Abstract
Background: The identification of the type and sequence of cognitive decline
in preclinical mild cognitive impairment (MCI) prior to Alzheimer’s disease (AD) is
crucial for understanding AD pathogenesis and implementing therapeutic interventions.
Objective: To model the longitudinal courses of different neuropsychological
functions in MCI due to AD.
Methods: We investigated the prodromal phase of MCI over a 12-year period in
27 initially healthy participants with subsequent MCI preceding AD (NC-MCI) and 60
demographically matched healthy individuals (NC-NC). The longitudinal courses of cognitive
performance (verbal and visual episodic memory, semantic memory, executive functioning,
constructional praxis, psychomotor speed, language, and informant-based reports) were
analyzed with linear mixed effects models.
Results: The sequence with which different cognitive functions declined in
the NC-MCI relative to the NC-NC group began with verbal memory and savings performance
approximately eight years, and verbal episodic learning, visual memory, and semantic
memory (animal fluency) circa four years prior to the MCI diagnosis. Executive
functioning, psychomotor speed, and informant-based reports of the NC-MCI group declined
approximately two years preceding the MCI diagnosis.
Conclusions: Measurable neuropsychological deterioration occurs up to
approximately eight years preceding MCI due to AD.
