Study vailidates first 'gold standard' technique for identifying early signs of Alzheimer's

A new study led by researchers from the University of California-Los Angeles has validated the first "gold standard" technique to measure atrophy, or loss of tissue, in the hippocampus of the brain - one of the earliest indicators of Alzheimer's disease.

The researchers say their study provides "pathological confirmation" that hippocampal morphometry is a valid biomarker for Alzheimer's.

Not only will the technique be used in Alzheimer's research across the globe - aiding the development of new drugs to prevent or treat the disease - the team says clinicians may soon be using the method for early diagnosis of Alzheimer's disease.

Researchers at the Mary S. Easton Center for Alzheimer's Disease Research at UCLA published their findings in the journal Alzheimer's and Dementia.

Around 5.3 million people in the USA are living with Alzheimer's disease, of whom 5.1 million are aged 65 and older. 

Over the next 10 years, it is estimated that the number of seniors affected by the condition will increase by 40% to 7.1 million, emphasizing the need for new prevention and treatment strategies for the condition.

In Alzheimer's disease, loss of memory is one of the first symptoms to show. Through structural magnetic resonance imaging (MRI) examinations, researchers have found this is caused by atrophy in the hippocampus - a region of the brain associated with memory formation - possibly due to the formation of beta-amyloid plaques and tau tangles.

Such MRI exams are already used in clinical and research settings to diagnose Alzheimer's and assess disease progression. 

However, the researchers note that the validity of structural MRI for these purposes has been questioned; a number of different structural MRI techniques are currently being used, all of which can present different results.

For example, different structural MRI approaches applied to same hippocampus can show differences in size of up to 2,000 cubic millimeters. To put this into perspective, an average hippocampus measures around 3,000-4,000 cubic millimeters in total.

What is more, the researchers note that no previous studies have definitively concluded that hippocampal volume corresponds with tissue loss.

Strong correlation between hippocampal volume and Alzheimer's indicators

The European Alzheimer's Disease Consortium-Alzheimer's Disease Neuroimaging Initiative (EADC-ADNI) was set up in an attempt to create a clear-cut structural MRI technique to measure hippocampal atrophy in relation to Alzheimer's disease.

From an in-depth analysis of the most commonly used structural MRI techniques for Alzheimer's, the EADC-ADNI developed the Harmonized Hippocampal Segmentation Protocol (HarP). The researchers set out to validate the technique in this latest study.

Using a powerful 7 Tesla MRI scanner, the team analyzed the brains of nine deceased Alzheimer's patients and seven cognitively normal deceased patients for around 60 hours each, which the researchers say provided "unprecedented visualization" of their hippocampal tissue.

The researchers then used HarP to measure the hippocampal volumes of all patients, before assessing the accumulation of tau proteins in each brain and the loss of brain cells - two key indicators of Alzheimer's.

From this, the team found there was a strong correlation between hippocampal volume and tau protein accumulation and brain cell loss. The researchers say this provides "pathological confirmation" that hippocampal morphometry is a valid biomarker for Alzheimer's and that HarP is an effective technique to measure it.

"As a result of the years of scientifically rigorous work of this consortium, hippocampal atrophy can finally be reliably and reproducibly established from structural MRI scans.

This hippocampal protocol will now become the gold standard in the field, adopted by many if not all research groups across the globe in their study of Alzheimer's disease. It will serve as a powerful tool in clinical trials for measuring the efficacy of new drugs in slowing or halting disease progression."

This gold standard MRI approach can be used immediately in clinical trials for Alzheimer's and other research settings. Next, the team hopes to validate the technique so it can be used as standard protocol for diagnosing Alzheimer's patients and monitoring disease progression.

The National Institute on Aging, the Jim Easton Consortium for Alzheimer's Drug Discovery and Biomarker Development, the National Institutes of Health and the Alzheimer's Association provided funding for the study.

Earlier this week, a new report from the Alzheimer's Association revealed that only 45% of patients with Alzheimer's or their caregivers say they were given their diagnosis by their doctors.

References:

1.  Relationship between hippocampal atrophy and neuropathology markers: A 7T MRI validation study of the EADC-ADNI Harmonized Hippocampal Segmentation Protocol, Liana Apostolova, et al., Alzheimer’s and Dementia, doi: http://dx.doi.org/10.1016/j.jalz.2015.01.001, published online 22 January 2015, abstract.
2.  UCLA news release, accessed 26 March 2015.
3.  Additional source: Alzheimer's Association, 2015 Alzheimer's disease facts and figures, accessed 26 March 2015.