Impact of Alzheimer's pathology on cognitive trajectories in nondemented elderly

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Abstract
Objective Some individuals who are asymptomatic for dementia while alive have substantial Alzheimer's disease (AD) neuropathology at autopsy. We investigated whether cognitive trajectories differ between clinically normal elderly individuals with and without AD neuropathology and how they compare with trajectories of clinically impaired individuals before dementia diagnosis. Methods Eighty-one elderly participants in the Baltimore Longitudinal Study of Aging (BLSA) were followed prospectively with neurological and neuropsychological assessments before autopsy evaluation at death. Trajectories of cognitive change were estimated for a number of domains using cognitive data before a clinical diagnosis of dementia. Results Clinically normal elderly individuals with and without AD-type neuropathology have similar cognitive trajectories across different cognitive domains. In contrast, individuals with mild cognitive impairment/AD show steeper rates of longitudinal decline in several aspects of cognition compared with clinically normal elderly individuals regardless of whether the latter have AD neuropathology. Moreover, the cognitive differences between impaired and unimpaired groups can be detected years before a diagnosis of dementia. Interpretation Clinically normal individuals with and without AD neuropathology do not differ in rates of cognitive decline across a number of cognitive domains. Understanding the factors that protect some individuals with AD pathology from cognitive impairment may contribute to the maintenance of cognitive health in the elderly. Ann Neurol 2006;60:688–695