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Background: Neuroimaging markers of cerebral small vessel disease (SVD) are common in older individuals, but the pathophysiological mechanisms causing these lesions remain poorly understood. Although hypertension is a major risk factor for SVD, the direct causal effects of increased blood pressure are unknown. The Hyperintense study is designed to examine cerebrovascular and structural abnormalities, possibly preceding SVD, in young adults with hypertension. These patients undergo a diagnostic work-up that requires patients to temporarily discontinue their antihypertensive agents, often leading to an increase in blood pressure followed by a decrease once effective medication is restarted. This allows examination of the effects of blood pressure increase and decrease on the cerebral small vessels. Methods: Hyperintense is a prospective observational cohort study in 50 hypertensive adults (18–55 years) who will temporarily discontinue antihypertensive medication for diagnostic purposes. MRI and clinical data is collected at four timepoints: before medication withdrawal (baseline), once antihypertensives are largely or completely withdrawn ( T = 1), when patients have restarted medication ( T = 2) and reached target blood pressure and 1 year later ( T = 3). The 3T MRI protocol includes conventional structural sequences and advanced techniques to assess various aspects of microvascular integrity, including blood-brain barrier function using Dynamic Contrast Enhanced MRI, white matter integrity, and microperfusion. Clinical assessments include motor and cognitive examinations and blood sampling. Discussion: The Hyperintense study will improve the understanding of the pathophysiological mechanisms following hypertension that may cause SVD. This knowledge can ultimately help to identify new targets for treatment of SVD, aimed at prevention or limiting disease progression.

Background: Cerebral small vessel disease (SVD) and Alzheimer's disease (AD) pathology, namely b-amyloid (Ab), commonly cooccur. Exactly how they overlap remains a source of uncertainty. Using quantifiable biomarkers across multiple imaging modalities, we examined whether the presence of vascular risk factors and/or baseline cerebral SVD was related to a greater burden of Ab and its progression over time. Methods:Participants with baseline diffusion tensor imaging (DTI), magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) scans (n¼216; mean age 73.29 6 7.08 years, 91 (42.1%) females) were drawn from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (https://ida.loni.usc.edu). Peak width of skeletonized mean diffusivity (PSMD) was processed as a novel DTI marker of SVD (Baykara et al., 2016). Separate linear regression models were used for dependant variables of amyloid burden (quantified as the global standardized uptake value ratio (SUVR)) and SVD burden (quantified as white matter hyperintensity (WMH) volume and PSMD) at baseline, and then global SUVR and WMH change over 24 months. Age, sex, APOE e4 carrier status and vascular risk factors were included as independent variables. Results: At baseline (Table 1), APOE e4 genotype had the strongest association with SUVR (b .444, p<.001). WMH volume was the strongest correlate of PSMD (b .426, p<.001), followed by sex (b .174, p¼.009) and fast-

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