Table 2:

Clinical and Cognitive Evaluation for MCI due to AD

Step 1 : Establish clinical and cognitive criteria: Determine that the clinical and cognitive syndrome is consistent with MCI and the patient is not demented
Guideline	Procedures
Concern regarding a change in cognition	History & Observation –
	• Concern of a change in cognition from prior level
	• Reported by patient and/or informant, or observed by clinician
Objective evidence of impairment in one of more areas of cognition (e.g, memory, attention, language, visuospatial skills, executive function)	Neurocognitive Testing
	• Impairment in episodic memory (learning and retention of new information such as word lists), the most common symptom.
	• Deficit in episodic memory is the best predictor of progression to Alzheimer’s dementia
	• Other cognitive areas should also be evaluated.
	• Sample battery: Rey Auditory Verbal Learning Test (memory), the Trail Making Test Parts A & B (executive function), the Boston Naming Test, letter and category fluency (language), figure copying (spatial skills), and digit span forward (attention). (See Budson & Solomon,8 for discussion of these & other tests.)
	• Patients with MCI typically score 1 to 1.5 standard deviations below the mean on cognitive tests.
	• Note that cognitive assessments are influenced by age, education, motivation, and cultural variation. Not all tests provide normative data taking these factors into account.
	• Evaluation by a neuropsychologist is appropriate & helpful in these patients with mild deficits. Brief or informal office testing may not be sensitive enough to detect deficits.
Preservation of independence in functional abilities	History, Questionnaires
	• MCI patients maintain independence of function in daily life although they may experience more difficulty or take longer in carrying out complex tasks (e.g., balancing the checkbook, household projects, meal planning & preparation).
	• Interviews with friends or family will usually detect these changes
	• Standardized and validated scales completed by family or friends can be helpful (see Budson & Solomon,8 for a discussion specific scales)
Not demented	History, Observation, Questionnaires
	• There is no significant impairment in occupational or social function

Step 2: Examine etiology of MCI consistent with AD pathophysiological process: Determine the likely primary cause of signs & symptoms.
Guideline	Procedures
Rule out other possible causes of cognitive decline.	History, neurocognitive testing, imaging, & laboratory studies
Possibilities include: vascular, Lewy body, other degenerative disease, traumatic, depression, medical comorbidities, mixed dementia, other (see Budson & Solomon,8 for complete list & description of the various disorders).	• History & testing may be consistent with various clinical phenotypes
	• CT & MRI may show vascular infarcts & patterns of atrophy
	• Laboratory studies (e.g., B12, TSH, Lyme titer) may find other causes of cognitive deficits
Provide evidence of longitudinal decline in cognition	History, serial neuropsychological testing
	• Documentation of progressive cognitive decline increases the probability of MCI due to AD
	• Decline can be determined by history and / or neuropsychological testing
Report history consistent with AD genetic factors	Genotyping
	• Although genotyping is not part of the routine workup for MCI or AD, if an autosomal dominant form of the gene is known to be present (i.e. mutation in APP, PS1, PS2), then the development of MCI is highly likely to be the prodrome of AD
	• The vast majority of these cases develop early onset AD in the patient’s 40s or 50s.
	• The presence of one or two ε4 alleles in the apolipoprotein protein E increases the risk for late onset AD.
Evaluate for atrophy of temporal (medial, basal, and lateral) and medial parietal cortex and other biomarkers when available and clinically useful.	Biomarkers
	• Although the use of biomarkers is not recommended routinely, they are available to the clinician when desired.
	• There are two categories of biomarkers, those associated with Aβ protein deposition and those associated with downstream neurodegeneration (see Table 1)
	• We recommend routine review of CT & MRI patterns of atrophy, a marker of downstream neurodegeneration.
	• Presence of one biomarker category makes the “biomarker probability of AD etiology” “intermediate;” both categories must be positive for the “highest” probability. The “lowest” probability is present if both categories are negative.