III. CRITERIA FOR DIAGNOSIS
The following are the diagnostic guidelines for AD, VaD, dementia with Lewy’s bodies (DLB), and frontotemporal lobar degeneration (FTLD) (the four most common causes of dementia in order). Also presented are the guidelines for diagnosis of mild cognitive impairment (MCI), which bridges the spectrum between dementia and normal cognition.
A. Alzheimer’s disease.
AD is characterized by both amyloid and tau pathology. The National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s and Related Diseases Association 1984 criteria for the diagnosis of AD have recently been modified to take into account (1) Patients with the pathophysiologic process of AD, which can be found in those with normal cognition, MCI, and AD. This pathophysiologic process designated as AD-P is thought to begin years before the diagnosis of clinical AD. (2) The diagnostic criteria of other diseases such as Lewy’s body disease and frontotemporal dementia. (3) MRI, positron emission tomography (PET) for imaging the amyloid beta protein (Aβ), 18fluorodeoxyglucose (FDG) PET, and the CSF biomarkers A/42, total tau and phophotau. (4) Other clinical syndromes that do not present with amnesia but are related to AD pathology including posterior cortical atrophy and logopenic aphasia. (5) The dominantly inherited AD causing mutations in amyloid precursor protein, presenilin-1, and presenilin-2 (APP, PSEN1, PSEN2, respectively). (6) A change in age cut-offs noting persons under 40 and over 90 may have the same AD-P. (7) Many persons with possible AD in the past are now designated MCI.
Below we present the 1984 criteria for probable and possible AD. Patients who meet the 1984 criteria for probable AD still meet criteria for probable AD. Additionally, we present the proposed new 2011 criteria for AD in III.A.8.
1. Criteria for the clinical diagnosis of probable AD.
Dementia established by means of clinical examination and documented with the Mini-Mental State Examination, Blessed Dementia Rating Scale, or other similar examination and confirmed with neuropsychological tests.
Deficits in two or more areas of cognition.
Progressive worsening of memory and other cognitive function.
No disturbance of consciousness.
Onset between the ages of 40 and 90 years, most often after 65 years.
Absence of systemic disorders or other brain diseases that in and of themselves could account for the progressive deficits in memory and cognition.
2. Supporting findings in the diagnosis of probable AD.
Progressive deterioration of specific cognitive functions such as aphasia, apraxia, or agnosia.
Impaired activities of daily living and altered patterns of behavior.
Family history of similar disorders, particularly if confirmed neuropathologically.
Laboratory results as follows:
Normal results of lumbar puncture (LP) as evaluated with standard techniques.
Normal or nonspecific EEG changes (increased slow-wave activity).
Evidence of cerebral atrophy at CT with progression documented by means of serial observation.
3. Other clinical features consistent with the diagnosis of probable AD, after exclusion of causes of dementia other than AD.
Plateaus in the course of progression of the illness.
Associated symptoms of depression; insomnia; incontinence; delusions; illusions; hallucinations; catastrophic verbal, emotional, or physical outbursts; sexual disorders; and weight loss.
Other neurologic abnormalities for some patients, especially those with advanced disease, and including motor signs such as increased muscle tone, myoclonus, or gait disorder.
Seizures in advanced disease.
CT findings normal for age.
4. Features that make the diagnosis of probable AD uncertain or unlikely.
Sudden, apoplectic onset.
Focal neurologic findings such as hemiparesis, sensory loss, visual field deficits, and incoordination early in the course of the illness.
Seizures or gait disturbance at the onset or early in the course of the illness.
5. Clinical diagnosis of possible AD.
May be made on the basis of the dementia syndrome, in the absence of other neurologic, psychiatric, or systemic disorders sufficient to cause dementia and with variations in onset, presentation, or clinical course.
May be made in the presence of a second systemic or brain disorder sufficient to produce dementia, which is not considered to be the principal cause of the dementia.
Should be used in research studies when a single, gradually progressive, severe cognitive deficit is identified in the absence of any other identifiable cause.
6. Criteria for the diagnosis of definite AD
are the clinical criteria for probable AD and histopathologic evidence obtained from a biopsy or autopsy.
7. Classification of AD for research purposes
should specify features that differentiate subtypes of the disorder such as familial occurrence, onset before 65 years of age, presence of trisomy 21, and coexistence of other relevant conditions such as Parkinson’s disease.
8. Proposed new criteria for AD.
In 2011, National Institute on Aging and the Alzheimer’s Association workgroup suggested new criteria for AD based on clinical and research evidence. All patients who met the 1984 criteria for probable AD described in III.A.1 would meet the current criteria. In addition, the following criteria are proposed: