Rate of cognitive decline and mortality in Alzheimer's disease

Background: Alzheimer's disease (AD) is associated with increased mortality, but survival in those with the disease varies widely. It is uncertain how much of the variation in survival is due to individual differences in rate of disease progression. Methods: During a 4-year period, 354 persons with AD underwent annual clinical evaluations that included administration of 17 cognitive function tests, from which global and specific measures of cognitive function were derived. A growth curve approach was used to assess individual rates of cognitive decline and proportional hazards models adjusted for age, sex, and education to examine the associations of baseline level of cognition and rate of cognitive decline with mortality. Results: During the 4-year study period, 242 persons survived and 112 died. At baseline, the global measure of cognition ranged from -1.68 to 1.36 (mean=0.03, SD=0.57), with higher scores indicating better function. Baseline level of cognition was not related to mortality (p=0.12). Global cognition declined an average of 0.56 unit/year, with substantial heterogeneity (SD=0.41). To determine mortality risk, persons were divided into quartiles based on rate of cognitive decline and survival contrasted in the quartile with the least decline with survival in each remaining quartile, adjusting for baseline level of cognition. Compared with those with the least decline, risk of death was increased more than threefold in the subgroup with mild decline, more than fivefold in those with moderately rapid decline, and more than eightfold in those with the most rapid decline. Similar results were found after controlling for baseline health and disability and in analyses using specific cognitive function measures. Conclusion: Mortality in AD is strongly associated with rate of cognitive decline.