ABSTRACT Background: Depression is a known risk factor for cognitive decline and dementia, but th... more ABSTRACT Background: Depression is a known risk factor for cognitive decline and dementia, but the evidence on associations between brain structure and depressive symptomatology is mixed. This study investigates the association of depressive symptoms with regional gray/white matter volumes in a large cohort of cognitively healthy, older, community dwelling individuals (68-73 years) from the PATH Through Life project at wave 3 (N=244). Method: Pre-processing and voxelwise analysis of regional gray/white matter volumes of T1-weighted images was conducted in SPM8. Individuals on antidepressant medication were excluded from these analyses (n=19). Results: Voxelwise analyses controlling for age, sex, anxiety, MMSE, BMI, diabetes and hypertension showed a positive association between increased depressive symptoms and greater regional gray matter volumes in the parietal, temporal and occipital lobes, and white matter volumes in the temporal and limbic cortex (α=0.001). No negative association was found. Conclusion: While these findings contrast with the growing evidence of pre-frontal and oribitofrontal cortex degeneration in depression, they complement other findings suggesting increased gray matter volumes in the cingulate gyrus as a marker of early neuronal pathology. Possible explanations for the current findings include that increased regional gray/white matter volumes may reflect neuronal overgrowth, deficits in the pruning process of neurogenesis, neural maturation following antidepressant treatment or the impact of early inflammatory processes in depression. Future research should consider i) increased regional volumes as a marker for early neurodegenerative processes and ii) the role that inflammatory processes play in the association between increased regional volumes, depressive symptoms and cognitive decline.
those from SPM8 are dramatically improved; FreeSurfer results lie between these (figure a). The D... more those from SPM8 are dramatically improved; FreeSurfer results lie between these (figure a). The Dartel Jacobian integration method has the strongest correlation and least mean difference with respect to manual measures (see table). Consideration of longitudinal changes reveals small but significant reductions in the manual measures, and in the closely correlated Dartel results (figure b). The modulated warped SPM8 segmentations appear to exhibit the best balance of accuracy and stability over time. Conclusions: Accurate estimation of TIV is possible in less than 10 minutes per subject with no manual interaction, making it suitable for even the largest studies given distributed computing resources. We will use the above-selected method to estimate TIV for all subjects in ADNI, and make these publicly available.
Ageing is characterized by chronically elevated inflammatory markers (IMs). Peripheral IM levels ... more Ageing is characterized by chronically elevated inflammatory markers (IMs). Peripheral IM levels have been found in negative correlations with brain structural measures including global and lobar volumes and the hippocampus. This study investigated the relationship between 10 peripheral IMs and voxel-based gray matter (GM) volumes in nondemented older adults (n = 463). Two proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-1β) and 2 vascular IMs (vascular cellular adhesion molecule-1 and plasminogen activator inhibitor-1) were negatively correlated with regional GM volumes. TNF-α and interleukin-1β were both significantly correlated with GM volumes in the left occipitotemporal area, left superior occipital gyrus, and left inferior parietal lobule; TNF-α was also significantly correlated with the bilateral medial prefrontal cortices and approached significance for the correlations with the bilateral hippocampi. Significant GM correlations with vascular cellula...
Changes in criteria and differences in populations studied and methodology have produced a wide r... more Changes in criteria and differences in populations studied and methodology have produced a wide range of prevalence estimates for mild cognitive impairment (MCI). Uniform criteria were applied to harmonized data from 11 studies from USA, Europe, Asia and Australia, and MCI prevalence estimates determined using three separate definitions of cognitive impairment. The published range of MCI prevalence estimates was 5.0%-36.7%. This was reduced with all cognitive impairment definitions: performance in the bottom 6.681% (3.2%-10.8%); Clinical Dementia Rating of 0.5 (1.8%-14.9%); Mini-Mental State Examination score of 24-27 (2.1%-20.7%). Prevalences using the first definition were 5.9% overall, and increased with age (P < .001) but were unaffected by sex or the main races/ethnicities investigated (Whites and Chinese). Not completing high school increased the likelihood of MCI (P ≤ .01). Applying uniform criteria to harmonized data greatly reduced the variation in MCI prevalence interna...
both cognitive ability and cognitive decline have been shown to predict mortality in older people... more both cognitive ability and cognitive decline have been shown to predict mortality in older people. As dementia, a major form of cognitive decline, has an established association with shorter survival, it is unclear the extent to which cognitive ability and cognitive decline predict mortality in the absence of dementia. to determine whether cognitive ability and decline in cognitive ability predict mortality in older individuals without dementia. the Sydney Memory and Ageing Study is an observational population-based cohort study. Participants completed detailed neuropsychological assessments and medical examinations to assess for risk factors such as depression, obesity, hypertension, diabetes, hypercholesterolaemia, smoking and physical activity. Participants were regularly assessed at 2-year intervals over 8 years. a community sample in Sydney, Australia. one thousand and thirty-seven elderly people without dementia. overall, 236 (22.8%) participants died within 8 years. Both cogn...
Journal of Alzheimer's disease : JAD, Jan 18, 2015
In recent years, microRNAs (miRNA), a class of non-coding RNA known to regulate protein expressio... more In recent years, microRNAs (miRNA), a class of non-coding RNA known to regulate protein expression post-transcriptionally, have been recognized as novel biomarkers of diseases. In this systematic review, we identify miRNAs that are differentially expressed in Alzheimer's disease (AD) and/or mild cognitive impairment (MCI) and evaluate their accuracy as potential blood biomarkers. Eligible studies of miRNAs in peripheral blood distinguishing patients with AD or MCI from cognitively normal controls were identified through standardized search strategies in Medline, PubMed, and Embase. MiRNAs that were differentially expressed were identified and where available their sensitivity and specificity for AD or MCI extracted from the retrieved studies. Eighteen studies investigated the diagnostic value of miRNAs as peripheral biomarkers of AD/MCI. Twenty miRNAs were significantly upregulated and 32 miRNAs downregulated in AD compared to controls in ten AD studies. Nine miRNAs were consist...
The Australian and New Zealand journal of psychiatry, Jan 13, 2015
Tourette syndrome is often associated with attention deficit hyperactivity disorder, obsessive co... more Tourette syndrome is often associated with attention deficit hyperactivity disorder, obsessive compulsive disorder and other co-morbidities, the presence of which can reduce health-related quality of life. The relationship between the number and type of co-morbidities and tic severity upon health-related quality of life has been insufficiently examined in Tourette syndrome populations and not at all in the Australian context. We hypothesised that an increased number of co-morbid diagnoses would be inversely related to health-related quality of life and that the presence of attention deficit hyperactivity disorder and obsessive compulsive disorder in particular would negatively impact health-related quality of life. In all, 83 people with a previously established diagnosis of Tourette syndrome, who responded to a letter of invitation sent to the Tourette Syndrome Association of Australia past-member database, formed the study sample. Participants completed the Gilles de la Tourette S...
The variability of episodic memory decline and hippocampal atrophy observed with increasing age m... more The variability of episodic memory decline and hippocampal atrophy observed with increasing age may partly be explained by genetic factors. KIBRA (kidney and brain expressed protein) and CLSTN2 (calsyntenin 2) are two candidate genes previously linked to episodic memory performance and volume of the hippocampus, a key memory structure. However, whether polymorphisms in these two genes also influence age-related longitudinal memory decline and hippocampal atrophy is still unknown. Using data from two independent cohorts, the Sydney Memory and Ageing Study and the Older Australian Twins Study, we investigated whether the KIBRA and CLSTN2 genetic polymorphisms (rs17070145, rs6439886) are associated with episodic memory performance and hippocampal volume in older adults (65-90 years at baseline). We were able to examine these polymorphisms in relation to memory and hippocampal volume using cross-sectional data and, more importantly, also using longitudinal data (2 years between testing ...
After participating in this activity, learners should be better able to:• Assess the changes in D... more After participating in this activity, learners should be better able to:• Assess the changes in DSM-5 relative to earlier versions.• Evaluate the implications of the DSM-5 for practicing geriatric psychiatrists. About every 20 years, the American Psychiatric Association revises its official classification of mental disorders. The fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was published in 2013, prompting considerable commentary, debate, and criticism. This article briefly describes the process leading up to DSM-5 and the main changes from the previous version (DSM-IV) that would be of interest to a geriatric psychiatrist. The changes in the areas of schizophrenia, bipolar disorder, depressive disorders, and anxiety disorders have been many, but the majority of them are minor and unlikely to have major treatment implications. The classification of neurocognitive disorders, however, has seen a major revision and elaboration in comparison to DSM-IV; of special note is the introduction of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;mild and major neurocognitive disorders,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; the latter equated with dementia. A common language has also been introduced for the criteria for the various etiological subtypes of neurocognitive disorders. All physicians treating patients with neurocognitive disorders should familiarize themselves with these criteria. Their use in research has the potential to harmonize the field.
To examine whether impaired fasting glucose (IFG) represents an intermediary condition between no... more To examine whether impaired fasting glucose (IFG) represents an intermediary condition between normal fasting glucose and diabetes mellitus and, specifically, whether elderly adults with IFG have higher disease burden, cardiovascular risk, and systemic inflammation and higher 2-year mortality and incident disease. Prospective observational study. Population-derived cohort. Individuals with a mean age of 78.6 ± 4.7 (N = 945). Disease was ascertained using a standardized questionnaire at baseline and 2 years. Fasting metabolic, inflammatory, and oxidative metabolism markers were measured. Disease prevalence, cardiovascular risk, and biochemical markers were compared to determine disease burden and metabolic disturbances in IFG. Adjusted odds ratios (ORs) for 2-year all-cause mortality and incident disease were determined. IFG prevalence was 41%. Individuals with IFG had higher baseline rates of heart disease than those with normal fasting glucose (NFG), similar to that in individuals with diabetes mellitus. IFG was characterized by higher inflammatory markers and oxidative metabolism end products and was an intermediary between NFG and diabetes mellitus for triglycerides and malondialdehyde. Discriminant analysis showed that IFG was independently associated with stroke and higher triglycerides and oxidative stress. Two-year all-cause mortality was 3.9%. The 2-year adjusted ORs for all-cause mortality, incident cardiac disease, stroke, and cancer were similar between IFG and NFG, using both American Diabetes Association and World Health Organization IFG criteria. IFG did not predict secondary cardiac events, stroke, or cancer. IFG was an intermediary condition for heart disease, inflammation, and oxidative stress in elderly adults but not for 2-year incident disease or all-cause mortality. Longer-term prospective studies are needed to clarify whether IFG in elderly adults portends greater morbidity and mortality.
The Australian and New Zealand journal of psychiatry, Jan 27, 2015
Information on the rates and predictors of polypharmacy of central nervous system medication in o... more Information on the rates and predictors of polypharmacy of central nervous system medication in older people with intellectual disability is limited, despite the increased life expectancy of this group. This study examined central nervous system medication use in an older sample of people with intellectual disability. Data regarding demographics, psychiatric diagnoses and current medications were collected as part of a larger survey completed by carers of people with intellectual disability over the age of 40 years. Recruitment occurred predominantly via disability services across different urban and rural locations in New South Wales and Victoria. Medications were coded according to the Monthly Index of Medical Specialties central nervous system medication categories, including sedatives/hypnotics, anti-anxiety agents, antipsychotics, antidepressants, central nervous system stimulants, movement disorder medications and anticonvulsants. The Developmental Behaviour Checklist for Adul...
Although there are seven mammalian sirtuins (SIRT1-7), little is known about their expression in ... more Although there are seven mammalian sirtuins (SIRT1-7), little is known about their expression in the aging brain. To characterize the change(s) in mRNA and protein expression of SIRT1-7 and their associated proteins in the brain of " physiologically " aged Wistar rats. We tested mRNA and protein expression levels of rat SIRT1-7, and the levels of associated proteins in the brain using RT-PCR and western blotting. Our data shows that SIRT1 expression increases with age, concurrently with increased acetylated p53 levels in all brain regions investigated. SIRT2 and FOXO3a protein levels increased only in the occipital lobe. SIRT3-5 expression declined significantly in the hippocampus and frontal lobe, associated with increases in superoxide and fatty acid oxidation levels, and acetylated CPS-1 protein expression, and a reduction in MnSOD level. While SIRT6 expression declines significantly with age acetylated H3K9 protein expression is increased throughout the brain. SIRT7 and Pol I protein expression increased in the frontal lobe. This study identifies previously unknown roles for sirtuins in regulating cellular homeostasis and healthy aging.
Investigations of the human connectome have elucidated core features of adult structural networks... more Investigations of the human connectome have elucidated core features of adult structural networks, particularly the crucial role of hub-regions. However, little is known regarding network organisation of the healthy elderly connectome, a crucial prelude to the systematic study of neurodegenerative disorders. Here, whole-brain probabilistic tractography was performed on high-angular diffusion-weighted images acquired from 114 healthy elderly subjects (age 76-94 years; 64 females). Structural networks were reconstructed between 512 cortical and subcortical brain regions. We sought to investigate the architectural features of hub-regions, as well as left-right asymmetries, and sexual dimorphisms. We observed that the topology of hub-regions is consistent with a young adult population, and previously published adult connectomic data. More importantly, the architectural features of hub connections reflect their ongoing vital role in network communication. We also found substantial sexual dimorphisms, with females exhibiting stronger inter-hemispheric connections between cingulate and prefrontal cortices. Lastly, we demonstrate intriguing leftlateralized subnetworks consistent with the neural circuitry specialised for language and executive functions, while rightward subnetworks were dominant in visual and visuospatial streams. These findings provide insights into healthy brain ageing and provide a benchmark for the study of neurodegenerative disorders such as Alzheimer's disease (AD) and
Alzheimer's disease affects up to 100,000 people in Australia, but pharmacological treatment ... more 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.
ABSTRACT Background: Depression is a known risk factor for cognitive decline and dementia, but th... more ABSTRACT Background: Depression is a known risk factor for cognitive decline and dementia, but the evidence on associations between brain structure and depressive symptomatology is mixed. This study investigates the association of depressive symptoms with regional gray/white matter volumes in a large cohort of cognitively healthy, older, community dwelling individuals (68-73 years) from the PATH Through Life project at wave 3 (N=244). Method: Pre-processing and voxelwise analysis of regional gray/white matter volumes of T1-weighted images was conducted in SPM8. Individuals on antidepressant medication were excluded from these analyses (n=19). Results: Voxelwise analyses controlling for age, sex, anxiety, MMSE, BMI, diabetes and hypertension showed a positive association between increased depressive symptoms and greater regional gray matter volumes in the parietal, temporal and occipital lobes, and white matter volumes in the temporal and limbic cortex (α=0.001). No negative association was found. Conclusion: While these findings contrast with the growing evidence of pre-frontal and oribitofrontal cortex degeneration in depression, they complement other findings suggesting increased gray matter volumes in the cingulate gyrus as a marker of early neuronal pathology. Possible explanations for the current findings include that increased regional gray/white matter volumes may reflect neuronal overgrowth, deficits in the pruning process of neurogenesis, neural maturation following antidepressant treatment or the impact of early inflammatory processes in depression. Future research should consider i) increased regional volumes as a marker for early neurodegenerative processes and ii) the role that inflammatory processes play in the association between increased regional volumes, depressive symptoms and cognitive decline.
those from SPM8 are dramatically improved; FreeSurfer results lie between these (figure a). The D... more those from SPM8 are dramatically improved; FreeSurfer results lie between these (figure a). The Dartel Jacobian integration method has the strongest correlation and least mean difference with respect to manual measures (see table). Consideration of longitudinal changes reveals small but significant reductions in the manual measures, and in the closely correlated Dartel results (figure b). The modulated warped SPM8 segmentations appear to exhibit the best balance of accuracy and stability over time. Conclusions: Accurate estimation of TIV is possible in less than 10 minutes per subject with no manual interaction, making it suitable for even the largest studies given distributed computing resources. We will use the above-selected method to estimate TIV for all subjects in ADNI, and make these publicly available.
Ageing is characterized by chronically elevated inflammatory markers (IMs). Peripheral IM levels ... more Ageing is characterized by chronically elevated inflammatory markers (IMs). Peripheral IM levels have been found in negative correlations with brain structural measures including global and lobar volumes and the hippocampus. This study investigated the relationship between 10 peripheral IMs and voxel-based gray matter (GM) volumes in nondemented older adults (n = 463). Two proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-1β) and 2 vascular IMs (vascular cellular adhesion molecule-1 and plasminogen activator inhibitor-1) were negatively correlated with regional GM volumes. TNF-α and interleukin-1β were both significantly correlated with GM volumes in the left occipitotemporal area, left superior occipital gyrus, and left inferior parietal lobule; TNF-α was also significantly correlated with the bilateral medial prefrontal cortices and approached significance for the correlations with the bilateral hippocampi. Significant GM correlations with vascular cellula...
Changes in criteria and differences in populations studied and methodology have produced a wide r... more Changes in criteria and differences in populations studied and methodology have produced a wide range of prevalence estimates for mild cognitive impairment (MCI). Uniform criteria were applied to harmonized data from 11 studies from USA, Europe, Asia and Australia, and MCI prevalence estimates determined using three separate definitions of cognitive impairment. The published range of MCI prevalence estimates was 5.0%-36.7%. This was reduced with all cognitive impairment definitions: performance in the bottom 6.681% (3.2%-10.8%); Clinical Dementia Rating of 0.5 (1.8%-14.9%); Mini-Mental State Examination score of 24-27 (2.1%-20.7%). Prevalences using the first definition were 5.9% overall, and increased with age (P < .001) but were unaffected by sex or the main races/ethnicities investigated (Whites and Chinese). Not completing high school increased the likelihood of MCI (P ≤ .01). Applying uniform criteria to harmonized data greatly reduced the variation in MCI prevalence interna...
both cognitive ability and cognitive decline have been shown to predict mortality in older people... more both cognitive ability and cognitive decline have been shown to predict mortality in older people. As dementia, a major form of cognitive decline, has an established association with shorter survival, it is unclear the extent to which cognitive ability and cognitive decline predict mortality in the absence of dementia. to determine whether cognitive ability and decline in cognitive ability predict mortality in older individuals without dementia. the Sydney Memory and Ageing Study is an observational population-based cohort study. Participants completed detailed neuropsychological assessments and medical examinations to assess for risk factors such as depression, obesity, hypertension, diabetes, hypercholesterolaemia, smoking and physical activity. Participants were regularly assessed at 2-year intervals over 8 years. a community sample in Sydney, Australia. one thousand and thirty-seven elderly people without dementia. overall, 236 (22.8%) participants died within 8 years. Both cogn...
Journal of Alzheimer's disease : JAD, Jan 18, 2015
In recent years, microRNAs (miRNA), a class of non-coding RNA known to regulate protein expressio... more In recent years, microRNAs (miRNA), a class of non-coding RNA known to regulate protein expression post-transcriptionally, have been recognized as novel biomarkers of diseases. In this systematic review, we identify miRNAs that are differentially expressed in Alzheimer's disease (AD) and/or mild cognitive impairment (MCI) and evaluate their accuracy as potential blood biomarkers. Eligible studies of miRNAs in peripheral blood distinguishing patients with AD or MCI from cognitively normal controls were identified through standardized search strategies in Medline, PubMed, and Embase. MiRNAs that were differentially expressed were identified and where available their sensitivity and specificity for AD or MCI extracted from the retrieved studies. Eighteen studies investigated the diagnostic value of miRNAs as peripheral biomarkers of AD/MCI. Twenty miRNAs were significantly upregulated and 32 miRNAs downregulated in AD compared to controls in ten AD studies. Nine miRNAs were consist...
The Australian and New Zealand journal of psychiatry, Jan 13, 2015
Tourette syndrome is often associated with attention deficit hyperactivity disorder, obsessive co... more Tourette syndrome is often associated with attention deficit hyperactivity disorder, obsessive compulsive disorder and other co-morbidities, the presence of which can reduce health-related quality of life. The relationship between the number and type of co-morbidities and tic severity upon health-related quality of life has been insufficiently examined in Tourette syndrome populations and not at all in the Australian context. We hypothesised that an increased number of co-morbid diagnoses would be inversely related to health-related quality of life and that the presence of attention deficit hyperactivity disorder and obsessive compulsive disorder in particular would negatively impact health-related quality of life. In all, 83 people with a previously established diagnosis of Tourette syndrome, who responded to a letter of invitation sent to the Tourette Syndrome Association of Australia past-member database, formed the study sample. Participants completed the Gilles de la Tourette S...
The variability of episodic memory decline and hippocampal atrophy observed with increasing age m... more The variability of episodic memory decline and hippocampal atrophy observed with increasing age may partly be explained by genetic factors. KIBRA (kidney and brain expressed protein) and CLSTN2 (calsyntenin 2) are two candidate genes previously linked to episodic memory performance and volume of the hippocampus, a key memory structure. However, whether polymorphisms in these two genes also influence age-related longitudinal memory decline and hippocampal atrophy is still unknown. Using data from two independent cohorts, the Sydney Memory and Ageing Study and the Older Australian Twins Study, we investigated whether the KIBRA and CLSTN2 genetic polymorphisms (rs17070145, rs6439886) are associated with episodic memory performance and hippocampal volume in older adults (65-90 years at baseline). We were able to examine these polymorphisms in relation to memory and hippocampal volume using cross-sectional data and, more importantly, also using longitudinal data (2 years between testing ...
After participating in this activity, learners should be better able to:• Assess the changes in D... more After participating in this activity, learners should be better able to:• Assess the changes in DSM-5 relative to earlier versions.• Evaluate the implications of the DSM-5 for practicing geriatric psychiatrists. About every 20 years, the American Psychiatric Association revises its official classification of mental disorders. The fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was published in 2013, prompting considerable commentary, debate, and criticism. This article briefly describes the process leading up to DSM-5 and the main changes from the previous version (DSM-IV) that would be of interest to a geriatric psychiatrist. The changes in the areas of schizophrenia, bipolar disorder, depressive disorders, and anxiety disorders have been many, but the majority of them are minor and unlikely to have major treatment implications. The classification of neurocognitive disorders, however, has seen a major revision and elaboration in comparison to DSM-IV; of special note is the introduction of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;mild and major neurocognitive disorders,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; the latter equated with dementia. A common language has also been introduced for the criteria for the various etiological subtypes of neurocognitive disorders. All physicians treating patients with neurocognitive disorders should familiarize themselves with these criteria. Their use in research has the potential to harmonize the field.
To examine whether impaired fasting glucose (IFG) represents an intermediary condition between no... more To examine whether impaired fasting glucose (IFG) represents an intermediary condition between normal fasting glucose and diabetes mellitus and, specifically, whether elderly adults with IFG have higher disease burden, cardiovascular risk, and systemic inflammation and higher 2-year mortality and incident disease. Prospective observational study. Population-derived cohort. Individuals with a mean age of 78.6 ± 4.7 (N = 945). Disease was ascertained using a standardized questionnaire at baseline and 2 years. Fasting metabolic, inflammatory, and oxidative metabolism markers were measured. Disease prevalence, cardiovascular risk, and biochemical markers were compared to determine disease burden and metabolic disturbances in IFG. Adjusted odds ratios (ORs) for 2-year all-cause mortality and incident disease were determined. IFG prevalence was 41%. Individuals with IFG had higher baseline rates of heart disease than those with normal fasting glucose (NFG), similar to that in individuals with diabetes mellitus. IFG was characterized by higher inflammatory markers and oxidative metabolism end products and was an intermediary between NFG and diabetes mellitus for triglycerides and malondialdehyde. Discriminant analysis showed that IFG was independently associated with stroke and higher triglycerides and oxidative stress. Two-year all-cause mortality was 3.9%. The 2-year adjusted ORs for all-cause mortality, incident cardiac disease, stroke, and cancer were similar between IFG and NFG, using both American Diabetes Association and World Health Organization IFG criteria. IFG did not predict secondary cardiac events, stroke, or cancer. IFG was an intermediary condition for heart disease, inflammation, and oxidative stress in elderly adults but not for 2-year incident disease or all-cause mortality. Longer-term prospective studies are needed to clarify whether IFG in elderly adults portends greater morbidity and mortality.
The Australian and New Zealand journal of psychiatry, Jan 27, 2015
Information on the rates and predictors of polypharmacy of central nervous system medication in o... more Information on the rates and predictors of polypharmacy of central nervous system medication in older people with intellectual disability is limited, despite the increased life expectancy of this group. This study examined central nervous system medication use in an older sample of people with intellectual disability. Data regarding demographics, psychiatric diagnoses and current medications were collected as part of a larger survey completed by carers of people with intellectual disability over the age of 40 years. Recruitment occurred predominantly via disability services across different urban and rural locations in New South Wales and Victoria. Medications were coded according to the Monthly Index of Medical Specialties central nervous system medication categories, including sedatives/hypnotics, anti-anxiety agents, antipsychotics, antidepressants, central nervous system stimulants, movement disorder medications and anticonvulsants. The Developmental Behaviour Checklist for Adul...
Although there are seven mammalian sirtuins (SIRT1-7), little is known about their expression in ... more Although there are seven mammalian sirtuins (SIRT1-7), little is known about their expression in the aging brain. To characterize the change(s) in mRNA and protein expression of SIRT1-7 and their associated proteins in the brain of " physiologically " aged Wistar rats. We tested mRNA and protein expression levels of rat SIRT1-7, and the levels of associated proteins in the brain using RT-PCR and western blotting. Our data shows that SIRT1 expression increases with age, concurrently with increased acetylated p53 levels in all brain regions investigated. SIRT2 and FOXO3a protein levels increased only in the occipital lobe. SIRT3-5 expression declined significantly in the hippocampus and frontal lobe, associated with increases in superoxide and fatty acid oxidation levels, and acetylated CPS-1 protein expression, and a reduction in MnSOD level. While SIRT6 expression declines significantly with age acetylated H3K9 protein expression is increased throughout the brain. SIRT7 and Pol I protein expression increased in the frontal lobe. This study identifies previously unknown roles for sirtuins in regulating cellular homeostasis and healthy aging.
Investigations of the human connectome have elucidated core features of adult structural networks... more Investigations of the human connectome have elucidated core features of adult structural networks, particularly the crucial role of hub-regions. However, little is known regarding network organisation of the healthy elderly connectome, a crucial prelude to the systematic study of neurodegenerative disorders. Here, whole-brain probabilistic tractography was performed on high-angular diffusion-weighted images acquired from 114 healthy elderly subjects (age 76-94 years; 64 females). Structural networks were reconstructed between 512 cortical and subcortical brain regions. We sought to investigate the architectural features of hub-regions, as well as left-right asymmetries, and sexual dimorphisms. We observed that the topology of hub-regions is consistent with a young adult population, and previously published adult connectomic data. More importantly, the architectural features of hub connections reflect their ongoing vital role in network communication. We also found substantial sexual dimorphisms, with females exhibiting stronger inter-hemispheric connections between cingulate and prefrontal cortices. Lastly, we demonstrate intriguing leftlateralized subnetworks consistent with the neural circuitry specialised for language and executive functions, while rightward subnetworks were dominant in visual and visuospatial streams. These findings provide insights into healthy brain ageing and provide a benchmark for the study of neurodegenerative disorders such as Alzheimer's disease (AD) and
Alzheimer's disease affects up to 100,000 people in Australia, but pharmacological treatment ... more 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.
Background: Hypertension is an established risk factor for stroke and vascular dementia but recen... more Background: Hypertension is an established risk factor for stroke and vascular dementia but recent meta-analyses examining the association between Alzheimer's disease (AD) and hypertension have found no significant association. These meta-analyses included short term studies starting in late life which may have obscured the real effect of midlife hypertension. Objective: To examine the association of AD with midlife hypertension, by including only studies with a sufficiently long follow up duration. Methods: Relevant studies were found by searches of MEDLINE, EMBASE, and PubMed. Study outcomes were grouped by measures of blood pressure and definition of hypertension (e.g., systolic hypertension > 140 mmHg or > 160 mmHg). We assessed pooled effect estimates using random effects models and heterogeneity of pooled estimates through the I 2 statistic. Results: Literature search found 3,426 publications of which 7 were eligible studies. There was a significant association between systolic hypertension (>160 mm Hg) and AD (HR 1.25, 95CI 1.06-1.47, p = 0.0065). Similarly, for systolic hypertension > 140 mm Hg, there was a smaller but still significant association (HR 1.18, 95CI 1.02-1.35, p = 0.021). For diastolic hypertension, all four studies found no significant associations between diastolic hypertension and AD, and these data could not be pooled due to heterogeneity in reporting. Conclusions: Our study found that midlife stage 1 and stage 2 systolic hypertension is associated with increased risk of AD by 18 and 25%, respectively, although no association was found for diastolic hypertension. It is likely that assertive control of systolic hypertension starting in midlife is important to preventing AD.
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Papers by Perminder Sachdev