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Biomedical subjects

J T O'Brien

Publications and source records attributed to J T O'Brien.

At least 73 records · Page 4Linked to original sources
PubMed1997

Magnetic resonance imaging correlates of memory impairment in the healthy elderly: association with medial temporal lobe atrophy but not white matter lesions.

OBJECTIVE: To investigate the neuroradiological correlates of age-related cognitive decline in the elderly. DESIGN: A sample of healthy control subjects underwent magnetic resonance imaging (MRI) scanning and cognitive testing. SETTING: Melbourne, Australia. PARTICIPANTS: 40 volunteers over the age of 55 who were spouses of subjects seen in a hospital memory clinic, subjects from a register of normal volunteer subjects (not staff) kept for research purposes or residents of a retirement hostel. MEASURES: Hippocampal and amygdala (HA) atrophy, periventricular lesions (PVL) and deep white matter lesions (DWML) were rated by two radiologists blind to cognitive test score results. Cognitive assessment was by the Cambridge Cognitive Examination (CAMCOG). RESULTS: After controlling for age and education, lower scores on the memory subscale of the CAMCOG were associated with the presence of HA atrophy, but not with DWML or PVL. CONCLUSIONS: HA atrophy on MRI is associated with impaired memory performance in the healthy elderly, while PVL and DWML are not. Further study should determine whether HA atrophy is a risk factor for developing dementia.

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PubMed1997

Time course of response to electroconvulsive therapy in elderly depressed subjects.

OBJECTIVE: To assess the time course of response to electroconvulsive therapy (ECT) in elderly depressed subjects. In particular, to determine whether significant antidepressant response occurs during the first few treatments. DESIGN: A naturalistic study of elderly patients receiving ECT. SETTING: Acute admission wards of a UK old age psychiatric service. PATIENTS: 13 consecutive inpatients aged over 65 years, meeting inclusion criteria, with a diagnosis of current major depressive episode, who were treated with ECT. MAIN OUTCOME MEASURES: Severity of depression as assessed by the Montgomery and Asberg Depression Rating Scale (MADRS), psychomotor speed as assessed by Gibson's spiral maze test (GSM) and the Kendrick digit copying test (KDCT). RESULTS: The first ECT treatment reduced the mean MADRS score by 21% (p < 0.0001) and the second treatment the mean MADRS was reduced by 36% (p < 0.0001). A non-significant improvement on GSM scores was seen that paralleled improvement in the MADRS. The average number of ECT treatments needed to reduce the MADRS score by half was 3.73 +/- 1.85, though the actual number varied between 1 and 7. CONCLUSIONS: ECT is a highly effective treatment for depression in the elderly and significant antidepressant response can be demonstrated after only one treatment, arguing for careful mental state monitoring during treatment. However, considerable variability is seen in individual cases, implying that ECT should not be abandoned just because rapid response is not seen.

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PubMed1996

Enhanced adrenal sensitivity to adrenocorticotrophic hormone (ACTH) is evidence of HPA axis hyperactivity in Alzheimer's disease.

Adrenal sensitivity was assessed in 16 non-depressed patients with NINCDS/ADRDA Alzheimer's disease (AD) and 18 control subjects by measuring cortisol response to low dose (0.05 microgram/kg i.v.) exogenous adrenocorticotrophic hormone (ACTH). Controlling for sex and medication, both peak cortisol level (peak-baseline) and area under cortisol response curve (AUC above baseline) were significantly greater in AD subjects. This shows that HPA axis hyperactivity, as demonstrated by enhanced adrenal sensitivity to ACTH, occurs in AD. Similar findings have been reported to occur in depression. Among AD subjects, AUC cortisol response correlated with current age (r = 0.70, P = 0.001) and age at onset of dementia (r = 0.73, P = 0.001) and an inverse correlation was seen between cortisol AUC and cognitive test (CAMCOG) score (r = -0.51, P = 0.044). Our findings suggest that HPA axis hyperactivity in AD is associated with advancing age and cognitive dysfunction. Such changes may be cause, or consequence, of neuronal loss.

Adrenocorticotropic Hormone↗
PubMed1996

Clinical and magnetic resonance imaging correlates of hypothalamic-pituitary-adrenal axis function in depression and Alzheimer's disease.

BACKGROUND: An age-related dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is well recognised in animals, but still remains controversial in humans. There is increasing interest that raised corticosteroid levels, due to activation of the HPA axis, may cause both depressive symptoms and cognitive impairments. Steroid effects on cognition may be via the hippocampus, a major site of corticosteroid action and an important structure involved in learning and memory. METHOD: To investigate this further, we examined the relationship between the dexamethasone suppression test, cognitive function, depressive symptoms and hippocampal atrophy on magnetic resonance imaging (MRI) in 32 normal controls, 49 subjects with NINCDS/ADRDA Alzheimer's disease and 51 patients with DSM-III-R Major Depression. RESULTS: Controlling for differences in dexamethasone concentrations, post-dexamethasone cortisol levels were related to advancing age in controls and depressed subjects. However, among subjects with Alzheimer's disease, post-dexamethasone cortisol levels were independently associated with both minor depressive symptoms and hippocampal atrophy on MRI. CONCLUSION: An association between advancing age and increased HPA axis dysregulation is supported for controls and depressed subjects. In Alzheimer's disease, HPA axis changes were associated with depressive symptoms and hippocampal atrophy. Longitudinal studies are now needed to determine the causal direction of these associations.

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PubMed1996

Use of neural networks in brain SPECT to diagnose Alzheimer's disease.

UNLABELLED: The usefulness of artificial neural networks in the classification of 99mTc-HMPAO SPECT axial brain scans was investigated in a study group of Alzheimer's disease patients and age-matched normal subjects. METHODS: The cortical circumferential profiling (CCP) technique was used to extract information regarding patterns of cortical perfusion. Traditional analysis of the CCP data, taken from slices at the level of the basal ganglia, indicated significant perfusion deficits for Alzheimer's disease patients relative to normals, particularly in the left temporo-parietal and left posterior frontal areas of the cortex. The compressed profiles were then used to train a neural-network classifier, the performance of which was compared with that of a number of more traditional statistical (discriminant function) techniques and that of two expert viewers. RESULTS: The optimal classification performance of the neural network (ROC area = 0.91) was better than that of the alternative statistical techniques (max. ROC area = 0.85) and that of the expert viewers (max. ROC area = 0.79). CONCLUSION: The CCP produces perfusion profiles which are well suited to automated classification methods, particularly those employing neural networks. The technique has the potential for wide application.

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PubMed1994

Cortisol suppression by dexamethasone in the healthy elderly: effects of age, dexamethasone levels, and cognitive function.

The effects of age, cognitive function (measured by Cambridge cognitive examination (CAM-COG) score); and dexamethasone (DEX) levels on the dexamethasone suppression test were studied in 33 healthy older subjects (age 51-96). Three subjects (9.1%) were nonsuppressors and were older and had lower CAMCOG scores than the 30 suppressors. Significant correlations were observed between natural log-transformed postdexamethasone cortisol (LNCOR) levels and age (r = 0.40) and CAMCOG score (r = -0.45). Multiple regression analysis was used to investigate the relationship between LNCOR, age, DEX levels, and CAMCOG score. Age and DEX combined explained 41% of the variance in LNCOR values, whereas CAMCOG score and DEX levels explained 44% variance. As age and CAMCOG were highly correlated (r = -0.72), both together did not significantly improve the fit of regression equation (47% variance explained). These findings suggest an association between advancing age, impaired glucocorticoid feedback, and cognitive dysfunction in healthy human subjects. Although any causal connection remains to be demonstrated, results would be consistent with the "glucocorticoid cascade" hypothesis of human aging.

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PubMed1994

The differentiation of depression from dementia by temporal lobe magnetic resonance imaging.

Temporal lobe Magnetic Resonance Imaging (MRI) was performed in 43 patients with NINCDS/ADRDA Alzheimer's disease (AD) (33 probable, 7 possible, 3 definite) and 32 subjects with DSM-III-R Major Depression (DEP) matched for age, sex and level of education. Hippocampus (anterior and posterior, right and left), amygdala, entorhinal cortex, parahippocampal gyrus and cerebral cortex were rated for atrophy on a 4-point scale. Good discrimination between groups could be achieved using a cut-off of 2 or more on anterior hippocampal atrophy rating (sensitivity 93%; specificity 84%; 89% cases correctly grouped overall). Even among a subgroup of 9 mild AD subjects and 10 cognitively impaired DEP subjects (matched on mini-mental state score), the same cut-off correctly grouped 84% (16/19) cases. Hippocampal atrophy increased with age in both AD and DEP subjects leading to a reduction in specificity (but not sensitivity) for those aged over 75. Within the AD group a significant correlation was observed between length of history and atrophy of the entorhinal cortex (r = 0.39, P = 0.009). We conclude that temporal lobe atrophy on MRI can provide good discrimination between AD and DEP subjects, including those DEP patients with cognitive impairment apparent on screening tests of cognitive function.

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PubMed1994

Volumetric and visual assessment of the mesial temporal structures in Alzheimer's disease.

BACKGROUND: Alzheimer's disease is the commonest cause of dementia. Clinical diagnosis of Alzheimer's disease may be difficult. Magnetic resonance imaging has a role to play in diagnosis. AIM: To assess whether volumetric and/or visual assessment of the mesial temporal structures is useful in separating patients with Alzheimer's disease from age matched controls. METHODS: Twenty-four patients with Alzheimer's disease diagnosed by NINCDS/ADRDA criteria and 15 age matched controls were studied with magnetic resonance imaging (MRI) and volumetric techniques. Segmented volumes of the mesial temporal structures were assessed visually and volumetrically. RESULTS: Volumetric analysis demonstrated significant (p < .001) differences between the two groups, but showed overlap in individual cases. Discriminant function analysis predicted correct group membership (patient or control) in 85% of cases. Visual assessment alone demonstrated a sensitivity of 92% and a specificity of 93% in distinguishing the Alzheimer patients from controls. CONCLUSION: Volumetric and visual assessment of the mesial temporal structures is useful in separating Alzheimer patients from controls. Overlap is present in individual cases. Visual assessment was as useful in separating the two groups as the volumetric analysis.

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PubMed1994

The function of the hypothalamic-pituitary-adrenal axis in Alzheimer's disease. Response to insulin hypoglycaemia.

BACKGROUND: To investigate an association between HPA axis dysfunction, depression and cognitive impairment, we assessed subjects with mild Alzheimer's disease (AD). METHOD: Sixteen non-depressed subjects with AD according to NINCDS/ADRDA criteria and 18 normal controls underwent the insulin hypoglycaemia (IH) test and the dexamethasone suppression test (DST). RESULTS: The AD subjects showed a blunted response of adrenocorticotrophic hormone (ACTH) to IH compared with controls (P = 0.019). ACTH response (area under curve) correlated with a score for cognitive ability (CAMCOG) (r = 0.64, P < 0.01). AD subjects had a shorter time to peak cortisol level than controls (P = 0.004), although total cortisol response was normal. CONCLUSIONS: The AD subjects show evidence of adrenal hyper-responsiveness and normal immediate (rate-sensitive) glucocorticoid feedback. An association between HPA axis dysfunction and organic brain pathology in AD subjects may be mediated by cell loss in the hippocampus.

Adrenocorticotropic Hormone↗
PubMed1993

Cognitive impairments in patients with seasonal affective disorder.

Eleven patients with seasonal affective disorder (SAD) and ten controls matched for age, IQ, and education were tested on a number of computerised tests designed to assess attention, memory, and learning. When depressed, patients showed no deficit in attention but were impaired on spatial memory and learning. They were also significantly slower to respond than controls, with a pattern that suggested slowed information processing centrally, rather than simple sensory or motor slowing. On recovery from depression, improvement was seen in most tests, although impairment remained in latency to respond on a test of spatial memory. This continuing impairment correlated with residual depressive symptoms but not with ventricular brain ratio (VBR).

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PubMed1992

A study of regional cerebral blood flow and cognitive performance in Alzheimer's disease.

Thirty five patients with dementia of the Alzheimer type (DAT) and 35 controls matched for age, sex and handedness were investigated using single photon emission computer tomography (SPECT) with 99m technetium HMPAO. Regional cerebral blood flow (rCBF) was assessed semi-quantitatively in 18 cortical and 4 subcortical areas by normalising mean information density in each region to cerebellar mean information density. Analysis revealed significantly reduced rCBF to temporal, parietal, frontal and left occipital cortex in the patients whilst blood flow to subcortical areas showed no differences between the 2 groups. In addition, significant left-sided cortical hypoperfusion was seen in the DAT group but not in controls. When patients were sub-divided on the basis of disease severity, those with mild disease showed temporal, parietal and left frontal changes with more severely affected patients also showing right frontal and left occipital involvement. rCBF patterns did not distinguish between presenile and senile onset cases once duration and severity of illness were controlled. Eight cortical areas were also rated visually for perfusion deficits on a simple 4 point scale. Perfusion deficits were detected in 34 of 35 patients but in only 4 of 35 controls. In the DAT group significant correlations were found between many of the neuropsychological tests used and rCBF. Memory correlated with left temporal activity, praxis, perception, object assembly and block design with right parietal activity and language with activity throughout the left hemisphere. Significant correlations were also seen between subcortical and cortical blood flow, possibly explaining the correlations observed between many of the neuropsychological tests and thalamic blood flow.

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