The Role of Verbal Memory in Masking Symptoms of Alzheimer's Disease

Structured AbstractO_ST_ABSINTRODUCTIONC_ST_ABSVerbal memory tests like the Reys Auditory Learning Test (RAVLT) are widely used in Alzheimers disease assessments without consideration of females well-known advantages in verbal memory. This study explores if this form of cognitive reserve masks symptoms and delays diagnosis in females. METHODSWe employed a retrospective longitudinal cohort design (ADNI, PREVENT-AD) to model Immediate Recall subcomponents on the RAVLT over time in amyloid negative (A{beta}-) cognitively normal participants versus A{beta}+ participants that progressed to AD dementia. RESULTSOur Bayesian model successfully identified the inflection point where cognition deviates from normal onto the AD dementia trajectory. The timing of decline onset differed significantly across sexes, with A{beta}+ females maintaining normal cognition longer than A{beta}+ males. Among individuals with AD dementia, females experienced a steeper annual decline than males. DISCUSSIONDelayed onset of decline suggests that females preserve cognition despite neuropathology accumulation. This masked period represents a window for earlier detection and timely intervention before irreversible neurodegeneration. Research in ContextO_LISystematic review: The authors reviewed the literature from PubMed and Elsevier to identify verbal memory as a core feature in the Alzheimers Disease discourse. Our critical appraisal was complemented with meetings with expert neuropsychologists and neuroinformaticians. C_LIO_LIInterpretations: We find that females have superior performance on Reys Auditory Learning Test (RAVLT) Immediate Recall, females maintain performance for longer than males before being diagnosed with Alzheimers Disease, and once diagnosed, they decline faster than males. These findings underscore the importance of conducting Alzheimers Disease assessments with considerations for sex differences. C_LIO_LIFuture directions: We aim to continue the investigation of cognitive reserve in females in the context of the Amyloid, Tau and Neurodegeneration (ANT) framework. Considering the early stage of disease is of interest given that our results show the appearance of cognitive symptoms many years before official dementia diagnosis. C_LI Highlights- In cognitively healthy amyloid negative participants, females outperform males on the Reys Auditory Learning Test (RAVLT). - In the amyloid positive participants, females maintain normal verbal memory for 2.7 years longer than males. - After divergence from cognitive normality, females experience approximately a 25-50% steeper cognitive decline compared to males. - Our findings call attention to the female verbal memory advantage as an influential form of cognitive reserve that requires diagnostic consideration.