Background: Brain MRI-markers are risk factors of dementia and decline in cognition and daily functioning. It is unknown to what extent the associations of brain MRI-markers with cognition and daily functioning are part of the pathway leading to dementia. We aimed to investigate associations of brain MRI-markers with change in cognition and daily functioning during 15 years of follow-up, including their relation to dementia. Design, Setting, and Participants: Four hundred and sixty three stroke-free and non-demented participants from the population-based Rotterdam Study that underwent brain-MRI, yielding brain volumetrics, between 1995 and 1996. Measurements: We assessed cognition using the Mini-Mental State Examination (MMSE) and daily functioning using instrumental and basic activities of daily living (IADL and BADL) up to seven times between 1990 and 2011. Analyses were performed both including and excluding incident demented participants. Results: Smaller brain volume associated with larger decline in MMSE, IADL, and BADL. Larger white matter lesion volume associated with larger decline in MMSE. Frontal lobe volume associated strongest with decline in IADL and BADL, and temporal lobe volume with decline in MMSE. After excluding incident demented participants (n = 63), associations with IADL and BADL remained, while associations with MMSE disappeared. Conclusions: Smaller brain volumes and larger white matter volume associate with larger decline in cognition and daily functioning, during 15 years of follow-up. Importantly, the relation of brain volume with cognition, but not daily functioning, was driven by those individuals that ultimately developed dementia.

Gait is a complex sequence of movements, requiring cooperation of many brain areas, such as the motor cortex, somatosensory cortex, and cerebellum. However, it is unclear which connecting white matter tracts are essential for communication across brain areas to facilitate proper gait. Using diffusion tensor imaging, we investigated associations of microstructural organization in 14 brain white matter tracts with gait, among 2330 dementia- and stroke-free community-dwelling individuals. Gait was assessed by electronic walkway and summarized into Global Gait, and 7 gait domains. Higher white matter microstructure associated with higher Global Gait, Phases, Variability, Pace, and Turning. Microstructure in thalamic radiations, followed by association tracts and the forceps major, associated most strongly with gait. Hence, in community-dwelling individuals, higher white matter microstructure associated with better gait, including larger strides, more single support, less stride-to-stride variability, and less turning steps. Our findings suggest that intact thalamocortical communication, cortex-to-cortex communication, and interhemispheric visuospatial integration are most essential in human gait.