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. (van Veluw SJ et al., 2024)
• Distinct functional subnetworks of cognitive domains in older adults with minor cognitive deficits. (Drenth N et al., 2024)
• Identification of Distinct Brain MRI Phenotypes and Their Association With Long-Term Dementia Risk in Community-Dwelling Older Adults (Keller JA et al., 2024)
• White matter hyperintensity shape is associated with long-term dementia risk. (Keller JA et al., 2023)
• Functional connectivity in older adults-the effect of cerebral small vessel disease. (Drenth N et al., 2023)
• Iron loading is a prominent feature of activated microglia in Alzheimer’s disease patients. (Kenkhuis B et al., 2021)

Blood pressure and cognition

Observational studies

• Association of low blood pressure and falls: An analysis of data from the Leiden 85-plus Study. (Röthlisberger D et al., 2023)
• Disentangling the varying associations between systolic blood pressure and health outcomes in the very old: an individual patient data meta-analysis. (Bogaerts JMK et al., 2022)
• Do we AGREE on the targets of antihypertensive drug treatment in older adults: a systematic review of guidelines on primary prevention of cardiovascular diseases. (Bogaerts JMK et al., 2022)
• Blood pressure, antihypertensive medication and neuropsychiatric symptoms in older people with dementia: The COSMOS study. (de Jong-Schmit BEM et al., 2021)
• Managing hypertension in frail oldest-old-The role of guideline use by general practitioners from 29 countries. (Roulet C et al., 2020)
• Systolic Blood Pressure and Cognitive Decline in Older Adults With Hypertension. (Streit S, Poortvliet RKE, Elzen WPJD, Blom JW, & Gussekloo J, 2019)
• 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. (Streit S, Poortvliet RKE, & Gussekloo J, 2018)
• Low blood pressure predicts increased mortality in very old age even without heart failure: the Leiden 85-plus Study. (Poortvliet RK et al., 2013)

Intervention studies

• 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. (Bogaerts JMK et al., 2024)
• Effect of Discontinuation of Antihypertensive Treatment in Elderly People on Cognitive Functioning–the DANTE Study Leiden: A Randomized Clinical Trial. (Moonen JE et al., 2015)