BOSTON, Massachusetts — One of the first practical studies presented this week at the Alzheimer’s Association International Conference in Boston was on early detection of Alzheimer’s disease (AD). The first study suggests a combination of memory tests and brain imaging may identify the earliest stages of AD, before symptoms appear, when measures to slow the disease process might be most effective.
The study found that poor episodic memory (of events, time, places, people etc.) along with poor brain metabolism and associated synaptic dysfunction and elevated amyloid may identify otherwise normal adults at high risk for progression to AD dementia.
Dorene M. Rentz, PsyD, associate professor of neurology at HarvardMedicalSchool, Boston, reported the study. She noted “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.”
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 (amyloid) deposition and lower metabolism (as measured by a PET scan) in regions of the brain commonly affected in AD. [ If you’ve seen Dr. Craft’s video you will recall that impaired glucose metabolism in the brain is a major precursor to Alzheimer’s.]
“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 [no excess amyloid]. 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.” [i.e. well educated seniors may still show decent memory abilities even though significant damage is occurring, which may later give way to more aggressive AD decline.]
“Overall,” said Dr. Rentz, “our findings suggest that poor memory performance with lower metabolism and higher plaque deposition may help identify people who are at high risk for progression to Alzheimer’s disease dementia.” [But of the three the reduced brain metabolism might be most predictive.
FYI – Because there is some ambiguity here, additional biomarkers being developed at the Mayo clinic could further help clarify the picture with less expensive blood tests.
The team used a new technique called “metabolomics” that measures the chemical fingerprints of metabolic pathways in the cell — sugars, lipids, nucleotides, amino acids, and fatty acids — to detect the changes. Metabolomics can give scientists insight into the cellular processes that underlie diseases.
Identifying those changes could lead to biomarkers that can eventually be used for early diagnosis of Alzheimer’s, monitoring its progression in patients, and tracking therapeutic approaches.
The study was funded, in part, by grants from the National Institute of Environmental Health Sciences and the National Institute on Aging.
Ref:
http://www.medscape.com/viewarticle/807820?nlid=32054_1882&src=wnl_edit_dail&uac=117439PN
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