Utilizing semantic intrusions to identify amyloid positivity in mild cognitive impairment
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Abstract
Objective Semantic intrusion (SI) errors may highlight specific breakdowns in memory associated with preclinical Alzheimer disease (AD); however, there have been no investigations to determine whether SI errors occur with greater frequency in persons with amnestic mild cognitive impairment (aMCI) confirmed as amyloid positive (Amy+) vs those who have clinical symptoms of aMCI-AD with negative amyloid scans (suspected non-AD pathology [SNAP]) or persons who are diagnosed with other brain disorders affecting cognition.
Methods Eighty-eight participants with aMCI underwent brain amyloid PET and MRI scans and were classified as early AD (Amy+), SNAP (Amy−), or other neurological/psychiatric diagnosis (Amy−). We focused on SI on the Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L) targeting proactive semantic interference (PSI; old semantic learning interferes with new semantic learning), failure to recover from PSI after an additional learning trial (frPSI), and retroactive semantic interference (new semantic learning interferes with memory for old semantic learning).
Results SIs on measures of PSI and frPSI distinguished between Amy+ AD and SNAP and other non-AD cases. PSI and frPSI intrusions evidenced moderately high associations with reduced volumes in the entorhinal cortex, superior temporal regions, and supramarginal gyrus. No such associations were observed in cases with SNAP.
Conclusions SIs on the LASSI-L related to PSI and frPSI uniquely differentiated Amy+ and Amy− participants with aMCI and likely reflect deficits with inhibition and source memory in preclinical AD not captured by traditional cognitive measures. This may represent a specific, noninvasive test successful at distinguishing cases with true AD from those with SNAP.
Glossary
- AD=
- Alzheimer disease;
- aMCI=
- amnestic mild cognitive impairment;
- Amy+=
- amyloid positive;
- Amy−=
- amyloid negative;
- ANOVA=
- analysis of variance;
- CDR=
- Clinical Dementia Rating;
- CI=
- confidence interval;
- DSM-V=
- Diagnostic and Statistical Manual of Mental Disorders, 5th edition;
- ERC=
- entorhinal cortex;
- FDR=
- false discovery rate;
- frPSI=
- failure to recover from proactive semantic interference;
- FTLD=
- frontotemporal lobar degeneration;
- HVLT-R=
- Hopkins Verbal Learning Test–Revised;
- LASSI-L=
- Loewenstein-Acevedo Scales for Semantic Interference and Learning;
- MCI=
- mild cognitive impairment;
- MMSE=
- Mini-Mental State Examination;
- PSI=
- proactive semantic interference;
- ROC=
- receiver operator characteristic;
- RSI=
- retroactive semantic interference;
- SNAP=
- suspected non-Alzheimer pathology;
- Tukey HSD test=
- Tukey honestly significant difference test
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received February 17, 2018.
- Accepted in final form May 31, 2018.
- © 2018 American Academy of Neurology
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