Alzheimer's disease is commonly diagnosed by two sets of criteria: Diagnostic and Statistical Manual of Mental disorders, 4th Edition (DSM-IV-TR), also known as DSM, and The National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorder Association, NINCDS-ADRDA, also referred to as NINCDS.
DSM requires the presence of both a memory disorder and cognitive impairment that negatively impacts the activities of daily living (ADL). NINCDS accepts the memory and cognitive criteria but does not require impairment of ADLs. In order to be diagnosed with Alzheimer's under the NINCDS criteria, the patient's physician must first rule out other diseases that account for the dementia. Both of these sets of criteria are presumptive diagnoses since, up until this time, there have been no accepted chemical or imaging techniques that can give a definitive diagnosis of Alzheimer's.
Despite this, diagnosing doctors have been able to identify distinctive, definitive changes seen on an MRI (temporal lobe), PET scan (hypometabolism of temperoparietal areas), and in the spinal fluid early on in the disease"”before any clear-cut diagnosis by the DSM and NINCDS criteria are noted. The real problem for most patients is in making the diagnosis in the earliest stage of Alzheimer's (age-associated or mild cognitive impairment before there is any interference with ADLs).
The DSM and the NINCDS criteria are accurate in 65 to 96% of all suspected Alzheimer's cases, but are specific to Alzheimer's (versus other dementias) in only 23 to 88%. In more advanced cases, there is a reduced certainty about what type of dementia is present.
Until now, drug trials that have attempted to prevent the progression of Alzheimer's disease have failed, probably due to the present inaccuracy of diagnosing the disease in its mild cognitive impairment form (treating diseases other than Alzheimer's). For instance, in the mildest form of dementia (amnestic mild impairment) where only subjective and objective memory is impaired without thought or impairment of ADLs, only 70% of those enrolled in the Alzheimer's disease prevention studies actually had Alzheimer's.
The New Requirements for Alzheimer's Diagnosis
The new criteria for diagnosing Alzheimer’s is much more accurate. It requires:
- An early and significant episodic memory impairment
- Gradual and progressive change of memory for more than 6 months
- Objective evidence of recall memory that does not improve or does not normalize with adequate cueing or recognition testing
PLUS one or more of the following supportive features (the new early markers for increasing the specificity of a patient having AD):
- Medial temporal atrophy on MRI
- Abnormal spinal fluid concentrations of (1) amyloid, (2) total tau or (3) phospho-tau
- Specific patterns of PET scanning producing hypometabolism of bitemporal parietal regions or Pittsburgh compound B
- Proven AD autosomal dominant mutation within the immediate family
In addition, one can exclude patients with:
- Sudden onset
- Focal neurologic defects
- Non-Alzheimer’s disease dementia
- Major depression
- Cerebrovascular disease