The new crystal ball: predicting future disease

Translated by Rumia Bose

Disease can be seen as the antechamber of death. We are often more scared of the suffering associated with a disease than of death itself. Dementia, cancer, heart attacks, living like a vegetable; is all this not preventable? Early detection may allow more effective treatment, or stop developing the disease at all. Articles with headings like these give us hope: “Test could predict risk of future heart disease for just £40 “¹, “Alzheimer’s blood test could predict onset up to 20 years in advance”², “Scientists unveil ‘game-changing’ method to predict breast cancer risk”³.
If you search the internet for “predicting illness”, you will come across something about almost every disease.

Predictive tests?

Are there reliable tests for predicting disease? I will use Alzheimer’s disease as a starting point for an answer to this question⁴. There is an astonishing amount of research on Alzheimer, including the predictive value of genetic testing, blood tests and brain scans. I will not beat about the bush: in general it is not possible to predict if you will develop a disease before its actual onset.

Genetic tests?

Let us start with genetics. Some families are prone to Alzheimer’s disease and almost always with development at a young age, before the 60th year and regularly much earlier. The name of this form, ” Autosomal Dominant Alzheimer’s Disease” (ADAD) refers to the genetic component. But only 1-2% of Alzheimer’s sufferers have this form. The most common form manifests itself after the 65th year, LOAD or Late Onset Alzheimer’s Disease. Heredity also plays a role in this type, but in a very complicated way. One gene plays a prominent role. You can determine if you have the AOPE4 variant of that gene which increases the risk of developing Alzheimer’s. But it is not known how much bigger the risk is. It is in any case clear that even if you have the AOPE4 variant, you don’t always develop Alzheimer’s, and also that you can develop Alzheimer’s even if you don’t have the APOE4 variant. Some dozens of other genes also play a role in this. Apart from which there are many factors beyond genes that play a role. The risk is higher with women, overweight, high blood pressure, diabetes and more. There are also factors which reduce the risk, such as a healthy diet, moderate alcohol consumption, social activities and support.

If testing were possible

In the practice you can only predict the chance of getting a disease with any accuracy if you know the cause, and then can check if you have the causal factor. This is the case with ADAD. If you have the related variant of the particular genes[note]these are not Alzheimer genes, see Autism is hereditary, but you don’t inherit autism for explanation[/note], then you will in time develop Alzheimer’s disease. You can find this out by having your DNA tested. But even that is relative, as some people with the affected variant only develop the disease in their eighties, though that is very exceptional. But would you then want to know when you were 20 if you were going to develop the disease at some point? Perhaps you would, if you wanted to know if you risked passing it on to your children. But perhaps not, because then you would have the sword of Damocles hanging above your head for dozens of years without there anything yet having developed?

Blood tests and scans

Genetics therefore always plays a role, but it is only for ADAD that genetic testing sometimes is of use. Blood testing is at the present moment of no value in predicting if you will develop Alzheimer’s. You can see with a brain scan if the brain is affected, but this is at a fairly advanced stage of the disease. This also does not clarify whether and in which cases the visible brain damage is a cause of the disease.

If there were a reliable test

But let us assume that there is a reliable test which you have undergone. The result may be that your chance of developing Alzheimer’s disease is 70%, while normally that would be around 40%. That makes you worried. But you do not have much information, because you will either get the disease or you won’t. Even if the chance is 70%, it may turn out that it does not develop. Or you get the disease anyway, even if the chance was 40%, or even 20%.
Can you do anything to prevent the disease? There are as yet no medicines against Alzheimer’s⁵. All the promising new drugs have ended up in the trash. What seems to help: a healthy lifestyle, healthy diet and activity -both social and physical- limited alcohol consumption and not smoking. But I would do all this anyway, even if your chance of developing the disease is small, because all this is also good for preventing cardiovascular disease, diabetes and cancer.

Tests on internet

In a nutshell: there are no reliable tests to predict Alzheimer before its onset. There are however tests for memory and other functions which are disrupted by Alzheimer’s disease. They can be very useful, but are nothing more than systematic and reliable tests to determine and measure the first symptoms of the disease when they have already presented. You can find tests on internet. But if you suspect that you or someone close to you has Alzheimer’s disease, then I would go to the GP and discuss it there.

Testing for other diseases

What I have explained here for Alzheimer’s disease holds true for practically all the commonly occurring diseases, such as most of the psychiatric disorders⁶, cardiovascular disease, diabetes, cancer, rheumatism, and more. Genetic tests, blood tests and scans are of very little use before the disease has developed. This however is not the case for some specific diseases, most with known familial predispositions, such as Huntington’s disease, cystic fibrosis, Duchenne’s dystrophy, some metabolic and endocrine diseases, and many more. In the case of these diseases, testing can be very useful even before a person is sick.
What about all those tests which the general practitioner or medical specialist orders? If you go to a doctor with complaints of illness, then he may order tests which are specific to your complaints. That is certainly useful. But testing without any relation to complaints or other determining factor is not particularly useful.

References

Long JM, Holtzman DM (2019): Alzheimer Disease: An Update on Pathobiology and Treatment Strategies. Cell 0. DOI: 10.1016/j.cell.2019.09.001

Janssens ACJW (2019): The new blood test for Alzheimer’s disease: developed in a study without patients. [Internet] [cited 2019 Aug 28];Available from: https://medium.com/@cecilejanssens/the-new-blood-test-for-alzheimers-disease-developed-in-a-study-without-patients-5022f4049e55

Melis RJF, Haaksma ML, Muniz-Terrera G (2019): Understanding and predicting the longitudinal course of dementia. Curr Opin Psychiatry 32:123–129.

Wald NJ, Old R (2019): The illusion of polygenic disease risk prediction. Genetics in Medicine 21:1705–1707.

Haer-Wigman L, Schoot V van der, Feenstra I, Silfhout ATV, Gilissen C, Brunner HG, et al. (2019): 1 in 38 individuals at risk of a dominant medically actionable disease. European Journal of Human Genetics 27:325.

Wray NR, Wijmenga C, Sullivan PF, Yang J, Visscher PM (2018): Common Disease Is More Complex Than Implied by the Core Gene Omnigenic Model. Cell 173:1573–1580.

Hersi M, Irvine B, Gupta P, Gomes J, Birkett N, Krewski D (2017): Risk factors associated with the onset and progression of Alzheimer’s disease: A systematic review of the evidence. Neurotoxicology 61:143–187

Ryman DC, Acosta-Baena N, Aisen PS, Bird T, Danek A, Fox NC, et al. (2014): Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis. Neurology 83:253–260

Bendlin BB, Carlsson CM, Gleason CE, Johnson SC, Sodhi A, Gallagher CL, et al. (2010): Midlife predictors of Alzheimer’s disease. Maturitas 65:131–137