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J T O'Brien

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

At least 55 records · Page 3Linked to original sources
PubMed2001

Visual hallucinations are associated with lower alpha bungarotoxin binding in dementia with Lewy bodies.

Patients with dementia with Lewy bodies (DLB) commonly experience psychotic symptoms, most notably visual hallucinations. Previously, it has been shown that visual hallucinations in DLB are associated with reduced cortical choline acetyltransferase activity, a marker of cholinergic innervation, but not with predominantly postsynaptic muscarinic M1 receptor binding. In the present investigation, nicotinic acetylcholine receptor (nAChR) levels in the temporal cortex (Brodmann's areas [BA] 20 and 36) were measured in a group of 24 prospectively assessed DLB patients; comparisons were made between groups with or without visual and auditory hallucinations and delusional misidentification. Visual hallucinations and delusional misidentification were associated with lower [(125)I]alpha bungarotoxin binding in areas 36 and 20 (P<.05), but not with changes in [(3)H]epibatidine binding. There were no significant associations with auditory hallucinations. [(3)H]epibatidine, but not [(125)I]alpha bungarotoxin, binding for all DLB cases was reduced compared to controls (P<.001). Loss of cortical alpha 7 nicotinic receptors may contribute to hallucinations and delusional misidentification in DLB, with implications for treatment and understanding the mechanisms of psychotic symptoms in dementia.

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PubMed2001

Combined magnetic resonance imaging and single-photon emission tomography scanning in the discrimination of Alzheimer's disease from age-matched controls.

OBJECTIVE: To compare the utility of temporal lobe magnetic resonance imaging (MRI) and single-photon emission tomography (SPET) scanning in discriminating between subjects with Alzheimer's disease (AD) and age-matched controls. METHODS: Thirty subjects with NINCDS-ADRDA AD (23 probable AD, 5 possible AD, 2 definite AD) and 22 age- and sex-matched controls underwent T1-weighted coronal MRI scanning (0.3 T) and technetium 99m-HMPAO SPET scanning. MRI scans were analyzed using a digitizer system with volumes of hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus, and whole cerebral cortex calculated. From SPET scans, regional cerebral blood flow (rCBF) was assessed in anterior and posterior frontal, parietal, occipital, and mesial temporal cortex using a region of interest analysis with the cerebellum as a reference area. RESULTS: Using MRI, the areas that best separated groups were left hippocampal and left amygdala volume, resulting in correct classification (patient vs. control) in 79% of cases (sensitivity 77%, specificity 82%). Exactly the same proportion of subjects were correctly classified by SPET, with the most discriminating rCBF changes being left parietal and right posterior frontal. Combining information from both scans improved the proportion of correctly classified subjects in a discriminant function to 90% (sensitivity 93%, specificity 86%; only 2 AD and 3 controls misclassified). All AD subjects had abnormalities on MRI and/or SPET (sensitivity for combined examinations 100%), while abnormalities on both MRI and SPET had a positive predictive value of 100% for dementia (including the detection of one control subject who later had dementia). Significant correlations between MRI and SPET measures were seen in control subjects but not in patients. CONCLUSION: Both 0.3 T MRI and single rotating gamma camera SPET were equally useful in separating AD subjects from age-matched controls, although the combination of both significantly enhanced discrimination. In particular, all AD subjects had abnormalities on either MRI or SPET and both techniques may have an important role in assisting with clinical diagnosis, though replication in other centers and examination of differentiation of AD from other causes of dementia need to be examined.

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PubMed2001

A neuropathological study of vascular factors in late-life depression.

OBJECTIVES: Depression is a common psychiatric disorder in late life and it may be associated with vascular disease processes. Although there are clinical and neuroimaging studies lending support to such a "vascular depression" hypothesis there have been no neuropathological studies to directly test this. Postmortem tissue was investigated to determine whether late life depression was associated with atheromatous change in large and medium vessels and microvascular disease in the brain. METHODS: Postmortem tissue was obtained from 20 patients with a history of at least one episode of DSM-IV major depression and 20 control subjects. Standard procedures were carried out to analyze and quantify Alzheimer type pathology (plaques, tangles, Braak staging) and cortical Lewy bodies. Coronary arteries, cerebral vessels, and aorta were rated for atheromatous disease on a 0-3 scale and the four neocortical areas were rated for microvascular disease. RESULTS: The two groups showed no significant differences in age, sex, or postmortem delay. There was a significant increase in atheromatous disease in the depressed group (p=0.023). No differences were found for microvascular disease, either in the brain generally or locally in the frontal lobes. No subject had any significant Alzheimer type or Lewy body pathology. CONCLUSIONS: Neuropathological evidence was found for an excess of atheromatous disease, related to the aortic and cerebral vessels, in late life depression. However, there was no evidence of an increase in microvascular disease. The findings broadly support the vascular depression hypothesis.

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PubMed2001

The natural history of psychosis and depression in dementia with Lewy bodies and Alzheimer's disease: persistence and new cases over 1 year of follow-up.

BACKGROUND: Few data are available regarding the natural course of psychiatric symptoms in dementia with Lewy bodies and Alzheimer's disease. To acquire this information is essential to inform differential diagnosis and treatment decisions. METHOD: The current study provides prospective data regarding a representative case-register cohort of patients with operationalized clinical diagnoses of dementia with Lewy bodies (N = 82) or Alzheimer's disease (N = 132), with verified accuracy of clinical diagnosis against postmortem examination. Psychosis (Columbia University Scale for Psychopathology in Alzheimer's Disease) and depression (Cornell Scale for Depression in Dementia) were assessed at baseline and annual follow-up. RESULTS: Visual hallucinations were significantly more likely to be persistent in patients suffering from dementia with Lewy bodies (chi2 = 19.1, df = 1, p < .0001). Although a number of other psychiatric symptoms were also more frequent at baseline in dementia with Lewy body patients, they were not significantly more likely to persist. Delusions and auditory hallucinations did, however, persist in more than 40% of patients across both diagnostic groups. Patients suffering from dementia with Lewy bodies were significantly more likely to develop new auditory hallucinations over the year of follow-up (chi2 = 14.4, df= 1, p < .0001). CONCLUSION: These results confirm that, although a number of psychiatric symptoms are common in dementia with Lewy bodies, it is only visual hallucinations that are significantly more persistent, with important treatment implications.

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PubMed2000

Quantifying fluctuation in dementia with Lewy bodies, Alzheimer's disease, and vascular dementia.

BACKGROUND: Case reports and clinical observations suggest that fluctuating cognition (FC) is common in the major dementias, particularly dementia with Lewy bodies (DLB), where it is one of three core clinical diagnostic features. OBJECTIVES: To examine the frequency, characteristics, and diagnostic utility of FC in dementia using clinical, attentional, and EEG markers. METHOD: - A total of 155 subjects (61 with AD, 37 with DLB, 22 with vascular dementia [VaD], 35 elderly controls) received clinical evaluation for FC using a semiquantified measure applied by experienced clinicians and 90-second cognitive choice reaction time (CRT) and vigilance reaction time (VIGRT) trials. Forty subjects also received an evaluation of mean EEG frequency across 90 seconds. RESULTS: Patients with DLB had a greater prevalence and severity of FC than did patients with AD or VaD rated using clinical, attentional, and EEG measures. The 90-second cognitive and EEG trials demonstrated that FC occurs on a second-to-second basis in patients with DLB. Patients with VaD had a higher prevalence of FC than did those with AD, although the profile of FC was different from that expressed by DLB cases. Optimal cutoff values on the clinical scale achieved good discrimination between the dementia groups (sensitivity 81%, specificity 92%, DLB versus AD; sensitivity 81%, specificity 82%, DLB versus VaD; sensitivity 64%, specificity 77%, VaD versus AD). CONCLUSION: Standardized assessment methods demonstrate that FC is significantly more common and severe in DLB than in other major dementias. The periodicity of FC is different in DLB and VaD cases, with important implications for the underlying causal mechanisms and for differential diagnosis.

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PubMed2000

MRI volumetric study of dementia with Lewy bodies: a comparison with AD and vascular dementia.

OBJECTIVE: To compare global and regional atrophy on MRI in subjects with dementia with Lewy bodies (DLB), AD, vascular dementia (VaD), and normal aging. In addition, the relationship between APOE-epsilon4 genotype and volumetric indices was examined. METHOD: MRI-based volume measurements of the whole-brain, ventricles, frontal lobe, temporal lobe, hippocampus, and amygdala were acquired in elderly subjects with DLB (n = 27; mean age = 75.9 years), AD (n = 25; 77.2 years), VaD (n = 24; 76.9 years), and normal control subjects (n = 26; 76.2 years). RESULTS: Subjects with DLB had significantly larger temporal lobe, hippocampal, and amygdala volumes than those with AD. No significant volumetric difference between subjects with DLB and VaD was observed. Compared with control subjects, ventricular volumes were increased in all patients with dementia, though those with DLB showed a relative preservation of whole-brain volume. There were no significant differences in frontal lobe volumes between the four groups. APOE-epsilon4 status was not associated with volumetric indices. CONCLUSION: The findings support the hypothesis that DLB is associated with a relative preservation of temporal lobe structures. In the differentiation of DLB and AD, this may have important implications for diagnosis.

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PubMed2000

Prospective validation of consensus criteria for the diagnosis of dementia with Lewy bodies.

OBJECTIVE: To determine the validity of a clinical diagnosis of probable or possible dementia with Lewy bodies (DLB) made using International Consensus criteria. BACKGROUND: Validation studies based on retrospective chart reviews of autopsy-confirmed cases have suggested that diagnostic specificity for DLB is acceptable but case detection rates as low as 0.22 have been suggested. METHODS: We evaluated the first 50 cases reaching neuropathologic autopsy in a cohort to which Consensus clinical diagnostic criteria for DLB, National Institute for Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD, and National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria for vascular dementia (VaD) had been prospectively applied. RESULTS: Twenty-six clinical diagnoses of DLB, 19 of AD, and 5 of VaD were made. At autopsy, 29 DLB cases, 15 AD, 5 VaD, and 1 progressive supranuclear palsy were identified. The sensitivity and specificity of a clinical diagnosis of probable DLB in this sample were 0.83 and 0.95. Of the five cases receiving a false-negative diagnosis of DLB, significant fluctuation was present in four but visual hallucinations and spontaneous motor features of parkinsonism were generally absent. Thirty-one percent of the DLB cases had additional vascular pathology and in two cases this contributed to a misdiagnosis of VaD. No correlations were found between the distribution of Lewy bodies and clinical features. CONCLUSION: The Consensus criteria for DLB performed as well in this prospective study as those for AD and VaD, with a diagnostic sensitivity substantially higher than that reported by previous retrospective studies. DLB occurs in the absence of extrapyramidal features and in the presence of comorbid cerebrovascular disease. Fluctuation is an important diagnostic indicator, reliable measures of which need to be developed further.

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PubMed2000

MRI volumetric correlates of white matter lesions in dementia with Lewy bodies and Alzheimer's disease.

The aim of the study was to examine the relationship between white matter changes on magnetic resonance imaging (MRI), brain atrophy and ventricular dilation in late-life dementias. T(1)-weighted, T(2)-weighted, and proton density MRI scans were acquired in subjects with Alzheimer's disease (AD, N=25) and dementia with Lewy bodies (DLB, N=27). Total brain and ventricular volumes were measured and white matter lesions rated using a semi-quantitative scale. Periventricular hyperintensities (PVH) were found to independently correlate with advancing age and increasing ventricular dilatation in all subjects. In contrast, deep white matter hyperintensities (DWMH) did not correlate with measures of brain atrophy, ventricular dilatation or age, but were associated with a history of hypertension. These findings support the hypothesis that PVH and DWMH are pathologically diverse and that white matter change in AD and DLB may be determined by similar processes. In particular, PVH appear to be linked to atrophic processes involving ventricular enlargement and DWMH to ischaemic risk factors.

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PubMed2000

Elevation in late-life depression of intercellular adhesion molecule-1 expression in the dorsolateral prefrontal cortex.

OBJECTIVE: Late-life depression may be associated with vascular disease. The authors investigated this association by determining whether intercellular adhesion molecule-1 (ICAM-1), a marker of ischemia-induced inflammation, is elevated in the dorsolateral prefrontal cortex in depression. METHOD: The authors studied postmortem tissue from 20 depressed subjects and a matched comparison group of 20 nondepressed subjects. They used immunocytochemistry to stain ICAM-1 in blood vessels on sections of the dorsolateral prefrontal cortex and occipital cortex and quantitative true color image analysis to measure the proportion of vessels expressing ICAM-1. RESULTS: ICAM-1 was significantly higher in both the gray and white matter of the depressed subjects' dorsolateral prefrontal cortex than the comparison subjects' dorsolateral prefrontal cortex. The difference between these groups was much smaller in the gray and white matter of the occipital cortex. CONCLUSIONS: These findings support the vascular depression hypothesis, which has important implications for the understanding and management of late-life depression.

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PubMed2000

Cognitive deficit induced by acute tryptophan depletion in patients with Alzheimer's disease.

OBJECTIVE: The study assessed the effects on global cognitive function and mood of a reduction of brain serotonin by means of acute tryptophan depletion in 16 patients with dementia of the Alzheimer type and in 16 cognitively intact comparison subjects. METHOD: In a double-blind, crossover design, subjects received a tryptophan-free amino acid drink to induce acute tryptophan depletion and, on a separate occasion, a placebo drink containing a balanced mixture of amino acids. On each occasion, ratings of depressed mood were made at baseline and 4 and 7 hours later, and the Modified Mini-Mental State was administered at baseline and 4 hours later. RESULTS: Patients with dementia of the Alzheimer type had a significantly lower mean score on the Modified Mini-Mental State after acute tryptophan depletion than after receiving placebo. The comparison group showed no difference in mean score on the Modified Mini-Mental State after acute tryptophan depletion and after receiving placebo. No significant changes in mood were found in either group. CONCLUSIONS: Acute tryptophan depletion significantly impaired cognitive function in patients with dementia of the Alzheimer type. Compromised serotonergic function, in combination with cholinergic deficit, may make an important contribution to cognitive decline in dementia of the Alzheimer type.

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PubMed2000

The Clinician Assessment of Fluctuation and the One Day Fluctuation Assessment Scale. Two methods to assess fluctuating confusion in dementia.

BACKGROUND: The identification of fluctuating confusion is central to improving the differential diagnosis of the common dementias. AIMS: To determine the value of two rating scales to measure fluctuating confusion. METHOD: The agreement between the clinician-rated scale and the scale completed by a non-clinician was determined. Correlations between the two scales were calculated; variability in attention was calculated on a computerised cognitive assessment and variability in delta rhythm on an electroencephalogram (EEG). RESULTS: The Clinician Assessment of Fluctuation and the computerised cognitive assessment were completed for 155 patients (61 Alzheimer's disease, 37 dementia with Lewy bodies, 22 vascular dementia, 35 elderly controls). A subgroup (n = 40) received a further evaluation using the One Day Fluctuation Assessment Scale and an EEG. The two scales correlated significantly with each other, and with the neuropsychological and electrophysiological measures of fluctuation. CONCLUSIONS: Both scales are useful instruments for the clinical assessment of fluctuation in dementia.

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PubMed1999

Medial temporal lobe atrophy on MRI in dementia with Lewy bodies.

OBJECTIVE: To investigate whether medial temporal lobe atrophy (MTA) on MRI is less frequent in dementia with Lewy bodies (DLB) compared with AD and vascular dementia (VaD), and to determine the diagnostic utility of MTA in the differential diagnosis of dementia. METHOD: Coronal T1-weighted 1.0-T MR images were acquired in patients with DLB (consensus criteria; n = 26; mean age, 75.9 years), AD (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association; n = 28; mean age, 77.4 years), VaD (National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences; n = 24; mean age, 76.9 years), and normal control subjects (n = 26; mean age, 76.2 years). Cognitive function was assessed using the Cambridge Cognitive Examination (CAMCOG), and MTA was rated visually using a standardized scale. RESULTS: MTA was more frequent and severe in all dementia groups compared with control subjects (AD, 100%; VaD, 88%; DLB, 62%; control subjects, 4%; p < 0.001). Comparing dementia groups, MTA scores were significantly lower in DLB than AD (p = 0.002), with a trend toward less atrophy in DLB compared with VaD (p = 0.07). The absence of MTA had a specificity of 100% and 88% for separating DLB from AD and VaD respectively, and a sensitivity of 38%. In patients with DLB, MTA increased with age (r = 0.58, p = 0.002), and in all dementia patients MTA correlated with memory impairment (combined memory score, r = -0.34, p = 0.003) but not total CAMCOG score or other subscales. CONCLUSION: Patients with DLB have significantly greater MTA than control subjects but significantly less than those with AD. The authors confirmed that the presence of MTA is useful in detecting AD but less useful in differentiating between dementias. However, in the differentiation of DLB from AD and VaD, the absence of MTA is highly suggestive of a diagnosis of DLB.

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PubMed1999

Apolipoprotein E epsilon4 allele, temporal lobe atrophy, and white matter lesions in late-life dementias.

OBJECTIVE: To examine the relationship between the apolipoprotein E (APOE) epsilon4 genotype, medial temporal lobe atrophy, and white matter hyperintensities on magnetic resonance imaging in late-life dementias. DESIGN: Structural magnetic resonance imaging study using T2-weighted and proton density-weighted axial scans and T1-weighted coronal scans. SETTING: Community-dwelling population of elderly patients prospectively chosen from a clinical case register of consecutive referrals to old age psychiatry services. SUBJECTS: Twenty-five subjects with Alzheimer disease (by criteria of the National Institute of Neurological and Communication Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association; mean age, 77.8 years), 22 subjects with dementia with Lewy bodies (consensus criteria; mean age, 77.2 years), and 24 subjects with vascular dementia (by criteria of the National Institute of Neurological Disorders and Stroke and the Association International pour la Recherche et l'Enseignement en Neurosciences; mean age, 76.9 years) were selected. Subjects were well matched for age, sex, duration of illness, and cognitive function. MAIN OUTCOME MEASURES: The APOE genotype was determined using the polymerase chain reaction method, and medial temporal lobe atrophy and white matter hyperintensities (periventricular and deep white matter) were visually rated using standardized scales. RESULTS: In all subjects with dementia, no significant associations were noted between APOE epsilon4 status and medial temporal lobe atrophy (mean score: 0 epsilon4 = 4.5, 1 epsilon4 = 4.5, and 2 epsilon4 = 4.3; P = .90), periventricular hyperintensities (0 epsilon4 = 3.3, 1 epsilon4 = 3.1, and 2 epsilon4 = 2.9; P = .83), and white matter hyperintensities (0 epsilon4 = 5.3, 1 epsilon4 = 4.9, and 2 epsilon4 = 4.9; P = .79). CONCLUSIONS: The APOE epsilon4 allele does not determine medial temporal lobe atrophy or white matter lesions, as measured by magnetic resonance imaging in patients with Alzheimer disease, vascular dementia, or dementia with Lewy bodies. Although APOE epsilon4 may modify the risk for acquiring dementia, this finding provides further evidence that APOE epsilon4 does not influence pathological processes thereafter.

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PubMed1999

Magnetic resonance imaging differences between dementia with Lewy bodies and Alzheimer's disease: a pilot study.

BACKGROUND: Temporal lobe atrophy on magnetic resonance imaging (MRI) has been suggested as a specific diagnostic marker for Alzheimer's disease (AD). No previous comparison with dementia with Lewy bodies (DLB) has been reported. METHOD: T1-weighted MRI scans were performed on 11 subjects with AD (nine with NINCDS/ADRDA probable AD and two with neuropathologically proven AD) and nine subjects with DLB (four with probable DLB diagnosed by clinical criteria and five with neuropathologically proven DLB). Groups were matched for age, duration of illness and cognitive test score. Two raters, blind to diagnosis and neuropathological findings, measured the volumes of the frontal lobes, temporal lobes, hippocampi, parahippocampal gyri, amygdalae, and caudate nuclei using a computerized volumetric analysis system. Scans were also rated for medial temporal atrophy on a four-point scale by an experienced rater. RESULTS: AD subjects had significantly smaller left temporal lobes and parahippocampal gyri than those with DLB. Medial temporal atrophy was present in 9/11 AD cases (82%) and absent in 6/9 (67%) of DLB cases. Two neuropathologically confirmed cases of DLB had severe medial temporal atrophy; both had concurrent AD-type pathology in the temporal lobe (Braak stage 4). CONCLUSIONS: This pilot study supports the hypothesis that a greater burden of pathology centres on the temporal lobes in AD compared with DLB, except in DLB cases with concurrent Alzheimer pathology. A larger study is needed to confirm these findings and to determine whether MRI has a role in assisting with the clinical differentiation between DLB and AD.

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PubMed1997

Clinical, magnetic resonance imaging and endocrinological differences between delusional and non-delusional depression in the elderly.

OBJECTIVE: To investigate neuroradiological, endocrinological and clinical differences between delusional and non-delusional depression. DESIGN: A cross-sectional study of depressed subjects. SETTING: Melbourne, Australia. PARTICIPANTS: Sixty-one subjects (inpatients) over the age of 55 meeting DSM-III-R criteria for major depression of whom 22 had delusional subtype of depression. MEASURES: Clinical assessment, including documentation of vascular risk factors. Cognitive assessment by the Cambridge Cognitive Examination (CAMCOG). Magnetic resonance imaging (MRI) scans were performed on a 0.3 Tesla scanner with temporal lobe atrophy, periventricular lesions (PVL) and deep white matter lesions (DWML) rated visually on 4-point scales. A standard 1 mg dexamethasone suppression test (DST) was performed. RESULTS: Subjects with delusional depression had significantly more vascular risk factors than those without delusions. There were no differences in measures of temporal lobe atrophy, PVL, DST results or cognitive test scores, though there was a non-significant trend for DWML to be more prevalent in those with delusions. Delusional depression was associated with a shorter duration of history and more frequent treatment with ECT. CONCLUSIONS: The increase in vascular risk factors and trend towards greater DWML on MRI suggests an organic contribution to delusional depression in the elderly. In contrast to some previous reports, we found no differences in cortical MRI appearance or neuroendocrine measures between groups.

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PubMed1997

Temporal lobe magnetic resonance imaging can differentiate Alzheimer's disease from normal ageing, depression, vascular dementia and other causes of cognitive impairment.

BACKGROUND: Previous work suggests that temporal lobe magnetic resonance imaging (MRI) can distinguish those with dementia of the Alzheimer type (DAT) from healthy age-matched controls. However, its specificity with regard to conditions such as vascular dementia, depression and other disorders associated with cognitive impairment has not been determined. METHODS: We studied 222 subjects using T1 weighted MRI with 5.1 mm coronal slices throughout the temporal lobe. Subjects included: healthy controls (N = 40); DSM-III-R major depression (N = 61); NINCDS/ADRDA DAT (N = 77) and OTHER (N = 44, comprising subjects with vascular dementia, Huntington's disease, schizophrenia, alcohol related cognitive impairment and a group of 'memory complainers'). Hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus and cerebral cortex were rated visually on a 0-3 scale by two experienced neuroradiologists blind to clinical diagnosis. RESULTS: Ratings of temporal lobe atrophy provided good separation between those with AD and all other groups. For example, anterior hippocampal atrophy had a sensitivity of 83% for detecting DAT, a specificity of 80% for controls, 87% for depressed subjects and 89% for OTHER. Other regions were less sensitive, but more specific for the diagnosis of DAT. In particular parahippocampal gyrus and entorhinal cortex had high specificity (97% for depressed subjects and 98% for OTHER). Because of an age-related increase in atrophy, sensitivity was highest for those over the age of 75, while specificity was highest for younger subjects. Significant correlations were observed between atrophy ratings of hippocampus, amygdala, entorhinal cortex and parahippocampal gyrus and CAMCOG memory score and length of history. CONCLUSIONS: Temporal lobe MRI may have an important role in assisting with the clinical diagnosis of DAT, particularly its differentiation from depression and other disorders that may cause diagnostic difficulties in clinical practice.

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