The association between orthostatic hypotension and dementia: A meta‐analysis of prospective cohort studies

Min, Min; Shi, Tingting; Sun, Chenyu; Liang, Mingming; Zhang, Yun; Wu, Yun; Sun, Yehuan

doi:10.1002/gps.4964

Cited by 24 publications

(19 citation statements)

References 45 publications

(96 reference statements)

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“…Although the association between OH and cognitive decline has been inconclusive, a recent meta-analysis of prospective cohort data showed the OH increased the risk of dementia, and this trend was preserved in two subtypes of dementia: Alzheimer’s disease (adjusted pooled hazard ratio 1.175, 95% CI 1.022–1.351) and vascular dementia (adjusted pooled hazard ratio 1.403, 95% CI 1.042–1.889) [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

The absence of orthostatic heart rate increase is associated with cognitive impairment in Parkinson’s disease

et al. 2020

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Orthostatic hypotension (OH) frequently accompanies autonomic dysfunction and is an important risk factor for cognitive impairment in Parkinson’s disease (PD). While OH is usually diagnosed based on an orthostatic blood pressure drop, the association between the heart rate response and cognitive impairment remains unclear. We retrospectively analyzed 143 cases of clinically diagnosed PD to determine the association between the absence of a heart rate response and cognitive impairment in PD with OH. Among the patients with OH, neurogenic OH was diagnosed in cases without a heart rate increase, while all other patients were diagnosed with non-neurogenic OH. Dementia was found in 23 of 143 PD cases (16.1%) in this cohort. The presence of OH was an independent risk factor for dementia in PD in addition to the disease severity, years of education and beta-blockers use. Neurogenic OH was significantly associated with dementia compared to the no OH group (hazard ratio [HR] 7.3, 95% confidence interval [CI] 2.2–24.6, P<0.01), an association that was preserved after adjusting for age, gender and other covariant factors. However, no such association was observed for non-neurogenic OH (HR 2.9, 95%CI 0.8–10.9, P = 0.12). While the cognitive impairment was significantly worse in the neurogenic OH group than the no-OH group, the groups were otherwise similar. The blood pressure decrease was significantly lower in both OH groups than in the no-OH group, despite no significant differences between the OH groups. Our finding showed that OH without a heart rate response was an important predictor of cognitive impairment in PD.

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Section: Discussionmentioning

confidence: 99%

The absence of orthostatic heart rate increase is associated with cognitive impairment in Parkinson’s disease

et al. 2020

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“…Despite views that, in the absence of clinical symptomology, hypotension represents a “non-disease” state, ( 38 ) recent evidence suggests that lower baseline systolic blood pressure predicts incident depression at a 2-year follow-up after adjustment for socioeconomic status and relevant clinical factors (cardiovascular disease, chronic illness, frailty) ( 39 ). In addition, individuals between the age of 30 and 75 years with asymptomatic hypotension are at increased risk for cognitive and affective disorders, including decreased memory and concentration ( 40 ), higher rates of hopelessness, ( 40 ) and an increased prevalence of dementia, which includes both Alzheimer’s disease and vascular dementia ( 7 ). Therefore, treatment of asymptomatic hypotension in the SCI population should be considered a clinical priority.…”

Section: Discussionmentioning

confidence: 99%

“…Yet 13-year all-cause and cardiovascular disease mortality risk was 2.4 to 3.4 times higher, respectively, in males 40 to 49 years with systolic hypotension compared to age-matched males with normal blood pressure ( 3 ), and in a recent meta-analysis all-cause mortality was 36% higher in association with orthostatic hypotension ( 4 ). Moreover, there is a growing body of evidence that links persistent asymptomatic hypotension and orthostatic hypotension with adverse changes in health-related quality of life, as well as an increased incidence of anxiety and depression ( 2 ), cognitive deficits ( 5 ), hopelessness ( 5 ) and dementia ( 6 , 7 ). Therefore, treatment to increase and normalize low blood pressure, even in asymptomatic patients with SCI, should be considered.…”

Section: Introductionmentioning

confidence: 99%

Double-blinded, placebo-controlled crossover trial to determine the effects of midodrine on blood pressure during cognitive testing in persons with SCI

et al. 2020

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Study Design: Clinical trial. Objectives: Individuals with spinal cord injury (SCI) above T6 experience impaired descending cortical control of the autonomic nervous system which predisposes them to hypotension. However, treatment of hypotension is uncommon in the SCI population because there are few safe and effective pharmacological options available. The primary aim of this investigation was to test the efficacy of a single dose of midodrine (10 mg), compared to placebo, to increase and normalize systolic blood pressure (SBP) between 110–120 mmHg during cognitive testing in hypotensive individuals with SCI. Secondary aims were to determine the effects of midodrine on cerebral blood flow velocity (CBFv) and global cognitive function. Setting: United States clinical research laboratory. Methods: Forty-one healthy hypotensive individuals with chronic (≥ 1-year post-injury) SCI participated in this 2-day study. Seated SBP, CBFv, cognitive performance were monitored before and after administration of identical encapsulated tablets, containing either midodrine or placebo. Results: Compared to placebo, midodrine increased SBP (4±13 vs. 18±24 mmHg, respectively; p<0.05); however, responses varied widely with midodrine (−15.7 to +68.6 mmHg). Further, the proportion of SBP recordings within the normotensive range did not improve during cognitive testing with midodrine compared to placebo. Although higher SBP was associated with higher CBFv (p=0.02), global cognitive function was not improved with midodrine. Conclusions: The findings indicate that midodrine increases SBP and may be beneficial in some hypotensive patients with SCI; however, large heterogeneity of responses to midodrine suggest careful monitoring of patients following administration.

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“…However, some authors question the link between dysautonomia and some of these manifestations. For instance, urinary incontinence (so-called pseudoincontinence) might be the result of visual-spatial agnosia that impedes the patient to find the way to the toilet, whereas orthostatic hypotension could be directly related to the process of ageing [ 10 ] and is associated with the risk of dementia [ 15 ].…”

Section: Dysautonomia In Alzheimer's Diseasementioning

confidence: 99%

Dysautonomia in Alzheimer's Disease

et al. 2020

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Alzheimer's disease is the most common neurodegenerative disorder, and its prevalence increases with age. Although there is a large amount of scientific literature focusing on Alzheimer's disease cardinal cognitive features, autonomic nervous system dysfunction remains understudied despite being common in the elderly. In this article, we reviewed the evidence for autonomic nervous system involvement in Alzheimer's disease. We identified four major potential causes for dysautonomia in Alzheimer's disease, out of which two are well-studied (comorbidities and medication) and two are rather hypothetical (Alzheimer's pathology and brain co-pathology). Although there appears to be some evidence linking Alzheimer's disease pathology to autonomic nervous system dysfunction, there is an important gap between two types of studies; histopathologic studies do not address dysautonomia manifestations, whereas clinical studies do not employ histopathologic diagnostic confirmation. Moreover, brain co-pathology is emerging as an important confounding factor. Therefore, we consider the correlation between dysautonomia and Alzheimer's disease to be an open question that needs further study. Nevertheless, given its impact on morbidity and mortality, we emphasize the importance of assessing autonomic dysfunction in patients with Alzheimer clinical syndrome.

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The association between orthostatic hypotension and dementia: A meta‐analysis of prospective cohort studies

Cited by 24 publications

References 45 publications

The absence of orthostatic heart rate increase is associated with cognitive impairment in Parkinson’s disease

The absence of orthostatic heart rate increase is associated with cognitive impairment in Parkinson’s disease

Double-blinded, placebo-controlled crossover trial to determine the effects of midodrine on blood pressure during cognitive testing in persons with SCI

Dysautonomia in Alzheimer's Disease

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