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Sydney Memory & Ageing Study
by CHeBA
Continued our strong contribution to the ENIGMA Network in 2020, with four papers that included
OATS data published. The ENIGMA Network is an international effort to understand brain structure and function, based on MRI and genetic data from the six populated continents across the globe. One of these papers were led by Dr Karen Mather, Leader of CHeBA’s Genetics & Epigenomics Group and
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Dr Nicola Armstrong, CHeBA collaborator from Murdoch University, WA. Their study brought together measures of blood pressure, genetic data and MRI scans from 26,654 research participants, including
OATS participants, to identify genetic variations for neuroimaging markers that indicate high risk of stroke in an individual. The study team involved 96 authors, including 10 from OATS, representing 17 individual studies from across 11 different countries. As well as providing the above important research findings, this study illustrates how many smaller pieces of a puzzle can come together to increase our understanding of brain function and risk of life changing events, like strokes. While the contribution of one research participant, one researcher, or one study, may appear small, it demonstrates the power of many. Conducted an evaluation of the relative contributions of genetic and Project Leaders environmental factors to lipid levels in blood from OATS participants which showed that only about 13% of the lipids measured in the study have significant heritability, indicating that environmental and possibly epigenetic factors have a considerable influence on lipid profiles in healthy older age groups. This research was led by Dr Wong, a CHeBA
PhD graduate, which he completed under the supervision of Dr Poljak and Professor Sachdev. Professor Henry Brodaty, In 2020 we farewelled Ms Suzy Forrester who has assisted with project Professor Perminder Sachdev administration and kept us organised since 2013.
Project Members
Dr John Crawford, Dr Teresa Lee, Dr Karen Mather, Dr Anne Poljak, Dr Anbu Thalamuthu, Professor Julian Trollor, Associate Professor Wei Wen
After 15 years of assessments, the Sydney Memory and Ageing Study (MAS) officially concluded in December of 2020, making the largest continuous running study of cognitive ageing in Australia.
MAS began in 2005 with the aim of better understanding predementia syndromes such as Mild Cognitive Impairment (MCI). Over time, MAS evolved to focus on individual and lifestyle factors associated with both healthy brain ageing and cognitive decline.
MAS is renowned for its data nationally and internationally. This is largely because the study has followed the same cohort (e.g., study participants) for a decade and a half. In that time, researchers have gathered a wealth of data around sociodemographic, clinical, neuropsychological, neuroimaging, biochemical, genetics, and proteomics factors associated with brain ageing. These many data points from the same participants have allowed us to look at individual changes over time and better understand what factors predict healthy cognitive ageing versus neurodegenerative diseases like dementia. The MAS baseline cohort consisted of 1037 older adults (aged 70-90) recruited from Sydney’s Eastern suburbs who did not have a diagnosis of dementia at the time. Participants underwent comprehensive biennial assessments (called “Waves”) comprised of neuropsychological tests, medical exams, participant Dr Katya Numbers, interviews, and questionnaires about SMAS Coordinator sociodemographic, health, lifestyle, and other factors. A knowledgeable informant (close friend or family member) was also interviewed at each Wave.
In 2020, there were of course unique challenges to the MAS study in the wake of COVID-19. MAS, like all research studies, was impacted by the global pandemic and ensuing lockdowns, and as a result, 1/3 of the remaining 258 active MAS participants completed phone-only interview and questionnaires in Wave 7. Nevertheless, the study concluded on time and the MAS team was able to create and distribute a novel COVID-19 questionnaire to all active participants before the end of the year so that we can better understand the unique impacts of COVID-19 on our older participants.
To date, MAS data has contributed to 181 publications in in respected international scientific journals, with 20 of those being published in 2020 alone. Twenty-six independent groups of researchers reached out and requested MAS data in 2020, across 14 different national and international research institutions. There are currently 25 higher degree students and postdoctoral fellows who are using MAS data as part of their research projects.
Highlights from 2020 – Snapshots
MAS wrapped up all participant and informant assessments after 15 years of continuous testing. All data has been entered and all consensus cases have been seen and diagnosed. MAS collected new data in 2020, including pure-tone audiometry data, and the Attitudes
About Scale and Purpose in Life scale, for new analyses. MAS distributed a novel COVID-19 questionnaire to 250 active participants with a 90% return rate. MAS joined Kings College London and Arizona
State University on a successful grant bid to examine impacts of the COVID-19 pandemic on older adults via the PLuS Alliance strategy. MAS contributed data 7 global consortia projects in 2020.
Funding: NHMRC Program Grants (ID350833; ID568969; APP1093083) https://www.nhmrc.gov.au/funding
Project Leaders
Professor Henry Brodaty, Professor Perminder Sachdev
Project Members
Dr Adam Bentvelzen, Dr John Crawford, Professor Brian Draper, Dr Nicole Kochan, Dr Karen Mather, Professor Julian Trollor
Worldwide Study Using MAS and OATS Data Unlocks Genetic Secrets of the Grey Matter
A major international collaboration using data CHeBA’s Sydney Memory & Ageing Study and the Older Australian Twins Study, has produced the first genetic map of the cerebral cortex, identifying more than 300 genetic variants that influence the structure of the key brain region.
The cerebral cortex, often referred to as the ‘grey matter’, plays a crucial role in thinking, information processing, memory and attention. It is the relatively thin, folded, outer layer of the brain. Its folds area way of packing in more neurons, or brain cells. The extent of the folds – which are measured by surface area –and the thickness of the cortex have previously been linked to cognitive abilities and various psychiatric traits, including schizophrenia, bipolar disorder, depression, attention deficit hyperactivity disorder (ADHD), and autism. However, until now, not a lot was known about the genetic variants that influence the size of the surface area and thickness of the cortex.
More than 360 scientists from 184 different institutions - including CHeBA’s Co-Directors Professor Perminder Sachdev and Professor Henry Brodaty and Leader of CHeBA’s Genetics & Epigenomics Group Dr Karen Mather - contributed to the global effort, which was published in the prestigious journal Science.
“The longitudinal studies being conducted at CHeBA have generated rich datasets that have led to many novel discoveries, often in collaboration with several researchers overseas. This paper is another example of the rich dividends that the work of over the last 15 years is yielding,” said Professor Perminder Sachdev.
Researchers identified 306 genetic variants that influenced the structure of the cerebral cortex. The study was conducted to identify genetic variants that influence brain structure to shed light on how genetics contribute to these differences among us.
Researchers found that the genetic variants that are linked to a smaller surface area of the cerebral cortex – or less folding – also contribute to a greater risk of ADHD, depression and insomnia.
The findings are now a resource that can be used by other scientists to help answer more questions about the genetic influences on the brain and how they relate to numerous behavioural or disease outcomes.
The researchers studied MRI scans and DNA from more than 50 thousand people.
It is only by sharing data through these major, international collaborations that researchers can continue to unpick the highly complex relationship between genes, brain structure and various disorders.
