Plasma β-Amyloid Level, Cognitive Reserve, and Cognitive Decline

To the Editor: Dr Yaffe and colleagues reported that a lower β-amyloid 42/40 level in plasma was associated with greater cognitive decline during a 9-year period in nondemented elderly persons.¹ Use of certain psychotropic medications, especially benzodiazepines^2- 3 and other medications with central anticholinergic effects,^4- 5 is quite common in elderly individuals and can result in significant cognitive deficits, particularly in APOE ε4 carriers. These deficits could be comparable with those related to the lower β-amyloid 42/40 level, especially in association with the ε4 allele, which appears to be more frequent in the group with the lowest β-amyloid 42/40 level. Yaffe et al did not explicitly comment on the use of these classes of medications in their study population; it would be important to ensure that group differences in the use of these medications did not contribute to their results.