Neurobiological aspects on brain function in neuro-psychiatric patients and in healthy subjects

Abstract: The levels of insulin-like growth factor-2 (IGF-2) were assessed in lumbar cerebrospinal fluid (CSF) from children with various kinds of brain damage and from Alzheimer (AD) patients and controls. Whole CSF was separated using acid gel chromatography and the presence of insulin-like growth factor binding protein and two different kinds of free IGF-2 m the CSF was established. The levels of CSF-IGF-2 were higher in the new-born infants than in children aged 6 months - 4 years. This difference was ascribed the immature blood-brain barrier in infants. Older children had levels similar to those reported in adults. Children with hydrocephalus had very low levels of IGF-2. The levels ofiGF in unseparated CSF was similar in AD patients and controls.The relationship between CSF spaces and cognitive function was investigated in patients with AD and controls, using a low field magnetic resonance imaging (MRI) technique and psychometric tests. The AD patients had larger relative CSF volumes in all locations investigated. The greatest differences between the two groups were found in the volumes of the temporal horns. The CSF volumes in the basal parts of the brain correlated inversely with episodic memory tests. The relative volumes of the lateral ventricles correlated with the degree of dementia. It was concluded that measurements of the relative CSF volumes of the temporal horns by MRI might be a reliable diagnostic sign of AD as well as providing an estimation of the severity of the disease.Demented subjects with either a severely disorganised sleep-wake schedule or regular sleep habits underwent serial blood saropling. The subjects with disorganised sleep-wake schedules had disturbed circadian rhythms of plasma melatonin (MT) and cortisol, whereas those with regular sleep habits had normal plasma MT and cortisol profiles. An 82-year old lady with vascular dementia and a disturbed sleep-wake pattern improved her sleep and normalised plasma MT and cortisol patterns after the removal of a beta-adrenergic blocker, substitution of cobalamin deficiency and cataract surgery. A man with frontal lobe dementia who was assessed repeatedly showed inability to suppress MT as assessed by a light test. A disorganised sleep-wake cycle in demented patients may in some cases be reflected by irregularities in the secretion of MT and cortisol.Eleven healthy elderly with normal levels of plasma cobalamin were hospitalised for a serial blood sampling procedure drawing blood every two hours over a 24 hourperiod. It was concluded that there was no circadian variation of plasma cobalamin, unsaturated binding capacity of transcobalamin and haptocorrin, or transcobalamin bound cobalamin other than what can be explained by posture. The proposed role for cobalamin in the regulation of the circadian rhythm could not be confirmed by this study.Different methods of assessing the circadian rhytm were reviewed. Awristworn, computerised instrument recording activity and light expsoure was introduced. The light exposure in 14 healthy elderly in Linköping, Sweden, under normal living conditions was analysed using the new instrument. The subjects were exposed to very little light, mostly indoor illumination. The median subject spent 60 % of the time in illumination <:1 Lux, 10 % in <: 100 Lux, and 2 % in <:1000 Lux. Only four subjects were exposed to <: 1000 Lux for 60 minutes or more, which is regarded as a minimum requirement for maximal MT suppression.In addition, simultaneous light recording and blood saropling was done over a 24 hour period. All subjects showed low day-time levels and distinct nocturnal rises of MT. Cosinor analysis was applied on the MT and light data. The time interval from the acrophase of light to the acrophase of MT was delayed with the progress of the autunm and diminishing light.