Biology subjects

Anstey, K. J.

Publications and source records attributed to Anstey, K. J..

4 recordsLinked to original sources

bioRxiv2018

Alzheimer’s environmental and genetic risk scores are differentially associated with ‘g’ and δ

IntroductionWe investigated the association of the Australian National University Alzheimers Disease Risk Index (ANU-ADRI) and an AD genetic risk score (GRS) with cognitive performance.\n\nMethodsThe ANU-ADRI (composed of 11 risk factors for AD) and GRS (composed of 25 AD risk loci) were computed in 1,061 community-dwelling older adults. Participants were assessed on 11 cognitive tests and activities of daily living. Structural equation modelling was used to evaluate the association of the ANU-ADRI and GRS with: 1) general cognitive ability (g) 2) dementia related variance in cognitive performance ({delta}) and 3) verbal ability, episodic memory, executive function and processing speed.\n\nResultsA worse ANU-ADRI score was associated with poorer performance in g, {delta}, and each cognitive domain. A worse GRS was associated with poorer performance in {delta} and episodic memory.\n\nDiscussionThe ANU-ADRI was broadly associated with worse cognitive performance, validating its further use in early dementia risk assessment.\n\nHighlightsO_LIAn environmental/lifestyle dementia risk index is broadly associated with cognitive performance\nC_LIO_LIAn Alzheimers genetic risk score is associated with dementia severity and episodic memory\nC_LIO_LIThe environmental risk index is more strongly associated with dementia severity than genetic risk\nC_LI\n\nResearch in ContextO_ST_ABSSystematic ReviewC_ST_ABSThe authors reviewed the literature using online databases (e.g. PubMed). Previous research has highlighted the need for dementia risk assessment tools to be evaluated on outcomes prior to dementia onset, such as cognitive performance. The relevant citations have been appropriately cited.\n\nInterpretationThe Australian National University Alzheimers Disease Risk Index (ANU-ADRI) was more broadly associated with cognitive performance than Alzheimers genetic risk. For the ANU-ADRI, stronger effects were observed for dementia-related variance in cognitive task performance that for variance in general cognitive function. This suggests that ANU-ADRI is more specifically associated with dementia-related processes and further validates its use in early risk assessment for dementia.\n\nFuture DirectionsAccordingly, future studies should seek to evaluate the association of the ANU-ADRI and genetic risk with AD biomarkers and longitudinal cognitive performance to evaluate differential trajectories in g and {delta}.

genetics↗

bioRxiv2017

Alzheimer’s Genetic Risk Score linked to Incident Mild Behavioral Impairment

Mild Behavioral Impairment (MBI) describes the emergence of later-life Neuropsychiatric Symptoms (NPS) as an at-risk state for cognitive decline and dementia and as a potential manifestation of prodromal dementia. How NPS mechanistically link to the development of Mild Cognitive Impairment (MCI) and Alzheimers disease (AD) is not fully understood. Potential mechanisms include either shared risk factors that are related to both NPS and cognitive impairment, or AD pathology promoting NPS. This is the first study to examine whether AD genetic loci, individually and as a genetic risk score, are a shared risk factor with MBI. 1377 older adults (aged 72-79; 738 males; 763 normal cognition) from the PATH Through Life project. MBI was assessed in accordance with Criterion 1 of the ISTAART-AA diagnostic criteria using the Neuropsychiatric Inventory. 25 LOAD risk loci were genotyped and a weighted genetic risk score (GRS) was constructed. Binomial logistic regression adjusting for age, gender, and education examined the association between LOAD GRS and MBI domains. An increase in the LOAD GRS and APOE*{varepsilon}4 were associated with higher likelihood of Affective Dysregulation; MS4A4A-rs4938933*C and MS4A6A-rs610932*G were associated with a reduced likelihood of Affective Dysregulation; ZCWPW1-rs1476679*C was associated with a reduced likelihood of Social Inappropriateness and Abnormal Perception; BIN1-rs744373*G and EPHA1-rs11767557*C were associated with higher likelihood of Abnormal Perception; NME8-rs2718058*G was associated with a reduced likelihood Decreased Motivation. These findings suggest a common genetic etiology between MBI and traditionally recognized memory problems observed in AD and improve our understanding of the pathophysiological features underlying MBI.

genetics↗

bioRxiv2017

Association between alcohol consumption and Alzheimer’s disease: A Mendelian Randomization Study

INTRODUCTIONObservational studies have suggested that light-moderate alcohol consumptions decreases the risk of Alzheimers disease, but it is unclear if this association is causal.\n\nMETHODSTwo-sample Mendelian randomization (MR) analysis was used to examine whether alcohol consumption, alcohol dependence or Alcohol Use Disorder Identification Test (AUDIT) scores were causally associated with the risk of Late Onset Alzheimers disease (LOAD) or Alzheimers disease age of onset survival (AAOS). Additionally, {gamma}-glutamyltransferase levels were included as a positive control.\n\nRESULTSThere was no evidence of a causal association between alcohol consumption, alcohol dependence or AUDIT and LOAD. Alcohol consumption was associated with an earlier AAOS and increased {gamma}-glutamyltransferase blood concentrations. Alcohol dependence was associated with a delayed AAOS.\n\nDISCUSSIONMR found robust evidence of a causal association between alcohol consumption and an earlier AAOS, but not alcohol intake and LOAD risk. The protective effect of alcohol dependence is potentially due to survivor bias.\n\nResearch in ContextO_ST_ABSSystematic ReviewC_ST_ABSThe authors reviewed the literature using online databases (e.g. PubMed). Previous research links light-moderate alcohol consumption to a decreased risk of Alzheimers disease (AD), however, prior studies based on observational study designs may be biased due to unmeasured confounders influencing both alcohol consumption and AD risk.\n\nInterpretationWe used a two-sample Mendelian randomization (MR) approach to evaluated the causal relationship between alcohol intake and AD. MR uses genetic variants as proxies for environmental exposures to provide an estimate of the causal association between an intermediate exposure and a disease outcome. MR found evidence of a causal association between alcohol consumption and an earlier AD age of onset, suggesting that light-moderate alcohol consumption does not reduce risk of Alzheimers disease.\n\nFuture DirectionsFuture studies should use alterative study designs and account for additional confounders when evaluating the causal relationship between alcohol consumption and AD.\n\nHighlightsO_LIWe evaluated causal relationships between alcohol intake and Alzheimers disease\nC_LIO_LIAlcohol consumption is causally associated with an earlier Alzheimers age of onset\nC_LIO_LINo evidence of causal assocations between alcohol intake and Alzheimers risk\nC_LI

genetics↗

bioRxiv2017

More Highly Myelinated White Matter Tracts are Associated with Faster Processing Speed in Healthy Adults

The objective of this study was to investigate whether the myelin content of white matter tracts is predictive of cogni-tive processing speed and whether such associations are modulated by age. Associations between myelin content and processing speed was assessed in 570 community-living individuals (277 middle-age, 293 older-age). Myelin content was measured using the mean T1w/T2w magnetic resonance ratio, in six white matter tracts (anterior corona radiata, superior corona radiata, pontine crossing tract, anterior limb of the internal capsule, genu of the corpus callosum, and splenium of the corpus callosum). Processing speed was estimated by extracting a principal component from 5 sep-arate tests of processing speed. It was found that myelin content of the bilateral anterior limb of the internal capsule and left splenium of the corpus callosum were significant predictors of processing speed, even after controlling for socio-demographic, health and genetic variables and correcting for multiple comparisons. A 1 SD increase in the myelin content of the anterior limb of the internal capsule was associated with 2.53% increase in processing speed and within the left splenium of the corpus callosum with a 2.20% increase in processing speed. In addition, significant differences in myelin content between middle-age and older participants were found in all six white matter tracts. The present results indicate that myelin content, estimated in vivo using a neuroimaging approach in healthy older adults is sufficiently precise to predict variability in processing speed in behavioural measures.

neuroscience↗