Alzheimer’s Disease: Imaging Key to Early Treatment


By Charlene Laino, Senior Writer, Gupta Guide

Published: May 28, 2013
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner


Increased accumulation of beta-amyloid in the brain is associated with gray matter atrophy and memory impairment in cognitively healthy older people, a subanalysis of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Aging has found.

The findings suggest PiB-PET imaging for amyloid deposits could be used to screen for cognitive impairment, Christopher C. Rowe, MD, of the University of Melbourne in Australia, and AIBL researchers reported inJAMA Neurology.

In a cross-sectional analysis, 29 cognitively healthy people with amyloid deposits on imaging had significantly more loss of cortical thickness in two brain regions associated with episodic memory impairment — the precuneus and hippocampus — versus 64 healthy people who tested negative (P<0.05, corrected for false discovery rate).

Additionally, longitudinal analysis showed a faster rate of gray matter atrophy over 36 months in the temporal lobe and hippocampi of 15 healthy controls with amyloid deposits, compared with 38 controls who did not have deposits (P<0.05).

“The earliest signs of gray matter atrophy were detected in the hippocampus and the posterior cingulate and precuneus regions, and with disease progression, atrophy became more extensive in the temporal lobes,” Rowe and colleagues wrote.

“These findings support the notion that amyloid deposition is not a benign process and that interventions with anti-amyloid therapy at these early stages have a higher chance to be effective,” they said in a summary of their findings.

Building on a previous AIBL subanalysis that found that accumulation of beta-amyloid in the brain correlated with worse cognitive function in mildly impaired older patients, the current analysis was designed to investigate the correlation between amyloid deposition, gray matter atrophy, and memory in 93 asymptomatic persons.

Participants underwent neuropsychological evaluations as well as Pittsburgh compound B positron emission tomography (PiB-PET) scans to look for amyloid deposits. Fifty-three cognitively healthy people underwent repeated scans and neuropsychological evaluations 18 and 36 months later for the longitudinal analysis. (Forty patients with Alzheimer’s disease were also studied, but not included in this story).

Among the findings:

  • The mean age of people with amyloid deposits was 78 years, while the average age of those without deposits was 72 years, a significant difference (P<0.05).
  • In the group with no amyloid deposits, gray matter atrophy was already present in several regions of the brain group, with rates of gray matter loss around 0.02 mm/y, and no significant correlation between cortical thickness and neocortical PiB retention was found.


“This is in agreement with previous reports on the rates of atrophy associated with aging, suggesting atrophy in these persons was not driven by AD pathology,” the researchers wrote.

  • In the asymptomatic persons with amyloid deposits, small significant patterns of gray matter loss in the temporal lobe increased from about 17% at 18 months to about 77% at 36 months (P<0.05).


Additionally, cortical thickness was significantly associated with episodic memory scores in the temporal lobe.

“These results suggest that while [these cognitively healthy people with amyloid deposits are] still performing within the normal range for these tests, there is a direct association between cortical thickness and memory performance, even at the presymptomatic stage of the disease,” the researchers noted.

U.S. researchers generally praised the work, but expressed some reservations.

“This is very well done research” and the correlation the researchers found between amyloid deposits and cortical atrophy in “normal” people is “extremely important,” commented Huntington Potter, PhD, director of Alzheimer’s disease programs at the University of Colorado Denver.

“But the researchers go further and almost imply that amyloid could be a cause of the atrophy. What they showed was a correlation, not cause and effect,” he told The Gupta Guide.

The researchers are correct in their conclusion that anti-amyloid agents — which include almost all of the immunotherapy drugs tested to date — would need to be given earlier, Potter continued.

But the question is whether anti-amyloid agents alone will work at all, he said. For years the principal hypotheses of Alzheimer’s disease etiology revolved around beta-amyloid accumulation leading to extracellular plaques and vascular wall deposits.

“But a more recent approach is to target tau pathology and tangles instead of amyloid,” Potter said.

Asked if a drug that targeted both would not be a better approach, Potter said that targeting both simultaneously has proven difficult, but that in the long run, that may indeed prove best.

Also, screening of the general population for amyloid deposits using PiB PET imaging would be prohibitively expensive, Potter said. “We need an easier, cheaper biomarker,” he said.

Ronald C. Peterson, MD, PhD, director of the Mayo Alzheimer’s Disease Research Center, also praised the AIBL researchers and said their work helps to establish a link between memory loss, amyloid deposits and brain atrophy in cognitively healthy people.

But due to the small size of the study and the fact it was not population-based and thus the results may not be generalizable, the findings need to be replicated before any firm conclusions can be made, Peterson told The Gupta Guide.


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