Spinal Fluid Test Predicts Alzheimer's Disease

Researchers correctly classify patients with Alzheimer’s Disease, independent of clinical diagnosis with better than 90 percent accuracy.

Synopsis

Researchers: Geet De Meyer, PHd, et al.

RESEARCH Without bias of prior diagnosis, researchers for the Alzheimer's Disease Neuroimaging Initiative examined three groups of subjects in a 5-year study to determine whether it is possible to identify patients with or who are predisposed to Alzheimer's Disease (AD). The results bring praise and stir an ethical dilemma.

Test Subject Group Ages 70-79 Study Population Identified AD Signature
Alzheimer's Disease Patients 102 90 %
Mild Cognitive Impairment 200 72 %
Cognitively Normal Participants 114 36 %

A cerebrospinal fluid β-amyloid protein 1-42/phosphorylated tau181P biomarker mixture model identified one feature linked to AD, while the other matched the "healthy" status. The AD signature was found in 90%, 72%, and 36% of patients in the AD, mild cognitive impairment, and cognitively normal groups, respectively. The cognitively normal group with the AD signature was enriched in apolipoprotein E ε4 allele carriers. [1]

So 9 out of 10 AD patients in their 70s have the requisite biomarker along with a third of the cognitively normal participants. Will any of the latter actually acquire the disease? Two additional subject groups were evaluated for validation. In the first study consisting of 68 autopsy-confirmed AD cases, 64 of 68 patients (94% sensitivity) were correctly classified with the AD feature. In another set of 57 patients with mild cognitive impairment followed up for 5 years, the model showed a sensitivity of 100% in patients progressing to AD. [1,2]

This study, which will need to be duplicated, seems to indicate if someones has an abnormal test result with the spinal tap, (s)he will develop Alzheimer’s Disease. It is just a question of when. At this point, no one can say a normal test result conclusively eliminates the possibility. Those with slightly abnormal test results may or may not develop AD. [3]

Dilemma of Predicted Outcomes

Predicting serious, long-term illness is like wielding a two-edge sword with tremendous emotional, social and financial consequences. The cost of long-term care for AD patients has been addressed in The Alzheimer's Association report entitled 2010 Alzheimer's Disease Facts and Figures. Therein, the only practical way to provide anything above sub-standard care is to purchase insurance in advance of the diagnosis. [4]

Insurance companies currently have a somewhat unfair advantage. Roughly 85% of insured persons offset the cost for 15% of the population that actually develop Alzheimer's Disease. [4] The ability to predict outcomes with better than 90% accuracy could alter enrollment requirements to prevent those who may actually require coverage from receiving it.

At this time, the spinal tap required to collect cerebrospinal fluid (CSF) is a procedure not routinely performed during physical exams. It involves putting a needle in the spinal sac in the lower back — something many patients may not willingly consent to. A cost that ranges from $300 to $500 could also be a hinderance to voluntary participation.

Foreknowledge of AD can be beneficial but it must be coupled with adequate guidelines to prevent abuse and should foster research to identify a cure. The identification of specific biomarkers could lead to such a cure or perhaps prevention.

Tags: aging, clinical research study, ethics, geriatrics, neurologist, neurology, statistics

References
  1. Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People, Archives of Neurology, August 8, 2010
  2. Geert De Meyer, PhD; Fred Shapiro, MLS; Hugo Vanderstichele, PhD; Eugeen Vanmechelen, PhD; Sebastiaan Engelborghs, MD, PhD; Peter Paul De Deyn, MD, PhD; Els Coart, PhD; Oskar Hansson, MD; Lennart Minthon, MD; Henrik Zetterberg, MD, PhD; Kaj Blennow, MD, PhD; Leslie Shaw, PhD; John Q. Trojanowski, MD, PhD; for the Alzheimer's Disease Neuroimaging Initiative. Arch Neurol. 2010;67(8):949-956. doi:10.1001/archneurol.2010.179
  3. Study shows testing for Alzheimer's is accurate, CNN Health, S. Grupta, MD
  4. Alzheimer's Facts and Figures, alz.org