INflammation and Small Vessel Disease Study

A prospective observational cohort study in patients with cerebral small vessel disease deterring whether changes in systemic inflammation predict brain white matter damage measured using MRI and cognitive decline. This is a study funded by a joint BHF-Dutch Heart Foundation research grant and will be conducted in both Cambridge UK and Nijmegen Netherlands with 100 of the 200 total participants recruited at each site, and data from both sites analysed together.

Inclusion Criteria:Have given written informed consent to participateBe aged 40 years and overHave symptomatic cerebral small vessel disease (SVD) defined as:Clinical lacunar stroke syndrome with lacunar infarct, as defined by the Standards for Reporting Vascular Changes on Neuroimaging (STRIVE) criteriaAnd/OR Symptoms of cognitive impairment due to SVD with lacunar infarct on MRIAnd/OR Gait apraxia/motor impairment presumed due to SVD with lacunar infarct on MRIExclusion Criteria:Unable/unwilling to consent including lack of capacity to consentContraindications to taking part in MRI study as assessed by the local MRI safety questionnaire, e.g., pacemakerVaccination or infection with fever in preceding monthAny stroke cause other than SVD including:Cardioembolic sourceCarotid or vertebral stenosis > 50% measured on NASCET (North American Symptomatic Carotid Endarterectomy Trial) criteriaMyocardial infarction in past yearAuto-immune/auto-inflammatory diseaseUse of immunomodulating drugsEstimated glomerular filtration rate (eGFR) =<59 ml/min/1.73m2 within past 3 months for Cambridge, and eGFR =<29 ml/min/1.73m2 within past 3 months for Nijmegen, in line with local guidelines. Estimated GFR will be calculated using the Modification of Diet in Renal Disease (MDRD) equation: 186 x (Creatinine / 88.4)-1.154 x (Age)- 0.203 x (0.742 if female) x (1.210 if black). Creatinine will be checked within 3 months of the MRI, and if this has not been done as part of clinical care it will be performed as a research procedure.Another diagnosed chronic neurological condition (e.g. Alzheimer's, Parkinson's disease, motor neurone disease, multiple sclerosis).Limited life expectancy due to another illness or chronic condition making the 2-year follow-up difficult (e.g. widespread malignancy).Known monogenic cause of small vessel disease (e.g. CADASIL - Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy)