A review of novel Cognitive Challenge Tests for the assessment of preclinical Alzheimer’s disease.

Abstract

Objectives: There is currently a lack of consensus among neuropsychologists about which cognitive assessment paradigms hold the most promise in identifying subtle cognitive deficits in preclinical Alzheimer’s Disease (AD) and which are most useful for monitoring risk of cognitive deterioration. Many widely used instruments are older versions of tests originally developed for the assessment of dementia or traumatic brain injury. Current efforts to digitize these measures provides more uniform and remote assessment, which is an advancement, but does not reflect significant changes in paradigmatic underpinnings or recent advances in cognitive neuroscience. Method: This work provides an overview of novel Cognitive Challenge Tests (CCTs) that employ semantic interference paradigms that uniquely measure the failure to recover from proactive semantic interference (frPSI). Other salient methods to measure meaningful cognitive change in early stage AD are also presented, as well as how they compare with traditional neuropsychological assessments. Finally, future directions for the development of more effective assessment paradigms are discussed. Results: frPSI is a cognitive marker which measures the persistent inability to learn new semantically competing stimuli despite multiple opportunities to do so. frPSI and deficits in semantic inhibitory control have repeatedly shown utility for the early detection of AD during its preclinical stages. These novel cognitive markers have been related to various biomarkers of AD and neurodegeneration among culturally diverse older adults. Conclusions: To meet the critical needs of a rapidly evolving field, cognitive assessment instruments must show sufficient scientific rigor including robust sensitivity, specificity, and predictive utility among culturally and linguistically diverse populations and importantly, be correlated to AD biomarkers.

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

“…The intrusion errors that occur when an examinee experiences frPSI (Cued B2) is a phenomenon that has previously shown a disconnection between corticolimbic structures such as the medial temporal lobes and prefrontal cortex as measured by resting fMRI ( Sánchez et al, 2017 ). Although beyond the scope of this study, this connectivity among brain structures when assessing these two distinctive subcomponents of frPSI can likely best be determined using functional PET and fMRI studies ( Curiel Cid et al, 2023 ).…”

“…Maximum initial learning (Cued A2) and retroactive semantic interference again assessing Cued A2 targets on the LASSI-L after an initial recall was not examined since this has not been found to be particularly useful (Loewenstein et al, 2016(Loewenstein et al, , 2021. For the current study, our focus was on different aspects of frPSI, since these aspects of the LASSI-L have had the most predictive utility in many studies nationally and internationally (Curiel Cid et al, 2023). As such, we focused on (a) correct responses and (b) semantic intrusion errors that occurred on the List B2 Cued Recall subscale of the LASSI-L.…”

FDG-PET-based neural correlates of Addenbrooke’s cognitive examination III scores in Alzheimer’s disease and frontotemporal degeneration

“…Specifically, specificity and positive predictive values were limited when diagnosing AD versus HC. Utilizing more challenging and specific memory paradigms may offer improved diagnostic capacity in this context ( Curiel-Cid et al, 2022 ; Valles-Salgado et al, 2022 ). In addition, patients with AD generally seek medical attention earlier than those with bvFTD ( Ellajosyula et al, 2022 ), and in our cohort, patients with AD were diagnosed at earlier stages according to CDR.…”

Neuropsychological Assessment for Early Detection and Diagnosis of Dementia: Current Knowledge and New Insights

“…The differentiation of predementia stages from cognitively normal individuals or mild dementia cases remains a challenge, especially in the general population [ 48 , 49 , 50 ]. Although comprehensive evidence-based guidelines for preclinical cognitive assessment do not yet exist, research on the prodromal dementia stages (particularly AD) has begun to delineate its earliest cognitive manifestations [ 51 , 52 , 53 ]. In this context, the use of cognitive tests is proving useful in distinguishing cognitively healthy individuals from those in the stages of SCD, predementia, and mild dementia [ 54 , 55 ].…”