Changes in LASSI-L performance over time among older adults with amnestic MCI and amyloid positivity: A preliminary study

Different aspects of failing to recover from proactive semantic interference predicts rate of progression from amnestic mild cognitive impairment to dementia

“…Among patients with aMCI, tests utilizing frPSI and semantic intrusions have been shown to better discriminate between those who are amyloid positive versus amyloid negative than the number of correct responses on frPSI (Curiel et al, 2018b;Loewenstein et al, 2018b;Kitaigorodsky et al, 2021;Zheng et al, 2021). On the other hand, among cognitively unimpaired older adults, the number of correct responses on frPSI have been shown to be very sensitive predictors of progression to PreMCI and aMCI independent of etiology (Curiel et al, 2018a;Crocco et al, 2021).…”

“…These measures tap failure to recover from PSI and have previously demonstrated excellent discriminatory power in differentiating aMCI from cognitively unimpaired older adults and have been highly related to neurodegeneration in AD-prone regions ( Loewenstein et al, 2016 , 2017b ). Intrusion errors on these subscales have also been sensitive to the downstream effects of amyloid load ( Curiel et al, 2018b ; Loewenstein et al, 2018b ; Kitaigorodsky et al, 2021 ) including tau deposition, and neurodegeneration thought to reflect deficits in self-monitoring, and inhibitory control ( Loewenstein et al, 2018a ; Torres et al, 2019 ; Cid et al, 2020 ).…”

“…Greater numbers of semantic intrusions differentiate individuals with aMCI who are amyloid PET positive from aMCI who are amyloid PET negative ( Loewenstein et al, 2018b ) while the other neuropsychological deficits studied did not. Semantic intrusion errors have also differentiated amyloid PET-positive aMCI from other neurological and neuropsychiatric conditions with MCI due to non-AD conditions that were amyloid PET-negative ( Kitaigorodsky et al, 2021 ). Semantic intrusion errors that occur on measures of failure to recover from PSI have also been associated with corticolimbic disconnection in asymptomatic middle-aged children of a parent with AD ( Sánchez et al, 2017 ).…”

“…Two distinct aspects of frPSI are as follows: (a) the continued suppression of correct responses despite a second learning trial because of putative interference from competing items from the first list of words (List A); and (b) the inability to inhibit competing responses from the first list (semantic intrusions), despite multiple opportunities to do so ( Torres et al, 2019 ; Loewenstein et al, 2021 ). These two aspects of frPSI may be measured independently and may be important in distinguishing those with aMCI who are amyloid positive from those who are amyloid negative ( Loewenstein et al, 2018b ; Kitaigorodsky et al, 2021 ). This has the potential to improve screening for AD, particularly in settings where biomarkers are not readily available or to refer for more advanced biomarker assessment for diagnostic clarification, prognostication, and/or inclusion in emerging AD clinical trials.…”

A Novel Computerized Cognitive Test for the Detection of Mild Cognitive Impairment and Its Association with Neurodegeneration in Alzheimer’s Disease Prone Brain Regions

“…Unlike other traditional paradigms, the LASSI-L then facilitates the assessment of an individual’s ability to recover from PSI through an additional learning trial of the competing list. A growing body of evidence indicates that maximum learning of the initial targets, PSI, frPSI and semantic intrusion errors on the LASSI-L are very sensitive in discriminating between older adults who are cognitively healthy and those with PreMCI or MCI due to AD with amyloid PET biomarker positivity [ 12 ] [ 14 ] [ 15 ] [ 16 ]. Multiple studies highlighted that LASSI-L deficits, particularly frPSI, are related to volumetric reductions in AD-prone brain regions [ 12 ] [ 17 ] [ 18 ] [ 19 ].…”