, Volume 62, Issue 3, pp 448–458 | Cite as

Type 2 diabetes mellitus, brain atrophy and cognitive decline in older people: a longitudinal study

  • Michele L. CallisayaEmail author
  • Richard Beare
  • Chris Moran
  • Thanh Phan
  • Wei Wang
  • Velandai K. Srikanth



The aims of the study were to examine whether type 2 diabetes mellitus is associated with greater brain atrophy and cognitive decline, and whether brain atrophy mediates associations between type 2 diabetes and cognitive decline.


Participants without dementia aged 55–90 years from the Cognition and Diabetes in Older Tasmanians (CDOT) study underwent brain MRI (ventricular and total brain volume) and neuropsychological measures (global function and seven cognitive domains) at three time points over 4.6 years. Mixed models were used to examine longitudinal associations of type 2 diabetes with cognitive and MRI measures, adjusting for covariates. A test of mediation was used to determine whether brain atrophy explained associations between type 2 diabetes and cognitive decline.


A total of 705 participants (diabetes: n = 348, mean age 68.2 years [SD 7.0]; no diabetes: n = 357, mean age 72.5 years [SD 7.1]) were available at baseline. Adjusting for age, sex, education and vascular risk factors, there were significant diabetes × time interactions for verbal memory (β −0.06; 95% CI −0.09, −0.02) and verbal fluency (β −0.03; 95% CI −0.06, −0.00). Although people with diabetes had lower brain (β −14.273; 95% CI −21.197, −6.580) and greater ventricular (β 2.672; 95% CI 0.152, 5.193) volumes at baseline, there were no significant diabetes × time interactions (p > 0.05) or evidence of mediation of the diabetes–cognition relationship by brain atrophy.


In older community-dwelling people, type 2 diabetes is associated with decline in verbal memory and fluency over ~5 years. The effect of diabetes on brain atrophy may begin earlier (midlife).


Brain atrophy Brain imaging Cognition Dementia Longitudinal study Type 2 diabetes mellitus 



Diastolic blood pressure


Systolic blood pressure


White matter hyperintensity



The results of this study have been presented in abstract form at the Alzheimer’s Association International Conference, London, 2017, and the Australian Dementia Forum, Melbourne, 2017.

Contribution statement

MLC drafted the manuscript and analysed the data. RB completed the image processing and analysis. MLC, RB, CM, WW, TP and VKS interpreted the data and revised the manuscript. WW assisted with the statistical analysis. VKS was responsible for the study concept and design. All authors approved the final version of the manuscript. MLC and VKS are the guarantors of this work.


This study was funded by the National Health and Medical Research Council (NHMRC) (project grant 403000 and 436797), Australia. MLC is funded by an NHMRC Boosting Dementia Research Leadership Fellowship (1135761). CM is funded by an NHMRC/ARC Dementia Early Career Fellowship (1109482). VKS is a recipient of NHMRC project grants (403000 and 436797) and an NHMRC Practitioner Fellowship (APP1137837). WW, RB and TP have no funding to declare.

Duality of interest

MLC, RB, CM, WW and VKS have no conflicts of interest to declare. TP is on the Genzyme advisory board on Fabry disease, and has received payment for lectures including service on speakers’ bureaus for Bayer, Boehringer Ingelheim, Pfizer and Genzyme.

Supplementary material

125_2018_4778_MOESM1_ESM.pdf (162 kb)
ESM (PDF 162 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Michele L. Callisaya
    • 1
    • 2
    • 3
    Email author
  • Richard Beare
    • 2
    • 4
  • Chris Moran
    • 2
    • 5
    • 6
  • Thanh Phan
    • 3
  • Wei Wang
    • 2
  • Velandai K. Srikanth
    • 1
    • 2
    • 5
  1. 1.Menzies Institute for Medical ResearchUniversity of TasmaniaHobartAustralia
  2. 2.Peninsula Clinical School, Central Clinical SchoolMonash UniversityMelbourneAustralia
  3. 3.Stroke and Aging Research Group, Department of Medicine, School of Clinical SciencesMonash UniversityMelbourneAustralia
  4. 4.Developmental ImagingMurdoch Children’s Research InstituteMelbourneAustralia
  5. 5.Department of Geriatric Medicine, Frankston Hospital, Peninsula HealthMelbourneAustralia
  6. 6.Department of Aged Care, Alfred HealthMelbourneAustralia

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