A change point model for estimating the onset of cognitive decline in preclinical Alzheimer's disease

Dementia is characterized by accelerated cognitive decline before and after diagnosis as compared to normal ageing. Determining the time at which that rate of decline begins to accelerate in persons who will develop dementia is important both in describing the natural history of the disease process and in identifying the optimal time window for which treatments might be useful. We model that time at which the rate of decline begins to accelerate in persons who develop dementia relative to those who do not by using a change point in a mixed linear model. A profile likelihood method is proposed to draw inferences about the change point. The method is applied to data from the Bronx Ageing Study, a cohort study of 488 initially non-demented community-dwelling elderly individuals who have been examined at approximately 12-month intervals over 15 years. Cognitive function was measured using the Buschke Selective Reminding test, a memory test with high reliability and known discriminative validity for detecting dementia. We found that the rate of cognitive decline as measured by this test in this cohort increases on average 5.1 years before the diagnosis of dementia.