. Serum lipoprotein levels, statin use, and cognitive function in older women. Arch Neurol. 2002 Mar;59(3):378-84. PubMed.

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  1. Jick et al., 2000; Wolozin et al., 2000). On the other hand, the literature linking cholesterol and cognitive decline is less clear, because some studies have suggested that ApoE4, rather than cholesterol, is more strongly associated with cognitive decline (Jarvik et al., 1995). The current study supports a relationship between cholesterol and cognitive decline, but does not dissect out the respective roles of ApoE4 and cholesterol. Further studies will be needed to clarify this issue.

    The exact mechanism is unclear. Cholesterol level clearly modulates Aβ production, but it is unclear whether peripheral cholesterol and statins that have poor CNS penetration can actually lower Aβ in the brain at normal therapeutic doses of statins (Fassbender et al., 2001; Refolo et al., 2001; Simons et al., 1998; Wolozin, 2001). In addition, it is important to note that other cholesterol-related compounds, such as cholesterol esters, also modulate Aβ production (see ARF news item). Peripheral cholesterol or statins could also impact on apoE in the CNS, and on endothelial health (see ApoE chat transcript). Hence, multiple mechanisms could account for the putative protective effect of statins. What does appear to be increasingly clear, though, is that a protective effect does exist and is therefore worth investigating.

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