Psychiatric Times.
No. 2
Assessing Statins for Alzheimer Disease: Conflicting Evidence
By Kenneth J. Bender, PharmD, MA |
February 1, 2007
In his assessment of the pleiotropic effects of statins, Crisby11 emphasizes that inflammation in the CNS is an early hallmark of many neurodegenerative diseases, including AD. Crisby points out that apoE is involved in the clearance of cholesterol-laden neurodegenerative products following brain injury and that apoE isoforms have been found to exert antioxidant and anti-inflammatory actions.10
Wolozin and colleagues5 note their own recently reported evidence of such effects in a small postmortem comparative study. Brain sections of one group of 10 patients with AD who had not received statins were compared with those of a group of 6 who had received the medication for at least a year. Wolozin and coauthors found a “striking” reduction in microglial activation in the statin-treated patients.
“These results are consistent with prior reports indicating that statins reduce inflammation and dampen the immune response in vivo,” they declare.5
Although acknowledging that the benefit and mechanism of action of the statins for AD remain to be elucidated, Kivipelto and colleagues3 indicate that multifaceted therapeutic strategies are appropriate for diseases with complex etiologies. In their view, targeting cholesterol in treatment or prevention of AD remains an appropriate strategy. “Even if the mechanisms involved are not fully known to us at the present,” they conclude, “it seems that minding heart health may protect the brain as well.”
References
1. Sparks DL, Sabbagh MN, Connor DJ, et al. Atorvastatin for the treatment of mild-to-moderate Alzheimer's disease: preliminary results: Arch Neurol. 2005;62:753- 757.
2. Sparks DL, Connor DJ, Sabbagh MN, et al. Circulating cholesterol levels, apolipoprotein E genotype and dementia severity influence the benefit of atorvastatin treatment in Alzheimer's disease: results of the Alzheimer's Disease Cholesterol-Lowering Treatment (ADCLT) trial. Acta Neurol Scand. 2006;114(suppl 185):3-7.
3. Kivipelto M, Solomon A, Winblad B. Alzheimer's disease: back to the future. Acta Neurol Scand. 2006;114 (suppl 185):119-120.
4. Rockwood K. Epidemiological and clinical trials evidence about a preventative role for statins in Alzheimer's disease. Acta Neurol Scand. 2006;114(suppl 185):71-77.
5. Wolozin B, Manger J, Bryant R, et al. Re-assessing the relationship between cholesterol, statins and Alzheimer's disease. Acta Neurol Scand. 2006;114(suppl 185):63-70.
6. Sparks DL. Coronary artery disease, hypertension, ApoE, and cholesterol: a link to Alzheimer's disease? Ann NY Acad Sci. 1997;826:128-146.
7. Höglund K, Wallen A, Blenow K. Effect of statins on ß-amyloid metabolism in humans: potential importance for the development of senile plaques in Alzheimer's disease. Acta Neurol Scand. 2006;114(suppl 185):87-92.
8. Park IH, Hwang EM, Hong HS, et al. Lovastatin enhances Abeta production and senile plaque deposition in female Tg2576 mice. Neurobiol Aging. 2003;24:637-643.
9. Ishii K, Tokuda T, Matsushima T, et al. Pravastatin at 10 mg/day does not decrease plasma levels of either amyloid-beta (Abeta) 40 or Abeta 42 in humans. Neurosci Lett. 2003;350:161-164.
10. Sparks DL, Sabbagh MN, Connor DJ, et al. Statin therapy in Alzheimer's disease. Acta Neurol Scand. 2006;114(suppl 185):78-86.
11. Crisby M. The role of pleiotropic effects of statins in dementia. Acta Neurol Scand. 2006;114(suppl 185):115-118.
