Regional cerebral oxygen supply and utilization in dementia. A clinical and physiological study with oxygen-15 and positron tomography. By R.S.J. Frackowiak, C. Pozzilli, N.J. Legg, J. Marshall, G.L. Lenzi and T. Jones (From the MRC Cyclotron Unit and the Department of Medicine [Neurology], Hammersmith Hospital, London W12 OHS, the National Hospital for Nervous Diseases, Queen Square, London WC1 and III Neurological Clinic, University of Rome, Italy). Brain 1981: 104; 753–778
Cambridge
It has been known since 1945 that blood flow is altered in patients with dementia, and subsequent work has also shown that cerebral oxygen uptake and utilization are impaired proportional to the degree of cognitive impairment. More difficult to assess has been any change in regional blood flow. Initial efforts have not revealed a pattern that discriminates dementia from other conditions. These studies also leave open the question of whether alterations in blood flow faithfully reflect altered oxygen metabolism, as seems likely on theoretical grounds. And it is another step in the argument to show that, if there are regional changes in oxygen extraction and utilization, these correlate with the multi-infarct category of dementia suggested by (Sir Bernard) Tomlinson, Garry Blessed and (Sir Martin) Roth from Newcastle in 1970. Now, with the introduction of positron emission tomography using oxygen-15 (15O), it is possible to correlate oxygen utilization with the type and degree of dementia, to explore disease mechanisms, and to consider whether the concept that dementia may result from chronic brain ischaemia is valid.
Richard Frackowiak and his colleagues study 22 individuals, relatively young and with mild disease, in whom specific underlying comorbidity other than vascular disease, including affective disorders masquerading as dementia, is excluded through serial assessment over 6 months and in whom sufficient compliance with brain imaging can be achieved. The vascular flavour of these cases is apparent from three sudden deaths occurring during the study from cardiovascular causes, and a high frequency of hypertension, diabetes or conditions increasing the risk of stroke. Fourteen healthy hospital workers, screened for the absence of vascular risk factors, serve as controls. Other than a difference in mean systolic and diastolic blood pressures, these cases and controls are comparable for baseline physiological data. The demented individuals are categorized as those with and without vascular disease on the basis of an ‘ischaemia score’ and appearances on computerized tomography. Cognitive ability is assessed using the Newcastle Dementia Scale, the Information Memory Concentration Test and the Regional Functional Score based on bedside tests of cognitive ability, from all of which is derived a Combined Dementia Score (0–10) allowing cases to be banded in mild, moderate and severe categories of cognitive impairment. Taking these clinical and structural brain imaging indices together, and with some rounding of corners where the evidence is ambiguous, there are nine vascular cases (of whom four have Binswanger's chronic sub-cortical leucoencephalopathy defined as periventricular white matter low attenuation in association with hypertension) and 13 with a presumed degenerative basis. These groups have moderate or severe dementia in roughly equal distributions, usually with progression in those undergoing serial assessment. Later, pathological confirmation is obtained for one multi-infarct and two degenerative cases. All 22 individuals are studied once, and six and four from the degenerative and vascular groups, respectively, on a second occasion.
The team has previously described and validated its techniques for arterial blood sampling and the depiction of regional cerebral blood flow and oxygen metabolism using 15O tracer emission over 5 min to achieve a resolution of around 14 mm x 14 mm in the transaxial orbitomeatal plane mapped onto a computerized tomographic matrix in order to achieve accurate re-positioning in serial studies (Fig. 1). Comparisons are made between five paired 5 cm2 (81 pixels) regions of interest across the two hemispheres. Although Dr Frackowiak and his colleagues have studied both cerebral blood flow and oxygen metabolism, their results indicate that the extraction and utilization of oxygen by the brain parenchyma matches supply such that regional blood flow, extraction and utilization are always coupled. And they consider that, allowing for the technical artefacts of resolution and tracer modelling, and movements especially during breathing and re-positioning, their measurements faithfully represent those that might be obtained using more invasive methodologies and reflect accurately the physiological properties of tissue blocks under examination.
|
Compared with hospital workers, those with dementia have about a 30% and 23% reduction in regional blood flow and oxygen utilization in grey and white matter, respectively. These differences increase with the severity of cognitive impairment such that the Combined Dementia score correlates inversely with indices of oxygen metabolism. Although the reductions in oxygen utilization and blood flow are diffuse, with no inter-hemispheric differences, significant regional variations are superimposed and with patterns that differ between degenerative and vascular cases (Fig. 2). Whether regional vascular and degenerative neuropathology signifies more general pathological processes, reflected by the global changes in blood flow, or themselves determine a diffuse perturbation of brain function and metabolism is not yet clear. In general, the parietal lobe suffers most, the occipital least and the frontal, temporal and basal ganglia display intermediate changes. In degenerative dementia, the temporal lobe initially is most abnormal when the degree of dementia is still mild whereas all regions ‘catch-up’ as severity increases. The frontal lobe is usually spared in the vascular cases and the occipital region maintains blood flow and oxygen utilization in degenerative dementia. The evolving patterns observed in these groups are also seen in individual cases studied serially. But the regional variations do not correlate with specific clinical functions such as aphasia or apraxia.
|
Thus, ‘a decline in cerebral blood flow and mean cerebral oxygen utilization [is] correlated with increasing severity of dementia in both degenerative and vascular dements ... the decline [is] coupled, both for the cerebral hemisphere as a whole and regionally ... in the vascular group, parietal defects [are] the most pronounced ... in the degenerative group ... a profound depression in the frontal regions with relative sparing of occipital areas characterize[s] the severe degenerative dements’. And in concluding that ‘there [is] no increase in regional oxygen extraction ratio globally and therefore no evidence to support the existence of a chronic ischaemic brain syndrome’, Dr Frackowiak and the pioneering team studying functional brain imaging in London during the early 1980s, anticipate the interplay of degenerative and vascular pathology described in the current issue (page 2830).
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||