A novel cognitive assessment paradigm to detect Pre-mild cognitive impairment ( PreMCI ) and the relationship to biological markers of Alzheimer's disease

Abstract

Objective: A number of older adults obtain normal scores on formal cognitive tests, but p resent clinical concerns that raise suspicion of cognitive decline. Despite not meeting full criteria for Mild Cognitive Impairment (MCI), these PreMCI states confer risk for progression to Alzheimer’s disease (AD). This investigation addressed a pressing need to identify cognitive measures that are sensitive to PreMCI and are associated with brain biomarkers of neurodegeneration. Method Participants included 4 9 older adults with a clinical history suggestive of cognitive decline but norm al scores on an array of neuropsychological measures, thus not meeting formal criteria for MCI. The performance of these PreMCI participants were compared to 117 cognitively normal (CN) elders on the LASSI-L, a cognitive stress test that uniquely assesses the failure to recover from proactive semantic interference effects (frPSI). Finally, a subset of these individuals had volumetric analyses based on MRI scans. Results: PreMCI participants evidenced greater LASSI- L deficits, particularly with regards to frPSI and delayed recall, relative to the CN group. No differences on MRI measures were observed. Controlling for false discovery rate (FDR), frPSI was uniquely related to increased dilatation of the inferior lateral ventricle and decreased MRI volumes in the hippocampus, precuneus, superior parietal region, and other AD prone areas. In contrast, other LASSI-L indices and standard memory tests were not related to volumetric findings. Conclusions: Despite equivalent performance on traditional memory measures, the frPSI distinguished between PreMCI and CN elders and was associated with reductions in brain volume in numerous AD-relevant brain regions.

Disconnection of the right superior parietal lobule from the precuneus is associated with memory impairment in oldest-old Alzheimer's disease patients

“…Previous studies have demonstrated the role of the right SPL in memory, especially for, but not limited to, spatial storage ( Wager and Smith, 2003 ) and episodic memory ( Wagner et al., 2005 ). The SPL may also be important in managing working memory, including updating, ordering, and manipulations ( Crocco et al., 2018 ; Koenigs et al., 2009 ; Wager and Smith, 2003 ; Zou et al., 2013 ), and thus may be required for learning new information. Several studies also found that the SPL ( Bakkour et al., 2013 ; Prvulovic et al., 2002 ; Teipel et al., 2007 ) and precuneus ( Buckner et al., 2005 ; Klaassens et al., 2017 ; Scahill et al., 2002 ) were atrophied in AD.…”

Digital Biomarkers for the Early Detection of Mild Cognitive Impairment: Artificial Intelligence Meets Virtual Reality

“…Secondly, there is a need to integrate this new practice into current ones, i.e., neuropsychological evaluation. Including these data jointly in MCI assessment can allow a more sensitive measurement of the deficit by placing it on a continuum, reflecting a dimensional approach accounting for several other subclinical conditions, including Subjective Cognitive Decline (SCD; Roehr et al, 2019) or Pre-Mild Cognitive Impairment (Pre-MCI; Crocco et al, 2018;Grassi et al, 2018). This is far more crucial when considering that MCI can turn into dementia if the elderly person does not receive a timely diagnosis (Chiu, 2005), which should be built upon finer discrimination among the early stages of MCI and the collection of behavioral data, moving beyond a categorical, dichotomous approach rooted in previous diagnostic models, such as DSM- IV-TR or ICD-10 (American Psychiatric Association, 2000;World Health Organization, 2007;Negu et al, 2016), and the distinction between aMCI and naMCI.…”

“…Secondly, there is a need to integrate this new practice into current ones, i.e., neuropsychological evaluation. Including these data jointly in MCI assessment can allow a more sensitive measurement of the deficit by placing it on a continuum, reflecting a dimensional approach accounting for several other subclinical conditions, including Subjective Cognitive Decline (SCD; Roehr et al, 2019 ) or Pre-Mild Cognitive Impairment (Pre-MCI; Crocco et al, 2018 ; Grassi et al, 2018 ).…”

Memory Impairment in Relapsing-Remitting Multiple Sclerosis Using a Challenging Semantic Interference Task

“…The Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L) is a novel test first developed with the aim to detect preclinical and prodromal stages of Alzheimer's disease (18). Several studies have been conducted in the setting of Alzheimer's disease, showing a high diagnostic accuracy and a correlation with amyloid load, limbic connectivity, and brain volumes involved during the first stages of Alzheimer's disease (19)(20)(21)(22). Furthermore, the LASSI-L has shown to be superior to the Free and Cued Selective Reminding Test (FCSRT) in the prediction of Alzheimer's disease features on 18 F-Fluorodeoxyglucose positron emission tomography imaging (23).…”

“…These cues along with the 1:1 competing targets on the LASSI-L also serve to elicit considerably more proactive and retroactive semantic interference and semantic intrusion errors. These semantic deficits, and especially semantic intrusions have been associated with increased risk of neurodegeneration and frontal executive hypoactivation on fMRI in middle-aged offspring of patients with late-onset Alzheimer's disease, which may suggest deficits in source memory and disinhibition (19)(20)(21)(24)(25)(26). The CVLT does measure proactive interference because it has a group words on List B that semantically compete with List A.…”