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Why might some cholesterol-lowering drugs help preserve memory in people with dementia? Image credit: fzant/Getty Images.
  • Statins are a drug that reduces cholesterol in the bloodstream, and while they were initially designed to prevent heart disease and cardiac events, they are increasingly being used to prevent other conditions linked to cholesterol.
  • Some researchers believe that the most common forms of dementia may be caused in part by changes to cholesterol metabolism and blood flow to the brain.
  • A longitudinal cohort study of older adults with dementia in Sweden has shown that statin use is linked to improved cognition over a period of three years, with some statins performing better than others.

Every year there are 10 million new dementia cases, according to the World Health Organization (WHO), but few treatment or prevention options available.

The most common form of dementia is Alzheimer’s disease, which is characterized by a build-up of betamyloid plaques and tau peptide tangles in the brain.

The second most common cause of dementia is vascular dementia, which is caused when blood vessels in the brain get blocked, reducing blood flow to the region.

It can occur after a stroke, but individuals do not have to have a stroke to have vascular dementia. It is also possible that Alzheimer’s disease and vascular dementia can co-occur.

High cholesterol is linked to both Alzheimer’s disease and vascular dementia, particularly in men. Researchers hypothesize that cholesterol dysregulation prevents the normal breakdown of cholesterol in the body, leading to levels of low density lipoprotein cholesterol rising to levels that can cause various problems.

This could lead to atherosclerosis, which can increase the risk of vascular dementia, and it could also dysregulate the take up of the tau protein, which could accelerate its accumulation in the brain, a characteristic of Alzheimer’s disease.

That is also why statins could help decrease dementia risk in some cases. Statins are a drug that has been used for decades to reduce cholesterol levels in the blood, primarily with the aim of reducing heart disease and resulting cardiac events.

Dr. Clifford Segil, a neurologist at Providence Saint John’s Health Center in Santa Monica, CA, told Medical News Today:

“In patients with memory loss one of the most common types of dementia is vascular dementia or multi-infarct dementia and any medication which lowers cardiovascular and cerebrovascular risk factors like a statin, would lower patient’s chances of getting this type of dementia.”

Researchers from Karolinska University Hospital in Stockholm, Sweden, have recently looked at the Swedish Registry for Cognitive/Dementia Disorders (SveDem) to determine if statin use had an impact on cognition in older adults.

The results of their study are reported in a paper published in the journal Alzheimer’s Research and Therapy.

They investigated the records of 15,586 individuals with different forms of dementia, with an average age of 79.5 years at diagnosis, 10,869 of whom took statins. Data were collected from 2007, and all patients were followed until death, emigration or end of follow-up.

Dr. Sara Garcia-Ptacek, assistant professor and neurologist at the Cognitive Clinic, Karolinska University Hospital, lead researcher and lead author of the study, told MNT that “[t]he potential neuroprotective effects of statins have been discussed for a long time.“

“There were some clinical studies which were negative and some observational studies showing an association with dementia prevention and/or progression. SveDem is the world’s largest clinical dementia cohort and the indication and types of patients receiving statins have changed over time,“ she added. “We wanted to check what the association was between statin use and cognition in patients with Alzheimer’s in the SveDem cohort.”

Researchers for the SveDem used a mini-mental state examination (MMSE) to evaluate cognition and this data was recorded. Researchers for this paper analysed the scores recorded at baseline and follow-ups. Data from the cohort was disaggregated into the different types of statin taken by participants. Findings were adjusted for demographic characteristics, comorbidities and medications other than statins.

The researchers found that overall, statin users who took one defined daily dose of statins on average had a 0.63 more MMSE points after 3 years of follow-up compared to those who did not use statins.

Simvastatin, which was the most prescribed statin in Sweden at the time, was associated with 1.01 more MMSE points after 3 years compared to atorvastatin users. Patients under 79.5 years when diagnosed who took simvastatin had 0.80 more MMSE points compared to younger atorvastatin users after 3 years. Simvastatin users had 1.03 more MMSE points compared to rosuvastatin users after 3 years.

The study confirmed that, despite previous concerns that statins could cause confusion, that they are in fact safe in this group of older patients with dementia, and do not contribute to cognitive decline, said Dr. Segil.

Dr Garcia-Ptacek said: “Our current hypothesis is that these two things may be simultaneously true: acute changes when starting statins — for example, in brain cholesterol — could potentially cause confusion in sensitive individuals while the long-term effects could be protective. However, this is just an hypothesis which will need to be confirmed in future studies”

Further research needed to be done to determine the mechanism that could underlie these findings, she explained, adding:

“We need to examine how statins affect cholesterol, brain cholesterol and brain connectivity, and how the effects change with short or long-term treatment. We need to understand which patients potentially benefit from statins, if at all, in order to design a targeted clinical trial. We need to know how different genotypes (e.g. ApoE) modify this response. ApoE is a cholesterol transporter and the genetic [risk of Alzheimer’s the] allele ApoE4 confers [is higher].”

Dr. Segil, who was not involved in this research, said he wanted to see more data comparing the different types of statin: “This study investigated three different generic cholesterol-lowering medications, or ‘statins,’ which include rosuvastatin, simvastatin, and atorvastatin. I am intrigued to see long term follow-up in the patients who received these three medications to see if data supports neurologists like me using one of these over another [drug], due to data indicating one statin helps prevent memory loss more than another.“

“As a family of medications, statins often are not [well] tolerated, and rosuvastatin in clinical practice is better tolerated than atorvastatin, and I would be interested in seeing if rosuvastatin helped patients with memory loss in a follow-up study head to head with atorvastatin,” he pointed out.