Cortisol, cognition and the ageing prefrontal cortex

The structural and functional decline of the ageing human brain varies by brain region, cognitive function and individual. The underlying biological mechanisms are poorly understood. One potentially important mechanism is exposure to glucocorticoids (GCs; cortisol in humans); GC production is increasingly varied with age in humans, and chronic exposure to high levels is hypothesised to result in cognitive decline via cerebral remodelling. However, studies of GC exposure in humans are scarce and methodological differences confound cross-study comparison. Furthermore, there has been little focus on the effects of GCs on the frontal lobes and key white matter tracts in the ageing brain. This thesis therefore examines relationships among cortisol levels, structural brain measures and cognitive performance in 90 healthy, elderly community-dwelling males from the Lothian Birth Cohort 1936. Salivary cortisol samples characterised diurnal (morning and evening) and reactive profiles (before and after a cognitive test battery). Structural variables comprised Diffusion Tensor Imaging measures of major brain tracts and a novel manual parcellation method for the frontal lobes. The latter was based on a systematic review of current manual methods in the context of putative function and cytoarchitecture. Manual frontal lobe brain parcellation conferred greater spatial and volumetric accuracy when compared to both single- and multi-atlas parcellation at the lobar level. Cognitive ability was assessed via tests of general cognitive ability, and neuropsychological tests thought to show differential sensitivity to the integrity of frontal lobe sub-regions. The majority of, but not all frontal lobe test scores shared considerable overlap with general cognitive ability, and cognitive scores correlated most consistently with the volumes of the anterior cingulate. This is discussed in light of the diverse connective profile of the cingulate and a need to integrate information over more diffuse cognitive networks according to proposed de-differentiation or compensation in ageing. Individuals with higher morning, evening or pre-test cortisol levels showed consistently negative relationships with specific regional volumes and tract integrity. Participants whose cortisol levels increased between the start and end of cognitive testing showed selectively larger regional volumes and lower tract diffusivity (correlation magnitudes <.44). The significant relationships between cortisol levels and cognition indicated that flatter diurnal slopes or higher pre-test levels related to poorer test performance. In contrast, higher levels in the morning generally correlated with better scores (correlation magnitudes <.25). Interpretation of all findings was moderated by sensitivity to type I error, given the large number of comparisons conducted. Though there were limited candidates for mediation analysis, cortisol-function relationships were partially mediated by tract integrity (but not sub-regional frontal volumes) for memory and post-error slowing. This thesis offers a novel perspective on the complex interplay among glucocorticoids, cognition and the structure of the ageing brain. The findings suggest some role for cortisol exposure in determining age-related decline in complex cognition, mediated via brain structure

99mTc pertechnetate scintigraphy and premedication for the search for ectopic gastric mucosa in Meckel's diverticulum.

BACKGROUND: Meckel's diverticulum (MD) is the most common anomaly of the large intestinal tract (1-3%) and is more frequent in children (62% < 2 years) and in males (66%). It often involves ectopic gastric mucosa which manifests through gastrointestinal bleeding in 50% of cases. 99m-Technetium scintigraphy (99mTcO4) is one of the procedures available for the non-invasive diagnosis of ectopic gastric mucosa. METHODS: Twenty-eight patients (11 females, 17 males), including 16 children and 12 adults, aged 8 months-80 years old, were included in the study. The patients were admitted to hospital for hematochezia and melena (22) associated with abdominal pain (5): 3 patients repeatedly presented occult blood in their stools. Two patients only suffered from abdominal cramps and one only anemia. Patients were studied using plain abdominal radiographs and ultrasound; 10 underwent gastroscopy and colonoscopy; radiological contrast studies were performed in 5 patients. All tests were inconclusive. All the patients were premedicated with oral cimetidine (20 mg/kg in pediatric patients and 300 mg q.i.d. for adults, 48 hours before the test) or with ranitidine i.v. (1 mg/kg, max 50 mg, in 20 minutes, one hour before the test); barium meals and colonoscopy were deferred for 2-3 days after examination. An intravenous injection of 37-180 Mbq of 99mTcO4 was given followed by a dynamic study of the abdomen in anterior projection. Images were acquired for one hour or until the visualisation of abnormal foci of intake: in this case, lateral and oblique images were acquired for a better localisation of the suspicious area. Some patients were administered furosemide i.v. (0.75 mg/kg). All underwent a follow-up period of 12 months. RESULTS: Pertechnetate scintigraphy was positive in 10 cases and the presence of ectopic gastric mucosa was confirmed by surgery. The study was negative in 18 cases: 3 of them were discharged with a diagnosis of Salmonella infection, polyp of the small bowel or ulcer of the large bowel respectively; the other 15 patients did not show symptoms of onset during follow-up. CONCLUSIONS: These results confirm the high diagnostic accuracy of pertechnetate scintigraphy to detect ectopic gastric mucosa if associated with H2-receptor-blocking agent premedication

Gamma Knife radiosurgery in skull base meningiomas: a possible relationship between somatostatin receptor decrease and early neurological improvement without tumor shrinkage at short-term imaging follow-up

BACKGROUND: This study investigates a possible relationship between the effects of gamma knife (GK) on meningioma somatostatin receptors (SRs) and the high rate of early neurological improvement without tumour reduction at short-term imaging follow-up. METHODS: From December 1997 to December 2002, somatostatin receptor scintigraphy (SRS) using an 111Indium-labelled somatostatin analogue, Octreotide, was performed both before and 7-12 months after radiosurgery in 20 patients with intracranial meningiomas. Semiquantitative data were calculated as an SRS index. FINDINGS: The pre-GK SRS index was always > 1, averaging 4.44 +/- 3.20. There were no statistically significant differences between the pre-GK average values of primary (4.80 +/- 3.65) and residual (3.75 +/- 1.93) meningiomas. At the first clinical/MRI follow-up, the neurological examination had improved in 15/20 (75%) and had not changed in 5/20 patients. A corresponding slight tumour shrinkage on high-resolution MRI was documented in 3/20 cases only. The post-GK average SRS index was lower than pre-GK values both in primary (3.87 +/- 3.19) and in adjuvant (2.52 +/- 1.14) treatments, but the differences were not significant. However, the subgroup of patients with early neurological improvement showed a higher pre-GK average SRS index (5.21 +/- 3.33) and a more substantial post-GK average SRS index decrease (3.86 +/- 3.00) than the patients whose clinical condition remained stable (2.10 +/- 0.59 and 1.99 +/- 0.55, respectively). The difference between the two subgroups of patients proved to be statistically significant (P < 0.05). CONCLUSIONS: Our preliminary findings suggest a possible relationship between a decrease in the concentration of SRs on meningioma cells at short-term functional imaging follow-up after radiosurgery and early neurological improvement

Humanization of care in pediatrics and built-in psychological support in nuclear medicine [Umanizzazione delle cure in et\ue0 pediatrica e assistenza psicologica integrata in Medicina nucleare]

Objectives Aim of the present research is to detect anxiety and fear of examination in children and their parents during diagnostic procedures in nuclear medicine considering also other variables as knowledge of both procedures and diagnosis. Methods In 2010 an observational study with 132 children and 132 parents started through a semi structured survey and a non verbal observation of behavior. Results Study evidenced the association between anxiety and fear of examination in both groups. Furthermore at a higher level of knowledge in parents corresponds a higher level of knowledge in children. Children's anxiety level results higher in respect to their parents. Conclusions In consideration of such results a specific training of all operators has taken place in order to improve the practice of acceptance and support and achieve a complete humanization of care integrated with a psychological support

UMANIZZAZIONE DELLE CURE IN ETA' PEDIATRICA E ASSISTENZA PSICOLOGICA INTEGRATA IN MEDICINA NUCLEARE

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