Memory Tests Plus Brain Scans Detect Earliest Stages of AD

Megan Brooks

July 15, 2013

BOSTON, Massachusetts — A combination of memory tests and brain imaging may help identify the earliest stages of Alzheimer's disease (AD), before symptoms appear, when measures to slow the disease process might work best, a new study suggests.

The study found that poor episodic memory in the context of synaptic dysfunction and elevated amyloid may identify cognitively normal adults at high risk for progression to AD dementia.

Dorene M. Rentz, PsyD, associate professor of neurology at Harvard Medical School, Boston, reported the study findings here at the Alzheimer's Association International Conference (AAIC) 2013.

Failed Trials

Recent failed drug treatment trials in people with mild to moderate AD suggest that the time to intervene in AD is during the preclinical, or presymptomatic, stage, when cognitive performance is still normal but there is imaging evidence of amyloidosis and neuronal injury, Dr. Rentz explained.

She and her colleagues designed their study to see whether tests of memory and executive function in older cognitively normal adults relate to synaptic integrity by using fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and amyloid deposition with C 11 Pittsburgh Compound B (PiB PET).

"We sought to determine whether those normal individuals with lower scores on tests of memory and thinking ability also had extensive amyloid plaques and associated neuronal injury in AD brain regions consistent with preclinical AD," Dr. Rentz said.

The study included 129 adults aged 65 to 87 (mean age, 73.7 years) with Clinical Dementia Rating scores of 0.

The researchers found that amyloid burden and synaptic dysfunction independently predicted episodic memory performance. Individuals with worse memory performance had higher PiB deposition and lower FDG metabolism in regions of the brain commonly affected in AD.

"However, not all memory changes are a result of amyloid plaques," Dr. Rentz said. Some individuals had worse memory scores and lower FDG metabolism but a normal PiB scan. These memory changes, she said, may be due to other non-AD brain changes (eg, vascular) or possibly these changes occur earlier and precede amyloid plaques or "act as a catalyst that may eventually lead to amyloid plaques."

Individuals who performed worse on nonmemory executive function tests also had lower FDG metabolism (synaptic dysfunction) but a normal PiB scan (no amyloid deposition).

More highly educated individuals had normal performance on memory tests despite lower FDG metabolism and higher PiB retention. "This may mean that education has a protective effect on cognitive performance in the early stages of preclinical Alzheimer's," Dr. Rentz said.

People with higher education may maintain their cognitive abilities longer despite evidence of AD-like changes in the brain, she explained. "This means that memory tests may not be the best way to identify people in preclinical stages of AD. However, more sensitive tests are being developed to help overcome this problem."

"Overall," said Dr. Rentz, "our findings suggest that poor memory performance with both FDG metabolism and higher PiB deposition may help identify people who are at high risk for progression to Alzheimer's disease dementia."

Not "Ready for Prime Time"

"This study is important because it looks at how can we identify from the general population who might be at increased risk so that when we do have a therapy to stop or slow the progression of disease or when we understand more about lifestyle factors that may play a role, we can intervene, like we do now for heart disease," Heather Snyder, PhD, director of medical and scientific relations at the Alzheimer's Association, told Medscape Medical News.

Maria Carrillo, PhD, vice president of medical and scientific relations at the Alzheimer's Association, cautioned that more research is needed. Combining imaging and cognitive tests to spot the earliest signs of AD in the general population is "not ready for prime time," she told Medscape Medical News.

The study was funded by the National Institute on Aging and the Alzheimer's Association.

Alzheimer's Association International Conference (AAIC) 2013. Abstract 38645. Presented July 12, 2013.

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