Trajectories of Cognitive Decline following Dementia Onset: What Accounts for Variation in Progression?

Abstract

Background: Delineating the natural history of dementia progression has important clinical implications, including reducing caregiver burden and targeting effective drug trials. We examined whether trajectories of cognitive change differed reliably after diagnosis, and whether diverse predictors of such differences (demographic, psychological, biological, genetic, social) could be identified. Methods: Cognitive change was examined for incident dementia cases (mild: n = 156; moderate: n = 77; severe: n = 73) and controls (n = 249) from the Kungsholmen Project, a community-based study of adults 75 years and older. Results: For those with dementia, total variance attributed to between-person differences in cognitive decline was modest and linked to but a single predictor (history of cardiovascular disease). Although less variance in cognitive decline was observed for the similarly aged controls, numerous significant predictors of these differences were identified. Conclusion: The neurodegenerative process underlying dementia overshadows formerly significant predictors of cognitive change.

Aging-related magnification of genetic effects on cognitive and brain integrity

“…Concerning structural brain-imaging markers, longitudinal studies demonstrate more hippocampal atrophy for e4 carriers [29,30] that may contribute to the effects of APOE on functional brain activity. Consistent with the assumption that genetic effects diminish once individuals reach very low cognitive-performance levels (Figure 1), evidence indicates that APOE does not affect progression rate in clinical AD [31], or even the rate of decline from preclinical to clinical dementia [32].…”

The Influence of Multimorbidity on Clinical Progression of Dementia in a Population-Based Cohort

“…When we compare these results with those of the study done by MacDonald et al which used Kungsholmen Project data on disease trajectories in more advanced stages of cognitive decline and in which multimorbidity did not affect the rate of progression [11], we may conclude that it is typically in the earliest phase of dementia onset that multimorbidity is of influence. Also, their study only looked at cognitive function measured with MMSE.…”

Predictors of Future Cognitive Decline in Persons with Mild Cognitive Impairment

“…Recent work by others has sought to use information obtained from the MMSE or from the Clock Drawing Test to predict conversion to dementia in population-based samples, with modest success to date in terms of diagnostic accuracy (∼70%) [58,59]. In a community-based study of incident dementia cases, predictors of cognitive decline were found to differ from those identified in similarly-aged control cases [60]. This suggests that results of the present study may only be valid for those persons already identified as having mild cognitive impairment that does not reach criteria for dementia.…”