PET and MR imaging in Parkinson’s disease patients with cognitive impairment. A study of dopaminergic dysfunction, amyloid deposition, cortical hypometabolism and brain atrophy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. It is characterized by a severe loss of substantia nigra dopaminergic neurons leading to dopamine depletion in the striatum. PD affects movement, producing motor symptoms such as rigidity, tremor and bradykinesia. Non-motor symptoms include autonomic dysfunction, neurobehavioral problems and cognitive impairment, which may lead to dementia. The pathophysiological basis of cognitive impairment and dementia in PD is unclear. The aim of this thesis was to study the pathophysiological basis of cognitive impairment and dementia in PD. We evaluated the relation between frontostriatal dopaminergic dysfunction and the cognitive symptoms in PD patients with [18F]Fdopa PET. We also combined [C]PIB and [¹⁸F]FDG PET and magnetic resonance imaging in PD patients with and without dementia. In addition, we analysed subregional striatal [¹⁸F]Fdopa PET data to find out whether a simple ratio approach would reliably separate PD patients from healthy controls. The impaired dopaminergic function of the frontostriatal regions was related to the impairment in cognitive functions, such as memory and cognitive processing in PD patients. PD patients with dementia showed an impaired glucose metabolism but not amyloid deposition in the cortical brain regions, and the hypometabolism was associated with the degree of cognitive impairment. PD patients had atrophy, both in the prefrontal cortex and in the hippocampus, and the hippocampal atrophy was related to impaired memory. A single 15-min scan 75 min after a tracer injection seemed to be sufficient for separating patients with PD from healthy controls in a clinical research environment. In conclusion, the occurrence of cognitive impairment and dementia in PD seems to be multifactorial and relates to changes, such as reduced dopaminergic activity, hypometabolism, brain atrophy and rarely to amyloid accumulation.

Erectile dysfunction in cardiovascular risk population

The inability to achieve and to maintain erection, erectile dysfunction, is a bothersome symptom of elderly men. Moreover, there is a high comorbidity between cardiovascular diseases and erectile dysfunction. However, very little is known concerning the risk factors of ED in apparently healthy men without comorbidities affecting the arteries. A cross-sectional population survey was conducted from August 2005 to September 2007 in two rural towns of Harjavalta and Kokemäki in Finland. Excluding those with previously diagnosed cardiovascular diseases, diabetes or chronic kidney disease, every community-dwelling inhabitant was invited to take part in the survey. Of the 2939 45- to 70-year-old men invited, 2049 responded. Selecting those at risk for cardiovascular diseases, 1000 eligible men were examined. According to the International Index of Erectile Function short form 57% of the studied men reported erectile dysfunction. Increasing age, smoking, depressive symptoms, decreasing pulmonary function, sedentary lifestyle, non-marital status and low education level were associated with increasing risk of erectile dysfunction. However, hypertension, diabetes, obesity, hypercholesterolemia were not associated with erectile dysfunction, although these associations have been described in numerous previous studies. Moreover, erectile dysfunction was not associated with increasing risk of pre-diabetes. In apparently healthy men, increasing age, smoking, depressive symptoms, decreasing pulmonary function, sedentary lifestyle, non-marital status, low education level but not hypertension, obesity, hypercholesterolemia, diabetes or pre-diabetes were associated with increasing risk of erectile dysfunction.

Cardiac Imaging in the Diagnosis of Coronary Artery Disease: The Value of Quantitative Imaging of Myocardial Perfusion and Deformation

Atherosclerosis is a chronic and progressive disease of the vasculature. Increasing coronary atherosclerosis can lead to obstructive coronary artery disease (CAD) or myocardial infarction. Computed tomography angiography (CTA) allows noninvasive assessment of coronary anatomy and quantitation of atherosclerotic burden. Myocardial blood flow (MBF) can be accurately measured in absolute terms (mL/g/min) by positron emission tomography (PET) with [15O] H O as a radiotracer. We studied the coronary microvascular dysfunction as a risk factor for future coronary calcification in healthy young men by measuring the coronary flow reserve (CFR) which is the ratio between resting and hyperemic MBF. Impaired vasodilator function was not linked with accelerated atherosclerosis 11 years later. Currently, there is a global interest in quantitative PET perfusion imaging. We established optimal thresholds of [15O] H O PET perfusion for diagnosis of CAD (hyperemic MBF of 2.3 mL/g/min and CFR of 2.5) in the first multicenter study of this type (Turku, Amsterdam and Uppsala). In myocardial bridging a segment of the coronary artery travels inside the myocardium and can be seen as intramural course (CTA) or systolic compression (invasive coronary angiography). Myocardial bridging is frequently linked with proximal atherosclerotic plaques. We used quantitative [15O] H O PET perfusion to evaluate the hemodynamic effects of myocardial bridging. Myocardial bridging was not associated with decreased absolute MBF or increased atherosclerotic burden. Speckle tracking allows quantitative echocardiographic imaging of myocardial deformation. Speckle tracking during dobutamine stress echocardiography was feasible and comparable to subjective wall motion analysis in the diagnosis of CAD. In addition, it correctly risk stratified patients with multivessel disease and extensive ischemia.