With the advent of advances in biomarker detection and neuropsychological measurement, prospects have improved for identifying and tracking the progression of Alzheimer's disease (AD) from its earliest stages through dementia. While new diagnostic techniques have exciting implications for initiating treatment earlier in the disease process, much work remains to be done to optimize the contributions of the expanding range of tools at the disposal of researchers and clinicians. The present paper examines recent work in cerebrospinal fluid biomarkers, magnetic resonance imaging, positron emission tomography, neuropsychological measures, and functional assessment. The strengths and weaknesses of current methodologies are explored and discussed. It is concluded that AD from its mild cognitive impairment state through dementia represents a continuous process, and that progression over time can best be accomplished by interval-level variables. Biomarkers that are most sensitive to early AD may not be the most optimal for monitoring longitudinal change, and it is likely that multivariate models incorporating cognitive measures, functional variables and biomarker data will be the most fruitful avenues for future research.

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.

Background: The rise in incidence of Alzheimer’s disease (AD) has led to efforts to advance early detection of the disease during its preclinical stages. To achieve this, the field needs to develop more sensitive cognitive tests that relate to biological markers of disease pathology. Failure to recover from proactive interference (frPSI) is one such cognitive marker that is associated with volumetric reductions in the hippocampus, precuneus, and other AD-prone regions, and to amyloid load in the brain. Objective: The current study attempted to replicate and extend our previous findings that frPSI is a sensitive marker of early AD, and related to a unique pattern of volumetric loss in AD prone areas. Methods: Three different memory measures were examined relative to volumetric loss and cortical thickness among 45 participants with amnestic mild cognitive impairment. Results: frPSI was uniquely associated with reduced volumes in the hippocampus ( r = 0.50) precuneus ( r = 0.41), and other AD prone regions, replicating previous findings. Strong associations between frPSI and lower entorhinal cortex volumes and cortical thickness (r≥0.60) and precuneus ( r = 0.50) were also observed. Conclusion: Unique and strong associations between volumetric reductions and frPSI as observed by Loewenstein and colleagues were replicated. Together with cortical thickness findings, these results indicate that frPSI is worthy of further study as a sensitive and early cognitive marker of AD.

This research aimed to determine whether qualitative analysis of different types of intrusion errors on a verbal cognitive task was useful in detecting subtle cognitive impairment in preclinical stages prior to the progression to dementia. Different types of semantic intrusions on the Loewenstein-Acevedo Scales of Semantic Interference and Learning (LASSI-L) were compared across 160 individuals diagnosed as cognitively normal (CN), amnestic Mild Cognitive Impairment (aMCI), and dementia. The sample included Hispanics and non-Hispanic European Americans. Across diagnostic groups, the most common type of intrusion error was actual targets presented from a competing word list under conditions eliciting proactive semantic interference (PSI), and retroactive semantic interference (RSI), followed by intrusions that represented one of three overlapping semantic categories but none of the targets from List A or B. Nonsemantic intrusions rarely occurred. These competing list intrusions (CLI) and semantically related intrusions (SRI) differentiated between aMCI and CN participants. Further, these intrusion error were related to brain amyloid load, indicating their importance as potential primary markers of AD-related neurodegeneration. Ethnicity effects were not seen across the types of intrusion errors. Two types of intrusion errors (CLI and SRI) showed differences between the CN and aMCI group, with the aMCI group evidencing a higher rate of these intrusion errors compared with the CN group. These results support previous literature about the LASSI-L's sensitivity at the earliest stages of abnormal aging. (PsycINFO Database Record (c) 2019 APA, all rights reserved).