Alzheimer's disease can be very difficult to diagnose. Many factors come into play, and it takes time to reach a conclusion. Until recently, there were two sets of criteria that doctors used to make a diagnosis. One is found in the Diagnostic and Statistical Manual of Mental Disorders, also known as DSM. The second is issued by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorder Association (NINCDS).

The DSM criteria require the presence of a memory disorder as well as cognitive impairment that negatively impacts the activities of daily living (ADL), while the NINCDS solely requires the memory and cognitive criteria, but not impacted ADLs.

In addition, in order to diagnose a patient with Alzheimer's under the NINCDS criteria, the diagnosing doctor must first rule out other diseases that account for the dementia. It's important to keep in mind that both sets of criteria allow only for presumptive diagnoses since, until now, there have been no accepted chemical or imaging techniques that can give a definitive diagnosis of Alzheimer's.

Despite this fact, diagnosing doctors have been able to identify distinctive, definitive changes seen on an MRI, PET scan, and in the spinal fluid early on in the disease—before any clear-cut diagnosis by the DSM and NINCDS criteria has been made. Because this information on its own isn't enough to warrant a diagnosis, the real problem for most patients is not getting diagnosed in the earliest stage of Alzheimer's.

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 the type of dementia that is present.

Until now, drug trials that have attempted to prevent the progression of Alzheimer's disease have failed. In some cases this meant that the trials were treating diseases other than Alzheimer's. In the mildest form of dementia where only subjective and objective memory is impaired without thought or impairment of the patient's ability to handle the activities of daily living, only 70% of those enrolled in the Alzheimer's disease prevention studies actually had Alzheimer's.

The newest criteria for diagnosing Alzheimer's has a greater accuracy than the DSM and NINCDS alone. It requires: (1) an early and significant episodic memory impairment; (2) gradual and progressive change of memory for more than six months; and (3) objective evidence of recall memory that does not improve or normalize with adequate cueing or recognition testing.

The criteria also consider the new early markers for recognizing Alzheimer's disease. For a patient to be diagnosed under the latest criteria, he or she must also exhibit at least one of the following features:

• Medial temporal atrophy on MRI
• Abnormal spinal fluid concentrations of amyloid, total tau or phospho-tau
• Specific patterns of PET scanning that produce hypometabolism of bitemporal parietal regions or Pittsburgh compound B
• Proven Alzheimer's autosomal dominant mutation within the immediate family

It's important to remember that the technology and information isn't perfect yet. Coming to an Alzheimer's diagnosis still requires a “ruling out” process. Some of the factors or symptoms that should be considered during this phase include sudden onset, focal neurologic defects, non-Alzheimer's disease dementia, major depression and cerebrovascular disease.