Four steps to diagnosis of Alzheimer's disease

Medscape http://www.medscape.com/viewarticle/761284_3

Guideline	Procedures
Step 1: criteria for 'all cause dementia'
Interferes with the ability to function at work or with usual abilities and	History and observation
Represents a decline from previous ability and	Evidence of changes in functioning reported by either patient and/or informant or observed by clinician
Cannot be explained by delirium or major psychiatric disorder
Presence of cognitive impairment	History, observation, neuropsychological testing
	History-taking from a knowledgeable informantObjective mental status testing and/or neuropsychological testingNeuropsychological testing is recommended when history and mental status testing cannot provide a confident diagnosis
The cognitive or behavioural impairment involves a minimum of two domains	History, observation, neuropsychological testing
	Impaired ability to acquire/remember new information (eg, repeating questions, forgetting events or appointments, becoming lost in familiar places)Impaired reasoning and handling of complex tasks, poor judgement (eg, inability to handle finances, poor decision making)Impaired visuospatial abilities (eg, difficulty recognising faces or common objects)Impaired language function (speaking, reading, writing; eg, difficulty thinking of common words while speaking, hesitations in speech)Changes in personality, behaviour, comportment (eg, agitation, apathy, social withdrawal)
Difference between MCI and dementia	History and observation
	The fundamental difference between diagnoses of dementia versus MCI depends upon whether or not there is a significant change in the ability to function at work or in daily activities. This will necessarily require clinical judgment based upon the information provided by the patient and a knowledgeable informant.
Step 2: criteria for 'probable AD dementia'
Meets criteria for dementia	See criteria above for dementia, step 1
Insidious onset: symptoms have a gradual onset over months or years, not sudden over hours or days.	History
	From patient and knowledgeable informant
Clear cut history of worsening of cognition	History, serial neuropsychological testing
	From patient and knowledgeable informant
Initial cognitive deficits are evident and most prominent in one of the following categories	History, neuropsychological testing
Amnestic presentation – the most common presentationNon-amnestic presentations	Amnestic presentationImpairment of learning and recall of recently learned information
(1) Language presentation	Deficit in at least one other cognitive areaNon-amnestic presentations
(2) Visuospatial presentation	Language: most prominent deficits are word finding, but should also be deficits in other cognitive areas
(3) Executive dysfunction	Visuospatial: most prominent deficits are spatial cognition, but should also be deficits in other cognitive areasExecutive: most prominent deficits are reasoning, judgment and problem solving, but should also be deficits in other cognitive areas
Diagnosis of AD should not be made when there is evidence of another dementing illness	History, neuropsychological testing, imaging studies, laboratory studies
	Disorders to rule out include:Vascular cognitive impairment/vascular dementiaDementia with Lewy bodiesFrontal-temporal dementia – behavioural variantPrimary progressive aphasiaEvidence of neurological disease or non-neurological condition or medication that could have a substantial effect on cognition
Step 3: criteria for 'probable AD dementia with increased level of certainty'
Meets criteria for AD dementia	See criteria above for AD dementia, step 2
Probable AD dementia with documented decline	History, serial neuropsychological testing
	Evidence of progressive cognitive decline on subsequent evaluations from
	knowledgeable informant orcognitive testing (either formal neuropsychological evaluation or standardised mental status examinations)
Probable AD dementia in a carrier of a causative AD genetic mutation	Laboratory studies
	Presence of an early-onset familial genetic mutation
	APP, PSEN1, or PSEN2
	(Note that the apolipoprotein E ε 4 allele was not considered specific enough to meet criteria)
Step 4: evaluate the 'biomarker probability of AD aetiology'
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 desiredThere 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 and MRI patterns of atrophy, a marker of downstream neurodegenerationPresence of one biomarker category makes the 'biomarker probability of AD aetiology' 'intermediate;' both categories must be positive for a 'high' probability. The 'lowest' probability is present if both categories are negative