How does frailty influence the risk and expression of dementia in Alzheimer disease?

Dementia is a clinical syndrome in which impaired memory and thinking interferes with a person's daily life. The most common cause of dementia is mixed Alzheimer disease (AD) / vascular dementia. AD can be diagnosed clinically when someone is alive and, after death, by brain autopsy. Even so, not everyone who meets the autopsy diagnostic criteria for AD actually has dementia in life. Despite some study, why this discrepancy exists is still unclear. We plan to address it by looking at how overall health affects brain function. To do this, we must measure health problems, which we quantify with a frailty index. The frailty index counts the number of health problems that an individual has accumulated. Frailty increases the risk for many age-related illnesses (including heart disease, hip fracture and dementia). Now we want to know if this helps explain why brain autopsy findings alone do not account for the clinical features of dementia. We hypothesize that the frailer a person is, even though it is more likely that they will have cognitive impairment, this will be less clearly related to their brain autopsy findings. We will use data from two large, community-based, autopsy series in older people (Chicago USA; Cambridge UK). The people in those studies generously agreed to have their memory and thinking tested every 1-2 years and to donate their brains after they had died. These extremely valuable studies are well suited to what we plan to do. Our research team includes physicians who study both dementia in people and AD in brains, as well as scientists skilled in data analysis. We have team members at varying levels of their careers, from PhD student to established professor. Understanding how frailty affects brain function can improve our understanding of how dementia arises, and how it can be treated and even prevented.