title: Does left ventricular hypertrophy affect cognition and brain structural integrity in type 2 diabetes? Study design and rationale of the Diabetes and Dementia (D2) study.
abstract: BACKGROUND
  Cognitive impairment is common in type 2 diabetes mellitus, and there is a strong association between type 2 diabetes and Alzheimer's disease. However, we do not know which type 2 diabetes patients will dement or which biomarkers predict cognitive decline. Left ventricular hypertrophy (LVH) is potentially such a marker. LVH is highly prevalent in type 2 diabetes and is a strong, independent predictor of cardiovascular events. To date, no studies have investigated the association between LVH and cognitive decline in type 2 diabetes. The Diabetes and Dementia (D2) study is designed to establish whether patients with type 2 diabetes and LVH have increased rates of brain atrophy and cognitive decline.
  
  
  METHODS
  The D2 study is a single centre, observational, longitudinal case control study that will follow 168 adult patients aged >50 years with type 2 diabetes: 50% with LVH (case) and 50% without LVH (control). It will assess change in cardiovascular risk, brain imaging and neuropsychological testing between two time-points, baseline (0 months) and 24 months. The primary outcome is brain volume change at 24 months. The co-primary outcome is the presence of cognitive decline at 24 months. The secondary outcome is change in left ventricular mass associated with brain atrophy and cognitive decline at 24 months.
  
  
  CONCLUSIONS
  The D2 study will test the hypothesis that patients with type 2 diabetes and LVH will exhibit greater brain atrophy than those without LVH. An understanding of whether LVH contributes to cognitive decline, and in which patients, will allow us to identify patients at particular risk.
  
  
  BACKGROUND
  Australian New Zealand Clinical Trials Registry ( ACTRN12616000546459 ), date registered, 28/04/2016.
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, Austin Health, 245 Burgundy Street, Heidelberg, VIC, 3084, Australia.|Department of Medicine, University of Melbourne, Austin Health, Level 7, Lance Townsend Building, 145 Studley Road, Heidelberg, VIC, 3084, Australia.
authors.forename: Sheila K
authors.initials: SK
authors.lastname: Patel
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, Austin Health, 245 Burgundy Street, Heidelberg, VIC, 3084, Australia.
authors.forename: Carolina
authors.initials: C
authors.lastname: Restrepo
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, Austin Health, 245 Burgundy Street, Heidelberg, VIC, 3084, Australia.
authors.forename: Emilio
authors.initials: E
authors.lastname: Werden
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, Austin Health, 245 Burgundy Street, Heidelberg, VIC, 3084, Australia.
authors.forename: Leonid
authors.initials: L
authors.lastname: Churilov
authors.affiliation: Department of Medicine, University of Melbourne, Austin Health, Level 7, Lance Townsend Building, 145 Studley Road, Heidelberg, VIC, 3084, Australia.|Austin Health Endocrine Centre, Heidelberg, VIC, Australia.
authors.forename: Elif I
authors.initials: EI
authors.lastname: Ekinci
authors.affiliation: Department of Medicine, University of Melbourne, Austin Health, Level 7, Lance Townsend Building, 145 Studley Road, Heidelberg, VIC, 3084, Australia.|Department of Cardiology, Austin Health, Heidelberg, VIC, Australia.
authors.forename: Piyush M
authors.initials: PM
authors.lastname: Srivastava
authors.affiliation: Department of Medicine, University of Melbourne, Austin Health, Level 7, Lance Townsend Building, 145 Studley Road, Heidelberg, VIC, 3084, Australia.|Department of Cardiology, Austin Health, Heidelberg, VIC, Australia.
authors.forename: Jay
authors.initials: J
authors.lastname: Ramchand
authors.affiliation: Department of Medicine, University of Melbourne, Austin Health, Level 7, Lance Townsend Building, 145 Studley Road, Heidelberg, VIC, 3084, Australia.|Department of Cardiology, Austin Health, Heidelberg, VIC, Australia.
authors.forename: Bryan
authors.initials: B
authors.lastname: Wai
authors.affiliation: Department of Medicine, University of Melbourne, Austin Health, Level 7, Lance Townsend Building, 145 Studley Road, Heidelberg, VIC, 3084, Australia.|Department of Neurology, Austin Health, Heidelberg, VIC, Australia.
authors.forename: Brian
authors.initials: B
authors.lastname: Chambers
authors.affiliation: Department of Medicine, University of Melbourne, Austin Health, Level 7, Lance Townsend Building, 145 Studley Road, Heidelberg, VIC, 3084, Australia.|Department of Clinical Pharmacology, Austin Health, Heidelberg, VIC, Australia.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Callaghan
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, Austin Health, 245 Burgundy Street, Heidelberg, VIC, 3084, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Darby
authors.affiliation: Department of Clinical Neurological Sciences, London Health Sciences Centre, University of Western Ontario, London, Canada.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Hachinski
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, Austin Health, 245 Burgundy Street, Heidelberg, VIC, 3084, Australia.
authors.forename: Toby
authors.initials: T
authors.lastname: Cumming
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, Austin Health, 245 Burgundy Street, Heidelberg, VIC, 3084, Australia.
authors.forename: Geoff
authors.initials: G
authors.lastname: Donnan
authors.affiliation: Department of Medicine, University of Melbourne, Austin Health, Level 7, Lance Townsend Building, 145 Studley Road, Heidelberg, VIC, 3084, Australia. l.burrell@unimelb.edu.au.|Department of Cardiology, Austin Health, Heidelberg, VIC, Australia. l.burrell@unimelb.edu.au.
authors.forename: Louise M
authors.initials: LM
authors.lastname: Burrell
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, Austin Health, 245 Burgundy Street, Heidelberg, VIC, 3084, Australia. agbrod@unimelb.edu.au.|Department of Medicine, University of Melbourne, Austin Health, Level 7, Lance Townsend Building, 145 Studley Road, Heidelberg, VIC, 3084, Australia. agbrod@unimelb.edu.au.|Department of Neurology, Austin Health, Heidelberg, VIC, Australia. agbrod@unimelb.edu.au.
authors.forename: Amy
authors.initials: A
authors.lastname: Brodtmann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001315:Australia / Q000453:epidemiology; D001921:Brain / Q000000981:diagnostic imaging*; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000523:psychology; D003704:Dementia / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000523:psychology; D003924:Diabetes Mellitus, Type 2 / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000523:psychology; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000523:psychology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012107:Research Design; D011795:Surveys and Questionnaires
keywords: Alzheimer’s disease; Cognition; D2 study; Dementia; Left ventricular hypertrophy; Type 2 diabetes mellitus