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BACKGROUND AND PURPOSE: Both cerebral hypoperfusion and vascular risk factors have been implicated in early aging of the brain and the development of neurodegenerative disease. However, the current knowledge of the importance of cardiovascular health on resting brain perfusion is limited. The aim of the present study was to elucidate the relation between brain perfusion variability and risk factors of endothelial dysfunction and atherosclerosis in healthy aged subjects.METHODS: Thirty-eight healthy subjects aged 50-75 years old were included. Mean global brain perfusion was measured using magnetic resonance phase contrast mapping and regional brain perfusion by use of arterial spin labeling.RESULTS: Mean global brain perfusion was inversely correlated with caffeine and hematocrit, and positively with end-tidal PCO2. Furthermore, the mean global brain perfusion was inversely correlated with circulating homocysteine, but not with asymmetric dimethylarginine, dyslipidemia or the carotid intima-media thickness. The relative regional brain perfusion was associated with circulating homocysteine, with a relative parietal hypoperfusion and a frontal hyperperfusion. No effect on regional brain perfusion was observed for any of the other risk factors. A multiple regression model including homocysteine, caffeine, hematocrit and end-tidal PCO2, explained nearly half of the observed variability.CONCLUSION: Both intrinsic and extrinsic factors influenced global cerebral perfusion variation between subjects. Further, the results suggest that the inverse relation between homocysteine and brain perfusion is owing to other mechanisms, than reflected by asymmetric dimethylarginine, and that homocysteine may be a marker of cerebral perfusion in aging brains.

Although both impaired cardiac function and reduced cerebral blood flow are associated with ageing, current knowledge of the influence of cardiac function on resting cerebral blood flow (CBF) is limited. The aim of this study was to investigate the potential effects of cardiac function on CBF. CBF and cardiac output were measured in 31 healthy subjects 50-75 years old using magnetic resonance imaging techniques. Mean values of CBF, cardiac output and cardiac index were 43.6 ml per 100 g min(-1), 5.5 l min(-1) and 2.7 l min(-1) m(-2), respectively, in males, and 53.4 ml per 100 g min(-1), 4.3 l min(-1) and 2.4 l min(-1) m(-2), respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r(2) = 0.22, P = 0.008) and furthermore lower in males than in females (8.6% versus 12.5%, P = 0.003). Fractional brain flow was also inversely correlated with cerebral white matter lesion grade, although this effect was not significant when adjusted for age. Frequency analysis of heart rate variability showed a gender-related inverse association of increased low-to-high-frequency power ratio with CBF and fractional brain flow. The findings do not support a direct effect of cardiac function on CBF, but demonstrates gender-related differences in cardiac output distribution. We propose fractional brain flow as a novel index that may be a useful marker of adequate brain perfusion in the context of ageing as well as cardiovascular disease.

OBJECTIVE: The aim of this study was to investigate the extent of motor cortical functional reorganisation in patients with SPG4-linked hereditary spastic paraplegia by exploring cortical motor activation related to movements of clinically affected (lower) and unaffected (upper) limbs. METHODS: Thirteen patients and 13 normal controls matched for age, gender and handedness underwent O15-labelled water positron emission tomography during (1) right ankle flexion-extension, (2) right shoulder flexion-extension and (3) rest. Within-group comparisons of movement vs. rest (simple main effects) and between-group comparisons of movement vs. rest (group x behavioural state interaction) were performed using a random effects approach and statistical parametric mapping (SPM99). RESULTS: Patterns of motor activation were generally comparable between groups during both tasks, although patients had a tendency towards more widespread activation in sensorimotor cortical and cerebellar regions. Statistically significant differences were restricted to the ankle movement response, however, where patients showed significantly increased regional cerebral blood flow in the right and left primary motor cortices, the supplementary motor areas and the right premotor cortex compared to controls. CONCLUSIONS: Motor cortical reorganisation may explain this result, but as no significant differences were recognised in the motor response of the unaffected limb, differences in functional demands should also be considered

Udgivelsesdato: 2005-Aug-15, Hereditary spastic paraplegia (HSP) linked to the spastic gait gene 4 (SPG4) is controversial, as the "pure" form traditionally has been considered confined to the long axons of the spinal cord. However, recent immunolabeling experiments have demonstrated extensive Spastin expression in the cortex and striatum. This could indicate a more widespread neuropathology from mutations in the SPG4 gene than previously assumed. The aim of this study was therefore to ascertain the extent of cerebral involvement in SPG4 linked HSP by neuropsychological examination and measurement of the regional cerebral blood flow (rCBF) as an indirect marker of regional neuronal activity. Eighteen SPG4 patients and 18 matched control subjects were studied. Resting state rCBF was measured using Positron Emission Tomography (PET) and the (15)O-labelled water bolus technique and relative group differences were explored using Statistical Parametric Mapping (SPM 99). Neuropsychological assessment was performed using established and nationally validated tests (RH Basic Battery). Compared to healthy controls, the patient group had significantly decreased rCBF in the left fronto-temporal cortex (P<0.05), and more extensive changes were observed in a separate analysis of the most disabled individuals. The neuropsychological assessment revealed only significantly impaired recognition memory for faces. In summary, the findings support cerebral pathology in SPG4-linked HSP, although the decreased rCBF in fronto-temporal cortex was not associated with severe cognitive impairment.