The only definitive test for Alzheimer’s disease is examination of brain tissue (usually obtained at autopsy) for identification of the characteristic pathologic changes of Amyloid paque and Neurofibrillary tangles:
Alzheimer’s disease is usually diagnosed based on clinical criteria, but many patients diagnosed this way are later found to have other causes of dementia when their brains are examined at autopsy, in other words they were misdiagnosed as Alzheimer’s.
With more effective new therapies on the horizon, it is going to become more important to establish a diagnosis of Alzheimer’s more accurately and earlier, perhaps even pre-symptomatically (i.e. mild cognitive impairment or MCI), so that treatment to reverse the build up of plaque and tangles is more likely to be effective.
There has been interest in Apoprotein E (APOE) genotype and Alzheimer’s risk. APOE genes come in 3 types (2-4). If you have 2 copies of APOE4 (1-2% of the population) you are 15 times more likely to develop Alzheimer’s than averages, and if you have one copy of APOE4 you have are 3 times more likely to develop Alzheimer’s than average. Clearly, there is an association between APOE4 genoytpe and Alzheimer’s. However, not every patient with APOE4 develops Alzheimer’s, and you can develop Alzheimer’s without APOE4, so APOE genotyping is not recommended as a diagnostic test.
The ratio of cerebrospinal fluid levels of beta-amyloid and tau proteins can be predictive for Alzheimer’s, but this test requires a lumbar puncture, and is inconclusive in many cases.
Magnetic resonance imaging (MRI) of the brain has shown selective atrophy of the hippocampus in patients with early Alzheimer’s (a) vs. normal elderly controls (b), and this technique has been proposed as a diagnostic test for Alzheimer’s, but requires special computerized imaging processing not available at most imaging centers.
Fluorodeoxyglucose posititon emission tomogrpahy (FDG-PET) shows reduced metabolic activity (uptake of sugar) in the temporal and parietal lobes of patients with early Alzheimer’s (these regions are darker) vs. normal elderly controls (these regions are brighter), and this test is FDA approved, covered by Medicare, and widely available at imaging centers around the counrty:
A recent study compared the results of MRI, FDG-PET and analysis of CSF biomarkers in 97 MCI patients, to see which was best for predicting who would convert to Alzheimer’s first. During a mean follow-up of almost 3-years, 43 patients progressed to AD and 54 did not. Of the 3 tests, an abnormal FDG-PET was most predictive.
Before you all rush out and get your FDG-PET to see if you are high risk for Alzheimer’s, be warned that results may be unreliable when the test is performed at an inexperienced center. Data presented at this year’s American Academy of Neurology meeting showed that up to 2/3 of patients referred to a University dementia program had been misdiagnosed with Alzheimer’s dementia based on misread FDG-PET scans performed at community imaging centers.
The Amyvid™ (Florbetapir F 18) PET scan, which was FDA approved this year, actually quantifies the amount of amyloid plaque in affected patients’ brains (bright), and is probably a more promising new PET technique for predicting Alzheimer’s disease. However, this test is not yet covered by Medicare or other insurance covering, and costs between $1500 and $3000:
In sum, the hope for the future is that with earlier and more accurate diagnosis, future treatments could target Alzheimer’s in its earliest stages, before irreversible brain damage or mental decline has occurred. However, it is clear that none of the available diagnostic tests are perfect, and although promising, amyloid plaque PET scans are not yet covered by Medicare, so for now we mostly continue to make do with clinical diagnostic criteria.