Regarding long-term statin therapy: Are we trading stronger hearts for weaker brains?

Medical Hypotheses

Volumn 83, Issue 3, 2014, Pages 346-351

  Goldstein, Mark R ^a   Mascitelli, Luca ^b  

^a NCH Physician Group   (United States)

^b Julia Medical Service   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

3 HYDROXY 3 METHYLGLUTARYL COENZYME A; AMYLOID BETA PROTEIN[1-40]; AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN E2; APOLIPOPROTEIN E4; CHOLESTEROL; GERANYLGERANYL PYROPHOSPHATE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; MYELIN;

AGING; ALLELE; ARTICLE; BLOOD BRAIN BARRIER; BLOOD VESSEL WALL; BRAIN HYPOXIA; BRAIN INFARCTION; CEREBROVASCULAR DISEASE; CLINICAL FEATURE; DEMENTIA; DISEASE ASSOCIATION; HUMAN; LACUNAR STROKE; LEUKOARAIOSIS; LONG TERM CARE; META ANALYSIS (TOPIC); MORTALITY; NERVE CONDUCTION; NEUROPATHOLOGY; NEUROTOXICITY; NUCLEAR MAGNETIC RESONANCE IMAGING; OLIGODENDROGLIA; SCHWANN CELL; SPORADIC CEREBRAL AMYLOID ANGIOPATHY; VASCULAR AMYLOIDOSIS; WHITE MATTER LESION; ADVERSE DRUG REACTION; BRAIN; CARDIOVASCULAR DISEASE; DRUG EFFECTS; HEART; HOMEOSTASIS; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; PROSPECTIVE STUDY; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); SYNAPTIC TRANSMISSION; WHITE MATTER;

BLOOD-BRAIN BARRIER; BRAIN; CARDIOVASCULAR DISEASES; CEREBRAL AMYLOID ANGIOPATHY; CHOLESTEROL; HEART; HOMEOSTASIS; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; LONG TERM ADVERSE EFFECTS; MAGNETIC RESONANCE IMAGING; OLIGODENDROGLIA; PROSPECTIVE STUDIES; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SYNAPTIC TRANSMISSION; WHITE MATTER;

EID: 84908356833     PISSN: 03069877     EISSN: 15322777     Source Type: Journal    
DOI: 10.1016/j.mehy.2014.06.010     Document Type: Article

References (53)

1. Stone N.J., Robinson J., Lichtenstein A.H., Bairey Merz C.N., Lloyd-Jones D.M., Blum C.B., et al. ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013, 2013. [Epub ahead of print].
2. Ioannidis J.P.A. More than a billion people taking statins? Potential implications of the new cardiovascular guidelines. JAMA 2014, 311:463-464.
3. Rost N.S., Rosand J., Woo D. Can hyperlipidemia be protective to the brain? The paradox of lowering lipid levels in cerebrovascular disease. Clin Lipidol 2010, 5:295-298.
4. Ohwaki K., Yano E., Tamura A., Inoue T., Saito I. Hypercholesterolemia is associated with a lower risk of cerebral ischemic small vessel disease detected on brain checkups. Clin Neurol Neurosurg 2013, 115:669-672.
5. Jimenez-Conde J., Biffi A., Rahman R., Kanakis A., Butler C., Sonni S. Hyperlipidemia and reduced white matter hyperintensity volume in patients with ischemic stroke. Stroke 2012, 41:437-442.
6. Khan U., Porteous L., Hassan A., Markus H.S. Risk profile of cerebral small vessel disease and its subtypes. J Neurol Neurosurg Psychiatry 2007, 78:702-706.
7. Soljanlahti S., Autti T., Lauerma K., Raininko R., Keto P., Turtola H., et al. Familial hypercholesterolemia patients treated with statins at no increased risk for intracranial vascular lesions despite increased cholesterol burden and extracranial atherosclerosis. Stroke 2005, 36:1572-1574.
8. Bang O.Y., Saver J.L., Liebeskind D.S., Starkman S., Villablanca P., Salamon N., et al. Cholesterol level and symptomatic hemorrhagic transformation after ischemic stroke thrombolysis. Neurology 2007, 68:737-742.
9. Vergouwen M.D.I., de Hann R.J., Vermeulen M., Roos Y.B.W.E. Statin treatment and the occurrence of hemorrhagic stroke in patients with a history of cerebrovascular disease. Stroke 2008, 39:497-502.
10. Yates P.A., Villemagne V.L., Ellis K.A., Desmond P.M., Masters C.L., Rowe C.C. Cerebral microbleeds: a review of clinical, genetic, and neuroimaging associations. Front Neurol 2014, 4:205.
11. Haussen D.C., Henninger N., Kumar S., Selim M. Statin use and microbleeds in patients with spontaneous intracerebral hemorrhage. Stroke 2012, 43:2677-2681.
12. Lee S.-H., Bae H.-J., Yoon B.-W., Kim H., Kim D.-F., Roh J.-K. Low concentration of serum total cholesterol is associated with multifocal signal loss lesions on gradient-echo magnetic resonance imaging: analysis of risk factors for multifocal signal loss lesions. Stroke 2002, 33:2845-2849.
13. Flaherty M.L., Kissela B., Woo D., Kleindorfer D., Alwell K., Sekar P., et al. The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology 2007, 68:116-121.
14. Locatelli S., Lütjohann D., Schmidt H.H.-J., Otto C., Beisiegel U., von Bergmann K. Reduction of plasma 24S-hydroxycholesterol (cerebrosterol) levels using high-dosage simvastatin in patients with hypercholesterolemia: evidence that simvastatin affects cholesterol metabolism in the human brain. Arch Neurol 2002, 59:213-216.
15. Cibičková L. Statins and their influence on brain cholesterol. J Clin Lipidol 2011, 5:373-379.
16. Vecka M., Tvrzická E., Staňková B., Novák F., Nováková O., Žák A. Hypolipidemic drugs can change the composition of rat brain lipids. Tohoku J Exp Med 2004, 204:299-308.
17. Gouw A.A., Seewann A., van der Flier W.M., Barkhof F., Rozemuller A.M., Scheltens P., et al. Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations. J Neurol Neurosurg Psychiatry 2011, 82:126-135.
18. Pantoni L. Leukoaraiosis: from an ancient term to an actual marker of poor prognosis. Stroke 2008, 39:1401-1403.
19. de Groot M., Verhaaren B.F.J., de Boer R., Klein S., Hofman A., van der Lugt A., et al. Changes in normal-appearing white matter precede development of white matter lesions. Stroke 2013, 44:1037-1042.
20. Smith E.E., Schneider J.A., Wardlaw J.M., Greenberg S.M. Cerebral microinfarcts: the invisible lesions. Lancet Neurol 2012, 11:272-282.
21. Charidimou A., Gang Q., Werring D.J. Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry 2012, 83:124-137.
22. Smith E.E., Greenberg S.M. β-amyloid, blood vessels, and brain function. Stroke 2009, 40:2601-2606.
23. Gomis M., Sobrino T., Ois A., Millán M., Rodríguez-Campello A., de la Ossa N.P., et al. Plasma β-amyloid 1-40 is associated with the diffuse small vessel disease subtype. Stroke 2009, 40:3197-3201.
24. Longstreth W.T., Arnold A.M., Beauchamp N.J., Manolio T.A., Lefkowitz D., Jungreis C., et al. Incidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study. Stroke 2005, 36:56-61.
25. Debette S., Markus H.S. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ 2010, 341:c3666.
26. The LADIS Study Group 2001-2011: a decade of the LADIS (Leukoaraiosis And DISability) Study: what have we learned about white matter changes and small-vessel disease?. Cerebrovasc Dis 2011, 32:577-588.
27. Schmidt R., Petrovic K., Ropele S., Enzinger C., Fazekas F. Progression of leukoaraiosis and cognition. Stroke 2007, 38:2619-2625.
28. de Laat K.F., van Norden A.G.W., Gons R.A.R., van Oudheusden L.J.B., van Uden I.W.M., Bloem B.R., et al. Gait in elderly with cerebral small vessel disease. Stroke 2010, 41:1652-1658.
29. Srikanth V., Beare R., Blizzard L., Phan T., Stapleton J., Chen J., et al. Cerebral white matter lesions, gait, and the risk of incident falls: a prospective population-based study. Stroke 2009, 40:175-180.
30. Inzitari D., Simoni M., Pracucci G., Poggesi A., Basile A.M., Chabriat H., et al. Risk of rapid global functional decline in elderly patients with severe cerebral age-related white matter changes: the LADIS Study. Arch Intern Med 2007, 167:81-88.
31. Murray M.E., Senjem M.L., Peterson R.C., Hollman J.H., Preboske G.M., Weigand S.D., et al. Functional impact of white matter hyperintensities in cognitively normal elderly subjects. Arch Neurol 2010, 67:1379-1385.
32. Park K., Nakagawa Y., Kumagal Y., Nagahara M. Leukoaraiosis, a common brain magnetic resonance imaging finding, as a predictor of traffic crashes. PLoS One 2013, 8(2):e57255. 10.1371/journal.pone.0057255.
33. Tadic SD, Holstege G, Griffiths DJ. The CNS and bladder dysfunction. F1000 Medicine Reports 2012;4:20. doi:10.3410/M4-20.
34. Golomb B.A., Evans M.A. Statin adverse effects: a review of the literature and evidence for a mitochondrial mechanism. Am J Cardiovasc Drugs 2008, 8:373-418.
35. Goldstein M.R., Mascitelli L. Do statins cause diabetes?. Curr Diab Rep 2013, 13:381-390.
36. Arvanitakis Z., Leurgans S.E., Wang Z., Wilson R.S., Bennett D.A., Schneider J.A. Cerebral amyloid angiopathy pathology and cognitive domains in older persons. Ann Neurol 2011, 69:320-327.
37. Esiri M.M., Wilcock G.K. Cerebral amyloid angiopathy in dementia and old age. J Neurol Neurosurg Psychiatry 1986, 49:1221-1226.
38. Masuda J., Tanaka K., Ueda K., Omae T. Autopsy study of incidence and distribution of cerebral amyloid angiopathy in Hisayama, Japan. Stroke 1988, 19:205-210.
39. Tomonaga M. Cerebral amyloid angiopathy in the elderly. J Am Geriatr Soc 1981, 29:151-157.
40. Cole S.L., Grudzein A., Manhart I.O., Kelly B.L., Oakley H., Vassar R. Statins cause intracellular accumulation of amyloid precursor protein, β-secretase-cleaved fragments, and amyloid β-peptide via an isoprenoid-dependent mechanism. J Biol Chem 2005, 280:18755-18770.
41. Roriz-Filho J.S., Sá-Roriz T.M., Rosset I., Camozzato A.L., Santos A.C., Chaves M.L.F., et al. (Pre)diabetes, brain aging, and cognition. Biochim Biophys Acta 2009, 1792:432-443.
42. Kanekiyo T., Xu H., Bu G. ApoE and Aβ in Alzheimer's disease; accidental encounters or partners?. Neuron 2014, 81:740-754.
43. Chrast R., Saher G., Nave K.-A., Verheijen M.H.G. Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models. J Lipid Res 2011, 52:419-434.
44. Miron V.E., Zehntner S.P., Kuhlmann T., Ludwin S.K., Owens T., Kennedy T.E., et al. Statin therapy inhibits remyelination in the central nervous system. Am J Pathol 2009, 174:1880-1890.
45. Klopfleisch S., Merkler D., Schmitz M., Klöppner S., Schedensack M., Jeserich G., et al. Negative impact of statins on oligodendrocytes and myelin formation in vitro and in vivo. J Neurosci 2008, 28:13609-13614.
46. Maier O., de Jonge J., Nomden A., Hoekstra D., Baron W. Lovastatin induces the formation of abnormal myelin-like membrane sheets in primary oligodendrocytes. Glia 2009, 57:402-413.
47. Smolders I., Smets I., Maier O., van de Ven M., Steels P., Ameloot M. Simvastatin interferes with process outgrowth and branching of oligodendrocytes. J Neurosci Res 2010, 88:3361-3375.
48. Björkhem I., Meaney S. Brain cholesterol: long secret life behind a barrier. Arterioscler Thromb Vasc Biol 2004, 24:806-815.
49. Bartzokis G. Neuroglialpharmacology: myelination as a shared mechanism of action of psychotropic treatments. Neuropharm 2012, 62:2137-2153.
50. Lu P.H., Lee G.J., Raven E.P., Tingus K., Khoo T., Thompson P.M., et al. Age-related slowing in cognitive processing speed is associated with myelin integrity in a very healthy elderly sample. J Clin Exp Neuropsychol 2011, 33:1059-1068.
51. Sparks D.L., Lemieux S.K., Haut M.W., Baxter L.C., Johnson S.C., Sparks L.M., et al. Hippocampal volume change in the Alzheimer disease cholesterol-lowering treatment trial. Clev Clin J Med 2008, 75:S87-S92.
52. Pencina M.J., Navar-Boggan A.M., D'Agostino R.B., Williams K., Neely B., Sniderman A.D., et al. Application of new cholesterol guidelines to a population-based sample. N Engl J Med 2014, 370:1422-1431.
53. Briones T.L., Woods J. Dysregulation in myelination mediated by persistant neuroinflammation: possible mechanisms in chemotherapy-related cognitive impairment. Brain Behav Immun 2014, 35:23-32.