Memory Correlates of Alzheimer's Disease Cerebrospinal Fluid Markers: A Longitudinal Cohort Study

Background: Performance on episodic, semantic, and working memory tests is impaired in Alzheimer's disease (AD)-type dementia, but it is unclear which type of memory test is most strongly associated with early AD biomarkers in cerebrospinal fluid (CSF), and most useful for monitoring disease progression.

Objective: To examine the association between amyloid-beta 1-42 (A beta(42)) and tau in CSF with performance on different memory domains at baseline, and how these CSF markers are related with memory decline.

Methods: We included 263 individuals with normal cognition, mild cognitive impairment, AD-type dementia, and non-AD dementia from the European EDAR study. Assessment included CSF A beta(42) and t-tau analyses with INNO-BIA AlzBio3 Luminex assay, the CERAD wordlist learning and delayed recall, animal fluency test, and the CANTAB Paired Associates Learning (PAL) and Spatial Working Memory tasks. Follow-up assessments were performed within 3 years after baseline.

Results: At baseline, decreased CSF A beta(42) correlated most strongly with the PAL total errors adjusted and the wordlist delayed recall and increased CSF t-tau with the wordlist delayed recall. Over time, decreased CSF A beta(42) was associated with decline on the wordlist learning, whereas increased CSF t-tau were associated with decline in scores on the wordlist learning, wordlist delayed recall, and animal fluency. Associations were independent of baseline diagnosis.

Conclusion: Tests assessing episodic verbal and visuospatial memory are most useful for detection of AD pathology. Tests for episodic verbal memory and semantic memory are most useful for tracking memory decline.