Test of Reproducibility of [15O]H20-PET Assessment of Brain Perfusion

Small Vessel Disease of the Brain and Heart: a Perfusion PET Study of Training Effects

In the aging population, ischemic heart disease, stroke and dementia are increasingly prevalent. Diagnosis and treatment of the former two i.e., large-vessel coronary heart disease and endovascular thrombectomy of the brain in relation to stroke have improved significantly. Yet, the majority of elderly patients with ischemic heart disease do not have large-vessel heart disease and it seems that small vessel disease (SVD) may explain a large fraction of these cases as well as the cardiovascular morbidity in the elderly. Hence, the current development in diagnostics and treatments of ischemic heart disease does not address the most common subtype of ischemic disease seen in elderly patients.

It has been suggested that SVD is part of a multisystem disorder and several systematic reviews have addressed the hypothesis of a potential link between small vessel disease of the heart, brain, and kidneys. Cerebral SVD is prevalent in the aging population causing cognitive impairment, dementia, and an increased risk of stroke, and cerebral hypoperfusion is an acknowledged cause of vascular dementia and a possible cause of Alzheimer's disease. Further, cognitive impairment within multiple cognitive domains is highly prevalent in heart failure and is associated to an increased risk of dementia. The link between heart failure and dementia may be due to multisystem SVD, although a direct link between the two is possible.

Among other known risk factors such as age, hypertension, and female sex, diabetes is a major cause of SVD and is linked to coronary heart disease as well as cognitive impairment. The diagnosis of cerebral SVD relies on MRI detecting infarctions, haemorrhages, microbleeds and ischemic white matter changes, i.e. Fazekas score. In contrast, perfusion PET is used to image myocardial perfusion in patients with coronary SVD; and coronary SVD is recognized as a part of the pathophysiology in angina, coronary artery disease, and heart failure. Perfusion PET before and after adenosine-induced vasodilation allows for measuring, the myocardial flow reserve (MFR), i.e. perfusion capacity, which in the absence of regional perfusion defects, is a measure of coronary SVD. Prof. Eva Prescott have recently shown that reduced MFR obtained by 82Rb PET is a strong predictor of future microvascular events and all-cause mortality.

Exercise is well known to improve cognitive health but professor Carl-Johan Boraxbekk has shown that the effect on cognitive performance may be dependent on the initial cerebrovascular status, as patients with moderate to severe white matter changes did not improve after a 6 months physical activation intervention in contrast to patients with mild changes. Yet, it is possible to improve brain function in diabetic patients through either dietary or exercise interventions.

Systemic SVD is measured as cerebral SVD (reduced brain perfusion during acetazolamide-induced vasodilation) and coronary SVD (reduced heart perfusion during adenosine-induced vasodilation). The researchers anticipate that patients with type 2 dabetes have reduced perfusion capacity of the brain and heart correlating to reduced cognition and cardiorespiratory fitness (VO2-max).

The researchers wish to test how large the variance of their measurements of blood perfusion to the brain is in healthy participants when performing 2 identical examinations within 7 days of each other.

To adress this aim the researchers have defined the following assumption that they will refute or confirm through their study:

- PET-perfusion measurements at their department have a high reproducibility.

8 healthy participants over 60 years will undergo a [15O]H2O-PET scan in order to assess the blood perfusion capacity of the brain.

Within 7 days, the 8 healthy participants will undergo an additional [15O]H2O-PET scan assessing the blood perfusion capacity of the brain.

Afterwards the researchers will quantify the variance in their [15O]H2O-PET scan in the same individuals within a 7-day time window.

Inclusion Criteria:

• Age > 60 years
• No diagnosis of T2D according to WHO's criteria.
• Speaks and understands Danish (required for reliable cognitive testing)
• Able to provide informed and written consent

Exclusion Criteria:

• Moderate to high intensity training >2 times/week.
• Previous AMI, atrial fibrillation, significant cardiac valve disease, HFrEF (LVEF <45%), asthma.
• Previous stroke or significant neurological disease including cognitive dysfunction.
• Ongoing depression.
• Hypothyroidism
• Unable or unwilling to participate in training, e.g., due to injury, arthrosis or lung disease.