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Papers by Anya Topiwala

ObjectivTo assess the associations between gout, brain structure, and neurodegenerative disease i... more ObjectivTo assess the associations between gout, brain structure, and neurodegenerative disease incidence.MethodsUsing observational and Mendelian randomization analyses we investigated causal relationships between gout and brain health. Exposures included gout diagnosis (from self-report, linked health records and death records) and genetically proxied gout and serum urate. Outcomes were neuroimaging markers of brain structure and neurodegenerative disease incidence (ascertained through self-report, health records and death reports). Cox proportional hazards models were used to examine time to neurodegenerative disease diagnosis.Results11,735 UK Biobank participants (mean age 55.5±8.0 years and 50.5% female) had a diagnosis of gout (n=1165 in MRI subset). Dementia was ascertained in 3126 individuals over a mean follow-up time of 12.4±1.9 years. Gout patients had smaller global and regional brain volumes and higher brain iron markers. Genetic associations mirrored observational asso...

PLOS Medicine

Background Brain iron deposition has been linked to several neurodegenerative conditions and repo... more Background Brain iron deposition has been linked to several neurodegenerative conditions and reported in alcohol dependence. Whether iron accumulation occurs in moderate drinkers is unknown. Our objectives were to investigate evidence in support of causal relationships between alcohol consumption and brain iron levels and to examine whether higher brain iron represents a potential pathway to alcohol-related cognitive deficits. Methods and findings Observational associations between brain iron markers and alcohol consumption (n = 20,729 UK Biobank participants) were compared with associations with genetically predicted alcohol intake and alcohol use disorder from 2-sample mendelian randomization (MR). Alcohol intake was self-reported via a touchscreen questionnaire at baseline (2006 to 2010). Participants with complete data were included. Multiorgan susceptibility-weighted magnetic resonance imaging (9.60 ± 1.10 years after baseline) was used to ascertain iron content of each brain r...

The Routledge International Handbook of Psychosocial Epidemiology, 2017

Started approximately in the late 1980s, exoplanetology has up to now unveiled the main gross bul... more Started approximately in the late 1980s, exoplanetology has up to now unveiled the main gross bulk characteristics of planets and planetary systems. In the future it will benefit from more and more large telescopes and advanced space missions. These instruments will dramatically improve their performance in terms of photometric precision, detection speed, multipixel imaging, high-resolution spectroscopy, allowing to go much deeper in the knowledge of planets. Here we outline some science questions which should go beyond these standard improvements and how to address them. Our prejudice is that one is never too speculative: experience shows that the speculative predictions initially not accepted by the community have been confirmed several years later (like spectrophotometry of transits or circumbinary planets).

Brain iron deposition has been linked to several neurodegenerative conditions and reported in alc... more Brain iron deposition has been linked to several neurodegenerative conditions and reported in alcohol dependence. Whether iron accumulation occurs in moderate drinkers is unknown. Our objectives were to investigate causal relationships between alcohol consumption and brain iron levels and to examine whether higher brain iron represents a potential pathway to alcohol-related cognitive deficits. Multi-organ susceptibility-weighted magnetic resonance imaging was used to ascertain iron content of brain (quantitative susceptibility mapping (QSM) and T2*) and liver tissues (T2*), a marker of systemic iron. Observational associations between brain iron markers and self-reported alcohol consumption (n=22,254 UK Biobank participants) were compared with associations with genetically-predicted alcohol intake from two-sample Mendelian randomization (MR). Potential pathways to alcohol-related iron brain accumulation through elevated systemic iron stores (liver) were explored in causal mediation ...

Molecular Psychiatry

Alcohol’s impact on telomere length, a proposed marker of biological aging, is unclear. We perfor... more Alcohol’s impact on telomere length, a proposed marker of biological aging, is unclear. We performed the largest observational study to date (in n = 245,354 UK Biobank participants) and compared findings with Mendelian randomization (MR) estimates. Two-sample MR used data from 472,174 participants in a recent genome-wide association study (GWAS) of telomere length. Genetic variants were selected on the basis of associations with alcohol consumption (n = 941,280) and alcohol use disorder (AUD) (n = 57,564 cases). Non-linear MR employed UK Biobank individual data. MR analyses suggested a causal relationship between alcohol traits, more strongly for AUD, and telomere length. Higher genetically-predicted AUD (inverse variance-weighted (IVW) β = −0.06, 95% confidence interval (CI): −0.10 to −0.02, p = 0.001) was associated with shorter telomere length. There was a weaker association with genetically-predicted alcoholic drinks weekly (IVW β = −0.07, CI: −0.14 to −0.01, p = 0.03). Results ...

Background Alcohol consumption is widespread and increasing in some sectors of society. Whilst ad... more Background Alcohol consumption is widespread and increasing in some sectors of society. Whilst adverse effects on the brain of chronic heavy use are well characterised, the effects of more moderate use are poorly understood. Previous work has lacked prospectively gathered data on alcohol use. Robust evidence of harm would have important public health implications. Methods Associations between self-reported alcohol consumption data gathered over a thirty-year period (1985-2015), neuroimaging markers of brain structure and function, and cognition were examined in community dwelling older adults in the Whitehall II cohort (n=550). Structural, diffusion tensor, and resting state functional magnetic resonance imaging was performed in 2012 to 2015. Cognitive performance was determined cross-sectionally across multiple domains at the time of scanning and longitudinally throughout the study. Results No participants scored as alcohol dependent on the CAGE screening questionnaire. Higher alco...

BJPsych Open, 2021

Aims Assess how current practice reflects recommendations from the National Confidential Enquiry ... more Aims Assess how current practice reflects recommendations from the National Confidential Enquiry into Patient Outcome and Death (NCEPOD) Treat as One: bridging the gap between mental and physical healthcare report (January 2017). Develop template for electronic documentation of liaison psychiatry reviews and implement for trial period. Re-audit after trial period to assess for change in quality of documentation. Background The John Radcliffe Hospital (JR) is a tertiary centre and has a large liaison psychiatry department with 14 consultants. Patient reviews by the liaison team are documented using a blank note type, on an electronic system used by all specialties within the hospital trust. The NCEPOD Treat as One report makes recommendations for the content of documentation of liaison psychiatry reviews which aim to improve communication between specialties. Method 86 patients referred to liaison psychiatry at the JR in September 2018 were randomly selected. Four liaison psychiatry ...

Biological Psychiatry, 2015

The Practitioner, 2012

Perinatal mental illness influences obstetric outcomes, mother-baby interactions and longer term ... more Perinatal mental illness influences obstetric outcomes, mother-baby interactions and longer term emotional and cognitive development of the child. Psychiatric disorders have consistently been found to be one of the leading causes of maternal deaths, often through suicide. Postnatal depression and puerperal psychosis are two disorders most commonly associated with the perinatal period. The most efficient strategy to identify patients at risk relies on focussing on clinically vulnerable subgroups: enquiries about depressive symptoms should be made at the usual screening visits. Attention should be paid to any sign of poor self-care, avoidance of eye contact, overactivity or underactivity, or abnormalities in the rate of speech. Particular care should be taken to ask about suicidal ideation and thoughts of harming others, including the baby. One of the most important risk factors is a previous history of depression. The degree of risk is directly correlated with severity of past episod...

IMPORTANCE Poor cardiovascular health is an established risk factor for dementia, but little is k... more IMPORTANCE Poor cardiovascular health is an established risk factor for dementia, but little is known about its association with brain physiology in older adults. OBJECTIVE To examine the association of cardiovascular risk factors, measured repeatedly during a 20-year period, with cerebral perfusion at older ages. DESIGN, SETTING, AND PARTICIPANTS In this longitudinal cohort study, individuals were selected from the Whitehall II Imaging Substudy. Participants were included if they had no clinical diagnosis of dementia, had no gross brain structural abnormalities on magnetic resonance imaging scans, and had

The American Journal of Geriatric Psychiatry

Highlights • This is the first quantitative synthesis estimating the risk of aggressive behaviors... more Highlights • This is the first quantitative synthesis estimating the risk of aggressive behaviors in dementia and mild cognitive impairment.• Individuals with Alzheimer's disease have five times higher odds of aggression than healthy controls.• We found no differences in risks of aggression between mild cognitive impairment and normal population controls and between dementias of differing aetiologies.

Alcohol and Alcoholism, Oct 1, 2017

We aimed to investigate whether moderate alcohol consumption has favourable, adverse or no associ... more We aimed to investigate whether moderate alcohol consumption has favourable, adverse or no association with brain structure and function. Weekly alcohol intake and cognitive performance were measured repeatedly during a 30-year period (1985 to 2015) in communitydwelling adults enrolled in the Whitehall II cohort based in the United Kingdom (the Whitehall II imaging sub-study). Multimodal Magnetic Resonance Imaging (MRI) was performed at endpoint (2012-5).

Alcohols impact on telomere length, a proposed marker of biological age, is unclear. We performed... more Alcohols impact on telomere length, a proposed marker of biological age, is unclear. We performed the largest observational study to date and compared findings with Mendelian randomization (MR) estimates. Two-sample MR used data from a recent genome-wide association study (GWAS) of telomere length. Genetic variants were selected on the basis of associations with alcohol consumption and alcohol use disorder (AUD). Non-linear MR employed UK Biobank individual data. MR analyses suggest a causal relationship between alcohol and telomere length: both genetically predicted alcohol traits were inversely associated with telomere length. 1 S.D. higher genetically-predicted log-transformed alcoholic drinks weekly had a -0.07 S.D. effect on telomere length (95% confidence interval [CI]:-0.14 to -0.01); genetically-predicted AUD -0.06 S.D. effect (CI:-0.10 to -0.02). Results were consistent across methods and independent from smoking. Non-linear analyses indicated a potential threshold relation...

ObjectivesTo estimate the relationship between moderate alcohol consumption and brain health, det... more ObjectivesTo estimate the relationship between moderate alcohol consumption and brain health, determining the threshold intake for harm and identifying whether population subgroups are at differential risk.DesignObservational cohort study. Alcohol consumption was determined at baseline assessment visit using touchscreen questionnaire (2016-10). Multi-modal MRI brain and cognitive testing were performed subsequently (2014-20). Clinical data was extracted from linked Hospital Episode Statistics.SettingUK Biobank study. Brain imaging was performed on identical scanners with identical protocols at three UK centres (2014-20).Participants25,378 participants (mean age 54.9±7.4 years).Main outcome measuresBrain health as defined by structural and functional MRI brain measures.ResultsAlcohol consumption was negatively linearly associated with global brain grey matter volume (beta= -0.1, 95%CI= -0.11 to -0.09, p<2×10−16). The association with alcohol was stronger than other modifiable fact...

INTRODUCTION: Current prognostic models of dementia have had limited success in consistently iden... more INTRODUCTION: Current prognostic models of dementia have had limited success in consistently identifying at-risk individuals. We aimed to develop and validate a novel dementia risk score (DRS) using the UK Biobank (UKB) cohort.METHODS: The UKB sample was randomly divided into a training (n=166,487, 80%) and test set (n=41,621, 20%). Logistic LASSO regression and standard logistic regression were used to develop the UKB-DRS.RESULTS: The score consisted of age, sex, education, apolipoprotein E4 genotype, a history of diabetes, stroke, and depression, and a family history of dementia. The UKB-DRS had good-to-strong discrimination accuracy in the UKB hold-out sample (AUC [95%CI]=0.79 [0.77, 0.82]) and in an external dataset (Whitehall II cohort, AUC [95%CI]=0.83 [0.79,0.87]). The UKB-DRS modestly but significantly outperformed four published risk scores (i.e., Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI), Cardiovascular Risk Factors, Aging, and Dementia score...

The American Journal of Geriatric Psychiatry

Background: Trajectories of depressive symptoms over the lifespan vary between people, but it is ... more Background: Trajectories of depressive symptoms over the lifespan vary between people, but it is unclear whether these differences exhibit distinct characteristics in brain structure and function. Methods: In order to compare indices of white matter microstructure and cognitive characteristics of groups with different trajectories of depressive symptoms, we examined 774 participants of the Whitehall II Imaging Sub-study, who had completed the depressive subscale of the General Health Questionnaire up to nine times over 25 years. Twenty-seven years after the first examination, participants underwent magnetic resonance imaging to characterize white matter hyperintensities (WMH) and microstructure and completed neuropsychological tests to assess cognition. Twenty-nine years after the first examination, participants completed a further cognitive screening test. Results: Using K-means cluster modelling, we identified five trajectory groups of depressive symptoms: consistently low scorers...

ObjectivTo assess the associations between gout, brain structure, and neurodegenerative disease i... more ObjectivTo assess the associations between gout, brain structure, and neurodegenerative disease incidence.MethodsUsing observational and Mendelian randomization analyses we investigated causal relationships between gout and brain health. Exposures included gout diagnosis (from self-report, linked health records and death records) and genetically proxied gout and serum urate. Outcomes were neuroimaging markers of brain structure and neurodegenerative disease incidence (ascertained through self-report, health records and death reports). Cox proportional hazards models were used to examine time to neurodegenerative disease diagnosis.Results11,735 UK Biobank participants (mean age 55.5±8.0 years and 50.5% female) had a diagnosis of gout (n=1165 in MRI subset). Dementia was ascertained in 3126 individuals over a mean follow-up time of 12.4±1.9 years. Gout patients had smaller global and regional brain volumes and higher brain iron markers. Genetic associations mirrored observational asso...

PLOS Medicine

Background Brain iron deposition has been linked to several neurodegenerative conditions and repo... more Background Brain iron deposition has been linked to several neurodegenerative conditions and reported in alcohol dependence. Whether iron accumulation occurs in moderate drinkers is unknown. Our objectives were to investigate evidence in support of causal relationships between alcohol consumption and brain iron levels and to examine whether higher brain iron represents a potential pathway to alcohol-related cognitive deficits. Methods and findings Observational associations between brain iron markers and alcohol consumption (n = 20,729 UK Biobank participants) were compared with associations with genetically predicted alcohol intake and alcohol use disorder from 2-sample mendelian randomization (MR). Alcohol intake was self-reported via a touchscreen questionnaire at baseline (2006 to 2010). Participants with complete data were included. Multiorgan susceptibility-weighted magnetic resonance imaging (9.60 ± 1.10 years after baseline) was used to ascertain iron content of each brain r...

The Routledge International Handbook of Psychosocial Epidemiology, 2017

Started approximately in the late 1980s, exoplanetology has up to now unveiled the main gross bul... more Started approximately in the late 1980s, exoplanetology has up to now unveiled the main gross bulk characteristics of planets and planetary systems. In the future it will benefit from more and more large telescopes and advanced space missions. These instruments will dramatically improve their performance in terms of photometric precision, detection speed, multipixel imaging, high-resolution spectroscopy, allowing to go much deeper in the knowledge of planets. Here we outline some science questions which should go beyond these standard improvements and how to address them. Our prejudice is that one is never too speculative: experience shows that the speculative predictions initially not accepted by the community have been confirmed several years later (like spectrophotometry of transits or circumbinary planets).

Brain iron deposition has been linked to several neurodegenerative conditions and reported in alc... more Brain iron deposition has been linked to several neurodegenerative conditions and reported in alcohol dependence. Whether iron accumulation occurs in moderate drinkers is unknown. Our objectives were to investigate causal relationships between alcohol consumption and brain iron levels and to examine whether higher brain iron represents a potential pathway to alcohol-related cognitive deficits. Multi-organ susceptibility-weighted magnetic resonance imaging was used to ascertain iron content of brain (quantitative susceptibility mapping (QSM) and T2*) and liver tissues (T2*), a marker of systemic iron. Observational associations between brain iron markers and self-reported alcohol consumption (n=22,254 UK Biobank participants) were compared with associations with genetically-predicted alcohol intake from two-sample Mendelian randomization (MR). Potential pathways to alcohol-related iron brain accumulation through elevated systemic iron stores (liver) were explored in causal mediation ...

Molecular Psychiatry

Alcohol’s impact on telomere length, a proposed marker of biological aging, is unclear. We perfor... more Alcohol’s impact on telomere length, a proposed marker of biological aging, is unclear. We performed the largest observational study to date (in n = 245,354 UK Biobank participants) and compared findings with Mendelian randomization (MR) estimates. Two-sample MR used data from 472,174 participants in a recent genome-wide association study (GWAS) of telomere length. Genetic variants were selected on the basis of associations with alcohol consumption (n = 941,280) and alcohol use disorder (AUD) (n = 57,564 cases). Non-linear MR employed UK Biobank individual data. MR analyses suggested a causal relationship between alcohol traits, more strongly for AUD, and telomere length. Higher genetically-predicted AUD (inverse variance-weighted (IVW) β = −0.06, 95% confidence interval (CI): −0.10 to −0.02, p = 0.001) was associated with shorter telomere length. There was a weaker association with genetically-predicted alcoholic drinks weekly (IVW β = −0.07, CI: −0.14 to −0.01, p = 0.03). Results ...

Background Alcohol consumption is widespread and increasing in some sectors of society. Whilst ad... more Background Alcohol consumption is widespread and increasing in some sectors of society. Whilst adverse effects on the brain of chronic heavy use are well characterised, the effects of more moderate use are poorly understood. Previous work has lacked prospectively gathered data on alcohol use. Robust evidence of harm would have important public health implications. Methods Associations between self-reported alcohol consumption data gathered over a thirty-year period (1985-2015), neuroimaging markers of brain structure and function, and cognition were examined in community dwelling older adults in the Whitehall II cohort (n=550). Structural, diffusion tensor, and resting state functional magnetic resonance imaging was performed in 2012 to 2015. Cognitive performance was determined cross-sectionally across multiple domains at the time of scanning and longitudinally throughout the study. Results No participants scored as alcohol dependent on the CAGE screening questionnaire. Higher alco...

BJPsych Open, 2021

Aims Assess how current practice reflects recommendations from the National Confidential Enquiry ... more Aims Assess how current practice reflects recommendations from the National Confidential Enquiry into Patient Outcome and Death (NCEPOD) Treat as One: bridging the gap between mental and physical healthcare report (January 2017). Develop template for electronic documentation of liaison psychiatry reviews and implement for trial period. Re-audit after trial period to assess for change in quality of documentation. Background The John Radcliffe Hospital (JR) is a tertiary centre and has a large liaison psychiatry department with 14 consultants. Patient reviews by the liaison team are documented using a blank note type, on an electronic system used by all specialties within the hospital trust. The NCEPOD Treat as One report makes recommendations for the content of documentation of liaison psychiatry reviews which aim to improve communication between specialties. Method 86 patients referred to liaison psychiatry at the JR in September 2018 were randomly selected. Four liaison psychiatry ...

Biological Psychiatry, 2015

The Practitioner, 2012

Perinatal mental illness influences obstetric outcomes, mother-baby interactions and longer term ... more Perinatal mental illness influences obstetric outcomes, mother-baby interactions and longer term emotional and cognitive development of the child. Psychiatric disorders have consistently been found to be one of the leading causes of maternal deaths, often through suicide. Postnatal depression and puerperal psychosis are two disorders most commonly associated with the perinatal period. The most efficient strategy to identify patients at risk relies on focussing on clinically vulnerable subgroups: enquiries about depressive symptoms should be made at the usual screening visits. Attention should be paid to any sign of poor self-care, avoidance of eye contact, overactivity or underactivity, or abnormalities in the rate of speech. Particular care should be taken to ask about suicidal ideation and thoughts of harming others, including the baby. One of the most important risk factors is a previous history of depression. The degree of risk is directly correlated with severity of past episod...

IMPORTANCE Poor cardiovascular health is an established risk factor for dementia, but little is k... more IMPORTANCE Poor cardiovascular health is an established risk factor for dementia, but little is known about its association with brain physiology in older adults. OBJECTIVE To examine the association of cardiovascular risk factors, measured repeatedly during a 20-year period, with cerebral perfusion at older ages. DESIGN, SETTING, AND PARTICIPANTS In this longitudinal cohort study, individuals were selected from the Whitehall II Imaging Substudy. Participants were included if they had no clinical diagnosis of dementia, had no gross brain structural abnormalities on magnetic resonance imaging scans, and had

The American Journal of Geriatric Psychiatry

Highlights • This is the first quantitative synthesis estimating the risk of aggressive behaviors... more Highlights • This is the first quantitative synthesis estimating the risk of aggressive behaviors in dementia and mild cognitive impairment.• Individuals with Alzheimer's disease have five times higher odds of aggression than healthy controls.• We found no differences in risks of aggression between mild cognitive impairment and normal population controls and between dementias of differing aetiologies.

Alcohol and Alcoholism, Oct 1, 2017

We aimed to investigate whether moderate alcohol consumption has favourable, adverse or no associ... more We aimed to investigate whether moderate alcohol consumption has favourable, adverse or no association with brain structure and function. Weekly alcohol intake and cognitive performance were measured repeatedly during a 30-year period (1985 to 2015) in communitydwelling adults enrolled in the Whitehall II cohort based in the United Kingdom (the Whitehall II imaging sub-study). Multimodal Magnetic Resonance Imaging (MRI) was performed at endpoint (2012-5).

Alcohols impact on telomere length, a proposed marker of biological age, is unclear. We performed... more Alcohols impact on telomere length, a proposed marker of biological age, is unclear. We performed the largest observational study to date and compared findings with Mendelian randomization (MR) estimates. Two-sample MR used data from a recent genome-wide association study (GWAS) of telomere length. Genetic variants were selected on the basis of associations with alcohol consumption and alcohol use disorder (AUD). Non-linear MR employed UK Biobank individual data. MR analyses suggest a causal relationship between alcohol and telomere length: both genetically predicted alcohol traits were inversely associated with telomere length. 1 S.D. higher genetically-predicted log-transformed alcoholic drinks weekly had a -0.07 S.D. effect on telomere length (95% confidence interval [CI]:-0.14 to -0.01); genetically-predicted AUD -0.06 S.D. effect (CI:-0.10 to -0.02). Results were consistent across methods and independent from smoking. Non-linear analyses indicated a potential threshold relation...

ObjectivesTo estimate the relationship between moderate alcohol consumption and brain health, det... more ObjectivesTo estimate the relationship between moderate alcohol consumption and brain health, determining the threshold intake for harm and identifying whether population subgroups are at differential risk.DesignObservational cohort study. Alcohol consumption was determined at baseline assessment visit using touchscreen questionnaire (2016-10). Multi-modal MRI brain and cognitive testing were performed subsequently (2014-20). Clinical data was extracted from linked Hospital Episode Statistics.SettingUK Biobank study. Brain imaging was performed on identical scanners with identical protocols at three UK centres (2014-20).Participants25,378 participants (mean age 54.9±7.4 years).Main outcome measuresBrain health as defined by structural and functional MRI brain measures.ResultsAlcohol consumption was negatively linearly associated with global brain grey matter volume (beta= -0.1, 95%CI= -0.11 to -0.09, p<2×10−16). The association with alcohol was stronger than other modifiable fact...

INTRODUCTION: Current prognostic models of dementia have had limited success in consistently iden... more INTRODUCTION: Current prognostic models of dementia have had limited success in consistently identifying at-risk individuals. We aimed to develop and validate a novel dementia risk score (DRS) using the UK Biobank (UKB) cohort.METHODS: The UKB sample was randomly divided into a training (n=166,487, 80%) and test set (n=41,621, 20%). Logistic LASSO regression and standard logistic regression were used to develop the UKB-DRS.RESULTS: The score consisted of age, sex, education, apolipoprotein E4 genotype, a history of diabetes, stroke, and depression, and a family history of dementia. The UKB-DRS had good-to-strong discrimination accuracy in the UKB hold-out sample (AUC [95%CI]=0.79 [0.77, 0.82]) and in an external dataset (Whitehall II cohort, AUC [95%CI]=0.83 [0.79,0.87]). The UKB-DRS modestly but significantly outperformed four published risk scores (i.e., Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI), Cardiovascular Risk Factors, Aging, and Dementia score...

The American Journal of Geriatric Psychiatry

Background: Trajectories of depressive symptoms over the lifespan vary between people, but it is ... more Background: Trajectories of depressive symptoms over the lifespan vary between people, but it is unclear whether these differences exhibit distinct characteristics in brain structure and function. Methods: In order to compare indices of white matter microstructure and cognitive characteristics of groups with different trajectories of depressive symptoms, we examined 774 participants of the Whitehall II Imaging Sub-study, who had completed the depressive subscale of the General Health Questionnaire up to nine times over 25 years. Twenty-seven years after the first examination, participants underwent magnetic resonance imaging to characterize white matter hyperintensities (WMH) and microstructure and completed neuropsychological tests to assess cognition. Twenty-nine years after the first examination, participants completed a further cognitive screening test. Results: Using K-means cluster modelling, we identified five trajectory groups of depressive symptoms: consistently low scorers...