Details

Autor(en) / Beteiligte

• Sánchez-Valle, Raquel

Titel

Pioglitazone for prevention of cognitive impairment: results and lessons

Ist Teil von

• Lancet neurology, 2021-07, Vol.20 (7), p.500-502

Ort / Verlag

London: Elsevier Ltd

Erscheinungsjahr

2021

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• [...]randomised controlled trials (RCTs) of interventions to prevent cognitive decline, dementia, or Alzheimer's disease have shown negative or very modest results.2 In the absence of a gold standard, methods in RCTs to prevent cognitive decline are heterogeneous in timing, duration, type of intervention (eg, single-target vs multi-target or pharmacological vs non-pharmacological), population enrichment strategies (based on age, genetic profile, biomarker characterisation, or lifestyle and comorbidities), disease progression modelling, and outcome measures (sensitive vs clinically meaningful outcomes).2 In The Lancet Neurology, Daniel K Burns and colleagues3 report the main results of TOMMORROW, a trial aimed to evaluate the safety and efficacy of low-dose pioglitazone, an insulin-sensitising agent used in the treatment of type 2 diabetes, to delay cognitive impairment onset in a group of pre-selected non-diabetic participants at high risk of developing mild cognitive impairment. [...]pioglitazone did not delay the onset of mild cognitive impairment compared with placebo, nor did cognitive or functional changes from baseline differ between the treatment and placebo groups. In a huge research effort in 59 sites, 24 136 potential participants were screened, 3061 were categorised as at high risk and randomised, and 433 participants at low risk were allocated to the placebo arm.3 During the study period, fewer participants than estimated converted to mild cognitive impairment, suggesting that the model used for disease progression (which was based on longitudinal cohort data) had a limited capacity to predict outcomes in participants assigned to placebo.6,7 Logistical regression analysis of the target population showed that enriched inclusion of participants at high risk was driven by the combination of age and APOE status, and TOMM40 genotype did not contribute to improved risk prediction.