While the proposal that high cholesterol levels protect against dementia could be consistent with the data presented in our article, we feel that it is not supported by the preponderance of data in the field and that it requires a logical leap that extends well beyond the data presented in our article. The current literature supports either of 2 competing hypotheses: (1) Elevated cholesterol levels are associated with AD (2) Serum cholesterol levels are unrelated to AD (perhaps because a different pool of cholesterol, such as that in the brain or in neurons, is linked to AD). The observation that the incidence of AD is elevated in patients with apolipoprotein E type 4 (ApoE4) or heart disease, both of which are associated with elevated cholesterol levels, provides an indirect link between cholesterol and AD. Alternatively, 3 different articles have evaluated serum cholesterol levels without observing a link to AD. Prince et al1 and Wehr et al2 both failed to observe a clear link between cholesterol and AD, although they did confirm the linkage between ApoE4, which is associated with elevated cholesterol, and AD. (Because of the connection between ApoE4 and AD, our article incorrectly characterized these 2 articles as supporting an association between cholesterol and AD; we apologize for this error.) More recently, Jick and colleagues3 also failed to document a connection between elevated cholesterol and AD. While the relationship between cholesterol and AD remains ambiguous, it is quite clear that none of these articles provides any suggestion that elevated cholesterol levels protect against AD.
Wolozin B, Siegel G. In reply. Arch Neurol. 2001;58(7):1169-1170. doi: