rates of decline in alzheimer disease decrease with age阿尔茨海默病的几率下降随着年龄增长而减少.pdfVIP

Rates of Decline in Alzheimer Disease Decrease with Age 1 2 1,2 2 Dominic Holland *, Rahul S. Desikan , Anders M. Dale , Linda K. McEvoy , for the Alzheimer’s Disease Neuroimaging Initiative 1 Department of Neurosciences, University of California San Diego, La Jolla, California, United States of America, 2 Department of Radiology, University of California San Diego, La Jolla, California, United States of America Abstract Age is the strongest risk factor for sporadic Alzheimer disease (AD), yet the effects of age on rates of clinical decline and brain atrophy in AD have been largely unexplored. Here, we examined longitudinal rates of change as a function of baseline age for measures of clinical decline and structural MRI-based regional brain atrophy, in cohorts of AD, mild cognitive impairment (MCI), and cognitively healthy (HC) individuals aged 65 to 90 years (total n = 723). The effect of age was modeled using mixed effects linear regression. There was pronounced reduction in rates of clinical decline and atrophy with age for AD and MCI individuals, whereas HCs showed increased rates of clinical decline and atrophy with age. This resulted in convergence in rates of change for HCs and patients with advancing age for several measures. Baseline cerebrospinal fluid densities of AD-relevant proteins, Ab1–42, tau, and phospho-tau181p (ptau), showed a similar pattern of convergence with advanced age across cohorts, particularly for ptau. In contrast, baseline clinical measures did not differ by age, indicating uniformity of clinical severity at baseline. These results imply that the phenotypic expression of AD is relatively mild in individuals older than approximately 85 years, an