Episodic and semantic memory impairments in (very) early Alzheimer’s disease: The diagnostic accuracy of paired-associate learning formats

Abstract

Paired-associate learning (PAL) paradigms measure memory processes sensitive to the medial temporal lobe, which shows atrophy in early Alzheimer’s disease (AD). PAL tests have not yet been standard clinical procedure, neither are semantic memory tests. In early AD, impairments are more subtle. A literature review indicates that standard neuropsychological tests may not measure these impairments accurately. Therefore, I constructed new episodic and semantic memory tests. I investigated the diagnostic accuracy of these tests in 37 amnestic mild cognitive impairment (aMCI; of whom 21 had converted to AD at 1.3-year-follow-up), 43 early AD patients, and 80 non-demented controls. Main questions: (1) which tests best differentiate aMCI and AD from normal aging: most sensitively, most specifically?; (2) do PAL paradigms and/or semantic memory tests (fluency; naming) contribute to this differentiation? A free recall (non-PAL) test of unrelated words was most sensitive to aMCI and AD (91%), whereas a PAL-recognition-test (of semantically related word pairs of moderate association strength, including strongly related foils) was most specific (96%). Stepwise logistic regression analysis showed that differentiation was improved by a subordinate semantic fluency test. I conclude that a combination of episodic and semantic memory components best predicts AD. Future research should focus on comparing semantic and visuospatial PAL tests.

Keywords

• paired-associate learning
• recognition
• semantic memory
• mild cognitive impairment
• alzheimer’s disease
• sensitivity
• specificity