Early Diagnostic Tests for Alzheimers Disease

1. After neurological and psychiatric evaluation, neuropsychological testing is essential.

2. Reduced ability to discriminate among smells (odors).

3. Hippocampal and parahippocampal atrophy on MRI scan.

4. Temporoparietal blood flow and metabolism deficits on SPECT or PET.

5. Decreased A-Beta protein amyloid and increased tau protein levels in the cerebrospinal fluid.

6. Presence of apolipoprotein E e4 genotype.

I will cover each of these in more detail.

Neuropsychological (Cognitive) Testing

Neuropsychological testing typically reveals that loss of recent memory is the only deficit in the disease's earliest clinical stages, which progresses over time to widespread memory loss, great difficulty in naming objects, poor fluency in reciting verbal material, and defects in constructional (drawing a cube, for example) and visuospatial abilities (finding the way to the neighborhood store). However, age and education strongly influence test scores, and these patterns of deficits can occur in conditions other than Alzheimer's disease. (Mary O'Brien, the steady alcohol user, was wrongly diagnosed with Alzheimer's disease based on neuropsychological testing.) The great strength of neuropsychological testing is its ability to pick up subtle, very early memory deficits.

Difficulty Identifying Smells

It sounds a bit strange: difficulty in identifying smells occurs early in the course of Alzheimer's disease. But there is a sound physiologic explanation: neurofibrillary tangles, a neuropathologic hallmark of Alzheimer's disease, infiltrate the "olfactory" or smell tract of nerve cells that goes from above the nose to a brain region just below the hippocampus. There are reliable standard tests of smell or olfaction that involve scratching a card and identifying the smell using a multiple-choice format. Our research group recently showed that the inability in people with mild memory loss to accurately identify smells strongly predicts who will later be diagnosed with Alzheimer's disease. Although the findings were strong, a number of factors can distort he results of the smell test: natural smelling ability varies markedly among people, smell discrimination skills diminish gradually with age, and smoking worsens smelling ability. So this test can provide a guideline but is by no means foolproof.

Brain Imaging in Early Diagnosis

In an earlier chapter, I discussed how an MRI scan can detect reduced size of the hippocampus and how SPECT and PET can detect reduced blood flow or metabolism in the parietal and temporal lobes. These features distinguish Alzheimer's patients from normal elderly people, but may not be as good in predicting who will get Alzheimer's in a group of people with mild memory loss. There are a few situations where these imaging procedures may be helpful—for example, a fifty-

year-old man with mild memory loss who shows the typical MRI and SPECT/PET abnormalities is likely to be developing Alzheimer's disease.

Lumbar Puncture

A lumbar puncture is needed to examine the cerebrospinal fluid that bathes the brain and spinal cord. Studies conducted mainly in Sweden, plus smaller American studies, show high levels of cerebrospinal fluid tau protein (forms part of the neurofibrillary tangles) and low levels of A-Beta amyloid protein (forms part of the amyloid plaque) in Alzheimer's patients compared to normal elderly control subjects. However, high levels of tau are also found in other neurologic conditions, so its diagnostic utility for Alzheimer's remains uncertain.

A few other diagnostic tests—a simple eye test, Alz-50 protein, and the AD7Nc protein—were hyped up initially but fell by the wayside after subsequent research failed to replicate the original results.

Genetic Markers

Nearly half the patients with Alzheimer's disease have a family history of dementia. Allen Roses, formerly the head of the Alzheimer's Center at Duke University and currently a division chief at the drug company Glaxo-Wellcome, is the main proponent of using the apolipoprotein E e4 genotype on chromosome 19 as an early diagnostic marker of Alzheimer's disease. However, not everyone with this type of gene gets Alzheimer's disease, and some people who do not have this gene can still get the disease. Also, there are big differences among whites, African-Americans, and Hispanics in the risks associated with this gene. Expert consensus panels have concluded that apolipoprotein E genotyping should not be used for clinical diagnosis.

Scientists have identified abnormal genes for a few rare forms of Alzheimer's disease. Patients with abnormal presenilin 1 and presenilin 2 genes tend to develop Alzheimer's disease at a relatively young age: forty to sixty years. There is one large family pedigree of Volga Germans, now spread across the world, who provided the genetic material that helped identify one of these genetic mutations. But even in patients with early-onset disease, it is difficult to identify the presenilin 1 and 2 mutations because several dozen variations of each of these two main mutations have been identified, and there probably are many more waiting to be discovered. Therefore, complex laboratory techniques in specialized centers are necessary, and many uncertainties still remain in using such techniques to make an accurate diagnosis. The Clinical Picture Is More Important than Lab Tests

Once the initial hype settles down, the same issues tend to limit clinical applicability for all these tests: lack of specificity for Alzheimer's disease (which means that the same abnormalities are also seen in other diseases), uncertainty about whether they can be used at the stage of mild cognitive impairment to predict future Alzheimer's disease, and absence of replication in large-scale studies. If your doctor orders one of these (or other) tests, keep in mind that an abnormality on one of these tests does not necessarily mean you have Alzheimer's; the whole clinical picture needs to be taken into account before any diagnosis is made.

Unraveling Alzheimers Disease

Unraveling Alzheimers Disease

I leave absolutely nothing out! Everything that I learned about Alzheimer’s I share with you. This is the most comprehensive report on Alzheimer’s you will ever read. No stone is left unturned in this comprehensive report.

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