Is semantic learning strategy an early clinical marker for amnestic mild cognitive impairment and Alzheimer’s disease?

Before getting to dementia, there is a long period suffering from pathological changes in the brain of patients with Alzheimer’s disease (AD), which provides a window for early diagnosis. Mild cognitive impairment (MCI), which is characterized by concerns about cognitive decline but nearly no interference with activities of daily living (Petersen, 2004), is considered to be an intermediate stage from healthy aging to AD, in particular the amnestic type (aMCI) showing a conversion rate of over 10% per year (Landau et al., 2010). Although detections of beta-amyloid (Aβ) and tau with positron emission tomography (PET) or in the cerebrospinal fluid have been validated to have good sensitivity and specificity for identifying AD pathology at the very early stage and included in recent criteria for AD research (Dubois et al., 2014; Jack et al., 2018), they are still not available inmost clinical settings and not acceptable for most patients because of the high cost or invasive procedure. Since cognitive testing is easily performed and correlates with the pathophysiological changes throughout disease development and progression, searching for a validated cognitive marker has practical implication for the early identification of AD. Episodic memory impairment, which reflects hippocampal dysfunction, is the early and prominent symptom of typical AD. Screening for memory impairment may provide a brief, easily repeated, and inexpensive test to detect early stage of AD, for example, aMCI. Verbal learning and memory assessment is the most common tool and included in most global cognitive scales to evaluate the episodic memory of subjects with cognitive impairment or dementia in clinical practice and research worldwide, such as the 3-word registration and recall on the Mini-Mental State Examination (MMSE), 5-word free and cued recall on the Montreal Cognitive Assessment (MoCA), and word learning, delayed recall and recognition on the Alzheimer’s Disease Assessment Scale-Cognitive subscale. There are also several specific-designed verbal learning tests for identifying and analyzing memory deficits, including the Rey Auditory Verbal Learning Test, the Hopkins Verbal Learning Test (HVLT), the California Verbal Learning Test (CVLT), the Free andCued Selective RemindingTest (FCSRT), and the Memory Binding Test (MBT). However, not all of the above tests have been translated into Chinese and validated in Chinese population, especially in the older adults. MBT, previously known as Memory Capacity Test, was initially developed to evaluate the ability of verbal learning and memory, using controlled learning and cued recall for encoding specificity to obtain the maximum retrieval (Rentz et al., 2010). In a study entitled “Validation of the Chinese version of the memory binding test for distinguishing amnestic mild cognitive impairment from cognitively normal elderly individuals” in this issue of the journal, Wang and colleagues reported a high discriminative validity of aChinese version of the MBT in distinguishing aMCI from normal controls (NCs) and AD (Wang et al., 2019). In addition, the Chinese version of MBT showed a good test–retest reliability and a relatively high convergent validity with the MoCA, the MMSE, and the Clinical Dementia Rating. In this study, the MBT was translated into Chinese, and its wordlist was adapted according to the word frequency to satisfy Chinese culture and lexicon context. Then, the ChineseMBT was performed to 26 patients with AD, 67 subjects with aMCI, 30 subjects with subjective cognitive impairment (SCI), and 41 cognitively NCs. Among all the participants, 22 subjects repeated the assessment within 4–8 weeks after the first interview for test–retest reliability. Their results were supported by recent longitudinal studies that analyzed the association between MBT and imaging markers of AD and demonstrated a better sensitivity than FCSRT for identifying the early pathological changes of AD. The INSIGHT-preAD (INveStIGation of AlzHeimer’s PredicTors in subjective memory complainers) study group reported that the MBT, especially the free recall performance, correlated with cholinergic basal forebrain volume on magnetic resonance imaging (MRI) (Teipel et al., 2018) and amyloid burden on PET (Gagliardi et al., 2019) in subjects with SCI. Moreover, it was observed that decreased free recall of the MBT predicted preclinical stage of International Psychogeriatrics (2019), 31:12, 1695–1697 © International Psychogeriatric Association 2019