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

Objectives: To explore the trajectories and the change-points of global and five domain-specific cognitive functions before the onset of Alzheimer's disease (AD).

Methods: Data 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.

Results: 349 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).

Conclusions: The 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.