Spatial tests could reveal early sign of Alzheimer’s, says expert

Schrödinger at 75 conference hears that early detection pivotal for treating disease

Nobel Prize winner Prof John O’Keefe’s tells forum that his team of scientists are “trying to come up with simple spatial memory tests, which will allow us detect people who are at the early stages of the disease”. File photograph: Getty Images

Simple tests of spatial awareness could allow clinicians to spot early indications of Alzheimer's disease, Nobel Prize winner Prof John O'Keefe told the Schrödinger at 75 conference.

Early detection was critical for treating this disease, since Alzheimer’s is now believed to start decades before patients are diagnosed, he added.

Prof O'Keefe, a neuroscientist at the University College London (UCL), is reknowned for discovering "place cells" in the brain. These cells start firing off signals once we are in a particular place. For a lab rat roaming around a box, a place cell only becomes active in a small patch of the box, then turns off when it leaves. It was subsequently discovered that the brain also has cells that signal which direction an animal is facing, he said.

Teamwork between such cells allow us build a mental picture of, for example, a new city we visit, he explained. “The idea of a place is an abstract concept that is created by the mind itself,” said Prof O’Keeffe.


Importantly, this map is made in a part of the brain called the hippocampus. “We now know that [Alzheimer’s] disease starts in this part of the brain, the hippocampus, and then spreads out along nerve fibres to other parts,” he said, with a toxic protein (tau) the prime suspect.

Spatial awareness could be key to revealing early Alzheimer’s, he said. His team had been “trying to come up with simple spatial memory tests, which will allow us detect people who are at the early stages of the disease”, he told the conference.

The “four mountains test” was one such assessment. A person is shown four mountains, which vary in height and shape. They are then asked to recognise the mountains again – from another perspective. “It turns out that patients with damage to their hippocampus are very bad at this test,” added Prof O’Keefe.

“This part of the brain which we have been studying for many years actually is one of the first parts that becomes disrupted in Alzheimer’s disease,” he says. “We will be able to use that knowledge and also to construct tests which are going to identify people who are at the earliest stages of the disease and suitable for therapy.”

Prof O’Keefe shared the Nobel Prize for physiology or Medicine in 2014 for his research on neural processes involved in mental representation of the spatial environments. He was born in New York to Irish parents and has been based at UCL since 1967.

He also outlined about how billions of cells manage to create just one consciousness, and the riddle of how the delay of information we receive from the external environment, through sight and sound for example, match up with our internal knowledge. Unified consciousness is all about good timing, he explained.

“We believe the real world is out there, but it is a construct of the mind,” he said. “Even when remembering from the past or looking into the future, we view from the present. Why should this be so?” Some of the most important questions in brain research still surround the schism “between mind and brain”, he said.

The complexity of the brain was addressed by US physicist Prof Danielle Bassett from the University of Pennsylvania, who uses tools from "network science" and complex mathematical approaches to study neurons. "Instead of thinking about brain regions, we now must think about it as a vast network," she said.