Cerebral Blood Flow

Rationale: Healthy foods, including mixed nuts, may improve brain function, which is essential for cognitive and metabolic health, and may contribute to improved food intake regulation. It is therefore important to investigate the specific effects of walnuts on cerebral blood flow responses before and after intranasal insulin administration, as well as their associated functional benefits. The investigators hypothesize that long-term walnut consumption improves vascular function and insulin-sensitivity in the brain, thereby enhancing cognitive performance and appetite control in abdominally obese men and women. Objective: The primary objectives are to investigate in abdominally obese adults the effects of 24-week walnut consumption on (regional) vascular function and insulin-sensitivity in the brain, while the investigators will also assess changes in cognitive performance and appetite-related brain reward activity (secondary objectives). Cerebral blood flow responses before (brain vascular function) and after the administration of intranasal insulin spray (brain insulin-sensitivity) will be quantified by the non-invasive gold standard magnetic resonance imaging (MRI)-perfusion method Arterial Spin Labeling (ASL). Study design: This intervention study will have a randomized, controlled parallel design. The total study duration will be 24 weeks. Study population: Fifty-five abdominally obese men and (postmenopausal) women (aged 45-75 years) without a history of cardiovascular diseases or complaints will participate. This study population is expected to have a decreased cerebral blood flow at baseline and are also at increased risk of cognitive impairment, allowing for improvement by the intervention. Intervention: Study participants will receive daily 50 g (about 15% of energy) of raw walnuts (walnut intervention) or no walnuts (control intervention) for 24 weeks. Main study parameters/endpoints: At baseline and after 24 weeks (follow-up), participants will visit the research facilities for assessments. The primary endpoint is the difference in the cerebral blood flow response before and after intranasal insulin administration between the walnut and control intervention. Cognitive performance will be assessed, while the investigators will also focus on appetite-related brain reward activity (secondary outcomes).

This study aims to evaluate cerebral blood flow in stable term and preterm newborns using Doppler ultrasonography. By measuring and comparing PSV, EDV, RI, and PI in the main brain arteries, the study seeks to identify normal physiological differences in cerebral perfusion across different gestational ages. The main goal is to establish reference values that can guide clinical monitoring, allow early detection of blood flow problems, and improve neuroprotective care in newborns.

Due to historical exclusion of females from research, there are gaps in the understanding of female physiology, how it differs from males, and how sex-specific hormones contribute. As a result, many diagnoses and treatments are based on male physiology and may not be appropriate or effective for females. Females consistently experience greater risk and report worse neurological outcomes in many diseases, including stroke, cardiac arrest, and dementia. As research in females progresses, differences between sexes and changes throughout the lifespan (e.g., puberty, menopause) highlight the importance of understanding the effects of sex and sex-specific hormones on the body. The brain is arguably the most important organ in the body, consuming 20% of the body's total energy. Previous research supports higher blood flow to the brain in females, and research in animals suggests hormones such as estrogen, progesterone, and testosterone are responsible. However, it is extremely difficult to isolate these hormones in humans, due to natural fluctuations (i.e., menstrual cycle). Therefore, the investigators plan to explore the direct role of these sex-specific hormones in regulating blood flow to the brain by blocking hormone production in healthy males and females and giving back testosterone and estrogen, respectively. The investigators will then conduct a range of tests to look at blood flow to the brain at rest and during various stressors. This research will provide crucial insight into how males and females differ in regulation of brain blood flow and inform new treatments and therapies to a wide range of brain injuries and diseases, improving outcomes and reducing the sex disparity in clinical pathways.

The study aims to evaluate the safety, feasibility, and preliminary efficacy of six-month fasting-mimicking (FMD) relative to Dietary Guidance intervention in middle-aged adults at elevated risk for Alzheimer's disease due to the apolipoprotein (APOE) ε4 allele. Participants randomly assigned to the FMD intervention will consume a FMD for 5-days each month over a period of 6-months.

Disturbances in brain insulin sensitivity are associated not only with obesity and type 2 diabetes, but also with brain aging and cognitive decline. Longitudinal studies suggest that dietary patterns, particularly those high in dairy intake, may impact brain function via the gut-brain axis. Indeed, dairy foods are known to modulate gut microbiota and may, through this pathway, not only improve brain insulin sensitivity and cognitive performance, but also mental health and appetite regulation. However, underlying mechanisms remain largely unexplored. The primary objective of this study is to evaluate, in older adults with overweight or obesity, the effects of a high-dairy food pattern (4-5 daily servings of (butter)milk, cheese, yogurt, or cottage cheese) compared to a low-dairy food pattern (≤1 serving daily) on (regional) brain vascular function and insulin sensitivity. These outcomes will be quantified using the non-invasive MRI perfusion technique Arterial Spin Labeling (ASL), which assesses cerebral blood flow (CBF) in response to intranasal insulin, a validated physiological marker of brain insulin sensitivity. Secondary objectives include changes in cognitive performance (via the CANTAB neuropsychological test battery), gut microbiota composition (via shotgun metagenomic analysis of fecal samples), and appetite-related brain reward activity (via BOLD-fMRI with food cues). Exploratory analyses include conventional cardiometabolic risk markers (blood pressure, lipid and glucose metabolism), and perceivable (consumer) benefits.

This is a pilot study (small-scale study) that aims to understand more about how blood flow changes in people who have low blood sugar after bariatric surgery (post-bariatric hypoglycemia) compared to those who have had surgery without hypoglycemia, those who have hypoglycemia without surgery, or those who do not experience low blood sugar. This study has two phases. This is the first phase, and the purpose is to test comfort and feasibility of a novel in-ear wearable device (Lumia Health) that measures blood flow changes to the head. Information from the study will help the investigators determine if the device is suitable to be used in the second phase of the study.

Impaired brain vascular function precedes the development of reduced cognitive performance, while brain insulin-resistance is associated with cognitive decline. Evidence from epidemiological studies has already suggested beneficial effects of wild blueberry consumption on cognitive performance. However, underlying mechanisms have not yet been established, while well-controlled trials on longer-term effects of wild blueberries on cognitive performance are highly needed. This study hypothesizes that longer-term wild blueberry intake improves (regional) brain vascular function and insulin-sensitivity, thereby improving cognitive performance in older men and women. The primary objectives are to investigate in older adults the effect wild blueberry consumption on (regional) vascular function and insulin-sensitivity in the brain, and to focus on changes in cognitive performance as assessed with the CANTAB neuropsychological test battery (i.e., secondary objective). Cerebral blood flow responses before (brain vascular function) and after the administration of intranasal insulin spray (brain insulin-sensitivity) will be non-invasively quantified by the non-invasive gold standard magnetic resonance imaging (MRI)- perfusion method Arterial Spin Labeling (ASL).

Protein-rich foods may improve brain insulin-sensitivity, which is important for cognitive and metabolic health, and may also translate into an improved food intake regulation. It is therefore pertinent to delineate the effects of plant-derived proteins, which are a more sustainable alternative to animal-derived proteins, on brain insulin-sensitivity and related functional benefits. The hypothesis is that daily plant-derived or animal-derived protein supplementation improves brain vascular function and insulin-sensitivity, thereby improving cognitive performance and appetite control in overweight or obese older men and women. The primary objective is to investigate in overweight or obese older adults the effect of daily protein supplementation for two weeks with either a plant-derived protein or an animal-derived protein on vascular function and insulin-sensitivity in the brain, while changes in cognitive performance and appetite-related brain reward activity will also be evaluated (secondary study objectives). Cerebral blood flow responses before (brain vascular function) and after the administration of intranasal insulin spray (brain insulin-sensitivity) will be quantified by the gold standard magnetic resonance imaging (MRI)-perfusion method Arterial Spin Labeling (ASL).

During anesthesia, blood pressure-raising medications are often required to achieve an adequate blood pressure level. However, there is limited knowledge about what constitutes an adequate blood pressure to ensure sufficient blood flow to the brain. This project aims to map the relationship between blood pressure and brain blood flow using an MRI scanner. The results will contribute to a better understanding of this relationship and lead to improved management of brain blood flow during surgery on anesthetized patients. How does the project work? Day 1 Before planned surgery, participants will meet with an anesthesiologist for information and assessment. An MRI scan of the brain will be conducted while participants are awake. The MRI examination has no side effects or risks. The space inside the MRI scanner is tight, especially around the head. If discomfort is experienced, the examination will be stopped immediately. The machine is noisy, so hearing protection will be provided, and communication with staff will be possible throughout the examination. The scan takes approximately 30 minutes, during which participants only need to lie still and relax. Day 2 After planned surgery, an anesthesiologist and an anesthesia nurse will transfer participants to the MRI scanner while still under anesthesia. Participants will not be woken up between surgery and the MRI scan; instead, transportation will occur while still anesthetized, following standard hospital procedures. Participants will remain under the same anesthetic drugs as during the surgery. The same blood pressure-raising medication, norepinephrine, will be continuously used. No additional drugs, beyond those necessary for normal anesthesia, will be administered before the MRI examination. The entire project will take about 1.5 hours in addition to the surgery. If an arterial catheter (a blood pressure monitor via an artery in the wrist) is not already in place, one will be inserted while participants are asleep. Before the MRI examination: Baseline examination - If any abnormalities are detected, the scan will be stopped, and follow-up by a doctor will occur. Blood pressure increase - Blood pressure will be raised by approximately 30% (equivalent to mild physical activity, such as jogging). Follow-up scan at the higher blood pressure level. Blood pressure returns to normal. All blood pressure levels will remain within clinically acceptable ranges for anesthetized patients and will be regulated with the same medication as used during the surgery. After the MRI: Participants will be woken up in the anesthesia preparation room next to the MRI scanner. The arterial catheter will be removed before awakening. Participants will be transported to the postoperative unit for monitoring. The surgeon responsible for care will determine the discharge time. Possible Risks and Side Effects of Participation Transporting an anesthetized patient for an MRI scan outside the operating room carries some risks. However, the hospital has established procedures for daily transportation of anesthetized patients and a structured division of responsibilities to manage unexpected situations. Monitoring will be conducted by an experienced anesthesiologist and anesthesia nurse throughout the procedure. Routine monitoring includes blood pressure, heart rate, depth of anesthesia, and oxygen levels. No long-term effects have been observed from MRI scans or short-term anesthesia for these examinations. Most complications related to general anesthesia occur during induction or awakening, and these risks exist regardless of study participation. Study participation may slightly increase the risk of IV lines or breathing tubes becoming dislodged due to movement while anesthetized. A prolonged period under anesthesia may cause slight additional fatigue upon waking. To ensure understanding of the information about this study, participants will take a simple cognitive test (5 minutes) before surgery. If any unexpected complications arise during surgery, study participation will be discontinued. If the MRI scan reveals any abnormalities, referral to a neurologist or neurosurgeon for further evaluation will be provided. What Happens to Collected Data? The project will collect health information from medical records and MRI scans. All data will be pseudonymized (coded) so that it cannot be linked to individual participants. The key to decoding this information will be stored securely by the research nurse at the Neuro-Head-Neck Center (NHHC). Only authorized research personnel will have access to the pseudonymized data. Information will be protected in accordance with the General Data Protection Regulation (GDPR).