PAPER

Lipid lowering agents are associated with a slower cognitive decline in Alzheimer’s disease

I Masse¹, R Bordet², D Deplanque², A Al Khedr¹, F Richard³, C Libersa², F Pasquier⁴

¹ Department of Neurology, Memory Centre and EA 2691, Department of Neurology, University Hospital, Lille, France
² Department of Pharmacology, Clinical Investigation Centre and EA 1046, University Hospital, Lille
³ Clinical Epidemiology Centre, Lille University Hospital and INSERM U 508, Institut Pasteur, Lille
⁴ EA 2691 University of Lille, France, Institut de Médecine Prédictive et de Recherche Thérapeutique, Lille

Correspondence to:
Correspondence to:
Professor Florence Pasquier
Department of Neurology, University Hospital, 59037 Lille, France; pasquier{at}chru-lille.fr

Background: Data from epidemiological studies and animal models imply that disturbances in cholesterol metabolism are linked to Alzheimer’s disease susceptibility. Lipid lowering agents (LLAs) may have implications for the prevention of Alzheimer’s disease.

Objective: To investigate whether LLAs are associated with a slower cognitive decline in Alzheimer’s disease.

Methods: An observational study in 342 Alzheimer patients followed in a memory clinic for 34.8 months (mean age 73.5 years, mini-mental state examination score (MMSE) 21.3 at entry); 129 were dyslipaemic treated with LLAs (47% with statins), 105 were untreated dyslipaemic, and 108 were normolipaemic. The rate of cognitive decline was calculated as the difference between the first and last MMSE score, divided by the time between the measurements, expressed by year. Patients were divided into slow and fast decliners according to their annual rate of decline (lower or higher than the median annual rate of decline in the total population).

Results: Patients treated with LLAs had a slower decline on the MMSE (1.5 point/year, p = 0.0102) than patients with untreated dyslipaemia (2.4 points/year), or normolipaemic patients (2.6 points/year). Patients with a slower decline were more likely to be treated with LLAs. Logistic regression analysis, with low annual cognitive decline as the dependent variable, showed that the independent variable LLA (treated with or not) was positively associated with the probability of lower cognitive decline (odds ratio = 0.45, p = 0.002).

Conclusions: LLAs may slow cognitive decline in Alzheimer’s disease and have a neuroprotective effect. This should be confirmed by placebo controlled randomised trials in patients with Alzheimer’s disease and no dyslipaemia.

Abbreviations: AChEI, acetylcholinesterase inhibitor; DRS, dementia rating scale; HDL, high density lipoprotein; LLA, lipid lowering agent; MMSE, mini-mental state examination score; NSAID, non-steroidal anti-inflammatory drug; PROSPER, prospective study of pravastatin in elderly at risk; SSRI, selective serotonin reuptake inhibitor

Keywords: Alzheimer’s disease; lipid lowering agent; statin; fibrates

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Article

Lipid lowering agents to delay cognitive decline in Alzheimer’s disease?

F-E de Leeuw
J. Neurol. Neurosurg. Psychiatry 2005 76: 1611-1613. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Deschaintre, Y., Richard, F., Leys, D., Pasquier, F. (2009). Treatment of vascular risk factors is associated with slower decline in Alzheimer disease. Neurology 73: 674-680 [Abstract] [Full Text]  
• Helzner, E. P., Luchsinger, J. A., Scarmeas, N., Cosentino, S., Brickman, A. M., Glymour, M. M., Stern, Y. (2009). Contribution of Vascular Risk Factors to the Progression in Alzheimer Disease. Arch Neurol 66: 343-348 [Abstract] [Full Text]  
• Bruandet, A, Richard, F, Bombois, S, Maurage, C A, Deramecourt, V, Lebert, F, Amouyel, P, Pasquier, F (2009). Alzheimer disease with cerebrovascular disease and vascular dementia: clinical features and course compared with Alzheimer disease. J. Neurol. Neurosurg. Psychiatry 80: 133-139 [Abstract] [Full Text]  
• Ellul, J, Archer, N, Foy, C M L, Poppe, M, Boothby, H, Nicholas, H, Brown, R G, Lovestone, S (2007). The effects of commonly prescribed drugs in patients with Alzheimer's disease on the rate of deterioration. J. Neurol. Neurosurg. Psychiatry 78: 233-239 [Abstract] [Full Text]  
• Masters, C. L., Beyreuther, K. (2006). Alzheimer's centennial legacy: prospects for rational therapeutic intervention targeting the A{beta} amyloid pathway. Brain 129: 2823-2839 [Abstract] [Full Text]  
• Deplanque, D., Masse, I., Lefebvre, C., Libersa, C., Leys, D., Bordet, R. (2006). Prior TIA, lipid-lowering drug use, and physical activity decrease ischemic stroke severity. Neurology 67: 1403-1410 [Abstract] [Full Text]  
• Bordet, R, Gele, P, Duriez, P, Fruchart, J-C (2006). PPARs: a new target for neuroprotection.. J. Neurol. Neurosurg. Psychiatry 77: 285-287 [Full Text]  

eLetters:

Read all eLetters

Statins and Alzheimer’s disease: Pearls and pitfalls in the theorizing process

Vinod K Gupta

JNNP Online, 3 Jan 2006 [Full text]