Autonomic dysfunction as manifestation of ICANS: A case report.

RATIONALE: Anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy is a successful treatment for B-cell malignancies associated with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cardiovascular toxicities have also been reported in this setting. However, there is scarce data regarding development of autonomic disorders after CAR-T cell therapy. PATIENT CONCERNS: We report a case with a patient with non-Hodgkin B-cell lymphoma, refractory to 2 prior lines of immunochemotherapy, treated with CAR-T therapy. DIAGNOSES: Orthostatic hypotension secondary to autonomic dysfunction was diagnosed as manifestation of ICANS. INTERVENTIONS: The patient received metilprednisolone 1000 mg IV daily for 3 days and anakinra 100 mg IV every 6h. OUTCOMES: The vast majority of autonomic symptoms ceased and 4 months after CAR-T therapy, autonomic dysfunction was resolved. LESSONS: New-onset autonomic dysfunction can occur as manifestation of ICANS in patients who experience persistent neurologic and cardiovascular symptoms after resolution of acute neurotoxicity and should be early recognized. Differences in differential diagnosis, mechanisms and treatment approaches are discussed.

Severe postural hypotension and sinus bradycardia with thalidomide in patients with erythema nodosum leprosum.

Two men in their 60s and 40s were diagnosed with erythema nodosum leprosum based on the development of recurrent painful ulcers and nodules, respectively, for the previous 6 months. Thalidomide 100 mg four times a day, along with MB-MDT, was started in both patients. Both patients experienced severe dizziness on rising from a seated posture soon after initiation of thalidomide and a decrease in blood pressure and heart rate. Cardiovascular/neurology examination and routine blood investigations were normal. An autonomic nervous system assessment indicated bradycardia, postural hypotension and decreased cardiac autonomic function. The dosage of thalidomide was then gradually reduced over 4-5 days to 100 mg/day following a suspicion that thalidomide was the cause of postural hypotension. The dizziness subsided, and blood pressure and heart rate returned to normal.We concluded that thalidomide was the culprit behind bradycardia and dose- dependent postural hypotension.

Advice to People with Parkinson's in My Clinic: Orthostatic Hypotension.

Orthostatic hypotension (OH) is the most common manifestation of cardiovascular autonomic dysfunction in Parkinson's disease. In this viewpoint, we discuss five practical questions regarding OH in Parkinson's disease: 1) How common is the problem? 2) Why should people with Parkinson's disease and providers care about OH? 3) What are the symptoms of OH? 4) How to confirm a diagnosis of OH? And 5) How to treat OH? OH is an important non-motor symptom of Parkinson's disease for which we have available treatments to significantly mitigate morbidity and possibly positively impact the disease course.

Convolutional neural networks can detect orthostatic hypotension in Parkinson's disease using resting-state functional near-infrared spectroscopy data.

Neurological disorders such as Parkinson's disease (PD) often adversely affect the vascular system, leading to alterations in blood flow patterns. Functional near-infrared spectroscopy (fNIRS) is used to monitor hemodynamic changes via signal measurement. This study investigated the potential of using resting-state fNIRS data through a convolutional neural network (CNN) to evaluate PD with orthostatic hypotension. The CNN demonstrated significant efficacy in analyzing fNIRS data, and it outperformed the other machine learning methods. The results indicate that judicious input data selection can enhance accuracy by over 85%, while including the correlation matrix as an input further improves the accuracy to more than 90%. This study underscores the promising role of CNN-based fNIRS data analysis in the diagnosis and management of the PD. This approach enhances diagnostic accuracy, particularly in resting-state conditions, and can reduce the discomfort and risks associated with current diagnostic methods, such as the head-up tilt test.

Orthostatic Hypotension and Antihypertensive Treatment in Lung Transplant Recipients: A Cross-Sectional Study.

OBJECTIVES: Lung transplant is the ultimate treatment of many end-stage lung diseases. Calcineurin inhibitors, crucial in immunosuppression for lung transplant recipients, are linked to secondary hypertension, necessitating antihypertensive treatment. In addition, lung transplant recipients frequently experience orthostatic hypotension, occasionally stemming from autonomic dysfunction, but also commonly attributed as a negative side effect of antihypertensive treatment. Our study aimed to evaluate the frequency of orthostatic blood pressure irregularities and investigate the involvement of antihypertensive treatment as a potential risk factor in the occurrence among lung transplant recipients. MATERIALS AND METHODS: Fifty-six consecutive lung transplant recipients, both inpatient and outpatient, at the University Hospital Zurich (Switzerland) were monitored from 1999 to 2013. Transplant recipients underwent a Schellong test (an active standing test). Our evaluation encompassed their initial traits, such as the existence of supine hypertension. We computed the odds ratio for the comparison of the likelihood of experiencing orthostatic hypotension while using a minimum of 1 type of antihypertensive medication versus absence of antihypertensive drugs. RESULTS: Of the lung transplant recipients, 25% showed a positive Schellong test. Within this group, 64% had supine hypertension, and 29% displayed symptoms of orthostatic hypotension. Among the patients, 71% were using at least 1 type of antihypertensive medication. The odds ratio for showing orthostatic hypotension while taking at least 1 type of antihypertensive drug versus the absence of antihypertensive medications was 1.64 (95% exact CI, 0.39-6.90) with P = .50. This finding remained consistent regardless of age, sex, inpatient or outpatient status, and the duration since transplant. CONCLUSIONS: Orthostatic blood pressure dysregulation is prevalent among lung transplant recipients, frequently without noticeable symptoms. In our cohort, the use of antihypertensive medications did not elevate the risk of orthostatic hypotension.

Perfection is the enemy of good. A Letter to the Editor on "Orthostatic hypotension in Parkinson's disease: Sit-to-stand vs. supine-to-stand protocol and clinical correlates".

Orthostatic hypotension (OH) is prevalent in Parkinson's disease. Lim et al. report a higher OH detection rate with the supine-to-stand test compared to the sit-to-stand test. While they favour the supine-to-stand test, we argue that the sit-to-stand test, with adjusted blood pressure thresholds, remains a valuable and practical screening tool.

Treating Lows: Management of Orthostatic Hypotension.

ABSTRACT: Orthostatic hypotension is a prevalent clinical condition, caused by heterogenous etiologies and associated with significant morbidity and mortality. Management is particularly challenging in patients with uncontrolled hypertension. A thorough assessment is needed to draw an appropriate management plan. The treatment aims to improve postural symptoms while minimizing side effects and reducing iatrogenic exacerbation of supine hypertension. A personalized management plan including rationalizing medications, patient education, identification, and avoidance of triggers, as well as nonpharmacological therapies such as compression devices, dietary modifications, and postural aids, make the first steps. Among pharmacological therapies, midodrine and fludrocortisone are the most prescribed and best studied; pyridostigmine, atomoxetine, and droxidopa are considered next. Yohimbine remains an investigational agent. A multidisciplinary team may be required in some patients with multiple comorbidities and polypharmacy. However, there is a lack of robust efficacy and safety evidence for all therapies. Building robust real-world and stratified clinical trials based on underlying pathophysiology may pave the way for further drug development and better clinical strategies and in this challenging unmet medical need.

Cardiac autonomic regulation following a 246-km mountain ultra-marathon: An observational study.

Physical exercise requires integrated autonomic and cardiovascular adjustments to maintain homeostasis. We aimed to observe acute posture-related changes in blood pressure, and apply a portable noninvasive monitor to measure the heart index for detecting arrhythmia among elite participants of a 246-km mountain ultra-marathon. Nine experienced ultra-marathoners (8 males and 1 female) participating in the Run Across Taiwan Ultra-marathon in 2018 were enrolled. The runners' Heart Spectrum Blood Pressure Monitor measurements were obtained in the standing and supine positions before and immediately after the race. Their high-sensitivity troponin T and N-terminal proB-type natriuretic peptide levels were analyzed 1 week before and immediately after the event. Heart rate was differed significantly in the immediate postrace assessment compared to the prerace assessment, in both the standing (P = .011; d = 1.19) and supine positions (P = .008; d = 1.35). Postural hypotension occurred in 4 (44.4%) individuals immediately postrace. In 3 out of 9 (33.3%) recruited finishers, the occurrence of premature ventricular complex signals in the standing position was detected; premature ventricular complex signal effect was observed in the supine position postrace in only 1 participant (11.1%). Premature ventricular complex signal was positively correlated with running speed (P = .037). Of the 6 individuals who completed the biochemical tests postrace, 2 (33.3%) had high-sensitivity troponin T and 6 (100%) had N-terminal proB-type natriuretic peptide values above the reference interval. A statistically significant increase was observed in both the high-sensitivity troponin T (P = .028; d = 1.97), and N-terminal proB-type natriuretic peptide (P = .028; d = 2.91) levels postrace compared to prerace. In conclusion, significant alterations in blood pressure and heart rate were observed in the standing position, and postexercise (postural) hypotension occurred among ultra-marathoners. The incidence of premature ventricular complexes was higher after the race than before.

The recovery of sympathetic skin responses with levodopa in a patient with multiple system atrophy-parkinsonian type.

Herein, we report a 62-year-old female patient with Multiple system atrophy (MSA) at whom the sympathetic skin responses (SSRs) were absent at initial investigations. However, the levodopa therapy provided normalization of SSRs and moderately improvement in orthostatic hypotension-related symptoms. Based on this rare illustration, we discuss the possible mechanisms underlying the pathophysiology of autonomic dysfunction in MSA. We remark on the need for future clinical and experimental studies in this field.

A pathophysiological biomarker combination separates Lewy body from non-Lewy body neurogenic orthostatic hypotension ​.

PURPOSE: Neurogenic orthostatic hypotension (nOH) results from deficient reflexive delivery of norepinephrine to cardiovascular receptors in response to decreased cardiac venous return. Lewy body (LB) forms of nOH are characterized by low 18F-dopamine-derived radioactivity (a measure of cardiac noradrenergic deficiency), olfactory dysfunction by the University of Pennsylvania Smell Identification Test (UPSIT), and increased deposition of alpha-synuclein (α-syn) in dermal sympathetic noradrenergic nerves by the α-syn-tyrosine hydroxylase (TH) colocalization index. This observational, cross-sectional study explored whether combinations of these biomarkers specifically identify LB forms of nOH. METHODS: Clinical laboratory data were reviewed from patients referred for evaluation at the National Institutes of Health for chronic autonomic failure between 2011 and 2023. The cutoff value for low myocardial 18F-dopamine-derived radioactivity was 6000 nCi-kg/cc-mCi, for olfactory dysfunction an UPSIT score ≤ 28, and for an increased α-syn-TH colocalization index ≥ 1.57. RESULTS: A total of 44 patients (31 LB, 13 non-LB nOH) had data for all three biomarkers. Compared to the non-LB group, the LB nOH group had low myocardial 18F-dopamine-derived radioactivity, low UPSIT scores, and high α-syn-TH colocalization indexes (p < 0.0001 each). Combining the three biomarkers completely separated the groups. Cluster analysis identified two distinct groups (p < 0.0001) independently of the clinical diagnosis, with one cluster corresponding exactly to LB nOH. CONCLUSION: LB forms of nOH feature cardiac noradrenergic deficiency, olfactory dysfunction, and increased α-syn-TH colocalization in skin biopsies. Combining the data for these variables efficiently separates LB from non-LB nOH. Independently of the clinical diagnosis, this biomarker triad identifies a pathophysiologically distinct cluster of nOH patients.

Determinants of Orthostatic Hypotension in Type 2 Diabetes: Is Cardiac Autonomic Neuropathy the Main Factor?

OBJECTIVES: To evaluate the determinants of orthostatic hypotension (OH) in type 2 diabetes (T2D) and the usefulness of Δheart rate (HR)/Δsystolic blood pressure (SBP), index of cardiac baroreflex function, in identifying neurogenic OH. METHODS: In 208 participants with T2D, we diagnosed early cardiovascular autonomic neuropathy (CAN) and confirmed CAN according to 1 and 2 HR-based cardiovascular reflex tests (HR-CARTs). Through OH test we defined OH as SBP falls of ≥20 and ≥30 mm Hg with supine SBPs of <140 and ≥140 mm Hg, respectively. In participants with OH, we used the lying-to-standing and OH test and its diagnostic accuracy for neurogenic OH (as OH plus confirmed HR-CAN). RESULTS: OH was present in 25 participants and associated with lower HR-CART scores, higher glycosylated hemoglobin level, the presence of CAN, retinopathy, and peripheral vascular disease, the absence of hypertension, and physical activity (all, P < .05) but not with interfering drugs and ß-blockers. In a multiple logistic regression, HR-CAN was the main determinant of OH (odds ratio, 4.74) with physical activity and hypertension (odds ratios, 0.16 and 0.23; R2 = 0.22). ΔHR/ΔSBP had a good diagnostic accuracy for neurogenic OH (area under the receiver operating characteristic curve, 0.816 ± 0.087) and, at the cutoff of 0.5 bpm/mm Hg, a sensitivity of 100% and specificity of 63.2%. CONCLUSION: CAN remains the primary determinant of OH in T2D but does not explain all its variance. The index ΔHR/ΔSBP may represent a useful clinical tool to identify neurogenic OH.

Postural change, gait, and physical function in older adults.

In a more clinical setting, abrupt posture change may be used to determine the presence of orthostatic hypotension, a hemodynamic response with relationships to physical function. Certain gait features and physical function performance are also associated with risk of falling in older adults. However, the extent to which posture change is associated with subsequent gait and physical function has received little attention in the literature. This study aims to determine the effects of posture change on spatiotemporal parameters of gait and Timed Up-and-Go (TUG) performance. METHODS: Forty-two volunteers (age 73.21 ± 6.22 years) participated in the study. A custom Tekscan Strideway (Tekscan, Boston, MA.) gait system was used to measure gait velocity (VEL), cadence (CAD), stride length (SL), and percent of time spent in active propulsion (AP). Dependent t-tests were used to compare TUG time, VEL, CAD, SL and AP after at least 10 mins of seated rest and supine rest. RESULTS: Time to complete the TUG was significantly slower after supine rest compared to seated (11.47 ± 0.51 and 10.01 ± 0.33 s, respectively, p<0.001); VEL was significantly slower after supine rest compared to seated (0.888 ± 0.042 and 1.049 ± 0.033 m/s, respectively, p=0.003); CAD was significantly slower after supine rest compared to seated (111.21 ± 2.87 and 120.97 ± 2.56spm, respectively, p=0.001); and AP was significantly lower after supine rest compared to seated (56.87 ± 4.76 and 70.79 ± 4.05 %, respectively, p<0.001). No significant differences were detected in stride length between conditions. CONCLUSIONS: Among this sample of older adults, standing from a supine posture is associated with spatiotemporal gait parameters consistent with a risk for falling and aging. Additionally, TUG performance worsens significantly after supine rest. Future studies could explore the sensitivity and specificity of falls risk screening after supine rest.

Valsalva maneuver pressure recovery time is prolonged following spinal cord injury with correlations to autonomically-influenced secondary complications.

PURPOSE: This work's purpose was to quantify rapid sympathetic activation in individuals with spinal cord injury (SCI), and to identify associated correlations with symptoms of orthostatic hypotension and common autonomically mediated secondary medical complications. METHODS: This work was a cross-sectional study of individuals with SCI and uninjured individuals. Symptoms of orthostatic hypotension were recorded using the Composite Autonomic Symptom Score (COMPASS)-31 and Autonomic Dysfunction following SCI (ADFSCI) survey. Histories of secondary complications of SCI were gathered. Rapid sympathetic activation was assessed using pressure recovery time of Valsalva maneuver. Stepwise multiple linear regression models identified contributions to secondary medical complication burden. RESULTS: In total, 48 individuals (24 with SCI, 24 uninjured) underwent testing, with symptoms of orthostatic hypotension higher in those with SCI (COMPASS-31, 3.3 versus 0.6, p < 0.01; ADFSCI, 21.2 versus. 3.2, p < 0.01). Pressure recovery time was prolonged after SCI (7.0 s versus. 1.7 s, p < 0.01), though poorly correlated with orthostatic symptom severity. Neurological level of injury after SCI influenced pressure recovery time, with higher injury levels associated with more prolonged time. Stepwise multiple linear regression models identified pressure recovery time as the primary explanation for variance in number of urinary tract infections (34%), histories of hospitalizations (12%), and cumulative secondary medical complication burden (24%). In all conditions except time for bowel program, pressure recovery time outperformed current clinical tools for assessing such risk. CONCLUSIONS: SCI is associated with impaired rapid sympathetic activation, demonstrated here by prolonged pressure recovery time. Prolonged pressure recovery time after SCI predicts higher risk for autonomically mediated secondary complications, serving as a viable index for more "autonomically complete" injury.

Treatment of Orthostatic Hypotension During Acute Inpatient Rehabilitation After Spinal Cord Injury: Usual Care vs. Anti-hypotensive Therapy.

BACKGROUND: To compare the pharmacological treatment of hypotension and orthostatic hypotension (OH) initiated based upon a blood pressure (BP) threshold, regardless of symptoms (TXT), to usual care pharmacological treatment of symptomatic hypotension (UC), during acute inpatient rehabilitation (AIR) following spinal cord injury (SCI). METHODS: Block randomization, based on the neurological level of injury as: cervical lesions (C1-C8); high thoracic lesions (T1-T5), and low thoracic lesions (T6-T12), was used to determine responses to the primary question "was the therapy session affected by low BP or concern for low BP development?" Study participants and therapists were unaware of the group assignment. RESULTS: A total of 66 participants enrolled; 25 (38%) in the TXT group, 29 (44%) in the UC group, and 12 (18%) withdrew. Responses to the primary question were recorded for 32 participants, 15 in the TXT, and 17 in the UC group. There was an average of 81 ±â€…51 therapy sessions/participant in the TXT and 60 ±â€…27 sessions/participant in the UC group. Of those therapy sessions, low BP or concerns for low BP affected an average of 9 ±â€…8 sessions/participant in the TXT group and 10 ±â€…12 sessions/participant in the UC group. Neither the total number of therapy sessions (P = 0.16) nor group assignment (P = 0.83) significantly predicted the number of sessions affected by low BP. CONCLUSIONS: These data are not conclusive but indicate that the treatment of asymptomatic hypotension and OH does not increase time spent in therapy compared to UC treatment of symptomatic hypotension and OH in newly injured patients with SCI. CLINICAL TRIALS REGISTRATION: #NCT02919917.

Physiological Targets for Orthostatic Hypotension: Improving Nonpharmacological Interventions in Patients with Orthostatic Cerebral Hypoperfusion.

Orthostatic hypotension (OH) is a form of orthostatic intolerance (OI) and a key physiological indicator of autonomic dysfunction that is associated with an increased risk of major cerebrocardiovascular events. Symptoms of cerebral hypoperfusion have been reported in patients with OH, which worsens symptoms and increases the risk of syncope. Since pharmacological interventions increase blood pressure (BP) independent of posture and do not restore normal baroreflex control, nonpharmacological treatments are considered the foundation of OH management. While reductions in cerebral blood flow velocity (CBFv) during orthostatic stress are associated with a decrease in end-tidal CO2 (EtCO2) and hypocapnia in patients with OI, their contribution to the severity of OH is not well understood. These measures have been physiological targets in a wide variety of biofeedback interventions. This study explored the relationship between cardiovascular autonomic control, EtCO2 and cerebral hypoperfusion in patients (N = 72) referred for OI. Patients with systolic OH were more likely to be male, older, demonstrate reduced adrenal and vagal baroreflex sensitivity, and reduced cardiovagal control during head-up tilt (HUT) than patients without systolic OH. Greater reduction in CBFv during HUT was associated with a larger reduction in ETCO2 and systolic BP during HUT. While deficits in cardiovascular autonomic control played a more important role in systolic OH, reduced EtCO2 was a major contributor to orthostatic cerebral hypoperfusion. These findings suggest that biofeedback treatments targeting both the autonomic nervous system and EtCO2 should be part of nonpharmacological interventions complementing the standard of care in OH patients with symptoms of cerebral hypoperfusion.

Norepinephrine Reuptake Inhibition, an Emergent Treatment for Neurogenic Orthostatic Hypotension.

The NET (norepinephrine transporter) is situated in the prejunctional plasma membrane of noradrenergic neurons. It is responsible for >90% of the norepinephrine uptake that is released in the autonomic neuroeffector junction. Inhibitors of this cell membrane transporter, known as norepinephrine reuptake inhibitors (NRIs), are commercially available for the treatment of depression and attention deficit hyperactivity disorder. These agents increase norepinephrine levels, potentiating its action in preganglionic and postganglionic adrenergic neurons, the latter through activation of α-1 adrenoreceptors. Previous studies found that patients with neurogenic orthostatic hypotension can improve standing blood pressure and reduce symptoms of neurogenic orthostatic hypotension after a single administration of the selective NRI atomoxetine. This effect was primarily observed in patients with impaired central autonomic pathways with otherwise normal postganglionic sympathetic fibers, known as multiple system atrophy. Likewise, patients with normal or high norepinephrine levels may benefit from NRIs. The long-term efficacy of NRIs for the treatment of neurogenic orthostatic hypotension-related symptoms is currently under investigation. In summary, an in-depth understanding of the pathophysiology of neurogenic orthostatic hypotension resulted in the discovery of a new therapeutic pathway targeted by NRI.

Longitudinal prevalence of neurogenic orthostatic hypotension in the idiopathic Parkinson Progression Marker Initiative (PPMI) cohort.

BACKGROUND: Reported orthostatic hypotension (OH) prevalence in Parkinson's disease (PD) varies widely, with few studies evaluating specifically neurogenic-OH (nOH). The ratio of orthostatic heart rate (HR) to systolic blood pressure (SBP) change (Δ) is a valid screening method to stratify nOH/non-nOH but has had minimal epidemiologic application. OBJECTIVE: To estimate the prevalence of nOH and non-nOH in the PPMI using the ΔHR/ΔSBP ratio and examine associations between nOH and various motor and non-motor measures. METHODS: Longitudinal orthostatic vitals and motor and non-motor measures were extracted (baseline-month 48). Patients were consensus criteria classified as OH+/-, with ΔHR/ΔSBP sub-classification to nOH (ΔHR/ΔSBP < 0.5) or non-nOH (ratio ≥ 0.5). Prevalence was determined across visits. Independent linear mixed models tested associations between nOH/non-nOH and clinical variables. RESULTS: Of N = 907 PD with baseline orthostatic vitals, 3.9 % and 1.8 % exhibited nOH and non-nOH, respectively. Prevalence of nOH/non-nOH increased yearly (P = 0.012, chi-square), though with modest magnitude (baseline: 5.6 % [95 % CI: 4.3-7.3 %]; month 48: 8.6 % [6.4-11.5 %]). nOH patients were older than PD with no OH and nOH was associated with greater impairment of motor and independent functioning than non-nOH/OH- groups. Cognitive function and typical OH symptoms were worse in PD + OH, generally. CONCLUSIONS: nOH prevalence was greater than non-nOH in the PPMI early PD cohort, with modest prevalence increase over time. Our findings are consistent with prior studies of large cohorts that evaluated nOH, specifically. Those with early PD and nOH were likelier to be older and suffer from greater motor and functional impairment, but OH presence was generally associated with more cognitive impairment.

The correlation of orthostatic hypotension in Parkinson disease with the disease course and severity and its impact on quality of life.

We investigated the correlation of orthostatic hypotension (OH) in Parkinson disease (PD) with the disease course and severity, and its possible impact on quality of life. 171 PD patients were recruited and divided into the PD-NOH (n = 91) and PD-OH groups (n = 80). Clinical data were collected. The severity and quality of life of PD patients were evaluated. The impact of disease severity was analyzed using logistic regression analysis. The ROC curve was plotted. There were significant differences (P < .05) between PD-NOH and PD-OH groups in terms of the disease course, non-motor symptoms (somnipathy), Hoehn&Yahr stage, LEDD score, RBDSQ score, PDQ-39 score, MMSE score, MoCA, MDS-UPDRS Part III scores during off- and on-periods, and NMSS score. Hoehn&Yahr stage (OR 4.950, 95% CI 1.516-16.157, P = .008) was closely associated with the risk of OH in PD. PDQ-39 score (OR 1.079, 95% CI 1.033-1.127, P = .001) in PD patients with OH further decreased. Patients with PD-OH experienced severe impairment in 4 dimensions of quality of life, including motor function, cognitive function, physical discomfort, and activities of daily living. Different clinical symptoms of PD-OH were positively correlated with PDQ39 subscales. The area under the ROC curve of the Hoehn&Yahr stage in predicting the occurrence of OH was 0.679 (95% CI 0.600-0.758), and that of the Hoehn&Yahr stage combined with levodopa equivalent dose, and MDS-UPDRS Part III score during off-period was 0.793 (95% CI 0.727-0.862). Higher Hoehn&Yahr stage is associated with increased risk of OH in PD patients, and deteriorated quality of life of PD patients. Patients with different OH symptoms are affected in different dimensions of their quality of life. The Hoehn & Yahr stage can independently predict the risk of OH in PD patients.

Orthostatic hypotension, cognition and structural brain imaging in hemodynamically impaired patients.

BACKGROUND: Orthostatic hypotension (OH) is associated with an increased risk of dementia, potentially attributable to cerebral hypoperfusion. We investigated which patterns and characteristics of OH are related to cognition or to potentially underlying structural brain injury in hemodynamically impaired patients and healthy reference participants. METHODS: Participants with carotid occlusive disease or heart failure, and reference participants from the Heart-Brain Connection Study underwent OH measurements, neuropsychological assessment and brain MRI. We analyzed the association between OH, global cognitive functioning, white matter hyperintensity (WMH) volume and brain parenchymal fraction with linear regression. We stratified by participant group, severity and duration of OH, chronotropic incompetence and presence of orthostatic symptoms. RESULTS: Of 337 participants (mean age 67.3 ± 8.8 years, 118 (35.0%) women), 113 (33.5%) had OH. Overall, presence of OH was not associated with cognitive functioning (ß: -0.12 [-0.24-0.00]), but we did observe worse cognitive functioning in those with severe OH (≥ 30/15 mmHg; ß: -0.18 [-0.34 to -0.02]) and clinically manifest OH (ß: -0.30 [-0.52 to -0.08]). These associations did not differ significantly by OH duration or chronotropic incompetence, and were similar between patient groups and reference participants. Similarly, both severe OH and clinically manifest OH were associated with a lower brain parenchymal fraction, and severe OH also with a somewhat higher WMH volume. CONCLUSIONS: Severe OH and clinically manifest OH are associated with worse cognitive functioning. This supports the notion that specific patterns and characteristics of OH determine its impact on brain health.

Blood Pressure Variability and Plasma Biomarkers of Neuronal Injury and Alzheimer's Disease: A Clinic-Based Study of Patients with Diseases Along the Heart-Brain Axis.

 Higher blood pressure variability (BPV) predisposes to cognitive decline. To investigate underlying mechanisms, we measured 24-h ambulatory BPV, nocturnal dipping and orthostatic hypotension in 518 participants with vascular cognitive impairment, carotid occlusive disease, heart failure, or reference participants. We determined cross-sectional associations between BPV indices and plasma biomarkers of neuronal injury (neurofilament light chain) and Alzheimer's disease (phosphorylated-tau-181 and Aß42/Aß40). None of the BPV indices were significantly associated with any of the biomarkers. Hence, in patients with diseases along the heart-brain axis, we found no evidence for an association between BPV and selected markers of neuronal injury or Alzheimer's disease.