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We thank Dr Sakurai for his insightful comments. The observation that pioglitazone was associated with improvement in clinical and biomarker outcomes in patients with AD and diabetes mellitus reinforces the potential value of this line of therapeutics.1 There is increased risk for AD among patients with diabetes.2 Taken together, these observations suggest additional means of enriching samples for future trials of PPARγ agonists and other insulin-sensitizing agents beyond the typical APOE genotyping. We also concur that these agents are likely to be most useful in prevention, rather than response to, symptomatically expressed AD. Therefore, trials of patients with mild cognitive impairment (or biomarker evidence of incipient AD) and relative insulin resistance might have the highest likelihood of detecting clinical efficacy for insulin-sensitizing drugs as antidementia agents.
Geldmacher DS, Fritsch T, Landreth GE. Targets of the Peroxisome Proliferator–Activated Receptor γ Agonist Trials for the Prevention of Alzheimer Disease—Reply. Arch Neurol. 2011;68(4):542-543. doi:10.1001/archneurol.2011.58