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Biomedical subjects

Henry Brodaty

Publications and source records attributed to Henry Brodaty.

At least 19 recordsLinked to original sources
PubMed2021

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

Brain↗
PubMed2007

Progression of white matter hyperintensities in elderly individuals over 3 years.

OBJECTIVE: The aims of this study were to examine white matter hyperintensities (WMHs) in the brains of elderly individuals, the rate of progression, the anatomic regions most vulnerable, and the predictors of change. METHODS: We examined 51 healthy volunteers (mean age 71 years) with T2-weighted brain MRI on the same scanner 3 years apart. WMH volumes were determined by an automated method, and the anatomic location of change was determined for both deep WMHs (DWMHs) and periventricular WMHs (PVWMHs). RESULTS: The total brain WMH volume increased by 39.6%, i.e., 13.2% per year, with the change in DWMH being 43.8% and 29.7% in PVWMH. The increase was significant in all regions except the occipital lobe and cerebellum. Age, sex, and cerebrovascular risk factors were not significant predictors of WMH progression. The main predictor of progression was baseline level of WMH. The number of WMH lesions increased by a mean of 1.78, and the progression was mainly accounted for by an increase in very large (>16 mm) lesions. Eight subjects showed a slight decrease in WMH. CONCLUSIONS: White matter hyperintensities are progressive in most elderly individuals with an increasing rate of progression as the burden of lesions increases. The rate of progression is greater in deep white matter and in the anterior brain regions. Risk factors for progression are not well understood, and genetic and other environmental factors must be examined. Quantitation of white matter hyperintensities may serve as a surrogate marker of the progression of small vessel disease.

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PubMed2006

Prediction of cognitive decline after stroke using proton magnetic resonance spectroscopy.

Structural MRI measures have been used to predict cognitive decline in elderly subjects, but few studies have used proton magnetic resonance spectroscopy ((1)H-MRS) for this purpose, particularly after stroke. We studied the potential of (1)H-MRS to predict cognitive decline in patients with stroke or TIA and healthy ageing controls over 12 months and 3 years. Structural MRI and single-voxel (1)H-MRS in the frontal white matter and the occipito-parietal gray matter were performed at the index assessment (3-6 months post-stroke) in 49 stroke/TIA patients and 60 controls. Neuropsychological testing was performed at the index assessment and repeated at 12 months in 30 stroke/TIA patients and 49 controls, and at 3 years in 25 patients and 48 controls. In stroke/TIA patients, frontal NAA/Cr predicted cognitive decline over 12 months and 3 years, and in elderly control subjects frontal NAA predicted cognitive decline over 12 months only. In stroke/TIA patients, the (1)H-MRS measures were better predictors of cognitive decline than structural measures. (1)H-MRS may be useful in assessing early cognitive impairment after stroke/TIA and in normal ageing.

Aged↗
PubMed2006

Treating behavioral and psychological symptoms in patients with psychosis of Alzheimer's disease using risperidone.

OBJECTIVES: To examine the effect of risperidone on specific behavioral and psychological symptoms of dementia (BPSD) among patients with psychosis of Alzheimer's disease (AD). METHODS: Post hoc exploratory analysis of data on 479 nursing-home patients with psychosis of AD from three 12-week, double-blind, placebo-controlled clinical trials. Criteria for psychosis of AD were a diagnosis of AD or mixed dementia and a rating of >/= 2 on any delusion or hallucination item of the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale when entering the trial. Mean changes from baseline to endpoint were examined for items on the Cohen-Mansfield Agitation Inventory (CMAI) and BEHAVE- AD. RESULTS: On the CMAI, risperidone was significantly more effective than placebo in treating cursing or verbal aggression (p = 0.004), hitting (p < 0.001), performing repetitious mannerisms (p < 0.001), pacing, aimless wandering (p = 0.017), hoarding things (p = 0.02), hiding things (p = 0.02) and repetitive sentences or questions (p = 0.025). On the BEHAVE-AD, risperidone was significantly more effective than placebo in treating physical threats and/or violence (p = 0.001), agitation (other) (p = 0.001) and verbal outbursts (p = 0.026). Although analysis on individual hallucination and delusional items did not demonstrate specific responses, analyses of a composite of delusional items revealed significant drug-placebo differences. CONCLUSIONS: These data indicate that risperidone is effective in treating a variety of symptoms associated with psychosis of AD.

Aged↗
PubMed2006

Mild cognitive impairment.

Mild cognitive impairment is a syndrome defined as cognitive decline greater than expected for an individual's age and education level but that does not interfere notably with activities of daily life. Prevalence in population-based epidemiological studies ranges from 3% to 19% in adults older than 65 years. Some people with mild cognitive impairment seem to remain stable or return to normal over time, but more than half progress to dementia within 5 years. Mild cognitive impairment can thus be regarded as a risk state for dementia, and its identification could lead to secondary prevention by controlling risk factors such as systolic hypertension. The amnestic subtype of mild cognitive impairment has a high risk of progression to Alzheimer's disease, and it could constitute a prodromal stage of this disorder. Other definitions and subtypes of mild cognitive impairment need to be studied as potential prodromes of Alzheimer's disease and other types of dementia.

Aged↗
PubMed2006

A high-resolution single photon emission computed tomography study of verbal recognition memory in Alzheimer's disease.

BACKGROUND: In view of the recent technological advances and its ease of availability, we used single photon emission computed tomography (SPECT) to examine the performance of early Alzheimer's disease (AD) subjects on a verbal recognition memory task. METHODS: Eighteen early AD and 10 matched healthy control subjects underwent split-dose (99m)Tc-HMPAO (Ceretec) SPECT using a verbal recognition memory and control task. SPECT images co-registered with MRI scans were used to determine relative regional cerebral blood flow (rCBF) changes in regions of interest. RESULTS: In healthy control subjects, verbal recognition increased rCBF in the right occipital region, thalamus, left prefrontal pole, posterior parietal region and cerebellum, and decreased rCBF in the right hippocampus. AD subjects showed bilateral prefrontal, posterior parietal and occipital increases, unilateral increase in the left posterior temporal region, and bilateral reductions in the hippocampus. Although activation was significantly different between the two groups in the right thalamus and left medial prefrontal region, the verbal recognition task did not enhance discrimination between groups. CONCLUSIONS: Compared with controls, AD subjects activate a similar but more extensive bilateral network during verbal recognition, possibly reflecting an attempt to compensate for impaired processing.

Aged↗
PubMed2006

IPA survey of brief cognitive screening instruments.

BACKGROUND AND OBJECTIVES: Cognitive screening is a "first step" in detecting dementia and other neuropsychiatric syndromes and hence represents an important public health and clinical initiative. A plethora of cognitive screening instruments has been advocated in recent years, but the extent to which these instruments are used or their effectiveness is not well known. An International Psychogeriatric Association (IPA) survey was designed to determine which cognitive screening instruments were used most frequently by clinicians with special expertise in the neuropsychiatric aspects of old age and also to determine the ones considered most useful by these specialists. METHOD: Under the auspices of the IPA, the survey was mailed in the fall of 2004 to all IPA members as well as members of the American and Canadian Associations of Geriatric Psychiatry. The survey inquired about demographic information, the frequency of use of cognitive screening instruments, and the value attributed to the cognitive screening instruments. Participants also had an opportunity to provide written commentary. RESULTS: A total of 334 completed surveys were processed. The majority of respondents were geriatric psychiatrists (58%). Of the 20 different instruments that were listed on the survey, only six were selected as "routinely" or "often used" by the survey respondents. These instruments in declining order were: (1) the Folstein Mini-mental State Examination; (2) the Clock Drawing Test; (3) Delayed Word Recall; (4) the Verbal Fluency Test; (5) Similarities; and (6) the Trail Making Test. "Effectiveness" and "ease of administration" were the test characteristics most highly predictive of frequency of use. Open-ended comments highlighted patient factors that continue to provide challenges, including ethnicity/culture, language, education/literacy, and sensory impairment. Respondents concluded that "no single test is adequate." CONCLUSIONS: Psychogeriatricians worldwide routinely use a relatively small number of brief cognitive screening instruments. Further evaluation is necessary as the need increases for cognitive screening guidelines that inform public health initiatives related to dementia and neuropsychiatric syndromes.

Adult↗
PubMed2006

Family conflict in dementia: prodigal sons and black sheep.

OBJECTIVE: To describe family conflict in cases of dementia referred to the Guardianship Tribunal of New South Wales, Australia. METHOD: The file notes of 50 cases of family and systems conflict in cases of dementia presented to the Guardianship Tribunal were examined. Demographics, MMSE score, and type and severity of dementia were recorded. The documents and evidence presented to the Tribunal were coded and subjected to thematic analysis to identify the themes of the conflict, the protagonists and the position of the person with dementia with respect to the conflict. RESULTS: Family conflict was most commonly seen in mild to moderate dementia. Conflict occurred most frequently between siblings (with a group of siblings allied against a 'black sheep' member) and involved other systems such as service providers in 25% of cases. The person with dementia was usually involved in the conflict or in alliance with one or other of the family members in conflict, especially when paranoid ideation was fuelled by family members. Common themes included accusations of neglect, exploitation, lack of communication or sequestration of the person with dementia. No family had received family therapy prior to the application; conciliation during the hearing was successful in 30% of cases. Legal transactions such as Powers of Attorney were frequently made and frequently revoked by persons with dementia involved in family conflict. CONCLUSION: Dementia may be a great family divider, particularly when there are cracks in family solidarity. The understanding of family conflict in dementia has ramifications for both clinical and medico-legal practice. These findings may encourage family-centered interventions which address family dynamics and interpersonal conflict. They may also assist in capacity assessments of persons with dementia who change legal documents because of family conflict.

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PubMed2006

A tiered model of psychogeriatric service delivery: an evidence-based approach.

BACKGROUND: Previous models of mental health care for older persons have not considered the full spectrum of mental disorders. AIM: To describe a tiered model for comprehensive evidence-based planning of service delivery for mental disorders in late life. METHOD: The model depicts tiers of mental disorders in ascending order of severity and consequent interventions required. RESULTS: Interventions aim both to avert individuals from moving up tiers (prevention) and to move individuals down tiers (treatment). Individuals in the lower tiers have no mental disorders and prevention strategies are targeted at known risk factors. In the middle tiers, individuals with mild-moderate mental disorders will mainly be treated in primary care, often in collaboration with specialist mental health services for older people. Individuals in the top tiers with severe mental disorders usually require institutional care. CONCLUSION: The tiered model provides a basis for planning comprehensive service delivery.

Aged↗
PubMed2006

Longitudinal changes during aging using proton magnetic resonance spectroscopy.

OBJECTIVE: We aimed to examine the longitudinal change in proton magnetic resonance spectroscopy ((1)H-MRS) visible metabolites (N-acetyl aspartate [NAA], creatine [Cr], choline [Cho], and myo-Inositol [mI]) in brains of elderly individuals over 3 years and relate them to cognitive function. METHODS: Neurologically and psychiatrically normal volunteers (n = 40) were examined at baseline and 3 years later with (1)H-MRS in two voxels (frontal white matter n = 29, and occipitoparietal gray matter n = 36) and with detailed neuropsychological assessments. Longitudinal analyses were performed with age, educational level, sex, and white matter hyperintensities (WMH) in voxels as covariates. RESULTS: Frontal mI was significantly increased over time in male participants, but all other metabolites were stable over time. Neuropsychological performance was not significantly changed over 3 years, and there was no relationship between change in metabolite levels and change in neuropsychological function. CONCLUSIONS: MRS-visible metabolites are stable in elderly persons over 3 years, with the exception of mI which shows an increase. Increasing mI may be a marker of aging or a preclinical neurodegenerative process. MRS changes do not correlate with change in neurocognitive function during aging.

Aged↗
PubMed2006

What is the best dementia screening instrument for general practitioners to use?

OBJECTIVE: The objective of this study was to review existing dementia screening tools with a view to informing and recommending suitable instruments to general practitioners (GPs) based on their performance and practicability for general practice. METHOD: A systematic search of pre-MEDLINE, MEDLINE, PsycINFO, and the Cochrane Library Database was undertaken. Only available full-text articles about dementia screening instruments written in English or with an English version were included. Articles using a translation of an English language instrument were excluded unless validated in a general practice, community, or population sample. RESULTS: The General Practitioner Assessment of Cognition (GPCOG), Mini-Cog, and Memory Impairment Screen (MIS) were chosen as most suitable for routine dementia screening in general practice. The GPCOG, Mini-Cog, and MIS were all validated in community, population, or general practice samples, are easy to administer, and have administration times of 5 minutes or less. They also have negative predictive validity and misclassification rates, which do not differ significantly from those of the Mini-Mental Status Examination. CONCLUSIONS: It is recommended that GPs consider using the GPCOG, Mini-Cog, or MIS when screening for cognitive impairment or for case detection.

Aged↗
PubMed2006

Combined cerebral blood flow effects of a cholinergic agonist (milameline) and a verbal recognition task in early Alzheimer's disease.

RU 35926/CI-979 (milameline) is a partial muscarinic agonist with promnestic effects in animal models. Preliminary animal studies suggest that this agent has the capacity to reverse cholinergic dysfunction and that it may impact on regional cerebral blood flow (rCBF). A total of 10 subjects with Alzheimer's disease (AD) of mild severity underwent high resolution split-dose single photon emission computed tomography (SPECT) during performance of a verbal recognition and control task, both before and after 18 weeks treatment with melameline or placebo. SPECT images were coregistered with individual's magnetic resonance imaging scans allowing extraction of rCBF values from multiple anatomical regions of interest (ROI). The effect of milameline was examined in eight individuals who were found after unblinding to be taking active drug. Effects of milameline were most apparent in the frontal regions, basal ganglia and thalamus. In the group as a whole, the greatest increase in rCBF due to milameline treatment was observed in the left globus pallidus. Response to milameline treatment was associated with increases in rCBF in the cingulate gyrus bilaterally, and less so for the left thalamus. Milameline-related increases in rCBF values were exaggerated by the verbal recognition task. Milameline has a demonstrable effect on cerebral blood flow in mild AD. Consistent with emerging animal data, the effects on rCBF appear most prominent in frontal and subcortical regions in AD subjects. The effects on rCBF appear to be augmented by the performance of a cognitively demanding task, raising the possibility that such tasks could assist in building an awareness of the functional neuropsychopharmacology of drugs designed for cognitive enhancement.

Alzheimer Disease↗
PubMed2006

'Give me a break' - respite care for older carers of mentally ill persons.

BACKGROUND: The concept of respite care has been widely accepted and used throughout most developed countries, although primarily in connection with frail elderly, people with dementia, people with developmental disability or children. This paper aims at exploring older family carers' needs for, access to and use of respite services when caring for people with a mental illness (excluding dementia) in the community. METHOD: Data were collected through: semi-structured interviews with 26 mental health professionals, 21 family carers aged over 55 years and 25 respite service providers; demographic questionnaires; field notes; and local area, state and national documents relating to respite care services. Demographic data were analysed using descriptive statistics. All 72 interviews, field notes and other documents were analysed using content analysis. RESULTS: Current respite services are not adequate to meet the needs of mentally ill patients and older carers. The unique aspects of respite care for older carers of persons with mental illness are poorly understood. CONCLUSION: Bringing these issues to light creates the potential to address the unmet needs of older carers, improve provision of respite services, enhance quality of life of those who can benefit from respite services, and assist mental health professionals to work better with carers.

Aged↗
PubMed2006

A naturalistic study of galantamine for Alzheimer's disease.

OBJECTIVE: To collect descriptive data on the treatment of Alzheimer's disease with galantamine under naturalistic conditions. STUDY DESIGN: This was a prospective, open-label, observational study. PATIENTS: Subjects (n = 345) with mild to moderately severe dementia of the Alzheimer's type were recruited from 48 hospitals in Australia. METHODS: Subjects were enrolled and received treatment with galantamine for 6 months in a clinical practice setting. Subjects were assessed at baseline and 3 and 6 months after starting treatment using the Mini-Mental State Examination (MMSE), the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus) and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) [the latter only if the baseline MMSE score was at least 25]. Subjects were also assessed using an abridged Instrumental Activities of Daily Living (IADL) questionnaire that included questions on using the telephone, ability to travel more than 1km outside the home, taking medications and managing money, and an 11-item behaviour assessment scale that measured aggression, sleep disturbance, disinhibition, personality changes, irritability, depression, agitation, apathy, inertia, hallucinations and aberrant motor behaviour. RESULTS: Of the 345 subjects who were enrolled in the study (intent-to-treat [ITT] population), 229 completed the baseline, 3- and 6-month visits (per-protocol [PP] population). The mean age of the PP population was 78.0 +/- 6.8 years. At 6 months, most PP subjects (70%) showed an increase in MMSE score compared with baseline, with a mean increase in score of 2.0 +/- 3.1 points from a baseline of 20.8 +/- 4.2 points. In the ITT population, 44% of subjects (151/345) showed an increase in MMSE after 6 months. If data were unavailable the patient was classified as a nonresponder. Of the 21 PP patients who were assessed using ADAS-cog, 18 (86%) demonstrated a decrease in the ADAS-cog score, reflecting an improvement in cognition. Of the ITT population, 33% (19/57) had a decreased ADAS-cog score after 6 months. Most PP subjects (86%) were considered responders according to the CIBIC-plus score, with 65% showing some improvement over 6 months of treatment. Of the ITT population, 54% (187/345) showed no deterioration in CIBIC-plus score after 6 months.No deterioration in IADL or behaviour assessments occurred in the majority of PP subjects over 6 months. CONCLUSIONS: In a clinical practice setting, the majority of subjects receiving galantamine who completed the study maintained their ratings of cognition, function, behaviour or global assessment over the 6-month period.

Activities of Daily Living↗
PubMed2005

Global prevalence of dementia: a Delphi consensus study.

BACKGROUND: 100 years after the first description, Alzheimer's disease is one of the most disabling and burdensome health conditions worldwide. We used the Delphi consensus method to determine dementia prevalence for each world region. METHODS: 12 international experts were provided with a systematic review of published studies on dementia and were asked to provide prevalence estimates for every WHO world region, for men and women combined, in 5-year age bands from 60 to 84 years, and for those aged 85 years and older. UN population estimates and projections were used to estimate numbers of people with dementia in 2001, 2020, and 2040. We estimated incidence rates from prevalence, remission, and mortality. FINDINGS: Evidence from well-planned, representative epidemiological surveys is scarce in many regions. We estimate that 24.3 million people have dementia today, with 4.6 million new cases of dementia every year (one new case every 7 seconds). The number of people affected will double every 20 years to 81.1 million by 2040. Most people with dementia live in developing countries (60% in 2001, rising to 71% by 2040). Rates of increase are not uniform; numbers in developed countries are forecast to increase by 100% between 2001 and 2040, but by more than 300% in India, China, and their south Asian and western Pacific neighbours. INTERPRETATION: We believe that the detailed estimates in this paper constitute the best currently available basis for policymaking, planning, and allocation of health and welfare resources.

Aged↗