Research suggests diabetes may affect brain atrophy earlier than thought

Prof Velandai Srikanth

by Anne Crawford

Studies by Monash University’s Peninsula Clinical School researchers have deepened knowledge about the link between type 2 diabetes and dementia, and suggest that the effect of diabetes on brain atrophy may begin in middle rather than old age.

The studies were conducted by researchers led by Professor of Medicine, Velandai Srikanth, who are considered international leaders in the field of diabetes and dementia.

Although it has been known for some years that having type 2 diabetes increases the risk of developing dementia, the mechanisms underlying that link have not been clear nor have many studies looked at changes in the brains of people with type 2 diabetes over time.

Professor Srikanth, senior author, said the two longitudinal studies, marked “an important stage of understanding the mechanisms of diabetes-related dementia.”

One of the studies, published in Diabetologia, examined – in what is believed to be a first – whether type 2 diabetes mellitus is associated with greater brain atrophy and cognitive decline in community-based people, and whether brain atrophy explains the associations between type 2 diabetes and cognitive decline.

A group of 705 people aged 55 to 90 years without a history of dementia, who were part of the Cognition and Diabetes in Older Tasmanians (CDOT) Study, underwent brain MRI and neuropsychological measures at three times over 4.6 years.

The paper found that type 2 diabetes was associated with reduced cognitive function at the start of the study, and also with a greater decline in verbal memory and verbal fluency over time.

“The findings of accelerated decline in verbal memory and verbal fluency are important, as they may contribute to difficulties in everyday activities (such as remembering to take medication),” first author Dr Michele Callisaya said.

“Interestingly, brain volume was lower in people with type 2 diabetes at the start of the study. This suggests that the effect of type 2 diabetes on brain volume may begin earlier in life,” she said.

However, the rate of brain atrophy over the follow-up period did not differ between those with and without diabetes. “This may become apparent over longer follow-up, or if diabetes leads to strokes and other vascular complications in the brain.”

In the second study, published in Neurology, people who were enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study underwent brain MRI and cognitive tests annually for five years. Of the participants in this study, 124 people had type 2 diabetes mellitus and 693 did not; both groups were older than in the CDOT study and had a mean age of around 75 years.

“The results reflected those of the previous study; diabetes was associated with less brain volume when the participants went into the study but not with a greater loss of brain volume over time,” first author Dr Chris Moran said.

“It is therefore quite possible that the effect of diabetes on brain volumes happens early on – in middle age – before stabilising, and theoretically could get worse if diabetes is not well treated,” he said.

“What we did find however, was that higher levels of education seem to be protective against the negative effect of diabetes on the brain.”

The study also suggested that the combination of having lower brain tissue volume to begin with, combined with type 2 diabetes, may lead to higher risk of further and more rapid brain atrophy.

“One of the questions is, did we go back far enough to see when diabetes begins to have an effect?” Dr Moran asked.

Further studies are being conducted looking at people with type 2 diabetes in young adult and middle age.

Said Professor Srikanth, “the studies point towards the importance of prevention of diabetes, better management of diabetes, and adopting healthy behaviours early in life if we are to reduce the risk of developing dementia later in life.”

“Recommendations for good brain health include physical activity, following a healthy diet, maintaining a healthy weight, checking blood pressure and cholesterol, mentally challenging the brain and enjoying social activities,” Dr Callisaya added.

Professor Srikanth, a geriatrician and NHMRC Practitioner Fellow, heads a team of researchers and clinicians from different disciplines based at the Peninsula Clinical School, Central Clinical School, Monash University.  Dr Moran, also a geriatrician, is an NHMRC-ARC Dementia Research Fellow within his research unit. Associate Professor Michele Callisaya is a physiotherapist who holds an NHMRC Boosting Dementia Research Fellowship, and will be joining the team at Peninsula Clinical School in March 2019.


Callisaya ML, Beare R, Moran C, Phan T, Wang W, Srikanth VK. Type 2 diabetes mellitus, brain atrophy and cognitive decline in older people: a longitudinal study. Diabetologia. 2018 Dec 13. doi: 10.1007/s00125-018-4778-9. [Epub ahead of print]

Moran C, Beare R, Wang W, Callisaya M, Srikanth V; Alzheimer's Disease Neuroimaging Initiative (ADNI). Type 2 diabetes mellitus, brain atrophy, and cognitive decline. Neurology. 2019 Jan 23. pii: 10.1212/WNL.0000000000006955. doi: 10.1212/WNL.0000000000006955. [Epub ahead of print]