The relationship between Lifestyle Factors and Neurodegeneration in Midlife as expressed on fMRI: a Systematic Review Protocol Hinesh Topiwala,* Graciela Muniz Terrera, Kathryn Saunderson, Tom C. Russ, Marshall Dozier, Craig W. Ritchie Figure 3: fMRI may be able to reveal very early abnormalities in brain function of cognitively normal individuals that could reflect the initial stages of Alzheimer’s disease (2) Background There is an increasing recognition that neurodegeneration, which manifests clinically as dementia in later life, originates much earlier – in midlife, or even earlier.   Figure 1: Whole brain volume across the lifespan between 4 and 88 years of age. The curves are dashed around age 18–21, indicating the uncertainty in this area, since limited data was available for fitting this age range. Two separate fits were calculated for the younger (<19 years) and older (>19 years) groups (1) Method The systematic review will be conducted using Medline, Embase and PsycInfo (all via OVID platform). Each database will be searched using sensitive searches combining subject headings and free text terms adapted for each database. The search terms will cover the areas of neuroimaging, lifestyle, and regional changes in cerebral metabolism or blood flow, blood volume, or oxygenation. Titles and abstracts will be screened independently by Dr Hinesh Topiwala and Dr Kathryn Saunderson against the inclusion/exclusion criteria with any disagreements in the final lists of included studies resolved by discussion. In the next stage, the full articles will be examined against the inclusion/exclusion criteria. Differences between reviewers’ selections will be resolved by discussion and if required, screening by a third reviewer, Professor Craig Ritchie.   Lifestyle & Neurodegeneration Lifestyle factors may have a role in both the aetiology (as risk factors) and secondary prevention (as resilience factors) of neurodegeneration. Lifestyle is a way of living based on identifiable patterns of behaviour which are determined by the interplay between an individual’s personal characteristics, social interactions, and socioeconomic and environmental living conditions. Figure 2: The interaction of lifestyle factors with each other and the stage of an individual’s life course Figure 4: Flow diagram illustrating initial results of the systematic review fMRI changes as an early biomarker for Alzheimer’s Disease If early neurodegenerative changes, as expressed on fMRI, are consistent in pattern, they could act as potential early biomarker for Alzheimer’s disease. This could help to identify individuals with a high probability of progressing to Alzheimer’s dementia, as well as to monitor disease progression and to measure treatment response (both pharmacological and risk factor modification). Initial Results   The systematic review strategy was registered on Prospero (protocol registration number: CRD42016045237) on 05/08/2016. The search strategy was run on 02/09/2016. It produced 2895 results. Formal screening of results was commenced shortly after this using Covidence. References: 1. Hedman et al. Human brain mapping. 2012;33(8):1987-2002. 2. Jack et al. Lancet Neurology. 2010;9(1):119-28. * For further information contact Dr Hinesh Topiwala: hinesh.topiwala@ed.ac.uk