Small vessel blood pulsatility on 7T MRI relates to cognitive performance in memory clinic patients
Poster No:
2108
Submission Type:
Abstract Submission
Authors:
Merel van der Thiel1, Marieke van den Kerkhof1, Alida Postma1, Inez Ramakers2, Walter Backes1, Jacobus Jansen1
Institutions:
1Maastricht University Medical Center, Maastricht, Netherlands, 2Maastricht University, Maastricht, Netherlands
First Author:
Co-Author(s):
Introduction:
Alzheimer's disease (AD) and aging have been linked to altered cerebral hemodynamics [1]. However, studies have only focused on large intracranial vessels, due to challenges in spatiotemporal resolution. Ultra-high field MRI (7T) enables measurement of blood flow velocity waveforms in small arteries and the assessment of pulsatility damping from large to small vessels [2].
The lenticulostriate arteries (LSAs), branching from the middle cerebral artery (MCA), are of particular interest due to their vulnerability to damage. The LSAs supply the basal ganglia (BG), essential for executive functioning (EF) [3] and information processing speed (IPS) [4]. They are also vital for clearing metabolic waste (e.g., amyloid beta) through perivascular waste clearance (e.g., glymphatic), driven by the rhythmic motion of vessel walls [5]. Altered blood pulsatility can impair this clearance, potentially exacerbating cognitive decline.
This study examined the relationship between blood pulsatility in the LSAs and MCA, their respective damping factor (DF), and cognitive performance in cognitively healthy elderly and memory clinic patients.
The lenticulostriate arteries (LSAs), branching from the middle cerebral artery (MCA), are of particular interest due to their vulnerability to damage. The LSAs supply the basal ganglia (BG), essential for executive functioning (EF) [3] and information processing speed (IPS) [4]. They are also vital for clearing metabolic waste (e.g., amyloid beta) through perivascular waste clearance (e.g., glymphatic), driven by the rhythmic motion of vessel walls [5]. Altered blood pulsatility can impair this clearance, potentially exacerbating cognitive decline.
This study examined the relationship between blood pulsatility in the LSAs and MCA, their respective damping factor (DF), and cognitive performance in cognitively healthy elderly and memory clinic patients.
Methods:
Subjects: Seventeen patients (ten with subjective cognitive decline, two with mild cognitive impairment, and five with AD dementia)(7F, age (mean±sd)=67±16y) and 34 cognitively healthy controls (20F, age=67±11y) were included in this study.
MRI acquisition: All subjects underwent 7T MRI (Magnetom, Siemens Healthineers). A prospective cardiac-gated 2D phase contrast (PC) sequence measured LSA velocity, followed by a perpendicular PC sequence targeting the MCA ipsilateral to the largest LSA (Fig.1).
Image analysis: After correcting for background noise and aliasing, the voxel with the highest mean velocity over one cardiac cycle was analyzed (Fig.1) [2]. Pulsatility indices (PI) were calculated using Gosling's equation [6]: PI=(vmax-vmin)/vmean, where v represents velocity. Additionally, the DF=PI MCA/PI LSA.
Neuropsychological assessment: Raw neuropsychological test scores were converted to age-, sex-, and education-adjusted z-scores using normative data. Domain scores for IPS, EF, and memory were averaged into a global cognition z-score and analyzed separately. Episodic memory was assessed via the 15-Word Learning Test [7]. IPS was measured with the Letter Digit Substitution Test [8], and EF with the interference scores of the Trail Making Test and Stroop Color Word Test [9] .
Statistics: Partial Spearman's rank-order correlations between MCA and LSA PIs, DFs, and global cognition z-scores were computed for both groups, adjusting for age and sex (IBM SPSS v25). These analyses were repeated for the specific cognitive domains.
MRI acquisition: All subjects underwent 7T MRI (Magnetom, Siemens Healthineers). A prospective cardiac-gated 2D phase contrast (PC) sequence measured LSA velocity, followed by a perpendicular PC sequence targeting the MCA ipsilateral to the largest LSA (Fig.1).
Image analysis: After correcting for background noise and aliasing, the voxel with the highest mean velocity over one cardiac cycle was analyzed (Fig.1) [2]. Pulsatility indices (PI) were calculated using Gosling's equation [6]: PI=(vmax-vmin)/vmean, where v represents velocity. Additionally, the DF=PI MCA/PI LSA.
Neuropsychological assessment: Raw neuropsychological test scores were converted to age-, sex-, and education-adjusted z-scores using normative data. Domain scores for IPS, EF, and memory were averaged into a global cognition z-score and analyzed separately. Episodic memory was assessed via the 15-Word Learning Test [7]. IPS was measured with the Letter Digit Substitution Test [8], and EF with the interference scores of the Trail Making Test and Stroop Color Word Test [9] .
Statistics: Partial Spearman's rank-order correlations between MCA and LSA PIs, DFs, and global cognition z-scores were computed for both groups, adjusting for age and sex (IBM SPSS v25). These analyses were repeated for the specific cognitive domains.
· Fig 1. Example images and acquisition parameters of the time-of-flight (A) with MCA, the MIPs (B) for LSA planning and (C) largest LSA used for ipsilateral MCA phase-contrast MRI planning.
Results:
In patients, lower DF correlated with lower global cognition z-scores, and lower EF and memory scores. No other significant associations were observed (Fig.2).
·Fig 2. Associations between damping factor and global cognition (A1-B1), information processing speed (IPS)(A2-B2), executive functioning (EF)(A3-B3) and memory (A4-B4), with example profiles (C-D).
Conclusions:
This study found that less damping of intracerebral blood pulsations is associated with lower global cognition, EF and memory function in memory clinic patients.
This suggests that vascular stiffness may contribute to cognitive decline through stronger - i.e., insufficiently damped - blood flow pulsations from the MCA to LSAs, leading to capillary damage, reduced perfusion and impaired BG-localized cognitive processes [11]. This disruption may also damage surrounding tissue, resulting in enlarged PVS [2]. Furthermore, it may impede waste clearance mechanisms located at the small vessel level, exacerbating cognitive decline through toxic protein buildup. Enlarged PVS can further hinder waste removal, creating a cycle of fluid obstruction and PVS expansion.
These findings were observed only in memory clinic patients, indicating this process is characteristic of patients with presumed AD pathology and distinct from healthy aging. This shows that unique mechanisms involving the hemodynamics affect cognitive performance in memory clinic patients.
This suggests that vascular stiffness may contribute to cognitive decline through stronger - i.e., insufficiently damped - blood flow pulsations from the MCA to LSAs, leading to capillary damage, reduced perfusion and impaired BG-localized cognitive processes [11]. This disruption may also damage surrounding tissue, resulting in enlarged PVS [2]. Furthermore, it may impede waste clearance mechanisms located at the small vessel level, exacerbating cognitive decline through toxic protein buildup. Enlarged PVS can further hinder waste removal, creating a cycle of fluid obstruction and PVS expansion.
These findings were observed only in memory clinic patients, indicating this process is characteristic of patients with presumed AD pathology and distinct from healthy aging. This shows that unique mechanisms involving the hemodynamics affect cognitive performance in memory clinic patients.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 2
Lifespan Development:
Aging
Novel Imaging Acquisition Methods:
Imaging Methods Other
Physiology, Metabolism and Neurotransmission:
Cerebral Metabolism and Hemodynamics 1
Physiology, Metabolism and Neurotransmission Other
Keywords:
Aging
ANGIOGRAPHY
Blood
Cerebral Blood Flow
Cerebrovascular Disease
Cognition
Degenerative Disease
HIGH FIELD MR
Memory
Other - arterial stiffness; memory clinic patients
1|2Indicates the priority used for review
Abstract Information
By submitting your proposal, you grant permission for the Organization for Human Brain Mapping (OHBM) to distribute your work in any format, including video, audio print and electronic text through OHBM OnDemand, social media channels, the OHBM website, or other electronic publications and media.
The Open Science Special Interest Group (OSSIG) is introducing a reproducibility challenge for OHBM 2025. This new initiative aims to enhance the reproducibility of scientific results and foster collaborations between labs. Teams will consist of a “source” party and a “reproducing” party, and will be evaluated on the success of their replication, the openness of the source work, and additional deliverables. Click here for more information. Propose your OHBM abstract(s) as source work for future OHBM meetings by selecting one of the following options:
Please indicate below if your study was a "resting state" or "task-activation” study.
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Was this research conducted in the United States?
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.
Please indicate which methods were used in your research:
For human MRI, what field strength scanner do you use?
Which processing packages did you use for your study?
Provide references using APA citation style.
2. van den Kerkhof, M., et al. Impaired damping of cerebral blood flow velocity pulsatility is associated with the number of perivascular spaces as measured with 7T MRI. Journal of Cerebral Blood Flow & Metabolism, 0271678X231153374 (2023).
3. Monchi, O., Petrides, M., Strafella, A.P., Worsley, K.J. & Doyon, J. Functional role of the basal ganglia in the planning and execution of actions. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society 59, 257-264 (2006).
4. Houk, J.C. Information processing in modular circuits linking basal ganglia and cerebral cortex. (1994).
5. Iliff, J.J., et al. Cerebral Arterial Pulsation Drives Paravascular CSF–Interstitial Fluid Exchange in the Murine Brain. The Journal of Neuroscience 33, 18190-18199 (2013).
6. Gosling, R. & King, D. The role of measurement in peripheral vascular surgery: arterial assessment by Doppler-shift ultrasound. (SAGE Publications, 1974).
7. Van Der Elst, W., Van Boxtel, M.P., Van Breukelen, G.J. & Jolles, J. Rey's verbal learning test: normative data for 1855 healthy participants aged 24–81 years and the influence of age, sex, education, and mode of presentation. Journal of the International Neuropsychological Society 11, 290-302 (2005).
8. Van der Elst, W., van Boxtel, M.P., van Breukelen, G.J. & Jolles, J. The Letter Digit Substitution Test: normative data for 1,858 healthy participants aged 24–81 from the Maastricht Aging Study (MAAS): influence of age, education, and sex. Journal of clinical and experimental neuropsychology 28, 998-1009 (2006).
9. Van der Elst, W., Van Boxtel, M.P., Van Breukelen, G.J. & Jolles, J. The Stroop color-word test: influence of age, sex, and education; and normative data for a large sample across the adult age range. Assessment 13, 62-79 (2006).
10. Van der Elst, W., Van Boxtel, M.P., Van Breukelen, G.J. & Jolles, J. The concept shifting test: Adult normative data. Psychological assessment 18, 424 (2006).
11. Terada, S., et al. Trail making test B and brain perfusion imaging in mild cognitive impairment and mild Alzheimer's disease. Psychiatry Research: Neuroimaging 213, 249-255 (2013).