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Background Cerebral white matter hyperintensity (WMH) burden is a key biological risk factor underpinning late life depression (LLD) and cerebral hypoperfusion has been identified as an important cause of WMH. The aim of this study therefore is to clarify if orthostatic hypotension (OH) and lower systemic blood pressure (BP), both of which cause reduced cerebral blood flow, modify the relationship between depression and cerebral white matter disease in a cohort of community-dwelling older people aged ≥70 years. Methods This study uses data from wave 3 of TILDA. Participants were included if they were aged ≥70 years and had undergone assessment for depressive symptoms, brain MRI and cardiovascular measures. Depressive symptoms were measured using the 8-item Centre for Epidemiological Studies Depression Scale. Scheltens Score was used by a trained radiologist to calculate overall WMH burden. Orthostatic BP was measured by active stand. OH was defined as a drop in Systolic BP≥20 mmHg or drop in diastolic BP≥10 mmHg at 30, 60 or 90 seconds post standing. Results Participants with depressive symptoms (8%, 16/202) had a significantly higher burden of WMH measured by Scheltens Score (14.6 (95% CI:11.0–18.2) vs. 11.0 (95% CI:10.1–11.8); p=0.0211). Two-way interaction models demonstrated that the association between depressive symptoms and WMH burden is significant only in those with co-existing OH. Similarly, the two-way interaction between depressive symptoms and systolic BP shows that this association remains statistically significant only in those with both depressive symptoms and lower BP, i.e. &lt;130 mm Hg. Conclusion This study demonstrates that depressive symptoms are associated with cerebral WMH in a cohort of community-dwelling people aged ≥70 years but this relationship is modified by co-existing OH or lower BP. Identifying the processes that lead to WMH accumulation and progression in depression is crucial in order to inform strategies aimed at preventing and ameliorating LLD.

344 The Relationship between Late Life Depressive Symptoms and Cerebral White Matter Disease is Modified by Systemic and Orthostatic Blood Pressure