Neuroimaging markers have synergistic effect on cognitive decline

By Eleanor McDermid, Senior medwireNews Reporter

The Alzheimer disease (AD) neuroimaging markers β-amyloid (Aβ) and neurodegeneration have synergistic effects on the rate of cognitive decline in clinically normal people, research shows.

Elizabeth Mormino (Massachusetts General Hospital, Boston, USA) and co-workers assessed 166 participants of the Harvard Aging Brain Study who had no clinical evidence of AD. Based on brain imaging studies conducted during the first year of participation, the team classified 81 participants as stage 0 AD, because they were negative for both Aβ deposition and neurodegeneration. A further 19 were stage 1, being positive for Aβ deposition, and 28 were stage 2, being positive for both biomarkers.

In an editorial accompanying the study in JAMA Neurology, Susan Resnick (National Institute on Aging, Baltimore, Maryland, USA) notes that, rather than basing the Aβ cutoff according to the level found in people with cognitive impairment, the researchers used a statistical model to define the threshold for Aβ positivity. “This definition allowed the investigators to capture Aβ+ individuals at the earliest stages of amyloid deposition”, she observes.

The remaining 38 patients were, unexpectedly, negative for Aβ but positive for neurodegeneration, and were classified separately as having suspected non-AD pathophysiology.

Over an average 2.09 years of follow-up, both Aβ and neurodegeneration were significantly associated with the change in participants’ scores on annual neuropsychological testing. The effect of both biomarkers together was synergistic, with stage patients having significantly greater decline than expected from the additive effects of the biomarkers.

“These findings validate the usefulness of the preclinical staging criteria, and of Aβ and [neurodegeneration] status, for predicting the likelihood of cognitive change, as well as the potential sensitivity of cognitive outcomes to therapeutic response during the short follow-up intervals typical of clinical trials”, says Resnick.

Of note, stage 0 patients displayed a practice effect, causing improvement in their cognitive performance, with global cognition z scores rising from about 0.1 to 0.4. This effect was reduced in stage 1 patients and those with non-AD neurodegeneration, while stage 2 patients had significant cognitive decline.

Resnick says this finding highlights the important of repeated cognitive testing of clinically normal people, “because the absence of a predicted practice effect, rather than cognitive decline per se, may predict impending cognitive impairment.”

The practice effect was affected by Aβ levels; among patients considered negative for this biomarker, Aβ level was still associated with cognition, such that levels at the top end of the range for this group were associated with a reduced learning effect.

“The present study is another reminder that we still have much to learn about the pathophysiological events leading to clinical expression of AD and neurodegenerative pathology”, concludes Resnick.

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