Skip to main content

Advertisement

SpringerLink
Log in

Orthostatic hypotension in patients with Alzheimer’s disease: a meta-analysis of prospective studies

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Background

Orthostatic hypotension (OH) is a clinical sign associated with severe adverse health outcomes in older adults. It has been reported to be common in patients with Alzheimer’s disease (AD). The present meta-analysis aimed to investigate the prevalence and risk of OH in AD patients.

Methods

English-language articles published from January 1990 to August 2020 were searched in PubMed, ScienceDirect, Cochrane, and Web of Science with the keywords “Alzheimer” and “autonomic dysfunction” or “dysautonomia” or “postural hypotension” or “orthostatic hypotension.” All prospective clinical studies (case–control, cohort, and cross-sectional studies, and randomized controlled trials) that were regarded as pertinent were included in this study. For quality assessment, the Newcastle–Ottawa Scale was used. Odds ratios (OR) and risk ratios (RR) were extracted with 95% confidence intervals (CI) and combined using the random effects model after logarithmic transformation. The prevalence in the AD patients was also combined using the random effects model.

Results

The meta-analysis involved 11 studies (7 case–control and 4 case series) to assess the risk of OH in AD. It was found that AD increased the risk of OH with an RR of 1.98 (95% CI: 0.97–4.04) and an OR of 2.53 (95% CI:1.10–5.86) compared to healthy controls, and OH was present in 28% (95% CI: 0.17–0.40) of 500 AD patients.

Conclusion

There is an elevated risk of OH in AD by nearly 2.5-fold. Therefore, the evaluation of postural blood pressure changes should definitely be among the follow-up and treatment goals of AD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Lahrmann H, Cortelli P, Hilz M, Mathias CJ, Struhal W, Tassinari M (2006) EFNS guidelines on the diagnosis and management of orthostatic hypotension. Eur J Neurol 13(9):930–936. https://doi.org/10.1111/j.1468-1331.2006.01512.x

    Article  CAS  PubMed  Google Scholar 

  2. Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, Cheshire WP, Chelimsky T, Cortelli P, Gibbons CH, Goldstein DS, Hainsworth R, Hilz MJ, Jacob G, Kaufmann H, Jordan J, Lipsitz LA, Levine BD, Low PA, Mathias C, Raj SR, Robertson D, Sandroni P, Schatz I, Schondorff R, Stewart JM, van Dijk JG (2011) Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res 21(2):69–72. https://doi.org/10.1007/s10286-011-0119-5

    Article  PubMed  Google Scholar 

  3. Ricci F, De Caterina R, Fedorowski A (2015) Orthostatic hypotension: epidemiology, prognosis, and treatment. J Am Coll Cardiol 66(7):848–860. https://doi.org/10.1016/j.jacc.2015.06.1084

    Article  PubMed  Google Scholar 

  4. Mol A, Bui Hoang PTS, Sharmin S, Reijnierse EM, van Wezel RJA, Meskers CGM, Maier AB (2019) Orthostatic hypotension and falls in older adults: a systematic review and meta-analysis. J Am Med Dir Assoc 20(5):589-597.e585. https://doi.org/10.1016/j.jamda.2018.11.003

    Article  PubMed  Google Scholar 

  5. Brown WR, Thore CR (2011) Review: cerebral microvascular pathology in ageing and neurodegeneration. Neuropathol Appl Neurobiol 37(1):56–74. https://doi.org/10.1111/j.1365-2990.2010.01139.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Mu F, Jiao Q, Du X, Jiang H (2020) Association of orthostatic hypotension with Parkinson’s disease: a meta-analysis. Neurol Sci 41(6):1419–1426. https://doi.org/10.1007/s10072-020-04277-w

    Article  PubMed  Google Scholar 

  7. Soysal P, Veronese N, Smith L, Torbahn G, Jackson SE, Yang L, Ungar A, Rivasi G, Rafanelli M, Petrovic M (2019) Orthostatic hypotension and health outcomes: an umbrella review of observational studies. Eur Geriatr Med 10(6):863–870

    Article  PubMed  Google Scholar 

  8. Cremer A, Soumaré A, Berr C, Dartigues JF, Gabelle A, Gosse P, Tzourio C (2017) Orthostatic Hypotension and Risk of Incident Dementia: Results From a 12-Year Follow-up of the three-city study cohort. Hypertension 70(1):44–49. https://doi.org/10.1161/hypertensionaha.117.09048

    Article  CAS  PubMed  Google Scholar 

  9. Isik AT, Kocyigit SE, Smith L, Aydin AE, Soysal P (2019) A comparison of the prevalence of orthostatic hypotension between older patients with Alzheimer’s disease, Lewy body dementia, and without dementia. Exp Gerontol 124:110628. https://doi.org/10.1016/j.exger.2019.06.001

    Article  PubMed  Google Scholar 

  10. Rüb U, Del Tredici K, Schultz C, Thal DR, Braak E, Braak H (2001) The autonomic higher order processing nuclei of the lower brain stem are among the early targets of the Alzheimer’s disease-related cytoskeletal pathology. Acta neuropathologica 101(6):555–564. https://doi.org/10.1007/s004010000320

    Article  PubMed  Google Scholar 

  11. Tulbă D, Cozma L, Popescu BO, Davidescu EI (2020) Dysautonomia in Alzheimer's disease. Medicina (Kaunas, Lithuania) 56 (7). doi:https://doi.org/10.3390/medicina56070337

  12. Joseph A, Wanono R, Flamant M, Vidal-Petiot E (2017) Orthostatic hypotension: a review. Nephrologie Therapeutique 13(Suppl 1):S55-s67. https://doi.org/10.1016/j.nephro.2017.01.003

    Article  PubMed  Google Scholar 

  13. Jensen-Dahm C, Waldemar G, Staehelin Jensen T, Malmqvist L, Moeller MM, Andersen BB, Høgh P, Ballegaard M (2015) Autonomic dysfunction in patients with mild to moderate Alzheimer’s disease. J Alzheimers Dis 47(3):681–689. https://doi.org/10.3233/jad-150169

    Article  PubMed  Google Scholar 

  14. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097. https://doi.org/10.1371/journal.pmed.1000097

    Article  PubMed  PubMed Central  Google Scholar 

  15. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheim Dement 7(3):263–269. https://doi.org/10.1016/j.jalz.2011.03.005

    Article  Google Scholar 

  16. Parry SW, Reeve P, Lawson J, Shaw FE, Davison J, Norton M, Frearson R, Kerr S, Newton JL (2009) The Newcastle protocols 2008: an update on head-up tilt table testing and the management of vasovagal syncope and related disorders. Heart 95(5):416–420. https://doi.org/10.1136/hrt.2007.136457

    Article  CAS  PubMed  Google Scholar 

  17. Shibao C, Lipsitz LA, Biaggioni I (2013) Evaluation and treatment of orthostatic hypotension. J Am Soc Hypertens 7(4):317–324. https://doi.org/10.1016/j.jash.2013.04.006

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wells G, Shea B, O’Connell D, J Peterson, V Welch, M Losos, Tugwell. P (2012) The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses. http//www.ohri.ca/ programs/clinical epidemiology/oxford.asp.

  19. Kim JS, Park HE, Oh YS, Song IU, Yang DW, Park JW, Lee KS (2015) (123)I-MIBG myocardial scintigraphy and neurocirculatory abnormalities in patients with dementia with Lewy bodies and Alzheimer’s disease. J Neurol Sci 357(1–2):173–177. https://doi.org/10.1016/j.jns.2015.07.025

    Article  PubMed  Google Scholar 

  20. Siennicki-Lantz A, Lilja B, Elmståhl S (1999) Orthostatic hypotension in Alzheimer’s disease: result or cause of brain dysfunction? Aging 11(3):155–160

    CAS  PubMed  Google Scholar 

  21. Allan LM, Ballard CG, Allen J, Murray A, Davidson AW, McKeith IG, Kenny RA (2007) Autonomic dysfunction in dementia. J Neurol Neurosurg Psychiatry 78(7):671–677. https://doi.org/10.1136/jnnp.2006.102343

    Article  CAS  PubMed  Google Scholar 

  22. Allan LM, Ballard CG, Rowan EN, Kenny RA (2009) Incidence and prediction of falls in dementia: a prospective study in older people. PloS one 4(5):e5521. https://doi.org/10.1371/journal.pone.0005521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Burton EJ, McKeith IG, Burn DJ, Firbank MJ, O’Brien JT (2006) Progression of white matter hyperintensities in Alzheimer disease, dementia with lewy bodies, and Parkinson disease dementia: a comparison with normal aging. Am J Geriatr Psychiatry 14(10):842–849. https://doi.org/10.1097/01.JGP.0000236596.56982.1c

    Article  PubMed  Google Scholar 

  24. Vitiello B, Veith RC, Molchan SE, Martinez RA, Lawlor BA, Radcliffe J, Hill JL, Sunderland T (1993) Autonomic dysfunction in patients with dementia of the Alzheimer type. Biol Psychiatry 34(7):428–433. https://doi.org/10.1016/0006-3223(93)90233-4

    Article  CAS  PubMed  Google Scholar 

  25. Zakrzewska-Pniewska B, Gawel M, Szmidt-Salkowska E, Kepczynska K, Nojszewska M (2012) Clinical and functional assessment of dysautonomia and its correlation in Alzheimer’s disease. Am J Alzheimers Dis Other Dement 27(8):592–599. https://doi.org/10.1177/1533317512459792

    Article  Google Scholar 

  26. Ballard C, Shaw F, McKeith I, Kenny R (1998) High prevalence of neurovascular instability in neurodegenerative dementias. Neurology 51(6):1760–1762. https://doi.org/10.1212/wnl.51.6.1760

    Article  CAS  PubMed  Google Scholar 

  27. Passant U, Warkentin S, Karlson S, Nilsson K, Edvinsson L, Gustafson L (1996) Orthostatic hypotension in organic dementia: relationship between blood pressure, cortical blood flow and symptoms. Clin Auton Res 6(1):29–36. https://doi.org/10.1007/bf02291403

    Article  CAS  PubMed  Google Scholar 

  28. Isik AT, Soysal P, Usarel C (2016) Effects of Acetylcholinesterase Inhibitors on Balance and Gait Functions and Orthostatic Hypotension in Elderly Patients With Alzheimer Disease. Am J Alzheimers Dis Other Dement 31(7):580–584. https://doi.org/10.1177/1533317516666195

    Article  Google Scholar 

  29. Swaab DF, Raadsheer FC, Endert E, Hofman MA, Kamphorst W, Ravid R (1994) Increased cortisol levels in aging and Alzheimer’s disease in postmortem cerebrospinal fluid. J Neuroendocrinol 6(6):681–687. https://doi.org/10.1111/j.1365-2826.1994.tb00635.x

    Article  CAS  PubMed  Google Scholar 

  30. Brureau A, Zussy C, Delair B, Ogier C, Ixart G, Maurice T, Givalois L (2013) Deregulation of hypothalamic-pituitary-adrenal axis functions in an Alzheimer’s disease rat model. Neurobiol Aging 34(5):1426–1439. https://doi.org/10.1016/j.neurobiolaging.2012.11.015

    Article  CAS  PubMed  Google Scholar 

  31. Pascualy M, Petrie EC, Brodkin K, Peskind ER, Wilkinson CW, Raskind MA (2000) Hypothalamic pituitary adrenocortical and sympathetic nervous system responses to the cold pressor test in Alzheimer’s disease. Biol Psychiatry 48(3):247–254. https://doi.org/10.1016/s0006-3223(00)00879-9

    Article  CAS  PubMed  Google Scholar 

  32. Royall DR, Gao JH, Kellogg DL Jr (2006) Insular Alzheimer’s disease pathology as a cause of “age-related” autonomic dysfunction and mortality in the non-demented elderly. Med Hypotheses 67(4):747–758. https://doi.org/10.1016/j.mehy.2005.10.036

    Article  PubMed  Google Scholar 

  33. Braak H, Braak E (1995) Staging of Alzheimer’s disease-related neurofibrillary changes. Neurobiol Aging 16(3):271–278. https://doi.org/10.1016/0197-4580(95)00021-6

    Article  CAS  PubMed  Google Scholar 

  34. Femminella GD, Rengo G, Komici K, Iacotucci P, Petraglia L, Pagano G, de Lucia C, Canonico V, Bonaduce D, Leosco D, Ferrara N (2014) Autonomic dysfunction in Alzheimer’s disease: tools for assessment and review of the literature. J Alzheimers Dis 42(2):369–377. https://doi.org/10.3233/jad-140513

    Article  PubMed  Google Scholar 

  35. Feldstein C, Weder AB (2012) Orthostatic hypotension: a common, serious and underrecognized problem in hospitalized patients. J Am Soc Hypertens 6(1):27–39. https://doi.org/10.1016/j.jash.2011.08.008

    Article  PubMed  Google Scholar 

  36. Van Beek AH, Claassen JA (2011) The cerebrovascular role of the cholinergic neural system in Alzheimer’s disease. Behav Brain Res 221(2):537–542. https://doi.org/10.1016/j.bbr.2009.12.047

    Article  CAS  PubMed  Google Scholar 

  37. Tong XK, Hamel E (1999) Regional cholinergic denervation of cortical microvessels and nitric oxide synthase-containing neurons in Alzheimer’s disease. Neuroscience 92(1):163–175. https://doi.org/10.1016/s0306-4522(98)00750-7

    Article  CAS  PubMed  Google Scholar 

  38. Cai Z, Wan C-Q, Ke Z, Chen Y (2018) Orthostatic Hypotension in Alzheimer’s disease: A Meta-Analysis. Neuropsychiatry 8(5):1655–1660

    Article  Google Scholar 

  39. Freidenberg DL, Shaffer LE, Macalester S, Fannin EA (2013) Orthostatic hypotension in patients with dementia: clinical features and response to treatment. Cogn Behav Neurol 26(3):105–120. https://doi.org/10.1097/wnn.0000000000000003

    Article  PubMed  Google Scholar 

  40. Sambati L, Calandra-Buonaura G, Poda R, Guaraldi P, Cortelli P (2014) Orthostatic hypotension and cognitive impairment: a dangerous association? Neurol Sci 35(6):951–957. https://doi.org/10.1007/s10072-014-1686-8

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Unit for Aging Brain and Dementia, Department of Geriatric Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey

    Ahmet Turan Isik, Neziha Erken, Derya Kaya & Fatma Sena Dost

  2. Department of Statistics, Faculty of Science, Dokuz Eylul University, Izmir, Turkey

    Idil Yavuz

  3. Department of Internal Medicine, Yusufeli State Hospital, Artvin, Turkey

    Mehmet Selman Ontan

  4. Department of Geriatric Medicine, Adana State Hospital, Adana, Turkey

    Esra Ates Bulut

Authors
  1. Ahmet Turan Isik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Neziha Erken
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Idil Yavuz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Derya Kaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mehmet Selman Ontan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Esra Ates Bulut
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fatma Sena Dost
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ahmet Turan Isik.

Ethics declarations

Ethical approval

None.

Conflict of interest

None.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 16 KB)

Supplementary file2 (PDF 118 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Isik, A.T., Erken, N., Yavuz, I. et al. Orthostatic hypotension in patients with Alzheimer’s disease: a meta-analysis of prospective studies. Neurol Sci 43, 999–1006 (2022). https://doi.org/10.1007/s10072-021-05450-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-021-05450-5

Keywords

Search

Navigation