David A Loewenstein1, Rosie E Curiel2, Steven DeKosky2, Russell M Bauer2, Monica Rosselli2, Salvador M Guinjoan2, Malek Adjouadi2, Ailyn Peñate2, William W Barker2, Sindy Goenaga2, Todd Golde2, Maria T Greig-Custo2, Kevin S Hanson2, Chunfei Li2, Gabriel Lizarraga2, Michael Marsiske2, Ranjan Duara2. 1. From the Center on Aging (D.A.L., R.E.C.) and Department of Psychiatry and Behavioral Sciences (D.A.L., R.E.C.), University of Miami Miller School of Medicine; Wien Center for Alzheimer's Disease and Memory Disorders (D.A.L., A.P., W.W.B., S.G., M.T.G.-C., R.D.), Mount Sinai Medical Center, Miami Beach; McKnight Brain Institute (S.D.), Department of Neurology (S.D., R.D.), Department of Clinical and Health Psychology (R.M.B.), Center for Translational Research in Neurodegenerative Diseases (T.G.), and Clinical and Translational Science Institute (K.S.H., M.M.), University of Florida, Gainesville; Department of Psychology (M.R.), Florida Atlantic University, Boca Raton; FLENI Foundation (S.M.G.), University of Buenos Aires Schools of Medicine and Psychology, Argentina; Department of Electrical and Computer Engineering (M.A., C.L., G.L.), College of Engineering and Computing, Florida International University Center for Advanced Technology and Education; and Herbert Wertheim College of Medicine (R.D.), Florida International University, Miami. DLoewenstein@med.miami.edu. 2. From the Center on Aging (D.A.L., R.E.C.) and Department of Psychiatry and Behavioral Sciences (D.A.L., R.E.C.), University of Miami Miller School of Medicine; Wien Center for Alzheimer's Disease and Memory Disorders (D.A.L., A.P., W.W.B., S.G., M.T.G.-C., R.D.), Mount Sinai Medical Center, Miami Beach; McKnight Brain Institute (S.D.), Department of Neurology (S.D., R.D.), Department of Clinical and Health Psychology (R.M.B.), Center for Translational Research in Neurodegenerative Diseases (T.G.), and Clinical and Translational Science Institute (K.S.H., M.M.), University of Florida, Gainesville; Department of Psychology (M.R.), Florida Atlantic University, Boca Raton; FLENI Foundation (S.M.G.), University of Buenos Aires Schools of Medicine and Psychology, Argentina; Department of Electrical and Computer Engineering (M.A., C.L., G.L.), College of Engineering and Computing, Florida International University Center for Advanced Technology and Education; and Herbert Wertheim College of Medicine (R.D.), Florida International University, Miami.
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.
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.
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