Cognitive functioning during the transition from normal aging to dementia

Sammanfattning: The general aim of this thesis was to address unresolved issues regarding cognitive functioning in preclinical dementia. Increasing the knowledge about the preclinical period of dementia might have important clinical implications. For example, it may facilitate early detection, and thereby increase the efficiency of available interventions. All five empirical studies were based on data from the Kungsholmen Project - a longitudinal population-based study targeting persons living in the Kungsholmen parish of Stockholm, Sweden, who were ¡Ý75 years on October 1, 1987. In Study I and II, we investigated potential preclinical cognitive deficits in vascular dementia (VaD). It is well established that Alzheimer's disease (AD), the most common dementia disorder, is preceded by a preclinical phase with cognitive deficits. However, few studies have targeted the preclinical period in VaD, despite the fact that persons with VaD constitute approximately one fourth of dementia cases. In Study I, both preclinical VaD and preclinical AD persons showed cognitive impairment relative to controls on tasks assessing episodic memory 3 years before diagnosis. Although the results indicated a somewhat more widespread cognitive impairment in preclinical AD, there were no differences between the two dementia groups on any of the cognitive measures examined. In Study II, we observed an association between global cognitive functioning and incident VaD 3, but not 6, years before diagnosis. The association remained after controlling for demographic factors and history of vascular disorders. In Study III and IV, we examined level and change in cognitive performance for preclinical dementia and impending death. We found that excluding persons with preclinical dementia from the impending death group resulted in markedly attenuated effects of mortality on cognitive performance. However, both impending death and preclinical dementia were associated with poorer cognitive performance at cross-section for all examined tasks. In Study III, the impending death persons showed no accelerated decline relative to the controls on a measure of global cognitive functioning, whereas the preclinical dementia persons declined twice as fast. Study IV focused on a smaller sample that had completed a cognitive test battery. In contrast to Study III, we observed significant terminal -decline effects for select cognitive tasks even after controlling for preclinical dementia. These effects were only observed for tasks in which the controls showed no significant decline. In Study V, we examined the influence of preclinical dementia and impending death on the crosssectional relationship between age and cognitive performance. We found that removal of the preclinical dementia and impending death groups from the original sample affected the crosssectional age-cognition relationships relatively little. In sum, cognitive deficits constitute an early sign of VaD as well as of AD, with the pattern of preclinical cognitive impairment being similar for the two disorders. We also found that a considerable proportion of the impending-death effect is accounted for by preclinical dementia. Further, accelerated cognitive decline is most often a sign of impending dementia, although accelerated decline may be observed in the years preceding death for tasks showing little agerelated cognitive change. Finally, removal of persons in a preclinical phase of dementia or in close proximity to death affects the cross-sectional age-cognition relationship in an elderly sample relatively little, suggesting that the biological aging process exerts negative influences on cognitive functioning beyond those resulting from dementia and mortality.