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Biomedical subjects

H Brodaty

Publications and source records attributed to H Brodaty.

At least 19 recordsLinked to original sources

A prospective follow-up study of ECT outcome in older depressed patients.

BACKGROUND: This study examined the relationship between age and outcome of electroconvulsive therapy (ECT). METHOD: This was a naturalistic, prospective follow-up of 81 consecutive in-patients with primary major depression. ECT outcome was compared for three age groups - under 65, 65-74 and 75 years and over - on the Hamilton Rating Scale for Depression (HRSD), Global Assessment of Functioning scale (GAF) and clinical outcome rating scale. Assessments were performed pre-ECT, immediately post-ECT, 1-3 years later and, for patients suspected of having dementia, 5 years later. RESULTS: At post-ECT and follow-up, improvement on HRSD and clinical outcome ratings were comparable for patients in the three age groups. Improvements on GAF were also comparable post-ECT, but not between post-ECT and follow-up. At follow-up, 35.7% of the oldest group had dementia. Importantly, patients who did and did not develop dementia were clinically indistinguishable prior to ECT. The number and severity of common adverse events were similar pre- and post-ECT and were not associated with age. CONCLUSIONS: Depressive outcome and adverse effects of ECT are largely independent of age. Older patients receiving ECT appear to have a higher risk of developing dementia, possibly underpinned by cerebrovascular disease.

Adult↗

Reliability and validity of ratings of signal hyperintensities on MRI by visual inspection and computerised measurement.

Brain magnetic resonance imaging (MRI) scans on 98 elderly subjects, 62 with a diagnosis of schizophrenia and 36 healthy controls, were independently and blindly rated by two investigators using the visual rating methods of Fazekas et al. (Fazekas, F., Chawluk, J.B., Alavi, A., Hurtig, H.I., Zimmerman, R.A., 1987. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. American Journal of Neuroradiology 8, 421-426) and Victoroff et al. (Victoroff, J., Mack, W.J., Grafton, S.T., Schreiber, S.S., Chui, H.C., 1994. A method to improve interrater reliability of visual inspection of brain MRI scans in dementia. Neurology 44, 2267-2276) for periventricular, deep white matter and subcortical gray matter signal hyperintensities (SHs) on T2-weighted images. The hyperintense signal volumes were measured by manual delineation of the signals on a workstation using Analyze software (computerised method). The subjects also underwent a detailed neuropsychological assessment. There was a high correlation between two experienced raters for both visual ratings, and the correspondence between the two methods was high. The inter-rater reliability for the computerised method was modest but significant, and the association between the visual and computerised methods was good except for ratings for SHs in subcortical nuclei. The Fazekas and computerised methods, and to a lesser degree the Victoroff method, had modest but significant correlations with some neuropsychological test measures. In conclusion, we did not demonstrate a clear superiority in reliability or validity for one demanding computerised method of rating SHs. Visual ratings should therefore be considered adequate for most clinical and research purposes, but such ratings should be accompanied by adequate training and the provision of standard reference images.

Aged↗

Vascular dementia: diagnosis, management and possible prevention.

There has been a recent upsurge of interest in the clinical features of and risk factors for vascular dementia, and consensus is emerging on its diagnostic characteristics. We discuss these features and risk factors and the main intervention strategies, both for treatment and prevention.

Dementia, Vascular↗

Realistic expectations for the management of Alzheimer's disease.

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder characterized clinically by cognitive and functional deficits and behavioural disturbances. Over the past two decades, the devastating nature of AD has captured the attention of the general and medical communities alike. This is due partly to the increased prevalence of AD and the expansion of the aged population. Furthermore, and perhaps inappropriately, the media have encouraged speculation concerning a 'cure' for AD. Such treatment strategies are in the early stages of pre-clinical investigation and well-designed clinical trials are awaited. Nevertheless, other strategies, aimed at reducing the progression or effects through pharmacological symptomatic therapies and psychosocial interventions have demonstrated some clinical benefit and are now available and practicable. This paper critically evaluates the merits of both currently available and potential future therapeutic strategies according to primary, secondary and tertiary levels of preventative treatment.

Aged↗

Cognitive function in depression: a distinct pattern of frontal impairment in melancholia?

BACKGROUND: Although depressed patients demonstrate impaired performance on a range of neuropsychological tests, there is little research that examines either frontal cognitive deficits or possible differences in test performance between melancholic and non-melancholic subtypes. METHODS: Depressed subjects were administered a broad neuropsychological battery. In an overall analysis, 77 depressed subjects were compared with 28 controls. In a second set of analyses, the depressed sample was divided into melancholic and non-melancholic subsets according to DSM-III-R, the CORE system and the Newcastle scale. These depressed subsets were contrasted to controls and with each other using ANCOVA controlling for age, IQ, simple reaction time and Hamilton Depression scores where appropriate. RESULTS: The total depressed sample was impaired on most mnemonic tasks, simple reaction time and Trails B. Similar findings applied to DSM-III-R melancholic and non-melancholic subjects. When defined by the CORE and Newcastle (narrower definitions of melancholia), melancholic patients were additionally impaired on WCST (perseverative response) and (for Newcastle) digit symbol substitution. In contrast, the cognitive performance of the CORE and Newcastle-defined non-melancholic patients was largely unimpaired. CONCLUSIONS: Using narrower definitions of melancholia, i.e. CORE and (in particular) Newcastle, melancholic patients were impaired on mnemonic tasks and tasks of selective attention, and set-shifting while non-melancholic subjects were largely unimpaired in their cognitive performance. These differences may be due to impairment of specific neuroanatomical regions in narrowly defined melancholic patients, in particular the anterior cingulate.

Adult↗

Recall of depressive episode 25 years previously.

BACKGROUND: Lifetime rates of depression reported in epidemiological surveys are generally only twice the 12 month rates. Either people forget the symptoms of depression or many people who have a depressive episode remain depressed for many years. Both may be true. There is a need to examine the long-term clinical validity of interviews that are used to make lifetime diagnoses. METHODS: Forty-five patients who were part of a long-term follow-up study of depression were interviewed 25 years after the index episode. The diagnoses from the original, fully structured interviews were compared with the responses people made for that period when interviewed using the CIDI 25 years later. RESULTS: Twenty-seven patients met CIDI DSM-III-R criteria for depression at index episode. At the 25 year follow-up, 19 of the 27 reported the essential symptoms of 'depression or loss of interest' being present at the index time, and in 14 of the 27 the depressive symptoms recalled met criteria for DSM-III-R major depressive episode at that time. CONCLUSIONS: Seventy per cent of people who were hospitalized for a major depressive episode can recall being depressed but only half can recall sufficient detail to satisfy the diagnostic criteria when interviewed 25 years later. As depressive episodes, especially those severe enough to warrant admission, are recalled better than many other diagnoses, one must be cautious about the lifetime rates for mental disorders reported in retrospective epidemiological surveys.

Adult↗

Mid-sagittal anatomy in late-onset schizophrenia.

BACKGROUND: Of the midline brain structures, abnormalities have been demonstrated in the corpus callosum and cerebellum in young schizophrenic patients. Whether similar abnormalities are also present in late-onset schizophrenia (LOS) is not known. METHODS: The mid-sagittal cross-sectional areas of brain regions, in particular the corpus callosum and cerebellum, on magnetic resonance imaging were examined in a group of patients with late-onset schizophrenia (N = 25) and contrasted with two comparison groups - early-onset schizophrenia (EOS) (N = 24) and healthy volunteers (NC) (N = 30) matched for age and gender. RESULTS: While the mean corpus callosum area in the LOS group was smaller than in the EOS (by 10.2%) and NC (by 6.2%) groups, the three groups did not differ statistically in the corpus callosum area or the corpus callosum to cerebrum ratios. The cross-sectional cerebellar areas or the cerebellum: cerebrum ratios also did not differ across the groups. The brainstem was smaller in the schizophrenic groups because of smaller cross-sectional areas of the pons, a statistically significant difference which could not be accounted for by any gross lesions on visual inspection. CONCLUSION: We found no abnormality in the mid-sagittal area of the corpus callosum and cerebellum in our early- or late-onset schizophrenia subjects. The significance of the finding of a smaller pontine cross-sectional area is unclear and speculation on it awaits independent replication using a volumetric measure.

Age Factors↗

An electroencephalographic investigation of late-onset schizophrenia.

We performed awake and resting electroencephalograms (EEGs) on 22 subjects with DSM-III-R schizophrenic disorder of late onset (at or after age 50 years), and compared them with the EEGs of 33 healthy community controls matched for age and gender. The EEGs were rated qualitatively and a 2-minute, artifact-free tracing from each subject was quantified manually by an experienced neurophysiologist unaware of the identity of the subject group. The only significant difference was the presence of more generalized slowing in the EEGs of schizophrenia patients, which was at least partially accounted for by the effect of neuroleptic drugs. The schizophrenic subjects did not have a greater prevalence of epileptiform disturbances or abnormal asymmetry of the EEG compared to the control group. Our study does not suggest the presence of underlying dementia in schizophrenia of late onset.

Age of Onset↗

Quantitative study of signal hyperintensities on T2-weighted magnetic resonance imaging in late-onset schizophrenia.

OBJECTIVE: The authors investigated the extent and distribution of signal hyperintensities on T2-weighted magnetic resonance imaging (MRI) of the brains of subjects with late-onset schizophrenia. METHOD: The study group consisted of 25 subjects with DSM-III-R schizophrenia and onset at age 50 or more years (late-onset schizophrenia) matched group-wise with 24 subjects with early-onset schizophrenia and 30 psychiatrically healthy volunteers. The subjects underwent clinical and neuropsychological assessments and MRI scans. Transaxial T2-weighted and proton-density images were analyzed manually for signal hyperintensities in cerebral and cerebellar white matter, the basal ganglia, thalamus, and brainstem, and quantitative measures were obtained. RESULTS: Subjects with late-onset schizophrenia had greater periventricular hyperintensities measured as widths of periventricular rims and frontal and occipital caps than the two comparison groups. Hyperintense signals elsewhere in the white matter and in the basal ganglia and brainstem did not differ between groups, but the late-onset schizophrenia group had more signal hyperintensities in the thalamus than the normal comparison group. Signal hyperintensities in the frontal-subcortical circuit regions, when considered together, did not differ between groups. Periventricular hyperintensities had significant negative correlations with intelligence, memory, and frontal-executive functioning in the total group. CONCLUSIONS: The finding of increased periventricular hyperintensities and thalamic signal hyperintensities in late-onset schizophrenia suggests the possibility that cerebrovascular disease, in an interaction with some incompletely understood vulnerability factors, may play a role in the pathogenesis of schizophrenia with onset in advanced age.

Adult↗

Schizophrenia with onset after age 50 years. I: Phenomenology and risk factors.

BACKGROUND: Schizophrenia occurring for the first time in late life may be a distinct entity or part of a continuum. AIMS: Can late-onset schizophrenia (LOS) and early-onset schizophrenia (EOS) be differentiated by their phenomenology and risk factors to their development? METHOD: Convenience samples of 27 DSM-III-R defined LOS subjects, 30 EOS subjects and 34 control subjects were systematically assessed. RESULTS: Premorbidly, both groups of subjects with schizophrenia had personality traits that were different from controls but not from each other. The EOS subjects had more family members with a history of psychiatric illness or schizophrenia and less hearing impairment than the other two groups, which did not differ from each other. Clinically, LOS and EOS subjects were similar, except that EOS subjects had more negative symptom scores, tended to have more delusions of guilt/sin and of being controlled and more formal thought disorder, and had significantly poorer instrumental activities of daily living. CONCLUSIONS: Phenomenology and risk factors do not distinguish discrete LOS.

Age of Onset↗

Schizophrenia with onset after age 50 years. 2: Neurological, neuropsychological and MRI investigation.

BACKGROUND: Late-onset schizophrenia (LOS) may have a basis in age-related coarse brain disease, but empirical support for this is conflicting. AIMS: Is LOS characterised by more neurological disease than early-onset schizophrenia (EOS)? METHODS: DSM-III-R-defined LOS subjects (n = 27) were compared with 30 EOS and 34 volunteer control subjects on neurological status, neuropsychological test performance and brain magnetic resonance imaging (MRI). RESULTS: LOS and EOS groups had more 'soft' neurological signs and drug-induced movement abnormalities, and performed more poorly on tests assessing speed of information processing, memory and frontal executive functioning. On MRI, the LOS and EOS groups had greater lateral ventricular size than the control group. The LOS subjects also had more signal hyperintensities in periventricular white matter and subcortical nuclei than controls. CONCLUSIONS: LOS and EOS subjects were very similar on neuropsychological, neurological and structural neuroimaging parameters, except that there were more MRI periventricular hyperintensities in LOS subjects.

Age of Onset↗

Younger people with dementia: diagnostic issues, effects on carers and use of services.

OBJECTIVE: To determine difficulties experienced by carers of younger people with dementia. DESIGN: Cross-sectional questionnaire survey. PARTICIPANTS: 102 eligible carers of persons less than 65 years of age with dementia, recruited through support groups and clinicians' referrals. MAIN OUTCOME MEASURES: Problems with diagnostic process; professionals/services consulted; psychological, physical, occupational and financial impact of illness on carers and children; use of and satisfaction with services. MAIN RESULTS: Diagnostic problems were reported by 71% of carers. Mean time until diagnosis was 3.4 years (SD 2.8) after consulting 2.8 (1.4) professionals. Carers reported frustration (81%) and grief (73%). Adverse psychological effects were common, more so in female than male carers (p < 0.01). The younger the carer, the more psychological and physical effects were experienced (p < 0.01). Only 8% of carers considered that their children had encountered no problems because of the dementia. Of 61 working carers, 59% reduced their hours or stopped working after diagnosis, and 89% of all carers had experienced financial problems subsequent to diagnosis. Most carers (89%) had used a support service, but 25% had never used community support, 32% had never used respite. Proportions of carers rating services as good ranged between 43 and 100%. CONCLUSIONS: Younger people with dementia, and their carers, face difficulties in obtaining a diagnosis. Carers also experience psychological problems, financial worries, loss of employment and family conflict, and their children are affected. Most carers had used services, but some dissatisfaction existed.

Adult↗

Suicidal ideation and the 'wish to die' in dementia patients: the role of depression.

OBJECTIVE: To determine the prevalence of self-reported suicidal ideation and the 'wish to die' in dementia patients, their association with depressive symptoms and the type of dementia. DESIGN: The cohort was formed retrospectively of consecutive referrals between 1985 and 1994 of cognitively impaired patients who met American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, third edition and third edition, revised, criteria for dementia. They were assessed for depression using the 21-item Hamilton Rating Scale for Depression (HRSD) which includes an item on suicide. SETTING: An outpatient multidisciplinary memory disorders clinic in Sydney, Australia. PATIENTS: The sample comprised 221 patients with dementia: 148 with Alzheimer's disease according to NINCDS-ADRDA criteria, 24 with vascular dementia diagnosed by a Hachinski ischaemia scale score of seven or more, plus focal neurological signs, symptoms or computed tomography-visible lesions, and 49 with other dementias. MEASURES: Cognitive impairment was measured by the Mini-Mental State Examination and the Blessed orientation-information-memory-concentration test and dementia scales, depression by the 21-item HRSD, suicidal ideation and the 'wish to die' as defined by the suicide item on the HRSD, functional capacity by the activities of daily living scale and the instrumental activities of daily living scale. Caregiver psychological morbidity was assessed with the General Health Questionnaire. RESULTS: 12 patients (5.4%) felt life was not worth living, seven (3.2%) 'wished to die' or had thoughts of death, two (0.9%) had suicidal ideation or gestures and none had made any suicide attempts. The nine patients who 'wished to die' or had suicidal ideation scored 12 or more on the HRSD. Of these, six were clinically depressed. Suicidal ideation and the 'wish to die' were significantly correlated with the presence of depressive symptoms as measured by the HRSD (suicide item excluded), but only in those with Alzheimer's disease. There were no significant differences in HRSD scores between the dementia groups. Suicidal ideation was unrelated to the presence of insight into loss of memory. CONCLUSIONS: Suicidal ideation and/or the 'wish to die' is self-reported in 4% of dementia patients attending a memory disorders clinic and is associated with comorbid depressive symptoms, particularly in Alzheimer's disease.

Aged↗

Screening for cognitive impairment in general practice: toward a consensus.

We considered whether general practitioners should examine all older patients over a certain age for cognitive impairment in screening for early dementia. We invited presentations from key experts, selectively reviewed the literature, and developed a consensus statement. The efficacy of and benefits from unselective use of cognitive testing and informant questionnaires for detecting early dementia in older patients attending general practice are limited. Positive predictive values of cognitive screening for dementia are less than 50%, even for older patient populations. Higher values may be obtained by testing patients who have a relevant history of cognitive or functional decline. Whatever procedures are adopted for screening older general practice attenders for cognitive impairment or early dementia, investigation is still required into the relative merits of different health professionals performing the screening, the positive and negative effects on patients and their families, and the cost-benefit ratio. The majority view of workshop participants was that cognitive testing should occur for older patients when there is a reason to suspect dementia. Testing may occur in an individual considered to be at risk because of an informant history of cognitive or functional decline, clinical observation, or, sometimes, very old age. No single instrument for cognitive screening is suitable for global use. Screening programs must be supported by training and supplemented by education for professionals and families in management of dementia.

Age of Onset↗

Psychological morbidity in caregivers is associated with depression in patients with dementia.

The relationship between psychological morbidity in caregivers and depression in patients with dementia was examined using data collected on 193 patient-caregiver dyads attending a memory disorders clinic. Caregivers had high rates and levels of psychological morbidity which were associated with the severity of dementia (but neither the type nor duration), with the caregiver being a spouse and female and living with the person with dementia. A logistic regression analysis identified clinician-rated patient depression score and demanding problem behaviors as being independently and significantly associated with caregiver psychological morbidity. This new finding of a link between patient depression and caregiver psychological morbidity has implications for more focused treatment programs for both caregivers and patients.

Activities of Daily Living↗

First International Pharmacoeconomic Conference on Alzheimer's Disease: report and summary.

The First International Pharmacoeconomic Conference on Alzheimer's Disease (AD) was held in Amsterdam in July 1998. The meeting was held under the auspices of the International Working Group for Harmonization of Dementia Drug Guidelines (http://dementia.ion.ucl.ac.uk/harmon), bringing together academics, clinicians, purchasers, and representatives from industry. Presentations were given on the methodology of pharmacoeconomic studies in AD, particularly focusing on caregiver burden, quality of life (QOL), and resource utilization. Three economic models of AD were presented based on data from the United States, Canada, and the United Kingdom. In two studies, these data were then used to model the cost-effectiveness and effect on cost of treatment with donepezil. Both studies suggested a possible cost advantage for the use of donepezil, when compared with no placebo or treatment, particularly when donepezil is used appropriately in mild-to-moderate AD. These data need to be interpreted with care, as none of the cost or utility information were collected during the clinical trials. Additional data from a 2-year clinical trial of selegiline and vitamin E suggest that cognitive measures may be poor predictors of economic outcome, which is better measured directly. Both economic models of donepezil rely on short-term cognitive data to predict long-term outcome, a methodf that may not be useful in predicting economic savings. The issues facing pharmacoeconomists, researchers, clinicians, and families in the future were addressed in a series of workshops using a method of strategic futuring. The workshops attempted to see 7 years into the future for a range of areas, including consumer and caregiver use of pharmacoeconomic data; early detection and prevention; Japanese perspectives; activities of daily life and what will be daily life activities; caregiver burden; QOL at the end of life; new uses for new information and communication technology in clinical research; and physicians' use of pharmacoeconomic data. A range of exciting futures were predicted, although common themes that arose when considering barriers to achieving these futures included cost, education, political will, confidentiality, privacy, and ethics. The first conference was deemed to have been a success, having attracted more than 160 delegates and many distinguished speaker. A second conference is planned for the year 2000. Over the next 2 years, research needs to be broadened particularly in the methodological areas of resource utilization, QOL, and caregiver burden. Data from clinical trials with relevant economic and QOL outcomes will be needed by purchasers if drug treatments for dementia are to gain widespread use. It is also hoped that the models described at the meeting may become more freely available to politicians, purchasers, clinicians, and caregivers to help them make better decisions about treatment.

Aged↗

Regional cerebral blood flow in late-onset schizophrenia: a SPECT study using 99mTc-HMPAO.

Functional neuroimaging studies have been performed in many young patients with schizophrenia, but late-onset schizophrenia (LOS) remains largely unexamined by these techniques. We predicted that LOS would demonstrate regional cerebral blood flow (rCBF) abnormalities similar to those seen in early-onset schizophrenia (EOS), but with a basis in demonstrable coarse brain disease. The subjects were 15 LOS and 7 EOS patients and 27 healthy controls. Each was given a detailed clinical and neuropsychological assessment and underwent MRI and Tc99m-HMPAO single photon emission computed tomography (SPECT) scans. The LOS subjects had a significantly lower cerebral hemispheric perfusion than controls, with a lower perfusion in the frontal and temporal lobes bilaterally. The LOS group also had significantly lower left-to-right hemisphere blood flow ratios. EOS subjects had a lower frontal perfusion than the controls, which was significant in the left frontal region. The temporal perfusion in the EOS subjects was greater than in the LOS group, and not different from the control subjects. Left temporal perfusion was the most discriminating variable between LOS and control subjects on logistic regression. Correlations of perfusion with MRI were generally low with the exception that the asymmetry indices were significantly correlated, and basal ganglia perfusion correlated with basal ganglia hyperintensities on MRI. The total cerebral perfusion index correlated significantly with the mini-mental state examination (MMSE) score, and the temporal lobe perfusion correlated with MMSE scores and some verbal memory measures. In the schizophrenic groups, perfusion correlated nonsignificantly with symptom profiles. We conclude that our findings of temporal and frontal rCBF abnormalities, especially on the left side, in LOS are similar to those reported in schizophrenia in general. The results do not provide evidence for coarse brain disease underlying the rCBF abnormalities in LOS, or support the specificity of these abnormalities for particular subsyndromes of schizophrenia.

Age of Onset↗

Drugs for the prevention and treatment of Alzheimer's disease.

Alzheimer's disease affects up to 100,000 people in Australia, but pharmacological treatment has only been available in recent years. Currently available drugs provide modest relief of symptoms for varying periods of time but have no proven preventive action against the disease.

Aged↗