A comparative study of pathological outcomes in The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age and Brains for Dementia Research Cohorts

In the present study we have characterised and compared individuals whose brains were donated as part of The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age (UoM) with those donated through the Manchester arm of the UK Brains for Dementia Research (BDR) programme. The aim of this study was to investigate how differences in study recruitment may affect final pathological composition of cohort studies.UoM cohort was established as a longitudinal study of ageing and cognition whereas the BDR programme was established, prima facie, to collect brains from both demented and non-demented individuals for the purpose of building a tissue research resource. Consequently, the differences in recruitment patterns generated differences in demographic, clinical and neuropathological characteristics. There was a higher proportion of recruits with dementia (mostly Alzheimer’s disease (AD)) within the BDR cohort than in UoM cohort. In pathological terms, the BDR cohort was more ‘polarised’, being more composed of demented cases with high Braak pathology scores and non-demented cases with low Braak scores, and fewer non-AD pathology cases, than UoM cohort. In both cohorts, cerebral amyloid angiopathy (CAA) tended to be greater in demented than non-demented individuals. Such observations partly reflect the recruitment of demented and non-demented individuals into the BDR cohort, and also that insufficient study time may have elapsed for disease onset and development in non-demented individuals to take place. Conversely, in UoM cohort, where there had been nearly 30 years of study time, a broader spread of AD-type pathological changes had ‘naturally’ evolved in the brains of both demented and non-demented participants.