Objective: The purpose of this study was to examine the role of multiple pathologies in the expression of dementia in the oldest-old.Methods: A total of 183 participants of The 901 Study with longitudinal follow-up and autopsy were included in this clinical-pathologic investigation. Eight pathologic diagnoses (Alzheimer disease [AD], microinfarcts, hippocampal sclerosis, macroinfarcts, Lewy body disease, cerebral amyloid angiopathy, white matter disease, and others) were dichotomized. We estimated the odds of dementia in relation to each individual pathologic diagnosis and to the total number of diagnoses. We also examined dementia severity in relation to number of pathologic diagnoses.Results: The presence of multiple pathologic diagnoses was common and occurred more frequently in those with dementia compared with those without dementia (45% vs 14%). Higher numbers of pathologic diagnoses were also associated with greater dementia severity. Participants with intermediate/high AD pathology alone were 3 times more likely to have dementia (odds ratio 5 3.5), but those with single non-AD pathologies were 12 times more likely to have dementia (odds ratio 5 12.4). When a second pathology was present, the likelihood of dementia increased 4-fold in those with intermediate/high AD pathology but did not change in those with non-AD pathologies, suggesting that pathologies may interrelate in different ways. Conclusions:In the oldest-old, the presence of multiple pathologies is associated with increased likelihood and severity of dementia. The effect of the individual pathologies may be additive or perhaps synergistic and requires further research. Multiple pathologies will need to be targeted to reduce the burden of dementia in the population. Neurology ® 2015;85:535-542

Introduction We investigated the association between age of onset of hypertension and dementia risk in an oldest-old cohort. Methods Participants are from The 90+ Study, a population-based longitudinal study of people aged 90+ who are survivors from the Leisure World Cohort Study (LWCS). We estimated hypertension onset age using self-reported information from The 90+ Study and LWCS, collected about 20 years earlier. 559 participants without dementia were followed every 6 months for up to 10 years. Results 224 participants developed dementia during follow-up (mean=2.8 years). Compared with those without hypertension, participants whose hypertension onset age was 80-89 years had a lower dementia risk (HR=0.58, p=0.04) and participants with an onset age of 90+ years had the lowest risk (HR=0.37, p=0.004). Discussion Developing hypertension at older ages may protect against dementia. Understanding the mechanisms for this lower risk is important for determining ways to prevent dementia in the very elderly.