Ageing Brain and Cognition/Circulation pipeline
Focus
The focus of this pipeline is on brain research with a strong link to aging, cognition and circulation. Research topics within this pipeline are dementia, cerebral small vessel disease, glymphatic imaging and the heart-brain connection.
Studies
Imaging studies
Ongoing clinical studies within this pipeline are the heart-brain connection study, the WHIMAS study, the COPE study, the currently in preparation IMDEM study/trial and also includes collaborations with the AGES-Reykjavic consortium. This pipeline also has close links to the Medical Delta 2.0 dementia and stroke consortium and the new Medical Delta 3.0 Advanced imaging for diagnosis and prediction of dementia consortium (collaborations between LUMC, Erasmus MC and TU Delft; Medical Delta Programma ‘Geavanceerde beeldvorming voor diagnose en predictie van dementie’ | Medical Delta), which will leverage knowledge on new brain MRI technologies and brain MRI AI implementations for early risk assessment for cognitive decline and dementia. This pipeline involves collaborations between the departments of cardiology, general practice, geriatrics, nephrology, neurology, psychiatry, and radiology (alphabetic order).
Pre-clinical and post-mortem studies include animal models of dementia and cerebral small vessel disease and pathological hallmarks and biomarkers of aging, cognition and circulation.
Benefits and risks of high blood pressure in older people
The benefits and risks of high blood pressure in old age: challenging observational and interventional data.
Results of observational studies, in short
- In the Leiden 85-plus Study, an observational population-based prospective follow-up study of the oldest old, we showed that a lower blood pressure predicts a higher mortality over 5 years. This is a contrasting finding compared to the adult population.
- In indepth analyses in the Leiden 85-plus Study, we showed that the mortality risk, risk of decline in (cognitive) function and falling is highest in those with low blood pressure under anti-hypertensive treatment.
- Similar observational relations were found in the TULIP-consortium, a collaboration of cohort studies of oldest old populations from United Kingdom, Japan and New Zealand.
- In a systematic review of guidelines, we showed that starting treatment with antihypertensive medication varies over guidelines, as do the target values of treatment depending on age.
- We showed that GPs advised differently about starting anti-hypertensive medication in older patients in absence of clear guidelines.
Results of intervention studies, in short
- In the DANTE study (2015), a randomised controlled trial, we found that a 12 weeks deprescribing of antihypertensive medication in community-dwelling older persons with mild cognitive impairment did not improve quality of life or cognitive function.
In the DANTON study (2024), a randomised controlled trial, we found that an 18 weeks deprescribing of antihypertensive medication in older persons with dementia living in nursing homes did not improve neuropsychiatric symptoms and quality of life. In contrast, the risk of negative effects was higher in those who reduced their dose of anti-hypertensive medication. At 36 weeks, these effects continued.
Key references
Imaging studies
- Is CAA a perivascular brain clearance disease? A discussion of the evidence to date and outlook for future studies. (, 2024)
- Identification of Distinct Brain MRI Phenotypes and Their Association With Long-Term Dementia Risk in Community-Dwelling Older Adults (, 2024)
- White matter hyperintensity shape is associated with long-term dementia risk. (, 2023)
- Iron loading is a prominent feature of activated microglia in Alzheimer’s disease patients. (, 2021)
- Drenth N, Foster-Dingley JC, Bertens AS, Rius Ottenheim N, van der Mast RC, Rombouts SARB, van Rooden S, van der Grond J. Functional connectivity in older adults-the effect of cerebral small vessel disease. Brain Commun. 2023 Apr 19;5(3):fcad126. doi: 10.1093/braincomms/fcad126. eCollection 2023.
- Drenth N, van Dijk SE, Foster-Dingley JC, Bertens AS, Rius Ottenheim N, van der Mast RC, Rombouts SARB, van Rooden S, van der Grond J. Distinct functional subnetworks of cognitive domains in older adults with minor cognitive deficits. Brain Commun. 2024 Feb 15;6(1):fcae048. doi: 10.1093/braincomms/fcae048. eCollection 2024.
PMID: 38419735
Blood pressure and cognition
Observational studies
Poortvliet RK, Blom JW, de Craen AJ, Mooijaart SP, Westendorp RG, Assendelft WJ, Gussekloo J, de Ruijter W. Low blood pressure predicts increased mortality in very old age even without heart failure: the Leiden 85-plus Study. Eur J Heart Fail. 2013 May;15(5):528-33. doi: 10.1093/eurjhf/hfs203. Epub 2012 Dec 17.
Streit S, Poortvliet RKE, Gussekloo J. Lower blood pressure during antihypertensive treatment is associated with higher all-cause mortality and accelerated cognitive decline in the oldest-old. Data from the Leiden 85-plus Study. Age Ageing. 2018 Jul 1;47(4):545-550. doi: 10.1093/ageing/afy072. https://academic.oup.com/ageing/article/47/4/545/4993723?login=true
Streit S, Poortvliet RKE, Elzen WPJD, Blom JW, Gussekloo J. Systolic Blood Pressure and Cognitive Decline in Older Adults With Hypertension. Ann Fam Med. 2019 Mar;17(2):100-107. doi: 10.1370/afm.2367. https://www.annfammed.org/content/17/2/100.long
Röthlisberger D, Jungo KT, Bütikofer L, Poortvliet RKE, Gussekloo J, Streit S. Association of low blood pressure and falls: An analysis of data from the Leiden 85-plus Study. PLoS One 2023;18:e0295976. doi: 10.1371/journal.pone.0295976. eCollection 2023. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0295976
Bogaerts JMK, Poortvliet RKE, van der Klei VMGTH, Achterberg WP, Blom JW, Teh R, Muru-Lanning M, Kerse N, Rolleston A, Jagger C, Kingston A, Robinson L, Arai Y, Shikimoto R, Gussekloo J; TULIPS Consortium. Disentangling the varying associations between systolic blood pressure and health outcomes in the very old: an individual patient data meta-analysis. J Hypertens. 2022 Sep 1;40(9):1786-1794. doi: 10.1097/HJH.0000000000003219. Epub 2022 Jul 11. https://journals.lww.com/jhypertension/fulltext/2022/09000/disentangling_the_varying_associations_between.19.aspx
Bogaerts JMK, von Ballmoos LM, Achterberg WP, Gussekloo J, Streit S, van der Ploeg MA, Drewes YM, Poortvliet RKE. Do we AGREE on the targets of antihypertensive drug treatment in older adults: a systematic review of guidelines on primary prevention of cardiovascular diseases. Age Ageing. 2022 Jan 6;51(1):afab192. doi: 10.1093/ageing/afab192.
Roulet C, Rozsnyai Z, Jungo KT, A van der Ploeg M, Floriani C, Kurpas D, Vinker S, Kreitmayer Pestic S, Petrazzuoli F, Hoffmann K, Viegas RPA, Mallen C, Tatsioni A, Maisonneuve H, Collins C, Lingner H, Tsopra R, Mueller Y, Poortvliet RKE, Gussekloo J, Streit S. Managing hypertension in frail oldest-old-The role of guideline use by general practitioners from 29 countries. PLoS One. 2020 Jul 10;15(7):e0236064. doi: 10.1371/journal.pone.0236064. eCollection 2020. PMID: 32649727. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236064
de Jong-Schmit BEM, Poortvliet RKE, Böhringer S, Bogaerts JMK, Achterberg WP, Husebo BS. Blood pressure, antihypertensive medication and neuropsychiatric symptoms in older people with dementia: The COSMOS study. Int J Geriatr Psychiatry. 2021 Jan;36(1):46-53. doi: 10.1002/gps.5388. Epub 2020 Oct 8. https://onlinelibrary.wiley.com/doi/10.1002/gps.5388
Intervention studies
Moonen JE, Foster-Dingley JC, de Ruijter W, van der Grond J, Bertens AS, van Buchem MA, Gussekloo J, Middelkoop HA, Wermer MJ, Westendorp RG, de Craen AJ, van der Mast RC. Effect of Discontinuation of Antihypertensive Treatment in Elderly People on Cognitive Functioning–the DANTE Study Leiden: A Randomized Clinical Trial. JAMA Intern Med. 2015 Oct;175(10):1622-30. doi: 10.1001/jamainternmed.2015.4103. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2429535
Bogaerts JMK, Gussekloo J, de Jong-Schmit BEM, Le Cessie S, Mooijaart SP, van der Mast RC, Achterberg WP, Poortvliet RKE. Effects of the discontinuation of antihypertensive treatment on neuropsychiatric symptoms and quality of life in nursing home residents with dementia (DANTON): a multicentre, open-label, blinded-outcome, randomised controlled trial. Age Ageing. 2024 Jul 2;53(7):afae133. doi: 10.1093/ageing/afae133. https://pmc.ncbi.nlm.nih.gov/articles/PMC8753036/