[show abstract][hide abstract] ABSTRACT: This study investigates the functional equivalence of two measures of irregular word pronunciation--National Adult Reading Test (NART) and Schonell--which are popular instruments used to assess verbal neurocognitive functioning and to estimate premorbid IQ. We report norms for the NART in a pooled sample from 3 Australian population-based studies of adults aged 65-103 years. Norms were stratified by sex and age left school in 5-year age groups. The NART and the Schonell had a strong linear relation, allowing for the imputation of NART scores based on Schonell performance within 1 study. Neither measure was sensitive to the effects of sex after adjusting for the effects of age and education. Early school leavers performed worse on both measures. Data pooling enables greater precision and improved generalizability of NART norms than do methods that use single older adult samples.
Journal of Clinical and Experimental Neuropsychology 12/2010; 33(4):410-21. · 1.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: Previous research on the association between illness and depression in older people has relied on self-reported diagnoses with their inherent limitations in scope and reliability. This longitudinal study examined the association between depressive symptoms and medically-diagnosed chronic physical and neurodegenerative diseases and disability in community-living older people. In 1992, a random sample of 299 people aged 75 years and older underwent a clinical interview and medical examination by a physician experienced in geriatric medicine. This was repeated in 1995. The examination included diagnoses of chronic active physical illness, a standardized neurological examination, an assessment of functional disability and an abbreviated neuropsychological assessment. Depressive symptoms were assessed by the Centre for Epidemiological Studies - Depression scale. Multivariate analyses of concurrent associations, longitudinal associations and the impact of incident disease showed very few independent connections between individual diseases or the total burden of disease and depressive symptoms. However, in every circumstance, disability had a marked independent impact on depressive symptoms. Insofar as the diseases examined in this study are concerned, the association between physical disease and depressive symptoms in older people appears to be mediated through disability; disease may or may not result in disability but disability is likely to lead to increased depressive symptoms.
Aging and Mental Health 06/2010; 3(4):351-357. · 1.68 Impact Factor
[show abstract][hide abstract] ABSTRACT: It is been said that ‘traditional legal theory either presumes that judges have no operative emotions about litigants and issues before them, or mandates that any such emotions be actively suppressed, reflecting an untested, commonsense wisdom that emotion distorts the legal reasoning demanded by the judicial role’. In contrast to this presumption however, recent neuroscience research has demonstrated that emotion is likely to play a key facilitative role in legal decision-making via participation of the ventromedial cortex; in particular, areas of law where personal, social, and moral circumstances are considered, areas that include criminal law and sentencing. The leading High Court decision reflecting upon deliberation and reasoning in sentencing is Markarian v The Queen. This paper will evaluate the decision-making processes proposed by the judges in that decision, and potential alternative approaches, in the light of what is possible neurobiologically.
Australian Journal of Forensic Sciences 03/2010; 42(1):11-18. · 0.53 Impact Factor
[show abstract][hide abstract] ABSTRACT: This paper reviews the Sydney Older Persons Study, a longitudinal study following an initial cohort of 630 subjects aged 75 and over, community living in the inner west region of Sydney, carried out over seven years in four waves from 1991. We discuss the epidemiology of neurodegenerative disorders (NDDs) in relation to: each other, systemic disorders, death, lifestyle, risk factors and their impact on quality of life, service use and carers.
[show abstract][hide abstract] ABSTRACT: Objective: To examine the association between alcohol consumption and incident functional disability in community-living older people after adjustment for other risk factors.Method: Randomly sampled community-living people aged 75 years and older from the inner western suburbs of Sydney underwent a clinical interview and medical examination by a physician experienced in geriatric medicine. This was repeated three years later. The examination included an assessment of functional disability and chronic systemic and neurodegenerative illnesses and impairments. Self-reported alcohol consumption was recorded. The relationship between alcohol consumption and incident disability was examined by logistic regression analysis.Results: Cross-sectional analysis at the first wave showed that those who did not drink were more likely to be disabled than drinkers (39.3% and 30.4% respectively, p = 0.032). Although 11.3% were drinking at hazardous or harmful levels there was no concurrent association between disability and hazardous/harmful drinking. Incident disability between waves did not differ between non-drinkers at the first wave and those who drank at non-hazardous/harmful levels (35.3% and 29.3% disabled respectively, p=0.306). However 80% of those who drank at hazardous/harmful levels experienced incident disability as compared with 32.5% among non-drinkers and non-hazardous/harmful drinkers combined (p<0.001). Logistic regression showed that, among the risk factors examined, hazardous/harmful consumption had by far the strongest effect with an adjusted odds ratio of 12.9 (95% CI 3.1–53.9).Conclusion: Alcohol consumption at defined hazardous/harmful levels is a major independent risk factor for incident functional disability in older people.
[show abstract][hide abstract] ABSTRACT: Objectives: To examine the determinants of service use in a community dwelling sample aged 75 or over.Methods: Subjects (n = 537) were interviewed about use of community and medical services and the provision of unpaid support from their social network. Measures of disease and disability, detailed network support data and factors that may either enable or predispose subjects to service use were obtained and their prediction of service use examined.Results: Unpaid support and community service use were predicted predominantly by disability, with disease providing little additional prediction. Medical service use was predicted by both disease and disability. With disease and disability controlled for, other variables did not significantly predict medical service use or unpaid support; but did predict small additional variation in some community service use.Conclusions: Disability and disease are the major determinants of service use with other factors contributing to the use of some community services.
[show abstract][hide abstract] ABSTRACT: Objectives: Disability is an important predictor of health and community service utilisation. Understanding its pathogenesis has implications for planning of future health services. The aim of our study was to examine the contribution of systemic, psychiatric and neurodegenerative diseases to disability in an “old-old” population.Methods: 647 men and women over the age of 75 participated in the Sydney Older Person's Study. Disability in activities of daily living (ADL), instrumental activities of daily living (IADL) and mobility was assessed using self report, informant and clinician assessments. Diagnoses of systemic, psychiatric, neurodegenerative diseases were made by clinicians. Individual disease contribution to disability was assessed using multiple regression analysis. Contribution to disability by the groups of systemic, neurodegenerative and psychiatric diagnoses was assessed, using hierarchical regression. Results: Neurodegenerative diseases were the major contributors to ADL impairment. Systemic and psychiatric diseases played a role in IADL and mobility impairment, as did the neurodegenerative diseases. Of the neurodegenerative diseases, dementia/cognitive impairment and Parkinsonism/gait slowing particularly contributed to disability. Self-report under-identified the role of the neurodegenerative diseases in disability. It also introduced a gender effect, that the clinical measures did not share to the same extent.Conclusions: Neurodegenerative diseases are important contributors to disability and assessments and diagnosis of neurodegenerative diseases should be included in disability assessments. Self report under-identifies the importance of these conditions.
[show abstract][hide abstract] ABSTRACT: Inflammatory changes are a prominent feature of brains affected by Alzheimer's disease (AD). Activated glial cells release inflammatory cytokines which modulate the neurodegenerative process. These cytokines are encoded by genes representing several interleukins and TNFA, which are associated with AD. The gene coding for HLA-B associated transcript 1 (BAT1) lies adjacent to TNFA in the central major histocompatibility complex (MHC). BAT1, a member of the DEAD-box family of RNA helicases, appears to regulate the production of inflammatory cytokines associated with AD pathology. In the current study TNFA and BAT1 promoter polymorphisms were analysed in AD and control cases and BAT1 mRNA levels were investigated in brain tissue from AD and control cases.
Genotyping was performed for polymorphisms at positions -850 and -308 in the proximal promoter of TNFA and position -22 in the promoter of BAT1. These were investigated singly or in haplotypic association in a cohort of Australian AD patients with AD stratified on the basis of their APOE epsilon4 genotype. Semi-quantitative RT-PCR was also performed for BAT1 from RNA isolated from brain tissue from AD and control cases.
APOE epsilon4 was associated with an independent increase in risk for AD in individuals with TNFA -850*2, while carriage of BAT1 -22*2 reduced the risk for AD, independent of APOE epsilon4 genotype. Semi-quantitative mRNA analysis in human brain tissue showed elevated levels of BAT1 mRNA in frontal cortex of AD cases.
These findings lend support to the application of TNFA and BAT1 polymorphisms in early diagnosis or risk assessment strategies for AD and suggest a potential role for BAT1 in the regulation of inflammatory reactions in AD pathology.
Journal of Neuroinflammation 09/2008; 5:36. · 4.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gait disturbance and cognitive changes are common with ageing. The cerebellum contributes to motor coordination and participates in various aspects of cognition. However, no research has investigated the possible cerebellar contribution to gait and cognition in non-demented very old individuals. The current study aimed to determine the associations between indices of cerebellar size (vermal area and total volume) and measures of motor and cognitive integrity, as well as the role of variables known to impact on cerebellar size (alcohol consumption and chronological age) in a sample of 111 community dwellers (mean age: 85 years; range: 81-97 years). A marginally significant association was present between age and total vermal area. Significant correlations between current daily alcohol intake and some vermal areas were observed. These associations were more pronounced in men, particularly after controlling for cerebrum size. Multiple linear regression models revealed limited unique contributions of cerebellar predictors to neurological and cognitive measures. In summary, the results indicate that the cerebellum may be susceptible to alcohol-related shrinkage in non-demented very old individuals, more so in men, even at low dose. It also appears that the observed changes in cerebellum size in this population contribute little to neurological and cognitive changes.
European Archives of Psychiatry and Clinical Neuroscience 01/2007; 256(8):504-11. · 3.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: BVR was 77 years old when he sustained a large posterior cerebral artery territory infarct. Medical, cognitive and functional data collected on four occasions over 10 years initially revealed circumscribed neurological signs, no functional or cognitive deficits. BVR became significantly impaired only after two other strokes, 3 years before death. On brain MRI, the lesions involved large portions of the right occipital and temporal cortices, the right thalamus, and the left cerebellum, as well as thinning of the corpus callosum. Postmortem investigations revealed additional recent vascular lesions in the occipital region. This case study underscores the importance of comprehensive assessment methods combining neurological, neuroimaging and cognitive tools.
[show abstract][hide abstract] ABSTRACT: A number of different methods have been employed to correct hippocampal volumes for individual variation in head size. Researchers have previously used qualitative visual inspection to gauge hippocampal atrophy. The purpose of this study was to determine the best measure(s) of hippocampal size for predicting memory functioning in 102 community-dwelling individuals over 80 years of age. Hippocampal size was estimated using magnetic resonance imaging (MRI) volumetry and qualitative visual assessment. Right and left hippocampal volumes were adjusted by three different estimates of head size: total intracranial volume (TICV), whole-brain volume including ventricles (WB+V) and a more refined measure of whole-brain volume with ventricles extracted (WB). We compared the relative efficacy of these three volumetric adjustment methods and visual ratings of hippocampal size in predicting memory performance using linear regression. All four measures of hippocampal size were significant predictors of memory performance. TICV-adjusted volumes performed most poorly in accounting for variance in memory scores. Hippocampal volumes adjusted by either measure of whole-brain volume performed equally well, although qualitative visual ratings of the hippocampus were at least as effective as the volumetric measures in predicting memory performance in community-dwelling individuals in the ninth or tenth decade of life.
[show abstract][hide abstract] ABSTRACT: To identify the clinical correlates of functional incapacity in the community living "old-old."
One hundred six nondemented people aged 80 to 94.
Participants were medically and cognitively assessed, underwent magnetic resonance imaging scanning (MRI), and were interviewed regarding their functional status: activities of daily living (ADLs), instrumental ADLs (IADLs), and the complex IADL functions of reading, hobbies, and socializing.
Dependency in IADLs, but not ADLs, was present. After controlling for age, sex, and education, extrapyramidal (EP) signs were significantly associated with two of the three IADLs, with EP signs comprising a composite score of 10 EP signs (e.g., resting tremor) and a 5-meter timed walk. Cognitive test performance on a range of tests was also associated with functional status. A hierarchical model confirmed the association between the EP signs and cognitive test performance and functional scores, but no "pattern" of cognitive association emerged. Hippocampal volume was associated with socializing.
This study has shown that many nondemented very old people living in the community are losing capacity to perform IADL functions and that areas of incapacity are associated with the presence of EP signs and impaired cognition. These results highlight the need for health workers to include an assessment of EP and cognitive status in their evaluation of older persons living in the community, even in the context of a lack of dementia diagnosis. Furthermore, it signifies the need to directly evaluate IADL function to identify need for intervention and support if required. This group of old-old individuals may now be considered the "survivors" of their cohort, and early detection of the difficulties they are experiencing will enable clinicians to respond appropriately, thus providing them a higher quality of life for their years to come.
Journal of the American Geriatrics Society 02/2006; 54(1):3-10. · 3.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: There is suggestion that magnetic resonance imaging (MRI) fluid-attenuated inversion recovery (FLAIR) sequence may be more accurate than T2 images in detecting white matter lesions (WML) in older people. Comparative ratings of these two image sequences have not been directly investigated in very old individuals to date. We compared the ratings of periventricular and deep WML on these two sequences in a sample of 111 community dwellers (mean age 85.5 years) using semiquantitative methods. Periventricular WML were as commonly detected on T2 as on FLAIR but were more severely rated on the latter sequence. No such bias was observed for the deep WML. With one exception, correlations between the two sets of measures were significant at the P < 0.001 level (range: 0.34-0.75). Intrarater reliability coefficients were moderate to excellent for most ratings. These results suggest that ratings performed on T2-weighted images to detect WML in very old individuals are very comparable with those performed on FLAIR images although FLAIR may allow a finer grading of periventricular lesions. Absence of FLAIR does not preclude the identification of WML in this population. These findings have clinical and epidemiological relevance where the acquisition of supplementary MRI data may not always be possible.
European Journal of Neurology 05/2005; 12(5):399-402. · 4.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: Current definitions for the preclinical phase of dementia focus predominantly on cognitive measures, with particular emphasis on memory and the prediction of Alzheimer's disease. Incorporation of non-cognitive, clinical markers into preclinical definitions may improve their predictive power. The Sydney Older Persons Study examined 6-year outcomes of 630 community-dwelling participants aged 75 or over at recruitment. At baseline, participants were defined as demented, cognitively intact or having a syndrome possibly representing the preclinical phase of Alzheimer's disease, vascular dementia, an extrapyramidal dementia or various combinations of the three. Those with cognitive impairment in combination with gait and motor slowing were the most likely to dement over the 6-year period (OR 5.6; 95% CI 2.5-12.6). This group was also the most likely to die (OR 3.3; 95% CI 1.6-6.9). White matter indices on MRI scanning were not consistently correlated with gait abnormalities. Simple measures of gait may provide useful clinical tools, assisting in the prediction of dementia. However, the underlying nature of these deficits is not yet known.
Journal of the Neurological Sciences 04/2005; 229-230:89-93. · 2.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: Executive functions (EF) are generally described as showing greater sensitivity to ageing compared to other cognitive domains. Numerous pitfalls exist in the measurement of EF due to loose definitions and lack of agreement on these concepts and uncertainty about the constructs being measured. To this date, the validity of EF constructs has not been examined in the old-old population. Performance of 122 randomly selected community dwellers aged between 81 and 97 years on nine EF tasks (seven of which commonly used in clinical practice) was examined. Factor analytic procedures using structural equation modelling (SEM) failed to satisfactorily explain the data according to four a priori models, the first two models reflecting two major constructs commonly found in current models of EF ("set" and "switch"), the last two reflecting task requirements. The best measure for each task was extracted using statistically driven analyses and further SEM revealed an orthogonal two-factor model which provided a good fit of the data, explaining between 8% and 25% of the total variance. This model can be interpreted in terms of reactive and spontaneous flexibility as proposed by Eslinger and Grattan (1993), with the first factor reflecting internally driven strategies and the second environment dependent strategies. Furthermore, these findings also suggest that: (a) unique tasks of EF may not be applicable to all age groups due to individual experience and changes in strategies; and (b) current clinical instruments may be inadequate to measure very specific aspects of the complex construct of EF.
[show abstract][hide abstract] ABSTRACT: The purpose of this study was to define magnetic resonance imaging (MRI) correlates of normal brain ageing, with the specific objective of investigating whether the size of the hippocampus is selectively correlated with age related memory performance in non-demented individuals in their ninth and tenth decades of life.
Hippocampal size was estimated using MRI based volumetry and qualitative visual assessment in 102 community dwelling individuals aged between 81 and 94 years. Participants were evaluated on a variety of clinical and experimental instruments, including a comprehensive neuropsychological test battery. All participants underwent neurological examination, an extensive medical history was obtained, and an informant confirmed details of each participant's functional ability.
Both visual and volumetric hippocampal measures were identified as robust predictors of memory performance, even when the influence of age related illnesses and sociodemographic variables was accounted for. When the sample was reduced to include the most cognitively healthy participants who were rated by an informant as showing no evidence of cognitive decline, the left hippocampal measures remained significant predictors of delayed retention of verbal material.
These findings suggest that hippocampal volumes are selectively correlated with memory functioning in both normal and successful ageing.
[show abstract][hide abstract] ABSTRACT: Spatial function has been suggested to be disproportionately worse in people with dementia with Lewy bodies (DLB) than other dementia groups, and poor performance on the Mini-Mental State Examination pentagon copying (PC) task has been proposed as adequate for assessing this. We aimed to establish the prevalence of poor PC in the non-demented elderly; determine the validity of the use of PC as a spatial function test, and determine if poor PC is more common in DLB than non-DLB dementias.
In a population-based sample of 299 participants, 126 were rated as being cognitively normal (clinical rating scale [CDR] = 0), 95 mildly cognitively impaired (CDR = 0.5), and 78 met criteria for dementia, 19 of whom met criteria for probable DLB (pDLB) and 25 with none of the core features of DLB (non-DLB). The accuracy of PC performance was determined across CDR groups, and the relationship of PC to performance on a broad range of cognitive tests was evaluated. The dementia groups were compared cross-sectionally to determine differences in PC and other cognitive test performance, as well as 3 and 6 years earlier to determine cognitive differences at initial stages of cognitive decline.
Poor PC was common in the non-demented elderly (39% CDR = 0; 43% CDR = 0.5). In this non-demented group, PC was selectively related to tests of spatial function. Poor PC was not significantly different in the pDLB and non-DLB groups at any assessment time, however it became more prevalent as dementia severity increased. Memory function and verbal fluency were more impaired in the pDLB group in the early stages of the disorder.
PC appears to be a good measure of spatial function in the elderly. However, in contrast to other findings of poor spatial skills in DLB when dementia is in the mild to moderate stages, poor PC performance has not been shown to be a good early marker of DLB and its clinical correlates are yet to be determined.
[show abstract][hide abstract] ABSTRACT: The number of individuals aged over 80 years is the fastest increasing group in developed countries. White matter lesions (WML) observed on magnetic resonance imaging (MRI) have uncertain clinical significance, particularly in the old.
To determine the prevalence of periventricular and deep WML in survivors of an original cohort of randomly selected elderly community dwellers, and to examine their associations with clinical markers of vascular and extrapyramidal disorders of ageing, as well as quantitative cognitive measures.
Brain MRI, lifestyle interview, cognitive testing and medical examination were administered to 122 participants from the Sydney Older Persons Study 6-year review (mean age: 85.5 years). Apolipoprotein E (ApoE) genotype was also established. Presence and severity of periventricular and deep WML were ascertained using semi-quantitative rating methods and their relations to the cognitive and clinical variables investigated.
Periventricular WML were present in all participants in similar severity for all three regions sampled. In contrast, a gradient of severity was observed for the deep WML: most severe in the parietal region, followed by the frontal and occipital regions, and least severe in the temporal region. Associations with gender or with the ApoE epsilon4 allele were non-significant. WML were inconsistently associated with age and cognitive functioning or with the clinical markers of dementia. No frontal specificity emerged. Examination of individual lesion types did not change the general pattern of associations. Supporting evidence for a threshold effect was observed on some measures.
WML are extremely common in elderly, non-demented individuals. Unlike in younger individuals, MRI abnormalities may not be evidence of a current pathological process and their importance may change with advancing age.