Table 1.
Summary of findings: Association orthostatic hypotension and white matter hyperintensities.
| Author, year | Study design | Participants | OH assessment | Outcome assessment | Statistical adjustment | Outcomes |
|---|---|---|---|---|---|---|
| Buckley et al., 2020 23 | Cross-sectional cohort | N = 440 Irish community dwelling older adults.Mean age (yrs): 72 (range 65–92)51.5% female68.4% with OH | Continuous BP measurement for 2 minutes during active standing after 10 minutes supine rest. | Imaging: T3 MRI scanner, T2 and FLAIR images. Assessor: Radiologist, blinded to OH measurement.WMH: Scheltens score (0–84) converted in ordinal scale 0–10, 10–20, 20–30, >30. | Adjusted for: Age, sex, smoking, hypertension, hyperlipidemia, diabetes | Statistically significant association between OH and WMH at multiple time points.Increase ordinal Scheltens score, different timepoints: OR (95%CI)30 sec: 1.87 (1.11–3.14)70 sec: 2.50 (1.40–4.46)90 sec: 2.15 (1.15–3.99)110 sec: 2.48 (1.36–4.51) |
| Cui et al., 2020 24 | Cross-sectional cohort | N = 663 Chinese participants (aged >=60) presenting at community centers.Mean ± SD age (yrs): NOH: 68.1 ± 5.5, 1HOH: 69.1 ± 6.1, 2HOH: 69.2 ± 5.356.5% female32.3% one episode of OH14.6% two episodes of OH | Home measured OH (HOH), 3 consecutive days twice a day (morning before medication and after dinner). Measured in sitting position after 5 minutes, and 1 minute after standing up. Divided into 1 episode of HOH (1HOH), or ≥2 episodes of HOH (2HOH). | Imaging: 3 T MRI scanner, T2 and FLAIR images.Assessor: Experienced neuroradiologists, blinded to OH measurement.WMH: WMH volume (mL) with freesurfer programme, ratio WMH volume/total intracranial volume (TIV), Fazekas score, Fazekas score ≥2. | Adjusted for: Age, home SBP, smoking, LDL level, FPG, antihypertensive medication, anti-diabetes medication | Statistically significant association between OH and WMH.Fazekas score ≥2 (OR, 95%CI):1HOH : 2.12 (1.27–3.56) 2HOH : 4.91 (2.74–8.79)White matter volume (mL), beta (95%CI):1HOH : 0.73 (0.54–0.92) 2HOH : 1.54 (1.29–1.78)WMH/TIV ratio (%), beta (95%CI):1HOH : 0.05 (0.04–0.06)2HOH : 0.10 (0.09–0.12) |
| Foster-Dingley et al., 2018 34 | Cross-sectional cohort study (baseline data from randomized controlled trial) | N = 214 Older participants (+75) from DANTE study, Leiden, the Netherlands, with mild cognitive impairment using antihypertensive medication. Without serious cardiovascular disease or dementia.Mean ± SD age (yrs): 81 ± 4.157% female49% with OH. | Five minutes seated, blood pressure measurement at 1 and 3 minutes after standing up. | Imaging: 3 T MRI scan, T2 and FLAIR imagesAssessor: Volume with FMRIB Software Version 5.0.1. Library. Manual quality control check.WMH: WMH volume (mL) in automated manner | Adjusted for: Age and sex. | No statistically significant association between OH and WMH.White matter volume (mL), beta (p-value):−0.06 (p-value 0.37). |
| Huang et al., 2023 36 | Cross-sectional cohort | N = 211 patients with acute ischemic stroke attending First People’s Hospital of Huaihua, China.Mean ± SD age (yrs): 62.8 ± 10.834.5% female35.5% with OH. | Five minutes supine, blood pressure measurement at 1 and 3 minutes after standing up. | Imaging: UnclearAssessor: Two independent radiologists, blinded to the clinical history.WMH: Fazekas scale | Adjusted for: age, history of hypertension, history of CAD, hypotensive drugs | Statistically significant association between OH and WMH Increase in Fazekas scale (OR, 95%CI):1.29 (1.04–1.60) |
| Kario et al., 2002 37 | Cross-sectional cohort | N = 241 elderly hypertensive patients from participating clinics, Tochigi, Japan. Without renal failure, hepatic damage, coronary artery disease, stroke, symptomatic OH with SBP >30mmhg, diabetes mellitus.Mean ± SD age (yrs)NOH: 71 ± 6.5OH: 72 ± 6.256% female9.5% with OH | Tilt table test, supine position 10 minutes, OH measured between 6–10 minutes after tilting. | Imaging: 1.5 T MRI scan, T2 and FLAIR images.Assessor: Unclear, blinded to clinical history.WMH: Advanced deep WM lesion were defined as a detection of hyperintense multiple punctate lesions or early confluent stage or confluency. | Not adjusted | No statistically significant association between OH and WMH.Prevalence deep white matter lesions (%):NOH 31%OH 35% |
| Oh et al., 2013 29 | Cross-sectional cohort | N = 117 newly diagnosed Parkinson Patients from Seouls St. Mary’s Hospital, Seoul, Korea.Mean ± SD age (yrs):NOH 67.7 ± 11.1 OH 69.8 ± 8.061% female56% with OH | Tilt table test, supine position 30 minutes, OH measured between 2–5 minutes after tilting. | Imaging: 3 T MRI scanner, T2 and FLAIR images.Assessor: UnclearWMH: Scheltens Score (0–90). | Adjusted for (ANCOVA): age, history of hypertension, dm, LDL, serum homocysteine levels. | Statistically significant association between OH and WMH.Total Scheltens score, p-value:NOH 11.0 (8.2)OH 15.6 (9.6), p-value 0.017 |
| Pilleri et al., 2013 30 | Cross-sectional matched cohort (matched on OH) | N = 48 matched participants from 108 consecutive subjects from IRCCS San Camillo PD Unit (Venice, Italy) diagnosed with Parkinson.Mean ± SD age (yrs):NOH: 65.6 ± 8.7OH: 64.9 ± 9.754% female48% with OH (matched participants). | Tilt table test, supine position 10 minutes, OH measured every minute from 1 to 3 minutes after tilting. | Imaging: 1.5 T MRI, T2 and FLAIR images.Assessor: Independently performed by two trained physicians, blinded about patients’ clinical stateWMH: Scheltens Score (0–84). | Not adjusted | No statistically significant association between OH and WMH.Total Scheltens score, p-value:NOH 10.6 ± 7.5OH 10.3 ± 8.3, p-value 0.57 |
| Pilotto et al., 2021 31 | Cross-sectional cohort | N = 384 patients from imaging repositories diagnosed with Parkinson or Dementia Lewy Bodies constituted by 8 specialized Movement Disorder and Dementia Centers in the United States, Canada, Italy and Japan. Patients without neurogenic OH, comorbid neuropathy, conditions associated with cognitive deficits, antihypertensive or antipsychotic drugs, history of CVA/TIA, history of drug of alcohol abuse.Mean ± SD age (yrs): 68.4 ± 11.136.9 % female44.3 % with OH | 5 minutes of rest, blood pressure measurement within 3 minutes after standing up. | Imaging: Clinical imaging repository, T1- and T2 weighted images.Assessor: Analyzed in a centralized fashion by 4 independent raters.WMH: Scheltens scale for 4 regions (and per hemisphere). 0 = no WMH, 1= punctiform, 2 = early confluent, 3 = confluent. All added up. | Adjusted for (ANCOVA): age, sex, education, diagnosis and disease duration. | No statistically significant association between OH and WMH.Total Scheltens scale, p-value:NOH 5.5 ± 5.3OH 5.5 ± 5.5, p-value 0.49OH+SH- : 5.2OH+SH+ : 6.5, p-value 0.72 |
| Shin et al., 2021 33 | Cross-sectional cohort | N = 154 patients with Parkinson Disease with MRI and clinical assessment from Seouls St. Mary’s Hospital, Seoul, Korea.Mean ± SD age (yrs): 70.2 ± 9.048.7% female19.4% with OH | Tilt table test, supine position for 20 minutes, blood pressure measurement 3 or 5 minutes after tilting. | Imaging: 3 T MRI, FLAIR images.Assessor: neuroradiologist, blinded to clinical data.WMH: Periventricular and deep WMH both scored on Fazekas scale, total score 0–6. | Adjusted for: age, sex, disease duration, levodopa-equivalent dose, smell identification test score, depression. | No statistically significant association between OH and WMH.White matter grade (0–6), beta, p-value:−0.07 (0.29) |
| Soennesyn et al., 2012 28 | Cross-sectional cohort | N = 139 patients with mild dementia from dementia clinics in Norway. Mean (IQR) age (yrs): 76.9 (I71–81)57.0% female26.0% with OH | In supine position (duration unclear), blood pressure measurement within 3 minutes after standing up. | Imaging: 1.5 T MRI, FLAIR, T1 en T2 images.Assessor: Volumetric assessment with method developed/published by Firbank et al. Manually checked by physician.Visual assessment by experienced rater, blind to clinical data.WMH: Semi quantative assessment: Scheltens scale.Volumetric assessment (n = 82): White matter volume and WMH/TIV ratio. Both assessments divided in quintiles and comparison between lowest and highest quintile. | Adjusted for: age, sex, AD, history of hypertension, diabetes, coronary heart disease, heart failure, stroke APOEe4 allele, smoker. | No statistically significant association between OH and WMH.OH fractions in lowest and highest quintile (p-value):Semi quantative group:Lowest quintile 12/25, highest quintile 14/28 (p = 1.00)Volumetric group: Lowest quintile 10/17, highest quintile 10/19 (p = 0.97)Logistic and multinomial regression: no significant association (data not shown). |
| Ten Harmsen et al., 2018 32 | Cross-sectional cohort | N = 204 patients with Parkinson Disease evaluated at Radboud UMC, The Netherlands. Mean ± SD age (yrs): 64.6 ± 10.869.1% female26.0% with OH | In prospective cohorts (n = 78) OH was based on measurements in supine position (duration unclear), and blood pressure measurement 3 minutes after standing up.In retrospective cohort based on complaints of OH. | Imaging: 3 T MRI, FLAIR and T2 images.Assessor: Consistently by the same neuroradiologist under supervision.WMH: Periventricular and deep WMH both scored on Fazekas scale (0–3). | Adjusted for: age, sex, dopaminergic medicatie use, hypertension, hoehn & yahr stadium, cognitive decline. | Statistically significant association between OH and WMH.Fazekas score ≥ 2, (%, p-value), entire cohort: Periventricular WML : NOH: 25%, OH: 40% (p = 0.34)Deep WML:NOH: 15%, OH: 30% (p = 0.03)WMH, odds ratio (95CI%), entire cohort:Periventricular WML: 0.70 (0.32–1.43), Deep WML: 0.41 (0.18–0.92) |
| Wiersinga et al., 2023 35 | Cross-sectional cohort | N = 3971 patients visiting memory clinic in Amsterdam UMC, The Netherlands, from the Amsterdam Aging Cohort, no specific diagnosis.Mean ± SD age (yrs): 67.5 ± 10.844.9% Female9.5% with EOH18.2% with DPOH | Supine 3 minutes, OH after 1 and 3 minutes, divide in early OH (only at 1 minute) and delayed/prolonged OH (at 1 and 3 or only at 3 minutes). | Imaging: CT or 1.5 T MRI, FLAIR and T2 images.Assessor: Two trained specialists and supervised by a clinical radiologist according to the local dementia protocol.WMH: Fazekas score ≥ 2 | Adjusted for: age, sex, OH-inducing medication, MMSE score, CVD, diabetes and supine SBP. | No statistically significant association between OH and WMHFazekas score ≥ 2 (OR, 95%CI),EOH: 0.95 (0.73–1.23)DPOH: 1.04 (0.85–1.27) |
| Zimmerman et al., 2020 27 | Cross-sectional cohort | N = 495 patients from the TREND-study, including elderly patients without neurodegenerative diseases, in Tübingen, Germany. 93 patients with MRI data.Mean age (yrs): NOH 63.9, OH 62.946.9% female17.6% with OH | Supine (duration unclear) and blood pressure measurement at 30/90/150/210 sec of active standing, OH at any time point. | Imaging: 3 T MRI, T2 images.Assessor: Neurologist trained in the interpretation of MRI scans. WMH: Fazekas score (0–3). | Not adjusted | Borderline statistically significant association between OH and WMH.Fazekas score ≥ 1, (%, p-value):NOH: 68.8%, OH: 91.7% (p = 0.09) |
| Longitudinal studies | ||||||
| Jacob et al., 2021 25 | Cross-sectional and longitudinal cohort | N = 503 Community dwelling older adults from RUN-DMC study, Radboud University Nijmegen, The Netherlands, undergoing MRI. Aged between 50–80, visible SVD on MRI.Follow-up inclusion:Baseline with MRI: n = 503Re-examined at 5 years with MRI: n = 361Re-examined at 9 years with MRI: n = 296Mean ± SD age (yrs): 65.5 ± 8.856.5% female9.1% with OH. | Five minutes supine, blood pressure measurement at 1 minute after standing up. | Imaging: 1.5 T MRI, T2 and flair imagingAssessor: semi-automatic WMH segmentation. Visually checked by one trained rater, blinded for clinical data.WMH: WMH volumes (mL) using semi autonomic WMH segmentation | Adjusted for: age, sex, hypertension, OH inducing drugs. | Significant association between OH and WMH cross sectional. White matter volume (mL), beta (95%CI):0.18 (0.02–0.34)No statistically significant association between OH and WMH longitudinally WMH progression, OR (95%CI)3.63 (0.29–6.98) |
| Juraschek et al., 2024 15 | Cross-sectional and longitudinal cohort | N = 3147 community based older (65+) participants of the cardiovascular health study in the United States of America. Without dementia or stroke. Follow-up inclusion:Baseline with MRI: n = 3147Re-examined at 5 years with MRI: n = 1858Mean ± SD age (yrs): 72.7 ± 5.557.6% female15.9% with OH. | OH measured after supine rest of 20–30 minutes and 30 seconds of seating, measured 3 minutes after standing up. | Imaging: 1.5 T or 3 T MRI scan, T2 and flair imagesAssessor: Two trained readers using the same CHS protocol. Unaware of initial or follow-up scan.WMH: White matter grade (0–9), not further specified. | Adjusted for: age, sex, race, research clinic, BMI, HDL, triglycerides, diabetes, hypertension, SBP, DBP, diuretic use, beta blocker use, education, current drinking status, smoking. | No statistically significant association between OH and WMH.White matter grade, beta (95%CI):0.01 (−0.12–0.14)White matter worsening (change in grade), (95%CI): 0.04 (−0.10–0.19) |
BMI: body mass index; BP: blood pressure; CAD: coronary artery disease; CI: confidence interval; CT: computer tomography; CVD: cardiovascular disease; DBP: diastolic blood pressure; FLAIR: fluid-attenuated inversion recovery; FPG: fasting plasma glucose; HDL: high density lipoprotein; IQR: interquartile range; LDL: low density lipoprotein; mL: milliliter; MMSE: mini-mental state exam; MRI: magnetic resonance imaging; N: number; NOH: no orthostatic hypotension; OH: orthostatic hypotension; OR: odds ratio; SBP: systolic blood pressure; SD: standard deviation; TIV: total intracranial volume; WMH: white matter hyperintensities; WML: white matter lesions; yrs: years.