Structural brain MRI in late life with a special focus on the oldest old.

Abstract

People over the age 85, the oldest old, are the fastest growing segment of the population globally, with a substantial proportion developing dementia. Research into dementia in this age group is of public health importance, and absence of dementia could serve as a model of successful ageing. Neuroimaging studies of dementia in the 85-plus population are scarce. The aim of this thesis was to characterise the structural magnetic resonance imaging (MRI) profiles of brains with and without cognitive impairment in late life, with a special focus on the oldest old. A combined cohort aged 71 to 103 years from the Sydney Centenarian Study and Sydney Memory and Ageing Study comprised the sample. MRI-derived brain measures, including brain atrophy indices, white matter hyperintensities (WMHs) and brain infarcts, were examined by cognitive categories. The principal findings were as follows: first, in non-demented participants, a linear negative relationship was observed between age and grey matter volume, which continued into the 10th and 11th decades of life, with the greatest effects of age being on the medial temporal lobe and the parietal and occipital cortices. Second, thinner cortex and smaller hippocampus were strong indicators of dementia at all ages, as were deep WMHs and brain infarcts (≥ 2) at 80 but not at 95 years. Using a composite MRI pathology index, the association between structural MRI and dementia was much stronger at 80 than at 95 years. Brain vascular injuries were common at advanced age, irrespective of the cognitive status of the individual. Third, structural MRI could distinguish amnestic mild cognitive impairment (MCI), but not non-amnestic MCI, from normal individuals from 71 to 103 years. However, the MRI markers that were most indicative of amnestic MCI differed in the young old from the oldest old. This research is the first to extend our understanding of brain ageing on structural MRI into the 10th and 11th decades of life. MRI markers of dementia and amnestic MCI at advanced age could potentially assist in the early diagnosis of dementia and have implications for understanding the mechanisms of brain resilience in the oldest old.