Do abnormalities in dynamic cerebral auto-regulation underlie the pathophysiological processes behind syncope in older people?

Do abnormalities in dynamic cerebral auto-regulation underlie the pathophysiological processes behind syncope in older people? Introduction: The aim of this thesis was to investigate whether abnormalities in dynamic cerebral auto-regulation (dCA) explain the symptoms associated with orthostatic (OH) and post-prandial hypotension (PPH). Methods: Based on clinical symptoms and signs for the OH study: 4 Groups: Asymptomatic No OH (control), Symptomatic No OH, Asymptomatic OH, and Symptomatic OH. PPH study: double-blind placebo controlled cross-over study of glucose (50g) drink. 2 Groups: No PPH (control) and PPH. Baseline and head-up-tilt (HUT, for OH maximum 30 minutes study or to symptoms; PPH study maximum 60 minutes per visit). All had Transcranial Doppler ultrasound, beat-to-beat BP, ECG and CO2 monitoring. Baseline autonomic function, arterial stiffness, cardiac baroreceptor sensitivity (BRS) were calculated and dynamic cerebral auto-regulation (as the autoregulatory index ARI) assessed before and during tilt. Results: OH: n=85, mean age 73.9±7.1 years; PPH: n= 40, mean age 73.4±7.3 years Baseline: No significant differences were found between groups for cardiac BRS, arterial stiffness, cerebral blood flow velocity (CBFV) or dCA in either study. HUT both studies: falls in BP, CO2 and CBFV, increases in HR, and fall in ARI amongst symptomatic subjects prior to the end of HUT (maximum duration or symptom onset) compared to pre-HUT values. PPH study: fall in ARI with HUT irrespective of whether glucose or placebo phase. Conclusions: The development of symptoms during tilt in both studies was related to a fall in CBFV and impaired cerebral auto-regulation. Abnormalities in cerebral autoregulation may explain the symptoms of OH and PPH although these changes can only be detected during head-up-tilt

Advancing orthostatic hypotension diagnostics

This thesis investigated the diagnostics of orthostatic hypotension (OH). OH is defined as a sustained systolic/diastolic blood pressure (BP) drop larger than 20/10 mmHg within 3 minutes after standing up. OH is common among older adults aged above 65 years (6 – 31%) and geriatric outpatients (22-56%), sometimes accompanied by orthostatic intolerance (dizziness, light-headedness and blurry vision) and associated with poor clinical outcome (cardiovascular diseases, impaired cognitive performance and mortality). Current OH diagnostics is limited due to 1) contradictory evidence on the association between the OH definition and physical functioning and falls; 2) the uncertainty of the clinical value of continuous BP measurements, which may in contrast to intermittent sphygmomanometer measurements reflect the challenge posed to compensation systems and brain exposure to low perfusion pressures; and 3) the lack of assessment of systems compensating for orthostatic BP drops such as baroreflex sensitivity (i.e., heart rate increase in response to a BP drop to stabilize BP), peripheral vasoconstriction (i.e., narrowing of peripheral artery diameter in response to a BP drop to increase peripheral resistance and stabilize BP) and cerebral autoregulation (i.e., dilation of cerebral arterioles in response to a BP drop to keep cerebral blood flow constant). In conclusion, the currently used OH definition was found to be clinically valuable as patients diagnosed according to this definition are at increased risk of impaired physical functioning and falls. BP drop rate and BP recovery derived from continuous BP measurements were found to have added clinical value by their association with clinical outcome and may after confirmation of the results in further studies have to be incorporated in a new OH definition for continuous orthostatic BP measurements to better identify individuals with clinical consequences due to OH. Parameters expressing baroreflex sensitivity, cerebral oxygenation and cerebral autoregulation were by their sensitivity, test-retest reliability and validity in younger and older adults demonstrated to be potentially valuable, supporting further study on the clinical value of these parameters

Orthostatic intolerance predicts mild cognitive impairment: incidence of mild cognitive impairment and dementia from the Swedish general population cohort Good Aging in Skåne.

Contradictory results have been reported on the relationship between orthostatic hypotension (OH) and mild cognitive impairment (MCI)

Orthostatic hypotension predicts all-cause mortality and coronary events in middle-aged individuals (The Malmö Preventive Project)

Aims Orthostatic hypotension (OH) has been linked to increased mortality and incidence of cardiovascular disease in various risk groups, but determinants and consequences of OH in the general population are poorly studied. Methods and results Prospective data of the Swedish 'Malmö Preventive Project' (n = 33 346, 67.3% men, mean age 45.7 +/- 7.4 years, mean follow-up 22.7 +/- 6.0 years) were analysed. Orthostatic hypotension was found in 6.2% of study participants and was associated with age, female gender, hypertension, antihypertensive treatment, increased heart rate, diabetes, low BMI, and current smoking. In Cox regression analysis, individuals with OH had significantly increased all-cause mortality (in particular those aged less than 42 years) and coronary event (CE) risk. Mortality and CE risk were distinctly higher in those with systolic blood pressure (BP) fall >/=30 mmHg [hazard ratio (HR): 1.6, 95% CI 1.3-1.9, P /=15 mmHg (HR: 1.4, 95% CI 1.1-1.9, P = 0.024 and 1.7, 95% CI 1.1-2.5, P = 0.01). In addition, impaired diastolic BP response had relatively greater impact (per mmHg) on CE incidence than systolic reaction. Conclusion Orthostatic hypotension can be detected in approximately 6% of middle-aged individuals and is often associated with such comorbidities as hypertension or diabetes. Presence of OH increases mortality and CE risk, independently of traditional risk factors. Although both impaired systolic and diastolic responses predict adverse events, the diastolic impairment shows stronger association with coronary disease

Impaired Cerebral Autoregulation during Head Up Tilt in Patients with Severe Brain Injury

Early mobilization is of importance for improving long-term outcome for patients after severe acquired brain injury. A limiting factor for early mobilization by head-up tilt is orthostatic intolerance. The purpose of the present study was to examine cerebral autoregulation in patients with severe acquired brain injury and a low level of consciousness. Fourteen patients with severe acquired brain injury and orthostatic intolerance and fifteen healthy volunteers were enrolled. Blood pressure was evaluated by pulse contour analysis, heart rate and RR-intervals were determined by electrocardiography, middle cerebral artery velocity was evaluated by transcranial Doppler, and near-infrared spectroscopy determined frontal lobe oxygenation in the supine position and during head-up tilt. Cerebral autoregulation was evaluated as the mean flow index calculated as the ratio between middle cerebral artery mean velocity and estimated cerebral perfusion pressure. Patients with acquired brain injury presented an increase in mean flow index during head-up tilt indicating impaired autoregulation (P < 0.001). Spectral analysis of heart rate variability in the frequency domain revealed lower magnitudes of ~0.1 Hz spectral power in patients compared to healthy controls suggesting baroreflex dysfunction. In conclusion, patients with severe acquired brain injury and orthostatic intolerance during head-up tilt have impaired cerebral autoregulation more than one month after brain injury

Relationship Among Neurogenic Orthostatic Hypotension, Cerebral Hemodynamics, and Cognitive Functioning

Neurogenic orthostatic hypotension (NOH) is characterized by a drop in systolic blood pressure ≥20mmHg or diastolic blood pressure ≥10mmHg within three minutes of upright posture. A large drop in blood pressure can trigger cerebral hypoperfusion, which has been linked to deficits in cognitive function. The current thesis aimed to measure cerebral hemodynamics and cognitive function in 20 NOH patients and 20 controls in the supine and head-up tilt (HUT) positions. Information processing speed (IPS) was assessed using the Symbol-Digit Modalities Test and attention was measured using the Stroop Test. NOH patients had significantly slower IPS in both the supine(

Efficacy of Pharmacologic Treatment for Orthostatic Hypotension in the Elderly Population

The purpose of this literature review is to determine the efficacy and safety of pharmacologic treatments for orthostatic hypotension (OH), with an emphasis on researching the elderly population. In this review, three electronic search databases were utilized including PubMed, Google Scholar, and Dynamed from the years 1997 to 2019. Several keywords were used during the search. Criteria for chosen articles included that the article must be peer-reviewed, the studied population must have a median age of at least 50 years-old, at least 20 subjects must be involved, and the study must be published after the year 1995. The specific pharmacologic agents researched for the treatment of OH included midodrine, droxidopa, pyridostigmine, and fludrocortisone. There were 15 research articles chosen that included randomized control trials, systematic reviews, and meta-analyses. Although midodrine is the most researched and utilized pharmacologic treatment of OH, this drug may not be the best option when it comes to treatment in the elderly population due to an increase in supine hypertension. Pyridostigmine in combination with low-dose midodrine was found to be effective in relieving OH symptoms without increasing supine hypertension, but this evidence is based on limited randomized trials. More research is still needed to evaluate the efficacy and safety of these pharmacologic measures in the treatment of OH specifically in the elderly population and over a long period of time