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Cognitive stress test predicts high levels of beta-amyloid

A doctor takes notes while talking with a patient.A simple and inexpensive word recall test accurately predicted whether people had elevated brain levels of beta-amyloid. Scientists hope this non-invasive stress test that puts pressure on memory--similar to how an exercise stress test checks cardiovascular health--could help identify subtle signs of cognitive impairment that may have previously been missed by standard memory tests.

An NIA-supported team of researchers led by Dr. David Loewenstein of the Center for Cognitive Neurosciences and Aging and the University of Miami Miller School of Medicine developed the Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L) test. Their preliminary findings were published in the September 4, 2018 issue of Neurology.

Using the LASSI-L, study participants listen to a list of categorized objects (fruits, musical instruments, or clothing) and then after a brief delay, repeat as many of the words as they can recall. Shortly afterwards, they repeat the process with a different list of words from the same category. The research team found that semantic intrusions—recalling either a word from the previous list, or a word that fits the category but was not on either list—can indicate potential problems with memory, cognition, or control of verbal inhibition.

To evaluate whether LASSI-L results matched brain pathology related to cognitive impairment, the scientists conducted PET and MRI scans on a group of 88 study participants. The scans showed that those who had more semantic intrusions on the word test also had higher levels of the protein beta-amyloid that is associated with increased risk of mild cognitive impairment and developing Alzheimer's disease.

The study gave the first evidence that semantic errors on cognitive tests like the LASSI-L were more common in people with mild cognitive impairment who were beta-amyloid positive. The LASSI-L also helped sort out these people from individuals who showed clinical symptoms of mild cognitive impairment but had negative amyloid scans and people who were diagnosed with non-Alzheimer's brain disorders that impacted cognition.

Overall, the study showed that semantic intrusions on the LASSI-L helped researchers separate participants who were cognitively normal from those with harder to detect cognitive impairment. Previous memory test methods likely would have labelled the latter group as cognitively unimpaired since only their correct memory test results were counted.

Since it offers a potentially faster and less expensive way to screen people for high amyloid burden than current tests, the researchers hope to make LASSI-L a low-tech tool to assist in medical evaluations and clinical trial recruitment. Additional research with larger numbers of participants will be needed to further evaluate the potential of the LASSI-L for use as a screening tool. The test has been validated in English and Spanish. The team is now working to computerize it and increase the types of comparison brain and biomarker scans.

This research was funded by NIH grants 5 P50 AG047726602 and AG047649-01A1.

Reference: Loewenstein DA et al. Utilizing semantic intrusions to identify amyloid positivity in mild cognitive impairment. Neurology. 2018 Aug 3. pii: 10.1212/WNL.0000000000006128. doi: 10.1212/WNL.0000000000006128.