Trajectories of cognitive decline in different domains prior to AD onset in persons with mild cognitive impairment

Abstract

ObjectivesTo explore the trajectories and the change-points of global and five domain-specific cognitive functions before the onset of Alzheimer's disease (AD). MethodsData was retrieved from the Alzheimer's Disease Neuroimaging Initiative with follow-up from 2005 to 2022. Participants with mild cognitive impairment (MCI) at baseline and those who progressed to AD during follow-up were included. The time of AD onset was defined as the visit time when participant was first diagnosed as AD during follow-up. Global and five domain-specific cognitive functions (immediate memory, visuospatial ability, language, processing speed and executive function) were assessed by Mini-Mental State Examination, Immediate recalling trials of Rey Auditory Verbal Learning Test, Clock Drawing Test, Animal Fluency Test, Part A and B of Trail Making Test, respectively. Their trajectories and change-points before AD onset were explored by generalized additive mixed models and piecewise linear regression models, respectively. Results349 participants were diagnosed as MCI at baseline and converted to AD during follow-up, who were included in this study. They had been visited on an average of 4.6 times (SD = 2.1, range = 2.0–13.0), with a total of 1593 visits. Their mean baseline age and AD onset age were 74.4 (SD = 6.4, range = 60.0–88.4) and 77.0 (SD = 6.8, range = 60.5–94.7) years, respectively. Baseline age and educational year were significantly associated with global cognitive, immediate memory, language and executive function. Men presented better global cognitive function (β = 0.54, p < 0.05) but poorer immediate memory (β = −1.72, p < 0.05) than women. Immediate memory and visuospatial ability showed the earliest change-points at 4 years before the onset of AD (Note as T-4years), followed by language (T-3.5years), executive function (T-2.5 years), processing speed (T-2.0 years), and finally the global cognitive function (T-1.5years). ConclusionsThe trajectories of the six neuropsychological scores were non-linear and showed deterioration in functions over time. Immediate memory and visuospatial ability showed the earliest change-points prior to AD onset.