Introduction Although preclinical dementia is characterized by decline in cognition and daily functioning, little is known on their temporal sequence. We investigated trajectories of cognition and daily functioning in preclinical dementia, during 18 years of follow-up.
Methods In 856 dementia cases and 1712 controls, we repetitively assessed cognition and daily functioning with memory complaints, mini-mental state examination (MMSE), instrumental activities of daily living (IADL), and basic activities of daily living (BADL).
Results Dementia cases first reported memory complaints 16 years before diagnosis, followed by decline in MMSE, IADL, and finally BADL. Vascular dementia related to earlier decline in daily functioning but later in cognition, compared with Alzheimer's disease. Higher education related to larger preclinical cognitive decline, whereas apolipoprotein E (APOE) ε4 carriers declined less in daily functioning.
Discussion These results emphasize the long hierarchical preclinical trajectory of functional decline in dementia. Furthermore, they show that various pathologic, environmental, and genetic factors may influence these trajectories of decline.

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Alzheimer's & Dementia
Department of Radiology