30-point scale designed to help clinicians detect MCI (see Related Resources). The MoCA usually is given with the modified MMSE for a comprehensive cognitive assessment.

Nasreddine et al²³ administered the MoCA and MMSE to 94 patients who met clinical criteria for MCI, 93 patients with mild AD, and 90 healthy cognitively normal elderly persons, using a cutoff score of 26. MoCA showed:

90% sensitivity for detecting MCI (compared with 18% for the MMSE)
87% specificity to exclude normal elderly persons.

The average MoCA score in patients with AD was much lower than in individuals with MCI, but score ranges of these 2 groups overlapped. Therefore, a score

Neuropsychological testing can be more sensitive than office-based screening tools in defining MCI subtypes. In the Alzheimer’s Disease Cooperative Study (ADCS), the neuropsychological measures that most accurately predicted progression of patients with aMCI to AD within 36 months were the:

Clinical Point

Cholinesterase inhibitors, rofecoxib, and vitamin E have not been shown to prevent MCI from progressing to Alzheimer’s

Symbol Digit Modalities Test
New York University Paragraph Recall Test (Delayed)
Delayed 10-Word List Recall
Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog) total score.²⁴

Laboratory tests, imaging. Use laboratory studies (Table 5) to rule out reversible causes of MCI symptoms.⁸ Reserve CSF studies for suspected CNS infection (such as meningitis, human immunodeficiency virus, or neurosyphilis) and brain imaging for suspected cerebral pathology (such as infarct, subdural hematoma, normal pressure hydrocephalus, or tumor).

Table 4

Alzheimer’s Disease Functional Assessment and Change Scale (ADFACS)

Basic ADL	Instrumental ADL (IADL)
Toileting	Use of telephone
Feeding	Household tasks
Dressing	Using household appliances
Personal hygiene and grooming	Managing money
	Shopping
Bathing	Food preparation
Walking	Ability to get around inside and outside home
	Hobbies and leisure activities
	Handling personal mail
	Grasp of situations and explanations
The 16-item ADFACS total score ranges from 0 to 54 (best to worst): Rate basic ADLs from 0 (no impairment) to 4 (very severe impairment), for a total score range of 0 to 24. Rate IADLs from 0 (no impairment) to 3 (severe impairment), for a total score range of 0 to 30.
Use total scores to assess for functional decline from baseline. A decline from 0 to 1 on individual ADL and IADL items is not considered clinically significant.
ADL: activities of daily living
Source: Reprinted with permission from reference 21

Table 5

Lab studies to rule out reversible causes of MCI

Complete blood count with differential
Basic metabolic panel
Liver function tests
Serum calcium
Serum vitamin B12 and folate
Thyroid function tests
Rapid plasma reagin
HIV in high-risk individuals
CSF studies if CNS infection is suspected
CSF: cerebrospinal fluid; HIV: human immunodeficiency virus; MCI: mild cognitive impairment
Source: Reference 8

CASE CONTINUED: Subtle cognitive deficits

Mr. R scores 27/30 on the MMSE (losing 3 points on recall) and 25/30 on the MoCA (losing points on visuospatial/executive function, fluency, and delayed recall). Thyroid stimulating hormone, vitamin B12, folate, and rapid plasma reagin tests are unremarkable; brain MRI shows no significant abnormalities.

You refer Mr. R for neuropsychological testing, and most cognitive domains are normal. Exceptions include moderate impairment in immediate and delayed verbal and visual memory and mild executive dysfunction.

Based on your clinical evaluation and neuropsychological testing, you diagnose amnestic MCI. Mr. R shows abnormalities in memory and executive functioning without significant decline in basic and instrumental ADLs, is not taking medications, and has no other medical or psychiatric condition that could explain his cognitive deficits.

You discuss the diagnosis with him and his wife, including evidence on his risk for progression to dementia, neuroprotective strategies, and medications.

After an MCI diagnosis

Neuroprotection. Eliminate medications with anticholinergic effects, including:

tricyclic antidepressants
conventional antipsychotics
antihistamines
drugs used to treat urinary incontinence, such as oxybutynin
muscle relaxants, such as cyclobenzaprine
certain antiparkinsonian drugs, such as benztropine.

Encourage patients to avoid alcohol and sedatives. Collaborate with primary care providers to control cerebrovascular risk factors such as hyperlipidemia, diabetes mellitus, hypertension, and obesity. Treat depression, which may be a risk factor for developing dementia.