Would You Want To Know If You Had Alzheimer’s?

bloodtest

Lead researcher Howard Federoff and a colleague, both part of the team that has developed this revolutionary test, study results on a computer screen.

Would you want to know if you were going to get dementia? That is the frightening question posed by new research published online in Nature Medicine this week.

A new blood test that looks for tell-tale signs of Alzheimer’s in the fat composition of your blood has been developed by researchers at the Georgetown University Medical Center in the US. It is simple to administer, just like any other blood test, and it would be accurate around 90 per cent of the time.

Dementia cases are rising across the developed world as longevity increases the number of people living long enough to show symptoms. According to UK charity The Alzheimer’s Society: there are currently 800,000 people with dementia in the UK; this figure will exceed one million  by 2021; the proportion of people with dementia doubles with every 5 years of age; and one third of people over 95 have dementia.

Until now, it has been impossible to meaningfully test for dementia until the onset of symptoms and even then there can be ambiguity in the early stages.  This massively important breakthrough is detailed below and raises a number of  important questions:

  • Is it worth having a test for an incurable disease?
  • What happens if you get a false positive (or, indeed, a false negative)?
  • Will insurers want to know whether or not you have had the test done?
  • Would employers insist on the test for older employees?
  • If you held a job where judgement was critical – perhaps working as an air traffic controller – could you be required to take a test?
  • Would a positive result make it easier for someone to claim power of attorney over your interests?
  • Would it qualify you as disabled?
  • Would you be obliged to reveal results to the driving licence regulators?
  • Would you want counselling?
  • What would you tell your family?
  • Would test results be confidential in the planned new health service database in the UK?

Of course, knowing that you were destined to become seriously ill would enable you to plan while you still had your faculties. But the implications of this test are profound for society as a whole, for health providers and for each of us as individuals.

This test will be coming to a doctor’s surgery near you. We all need to prepare.

What will you do?

Below is the news release issued by Georgetown University Medical Center to describe their breakthrough and below that you will find the abstract and citation for the research and a link to the paper in Nature Medicine.

News Release:

Blood Test Identifies Those At-Risk for Cognitive Decline, Alzheimer’s Within 3 Years

Researchers have discovered and validated a blood test that can predict with greater than 90 percent accuracy if a healthy person will develop mild cognitive impairment or Alzheimer’s disease within three years.

Described in the April issue of Nature Medicine, the study heralds the potential for developing treatment strategies for Alzheimer’s at an earlier stage, when therapy would be more effective at slowing or preventing onset of symptoms. It is the first known published report of blood-based biomarkers for preclinical Alzheimer’s.

The test identifies 10 lipids, or fats, in the blood that predict disease onset. It could be ready for use in clinical studies in as few as two years and, researchers say, other diagnostic uses are possible.

“Our novel blood test offers the potential to identify people at risk for progressive cognitive decline and can change how patients, their families and treating physicians plan for and manage the disorder,” says the study’s corresponding author Howard J. Federoff, MD, PhD, professor of neurology and executive vice president for health sciences at Georgetown University Medical Center.

There is no cure or effective treatment for Alzheimer’s. Worldwide, about 35.6 million individuals have the disease and, according to the World Health Organization, the number will double every 20 years to 115.4 million people with Alzheimer’s by 2050.

Federoff explains there have been many efforts to develop drugs to slow or reverse the progression of Alzheimer’s disease, but all of them have failed. He says one reason may be the drugs were evaluated too late in the disease process.

“The preclinical state of the disease offers a window of opportunity for timely disease-modifying intervention,” Federoff says. “Biomarkers such as ours that define this asymptomatic period are critical for successful development and application of these therapeutics.”

The study included 525 healthy participants aged 70 and older who gave blood samples upon enrolling and at various points in the study. Over the course of the five-year study, 74 participants met the criteria for either mild Alzheimer’s disease (AD) or a condition known as amnestic mild cognitive impairment (aMCI), in which memory loss is prominent. Of these, 46 were diagnosed upon enrollment and 28 developed aMCI or mild AD during the study (the latter group called converters).

In the study’s third year, the researchers selected 53 participants who developed aMCI/AD (including 18 converters) and 53 cognitively normal matched controls for the lipid biomarker discovery phase of the study. The lipids were not targeted before the start of the study, but rather, were an outcome of the study.

A panel of 10 lipids was discovered, which researchers say appears to reveal the breakdown of neural cell membranes in participants who develop symptoms of cognitive impairment or AD. The panel was subsequently validated using the remaining 21 aMCI/AD participants (including 10 converters), and 20 controls. Blinded data were analyzed to determine if the subjects could be characterized into the correct diagnostic categories based solely on the 10 lipids identified in the discovery phase.

“The lipid panel was able to distinguish with 90 percent accuracy these two distinct groups: cognitively normal participants who would progress to MCI or AD within two to three years, and those who would remain normal in the near future,” Federoff says.

The researchers examined if the presence of the APOE4 gene, a known risk factor for developing AD, would contribute to accurate classification of the groups, but found it was not a significant predictive factor in this study.

“We consider our results a major step toward the commercialization of a preclinical disease biomarker test that could be useful for large-scale screening to identify at-risk individuals,” Federoff says. “We’re designing a clinical trial where we’ll use this panel to identify people at high risk for Alzheimer’s to test a therapeutic agent that might delay or prevent the emergence of the disease.”

Below are the details of the paper published in Nature Medicine:

Abstract

Alzheimer’s disease causes a progressive dementia that currently affects over 35 million individuals worldwide and is expected to affect 115 million by 2050. There are no cures or disease-modifying therapies, and this may be due to our inability to detect the disease before it has progressed to produce evident memory loss and functional decline. Biomarkers of preclinical disease will be critical to the development of disease-modifying or even preventative therapies. Unfortunately, current biomarkers for early disease, including cerebrospinal fluid tau and amyloid-β levels, structural and functional magnetic resonance imaging and the recent use of brain amyloid imaging or inflammaging, are limited because they are either invasive, time-consuming or expensive. Blood-based biomarkers may be a more attractive option, but none can currently detect preclinical Alzheimer’s disease with the required sensitivity and specificity. Herein, we describe our lipidomic approach to detecting preclinical Alzheimer’s disease in a group of cognitively normal older adults. We discovered and validated a set of ten lipids from peripheral blood that predicted phenoconversion to either amnestic mild cognitive impairment or Alzheimer’s disease within a 2–3 year timeframe with over 90% accuracy. This biomarker panel, reflecting cell membrane integrity, may be sensitive to early neurodegeneration of preclinical Alzheimer’s disease.

Citation

Plasma phospholipids identify antecedent memory impairment in older adults by Mark Mapstone, Amrita K Cheema, Massimo S Fiandaca, Xiaogang Zhong, Timothy R Mhyre, Linda H MacArthur, William J Hall, Susan G Fisher, Derick R Peterson, James M Haley, Michael D Nazar, Steven A Rich, Dan J Berlau, Carrie B Peltz, Ming T Tan, Claudia H Kawas & Howard J Federoff published in Nature Medicine. DOI:10.1038/nm.3466

Read the abstract and get the paper here.

Sources

News release from Georgetown University Medical Center here.

Get the research paper here.

UK Alzheimer’s Society here.

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