Symptoms of orthostatic intolerance are not correlated with changes in Middle Cerebral Artery Velocity

doi:10.21203/rs.3.rs-4764190/v1

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Symptoms of orthostatic intolerance are not correlated with changes in Middle Cerebral Artery Velocity

https://doi.org/10.21203/rs.3.rs-4764190/v1

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Background: Vascular diseases are recognized as a modifiable risk factor for the development of cognitive impairment. One potential underlying mechanism for this may be due to chronic alterations to cerebral blood flow (CBF), which has been linked to downstream consequences. Global decreases in CBF following a change in position are often manifested clinically as orthostatic hypotension, with changes in systolic blood pressure (SBP). This study describes clinical symptoms of orthostasis, depression, and dysautonomia in older adults and correlates these symptoms with objective measures of CBF velocity and systolic blood pressure following a supine to stand transition.

Methods: 88 adult participants were recruited from a longitudinal, observational study. Participants completed standardized questionnaires for orthostatic, depression and autonomic symptoms. Participants were fitted with standardized equipment to measure SBP and CBF at baseline, nadir, 1 minute standing, and 3 minutes standing, during a protocol defined supine to stand transition and subsequent 3-minute stand.

Results: Changes in CBF were not associated with any of the collected symptom scales. Changes in SBP were negatively associated with orthostatic symptoms. Change in SBP from baseline to stand after 1 minute was negatively associated with depression symptoms.

Discussion: Symptoms of orthostatic hypotension, dysautonomia, and depression are common in older adults. Participants reported more nonspecific symptoms of orthostasis such as fatigue, trouble concentrating, and head and neck discomfort than traditional symptoms such as dizziness or light-headedness. Our results suggest that changes in CBF may be asymptomatic, while changes in SBP are correlated with reported orthostatic hypotension symptoms.

Cerebral blood flow

Aging

Orthostatic hypotension

middle cerebral artery velocity

cognitive function

Alzheimer’s disease and other dementias are a growing cause of morbidity and mortality worldwide, and are the third leading cause of death in the Americas and Europe[1][2]. More than 500,000 individuals in Canada are currently living with dementia, and this number is expected to rise to 1 million by 2030[3]. Orthostatic hypotension, which can be defined as a decrease in blood pressure of 20mmHG or more in the absence of an associated cardiac response, has been linked with the development of dementia[4]^,[5] Multiple longitudinal studies have demonstrated a strong association between OH and the development of cognitive impairment[6]. OH is a common condition which has been reported to affect up to 20% of community dwelling older adults and up to 50% of older adults in an institutional or hospital setting[7]. Efforts to uncover the exact associations between OH and cognition are important to help determine if treatments for OH may be useful in mitigating the risk of dementia.

Clinical manifestations of OH are quite varied and may include mild dizziness, fatigue, and syncope. However, the majority of cases are asymptomatic, making identification of those at highest risk difficult[8]^,[9]. Clinical manifestations of OH are thought to occur because of global decreases in CBF following a change in posture from lying to standing. This is a potentially important physiological mechanism to explore as our group and others have demonstrated that those with lower CBF on standing have lower cognitive function[10]. Studies which aim to examine the relationship between postural changes in CBF and clinical symptoms of OH are lacking, but could show researchers those who are at greatest risk of cognitive consequences from changes in CBF. We performed a prospective, observational study in a cohort of community dwelling, older adults, which looked at the association between reported symptoms of OH and changes in CBF. Our primary hypothesis was that those participants who experienced greater changes in CBF would report a higher burden of symptoms of orthostatic hypotension. We also undertook an exploration of whether other commonly reported disease associations with OH including depression and autonomic dysfunction were correlated with changes in CBF.

Participants: Participants were recruited from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) Study at Parkwood Institute, London, ON. The COMPASS-ND Study is a Canadian cohort research initiative and a clinical study within the Canadian Consortium on Neurodegeneration in Aging (CCNA). All procedures were reviewed and approved by Clinical Trials Ontario (CTO750) at Western University and conformed with the Declaration of Helsinki. Baseline demographic data was collected in accordance with the COMPASS-ND protocol including age, sex, education level, medical history, and current medications. Participants’ cognitive diagnosis was initially determined using the COMPASS-ND protocol[11]. However, they were also subsequently categorized into larger groups for further comparison: cognitively impaired (CI, including Alzheimer’s Disease and mixed dementia), mild cognitive impairment (MCI, including MCI and vascular cognitive impairment), and cognitively intact (CNT, including cognitively intact individuals and subjective cognitive impairment)[12]. Neuropsychological testing including the Montreal Cognitive Assessment (MoCA) was administered in accordance with the COMPASS-ND protocol. Participants grouped as CNT (n = 22) had normal cognition or subjective cognitive impairment. To meet CNT group criteria, participants were required to have a Global Clinical Dementia Rating (CDR) equal to zero verbal memory assessed with Logical Memory with education adjusted cut-offs, Consortium to Establish a Registry for Alzheimer’s Disease (CERAD)[ word list recall score > 5 words (0–10 word scale) or Rey Auditory Verbal Learning-trial 7 (> 6 words), and MoCA total score > 24.

Participant grouped as MCI (n = 50) were assessed using the National Institute on Aging, Alzheimer’s Association Clinical Criteria (NIA-AA)[13]. MCI classification criteria included self-reported concerns of a change in cognitive function, impairment in one or more neuropsychological tests (Logical Memory, CERAD, MoCA < 25, CDR 0.5), preserved independence (Lawton & Brody scale score > 14), and absence of dementia based on CDR < 1. The participant group labelled as dementia (DEM) had evidence of functional decline in association with the memory decline described above.

Questionnaires

A trained member of the research team administered the Center for Epidemiologic Studies Depression Scale (CESD), Orthostatic Hypotension Questionnaire (OHQ), and Composite Autonomic Symptoms Score 31 (COMPASS 31). Participant answers were coded to numeric values and manually entered into a spreadsheet for analysis. If a handwritten answer was provided by the participant, the most appropriate numeric answer was selected.

CESD

The CESD was scored as per the CESD-Revised scoring system. The mean and standard deviation of the total scores were calculated. The proportion of participants scoring 16 or greater was also determined as this score is suggestive of significant depression[14].

OHQ

The orthostatic hypotension questionnaire (OHQ) was used as a standardized symptom questionnaire which has been validated in populations with orthostatic hypotension. The OHQ was scored as per the validated scoring system of the questionnaire[15]. Participants were excluded if any answers were incomplete or left blank. The Orthostatic Hypotension Symptom Assessment (OHSA), Orthostatic Hypotension Daily Activity Scale (OHDAS), and composite OHQ score were calculated as well as the mean and standard deviation respectively. The presence of any orthostatic hypotension symptoms was defined as a score > 0 on any question in the OHSA.

COMPASS31

The COMPASS 31 was scored as per the validated scoring system of the questionnaire [16]. Participants were excluded if any required answers were incomplete or left blank. Weighted scores for each symptom domain of orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor were calculated in addition to a total weighted score. The presence of any orthostatic intolerance symptoms was defined as a symptom domain score > 0.

Hemodynamic Testing Set-Up

Participants were instrumented with a portable transcranial Doppler ultrasound (TCD-X; Atys medical, Soucieu en Jarrest, France) device. The middle cerebral artery was insonated using a 2-MHz transducer on the right side of the head, and if the signal quality was inadequate or unacquired, the left side was insonated. Atrial finger blood pressure was monitored by a plethysmography (NOVA, Finapress Medical Systems, Amsterdam, Netherlands) device and adjusted to brachial blood pressures.

Following instrumentation, participants completed a practice supine-to-stand transition. Participants then lay resting in the supine position for 10 minutes, followed by an assisted supine-to-stand transition, where they then stood for 3 minutes. All beat-to-beat variables were measured continuously throughout the transitions. Baseline was defined as a 30 second average preceding the active transition (-45 seconds to -15 seconds), nadir was defined as the lowest average of three consecutive beats, standing at 1 minute was calculated as a 30 second average from + 30 to + 60 seconds, and standing at 3 minutes was calculated as a 30 second average from + 150 to + 180 seconds.

Statistical Analysis

Participant characteristics were summarized using mean and standard deviation for continuous data and frequency (percentage) for categorical data.

Multivariable linear regressions were performed to assess how MCAv changes are associated with symptoms of orthostatic hypotension, depression, and dysautonomia. The analyses were conducted separately for MCAv nadir, change in MCAv from baseline to 1 minute, and change in MCAv from baseline to 3 minutes. All the models were adjusted for age, sex, education, antihypertensive medication use, cognitive diagnosis, and change in SBP after 1 minute. Similar multivariable linear regression models were used to evaluate the association between SBP changes and symptoms of orthostatic hypotension, depression, and dysautonomia. Three separate models were created for SBP nadir, change in SBP from baseline to 1 minute, and change in SBP from baseline to 3 minutes, and the following covariates were included in the model: age, sex, education, antihypertensive medication use, and cognitive diagnosis. The above multivariable linear regression analyses were used to assess the associations of changes in MCAv and SBP with symptoms of orthostatic hypotension, depression, and dysautonomia.

For all multivariable linear regression models, the assumptions of linearity, homoscedasticity and normality were evaluated using residual plots. The multicollinearity was assessed using variance inflation factor < 10. All analyses were performed using RStudio version 2022.07.2 Build 576. Statistical significance level was set at p < 0.05 (two-sided).

Participant Characteristics

A total of 88 participants were included in the study. The characteristics of the population are summarized in Table 1. Of the total study population, 44.32% were female. Females represented 28.57%, 40%, and 61.90% of the cognitively impaired group (CI), mild cognitive impairment (MCI), and cognitively unimpaired (CNT) groups respectively. The mean participant age was 75.14 years (± 7.02). The (CI) group was older with a mean age of 81.43 (± 7.76), followed by the MCI group with a mean age of 75.48 (± 6.08), and then the CNT group with a mean age of 72.95 (± 5.95). Participants with dementia or MCI represented 76.14% of all participants. The mean total years of education was 15.99 (± 3.45). Antihypertensive medications were taken by 37.50% of total participants.

Orthostatic Hypotension Symptoms

Seventy-seven participants (87.50%) completed the OHQ. Fifty-seven participants (74.03%) reported at least one orthostatic symptom and the mean OHQ composite score was 5.36 (± 6.67). The mean OHSA score was 6.56 (± 7.46). Thirty-nine participants (50.65%) reported orthostatic symptoms that interfered with activities of daily life, as measured by the OHDAS. The mean score for each OHQ question is summarized in Table 1. The scores which demonstrated the highest level of frequency included Question 4 (“Fatigue”, (1.77 ± 2.59)), Question 5 (“Trouble concentrating”, 1.53 ± 2.30)), and Question 6 (“Head and neck discomfort” 1.20 ± 2.05)). Questions 8 and 10 are part of the OHDAS and ask participants to rate how much their symptoms interfere with certain activities of daily life from 0 to 10. Question 8 refers to “Activities that require standing for a long time” and had a mean score of 2.33 (± 3.18). Question 10 refers to “Activities that require walking for a long time”, with a mean score of 2.12 (± 3.22).

Depression Symptoms

Seventy-seven participants (87.50%) completed the CESD. The mean CESD score was 8.30 (± 9.19). Eighteen participants (23.4%) had a total score of ≥ 16, based on standardized scoring interpretation. There was no significant correlation found between total CES-D score and MCA velocity measured at 1 and 3 minutes respectively. There was a correlation between CES-D score and change in SBP measured at 1 minute which was not present at 3 minutes.

Autonomic Symptoms

Seventy-six participants (86.3%) completed the COMPASS 31 questionnaire. The mean overall weighted score was 14.84 (± 12.34). Ten participants (11%) reported autonomic symptoms, with a total weighted score greater than 0. Twenty-eight participants (36.84%) reported orthostatic intolerance symptoms. The mean weighted sub-score for orthostatic intolerance was 6.11 (± 8.55).

Middle Cerebral Artery Velocity

The mean change in MCAv from baseline to nadir was − 12.41 cm/s (± 7.01), which improved to -3.61 cm/s (± 3.84) at 1 minute and − 2.46 cm/s (± 3.98) at 3 minutes (Table 1).

Table 2 illustrates the correlation of change in MCAv from baseline to nadir, baseline to stand after 1 minute, and baseline to stand after 3 minutes, with each symptom scale. Change in MCAv from baseline at any time point was not associated with symptoms of orthostatic hypotension, depression, or dysautonomia.

Systolic Blood Pressure

There was a mean change in SBP from baseline to nadir of -29.85 ± 14.95 mmHg, which improved to -6.72 ± 16.43 mmHg at 1 minute and 3.79 ± 14.13 mmHg at 3 minutes (Table 1).

Table 3 illustrates the correlation of change in SBP from baseline to nadir, baseline to stand after 1 minute, and baseline to stand after 3 minutes, with each symptom scale. There was a significant association between the postural change in SBP and reported orthostatic symptoms. Change in SBP from baseline at all three time points was negatively associated with OHQ composite score (p = < 0.004) and OHSA (p = < 0.002) (Table 3). There was no significant correlation observed between changes in SBP and autonomic symptoms.

We have demonstrated that our original hypothesis of a correlation between symptoms of OH and CBF was not proven in this cohort of older adults. Orthostatic symptoms quantified by the OHQ composite score and OHSA were linearly correlated with changes in SBP during supine to stand transitions, however this correlation was not seen with changes in MCAv. This was despite the majority of participants demonstrating a significant postural change in CBF as measured by Middle Cerebral artery velocity suggesting either that changes in CBF are asymptomatic or that commonly reported symptoms of OH are caused by changes in peripheral blood pressure which do not manifest on the cerebral circulatory system.

Our results show that symptoms of orthostatic hypotension, dysautonomia, and depression are common in older adults with cognitive impairment. Almost 75% of participants reported orthostatic symptoms while 92.11% of participants reported autonomic symptoms, and 23.4% had reported severe depressive symptoms. Participants reported more nonspecific symptoms of orthostasis such as fatigue, trouble concentrating, and head and neck discomfort than traditional symptoms such as dizziness or light-headedness.

OH symptoms in older adults remain relatively understudied. The OHQ itself has been validated using a population with a median age of 67, however individuals as young as 29 were included[15]. A Swedish version of the OHQ has been validated in older adults with Parkinson’s disease and multisystem atrophy[17]. Our results suggest that older adults report more atypical symptoms of OH, such as fatigue, trouble concentrating, and head and neck discomfort, rather than classically described symptoms such as light-headedness and dizziness. This is in-keeping with previous research that found many patients with OH to be asymptomatic when screened for OH symptoms using OHQ Question 1 which describes lightheadedness and dizziness[18], and may explain why an association was found between reported OH symptoms and measured SBP in our study when all questions were included. It is notable that 76.14% of participants had either dementia or MCI by standardized criteria. This is relevant to clinical practice as older adults with cognitive impairment are often affected by orthostatic hypotension[19]. This study serves to highlight the non-specific nature of reported symptoms of orthostatic hypotension in older adults, and furthermore highlights the potential utility of standardized questionnaires in capturing these symptoms.

We, and others, previously shown that orthostatic changes have different effects on SBP and MCA velocity. They appear to have similar directionality (i.e. a decrease in SBP is often accompanied by a decrease in MCA velocity), however the magnitude of these effects are not the same. MCA velocity is controlled by a number of different physiological processes to systemic blood pressure, including neural control and cerebral autoregulation. This study shows that the change in systolic blood pressure is better correlated with symptoms experienced and remains the optimal way to screen patients who experience symptoms of orthostatic intolerance for orthostatic hypotension. As changes in MCA velocity have been correlated to worsening cognitive function, symptoms which correlate with changes in MCA velocity (if they exist) may aid clinicians in recognizing symptoms of decreased MCA flow earlier and examine if meaningful interventions are possible. Further studies which look to uncover if patients experience specific symptoms correlating to changes in MCA velocity are warranted in the future.

This study has looked to examine the presence of symptoms of orthostatic intolerance and hypotension in a mixed cohort of older adults with various degrees of cognitive impairment. We used standardized questionnaires which were not developed for this specific use. The questionnaires themselves were developed in younger cohorts of patients who have experienced different forms of orthostatic intolerance, rather than a community dwelling cohort. We chose these questions, however, as they contain the commonest symptoms reported by adults who experience orthostatic intolerance and orthostatic hypotension. We have attempted to use them to elucidate which symptoms may be more commonly reported by older adults with mild degrees of OH. Our cohort was powered to detect changes in MCA velocity and not for detecting true OH. This may explain the low number of participants who have reported higher scores on the standard questionnaires. Despite this, we have been able to show that even at low level changes in SBP, older adults may experience symptoms of orthostatic intolerance which provides avenues for screening.

In summary, our study demonstrates that symptoms of orthostatic hypotension, depression, and autonomic dysfunction are common in older adults with cognitive impairment. Orthostatic symptoms as measured by the OHQ correlate with changes in SBP during supine to stand transition, however this correlation was not seen between changes in MCAv and reported symptoms, suggesting that changes in MCAv may be asymptomatic. More commonly reported symptoms of OH included atypical symptoms such as fatigue, trouble concentrating, and head and neck discomfort rather than traditional symptoms such as dizziness or light-headedness. This finding suggests that clinicians should consider screening for OH using both traditional and atypical symptoms, such as those described in the OHSA. More research is needed into the relationship between MCAv, SBP, OH, and cognitive impairment.

On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Table 1. Participant characteristics and results by cognitive diagnosis.

	Total Mean (± SD)	CI (n=7)	MCI (n=60)	CNT (n=21)
Age, years (n=88)	75.14 (± 7.02)	81.43 (± 7.76)	75.48 (± 6.08)	72.95 (± 5.95)
Female, n (%)	39 (44.32 %)	2 (28.57%)	24 (40%)	13 (61.90%)
MoCA (n=87)	24.09 (± 3.79)	18.14 (± 2.97)	23.63 (± 3.37)	27.38 (± 1.28)
Cognitive diagnosis, n (%), (n=88)
AD	3 (3.41 %)	3 (42.86%)
CNT	11 (12.50 %)			11 (52.38%)
MCI	51 (57.95 %)		51 (85%)
Mixed	4 (4.55 %)	4 (57.14%)
SCI	10 (11.36 %)			10 (47.62%)
VCI	9 (10.23 %)		9 (15%)
Total education, years (n=88)	15.99 (± 3.45)	13.86 (± 4.06)	16.26 (± 3.58)	15.95 (± 2.67)
Antihypertensive medication use, n (%) (n=86)	33 (37.50 %)	3 (42.86%)	22 (36.67%)	8 (38.10%)
CESD (n=77)	8.30 (± 9.19)	9.8 (± 13.99)	7.90 (± 8.96)	8.95 (± 8.92)
Score ≥16	18 (23.4%)
OHQ Composite score (n=77)	5.36 (± 6.67)	5.57 (± 7.16)	4.95 (± 5.96)	6.45 (± 8.92)
Score >0	57 (74.03%)
OHSA	6.56 (± 7.46)	9 (± 5.83)	5.79 (± 6.75)	7.95 (±9.39)
Score >0	51 (66.23%)
OHDAS	5.69 (± 8.26)	6.6 (± 12.64)	5.63 (± 7.71)	5.6 (±8.92)
Score >0	39 (50.65%)
OHQ individual item
Question 1 score	0.86 (± 1.82)	2 (± 3.46)	0.73 (±1.55)	0.90 (± 1.97)
Question 2 score	0.61 (± 1.52)	0.6 (± 1.34)	0.69 (± 1.60)	0.40 (±1.39)
Question 3 score	0.60 (± 1.86)	1 (± 2.24)	0.50 (± 1.89)	0.75 (± 1.74)
Question 4 score	1.77 (± 2.59)	2.20 (± 2.86)	1.67 (± 2.51)	1.90 (± 2.85)
Question 5 score	1.53 (± 2.30)	2.20 (± 2.49)	1.40 (± 2.11)	1.70 (± 2.77)
Question 6 score	1.20 (± 2.05)	1 (± 2.24)	0.79 (± 1.38)	2.30 (± 2.99)
Question 7 score	0.62 (± 1.55)	1.40 (± 3.13)	0.52 (± 1.34)	0.70 (± 1.59)
Question 8 score	2.33 (± 3.18)	2 (± 4.47)	2.33 (± 3.03)	2.40 (± 3.39)
Question 9 score	0.62 (± 1.73)	1 (± 2.24)	0.65 (± 1.86)	0.45 (± 1.23)
Question 10 score	2.12 (± 3.22)	2.20 (± 3.19)	2.13 (± 3.14)	2.05 (± 3.58)
COMPASS31 Overall (n=76)	14.84 (± 12.34)	10.63 (± 7.40)	13.47 (± 11.77)	19.39 (± 13.93)
Score >0	70 (92.11%)
COMPASS 31 sub-scores
Orthostatic intolerance	6.11 (± 8.55)	3.2 (± 7.16)	5.57 (± 8.51)	8.2 (± 8.94)
Score >0	28 (36.84%)
Vasomotor	0.45 (± 0.99)	0.83 (± 1.18)	0.31 (± 0.82)	0.71 (± 1.28)
Secretomotor	2.79 (± 3.05)	2.14 (± 2.14)	2.65 (± 3.14)	3.32 (± 3.07)
Gastrointestinal	3.23 (± 3.11)	2.32 (± 3.32)	2.80 (±2.71)	4.55 (± 3.74)
Bladder	1.17 (± 2.06)	1.33 (± 1.99)	1.13 (± 2.00)	1.22 (± 2.31)
Pupillomotor	1.10 (± 1.12)	0.8 (± 0.84)	1.01 (± 1.08)	1.38 (± 1.28)
Middle cerebral artery velocity, cm/s (n=56)
D nadir	-12.41 (± 7.01)	-9.56 (± 5.18)	-12.58 (± 7.65)	-13.02 (± 5.64)
D 1 minute	-3.61 (± 3.84)	-3.14 (± 6.44)	-3.68 (±3.93)	-3.61 (± 2.45)
D 3 minutes	-2.46 (± 3.98)	-1.03 (± 4.07)	-2.60 (±4.18)	-2.61 (± 3.51)
Systolic blood pressure, mmHg (n=77)
D nadir	-29.85 (± 14.95)	-32.88 (± 16.42)	-29.18 (±13.88)	-30.86 (± 17.77)
D 1 minute	-6.72 (± 16.43)	-10.90 (± 16.71)	-5.69 (±16.91)	-8.36 (± 15.59)
D 3 minutes	3.79 (± 14.13)	-0.35 (± 15.98)	5.15 (± 14.62)	1.30 (± 12.44)

n, sample size; SD, standard deviation; CI, cognitively impaired; MCI, mild cognitive impairment; CNT, cognitively intact; MoCA, Montreal Cognitive Assessment; AD, Alzheimer’s disease; SCI, subjective cognitive impairment; VCI, vascular cognitive impairment; CESD, Center for Epidemiological Studies Depression Scale; OHQ, Orthostatic Hypotension Questionnaire; OHSA, Orthostatic Hypotension Symptom Assessment; OHDAS, Orthostatic Hypotension Daily Activity Scale; COMPASS, Composite Autonomic Symptoms Score 31.

Table 2. Results of linear regression models for change in middle cerebral artery velocity from baseline to nadir, baseline to stand after 1 minute, and baseline to stand after 3 minutes.

	MCAv baseline to nadir				MCAv 1 minute				MCAv 3 minutes
	Unadjusted		Adjusted *		Unadjusted		Adjusted *		Unadjusted		Adjusted *
	(95% CI)	p-value	(95% CI)	p-value	(95% CI)	p-value	(95% CI)	p-value	(95% CI)	p-value	(95% CI)	p-value
OHQ Composite	-0.05 (-0.30, 0.21)	0.72	-0.09 (-0.36, 0.17)	0.48	-0.24 (-0.70, 0.22)	0.31	-0.28 (-0.76, 0.19)	0.24	-0.21 (-0.66, 0.23)	0.34	-0.17 (-0.59, 0.25)	0.42
OHSA	-0.14 (-0.43, 0.15)	0.33	-0.07 (-043, 0.29)	0.70	-0.25 (-0.78, 0.29)	0.36	-0.22 (-0.87, 0.43)	0.50	-0.03 (-0.56, 0.49)	0.90	0.07 (-0.51, 0.65)	0.81
OHDAS	0.02 (-0.30, 0.35)	0.88	-0.12 (-0.46, 0.21)	0.46	-0.30 (-0.90, 0.30)	0.32	-0.36 (-0.97, 0.24)	0.23	-0.27 (-0.85, 0.32)	0.37	-0.28 (-0.82, 0.25)	0.29
CESD	-0.28 (-0.66, 0.09)	0.14	-0.33 (-0.74, 0.08)	0.11	-0.35 (-1.05, 0.36)	0.32	-0.05 (-0.82, 0.73)	0.91	-0.10 (-0.80, 0.60)	0.77	0.07 (-0.62, 0.75)	0.85
COMPASS31	-0.30 (-0.76, 0.17)	0.20	-0.33 (-0.97, 0.31)	0.30	-0.23 (-1.11, 0.65)	0.60	0.0004 (-1.20, 1.20)	0.99	-0.28 (-1.15, 0.58)	0.51	-0.003 (-1.08, 1.07)	0.99

CI, confidence interval; MCAv, middle cerebral artery velocity; OHQ, Orthostatic Hypotension Questionnaire; OHSA, Orthostatic Hypotension Symptom Assessment; OHDAS, Orthostatic Hypotension Daily Activity Scale; CESD, Center for Epidemiologic Studies Depression Scale; COMPASS 31, Composite Autonomic Symptoms Score 31.

* Adjusted for age, sex, education, antihypertensive medication use, cognitive diagnosis, and change in systolic blood pressure after 1 minute

Table 3. Results of linear regression models for change in systolic blood pressure from baseline to nadir, baseline to stand after 1 minute, and baseline to stand after 3 minutes.

	SBP baseline to nadir				SBP 1 minute				SBP 3 minutes
	Unadjusted		Adjusted *		Unadjusted		Adjusted *		Unadjusted		Adjusted *
	(95% CI)	p-value	(95% CI)	p-value	(95% CI)	p- value	(95% CI)	p-value	(95% CI)	p- value	(95% CI)	p-value
OHQ Composite	-0.12 (-0.21, -0.02)	0.01	-0.14 (-0.24, -0.05)	0.004	-0.11 (-0.19, -0.03)	0.01	-0.11 (-0.20, -0.03)	0.01	-0.10 (-0.20, 0.0004)	0.05	-0.11 (-0.22, -0.01)	0.03
OHSA	-0.18 (-0.28, -0.07)	0.002	-0.19 (-0.30, -0.07)	0.002	-0.17 (-0.27, -0.07)	<0.001	-0.18 (-0.28, -0.06)	0.002	-0.21 (-0.32, -0.09)	<0.001	-0.21 (-0.33, -0.09)	0.001
OHDAS	-0.08 (-0.19, 0.04)	0.18	-0.11 (-0.23, -0.0005)	0.05	-0.06 (-0.16, 0.05)	0.28	-0.07 (-0.17, 0.04)	0.21	0.02 (-0.11, 0.14)	0.79	-0.01 (-0.14, 0.11)	0.83
CESD	-0.09 (-0.23, 0.05)	0.22	-0.08 (-0.22, 0.06)	0.27	-0.13 (-0.26, -0.007)	0.04	-0.13 (-0.26, -0.005)	0.04	-0.15 (-0.29, 0.002)	0.05	-0.14 (-0.29. 0.006)	0.06
COMPASS31	-0.13 (-0.32, 0.07)	0.20	-0.17 (-0.38, 0.03)	0.10	-0.08 (-0.26, 0.10)	0.40	-0.10 (-0.29, 0.10)	0.32	-0.09 (-0.30, 0.12)	0.41	-0.12 (-0.34, 0.11)	0.30

CI, confidence interval; SBP, systolic blood pressure; OHQ, Orthostatic Hypotension Questionnaire; OHSA, Orthostatic Hypotension Symptom Assessment; OHDAS, Orthostatic Hypotension Daily Activity Scale; CESD, Center for Epidemiologic Studies Depression Scale; COMPASS 31, Composite Autonomic Symptoms Score 31.

* Adjusted for age, sex, education, antihypertensive medication use, cognitive diagnosis, and change in systolic blood pressure after 1 minute

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Symptoms of orthostatic intolerance are not correlated with changes in Middle Cerebral Artery Velocity

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Abstract

INTRODUCTION

METHODS

RESULTS

Participant Characteristics

Orthostatic Hypotension Symptoms

Depression Symptoms

Autonomic Symptoms

Middle Cerebral Artery Velocity

Systolic Blood Pressure

DISCUSSION

CONCLUSIONS

References

Tables

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