Left ventricular hypertrophy, brain atrophy and cognitive decline in type 2 diabetes mellitus: Diabetes & Dementia (D2) cohort study
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BACKGROUND
People with type 2 diabetes mellitus (T2DM) are at higher risk of cerebral small vessel disease and left ventricular hypertrophy (LVH), potentially contributing to cognitive decline and dementia. We aimed to describe brain volume and cognitive trajectories over 2 years in a cohort of people with T2DM and to determine whether LVH causes increased brain atrophy and cognitive decline.
METHODS
Diabetes and Dementia (D2) study is a multicentre observational cohort study in Melbourne, Australia. Participants aged >50 years were recruited via 2 hospital outpatient clinics, 3 private clinics, and study advertisements. Participants with pre-existing cognitive impairment, life-limiting medical illness, and severe chronic renal impairment were excluded. Participants attended study visits for brain MRI, transthoracic echocardiography (TTE), and cognitive testing at baseline and 2 years. The exposure was LVH determined on baseline TTE. Pre-specified outcomes were total brain volume (TBV) change and cognitive decline (z-score change≤-1 in any cognitive domain) over 2 years. Regression analyses examined associations between baseline variables and outcomes. A causal inference approach was utilized using inverse probability of treatment weighting to standardize for confounding covariates, excluding participants for non-positivity on age and baseline TBV.
RESULTS
Participants were recruited 20May2016 to 20March2020: 2378 screened, 702 eligible, 196 consented, 150 baseline and 123 2-year assessments with complete MRI, TTE, and cognitive data (17.4% attrition). At baseline, LVH was associated with female sex, older age, lower educational attainment, lower mood, hypertension, obesity, beta-blocker use, and smaller TBV. Participants with baseline cognitive impairment exhibited greater brain atrophy. Lower educational attainment, hypertension, and lower baseline cognitive scores were associated with cognitive decline. Causal inference analysis included 62 participants with no LVH (20(32%) women; mean [SD]=66.9[5.9] years), and 31 with LVH (17(55%) women, 67.4[5.4] years). LVH caused lower TBV change: standardized mean difference (95% CI) 6.3 (0.1, 12.5) cm 3 , P = .048. LVH had no effect on cognitive decline.
CONCLUSIONS
Brain atrophy and cognitive decline were associated with baseline cognitive impairment. LVH caused less brain atrophy and cognitive decline in people with T2DM. We conclude that guideline-directed LVH therapies such as beta-blockers have both cardioprotective (remodelling) and neuroprotective effects.
TRIAL REGISTRATION
ACTRN12616000546459 UTN: U1111-1181-6659
Clinical perspective
What is new?
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Causal inference modelling was used to ask whether left ventricular hypertrophy (LVH) caused increased brain atrophy and cognitive decline over 2 years
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LVH reversed in 40% of participants
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Increased brain atrophy was associated with baseline cognitive impairment
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Lower educational attainment, baseline cognitive scores and hypertension were associated with cognitive decline
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LVH caused less brain atrophy with no effect on cognitive decline
What are the clinical implications?
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LVH therapies, especially â-blockers, may have both cardioprotective (remodelling) and neuroprotective effects
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Cognitive impairment in people with T2DM should prompt aggressive risk factor management to prevent brain atrophy and cognitive decline
