Background: Delirium is associated with accelerated cognitive decline. The pathological substrates of this relationship are not yet known, that is, whether they are the same as those associated with the dementias, independent or inter-related. Here, we examine the hypothesis that the accelerated cognitive decline observed following delirium is independent of classical dementia neuropathology.
Methods: In three population-based cohorts (Epidemiological Clinicopathological Studies in Europe Collaboration) we examined the effects of delirium episodes on cognitive change. We then analysed these associations in relation to the extent of neurofibrillary tangles, amyloid plaques, vascular lesions and Lewy bodies in neuropathological autopsies (N = 987). Change in Mini-Mental State Examination scores (MMSE) over six years prior to death was modelled using random-effects linear regression, and interactions between delirium and pathology burden were assessed.
Results: Mean MMSE six years before death was 25 points. Individuals with delirium had worse initial scores (-2.8 points, p < 0.01). Cognitive decline attributable to delirium was -0.37 MMSE points/year (p < 0.01). Decline attributable to dementia pathology was -0.39 MMSE points/year (p < 0.01). However, the combination of delirium and dementia pathology resulted in the greatest decline, where the interaction contributed a further -0.16 MMSE points/year (p = 0.01).
Conclusions: Delirium in the presence of dementia related neuropathologies is associated with accelerated cognitive decline beyond that expected for delirium or the neuropathology itself. This suggests additional unmeasured but related neuropathological processes are initiated by the delirium. Age-related cognitive decline has many contributors and these findings at the population level support a role for delirium acting independently from classical dementia neuropathology.