The benefits and risks of statins in dementia are controversial. Some studies suggest that statins can lower the risk of dementia, but they can also cause reversible cognitive impairment. The results between studies still show different outcomes.

Statins are first-line therapy for hyperlipidemia and the primary prevention of coronary heart disease. The use of statins in the community is very high, especially in people over 65.

In 2012, the Food and Drug Administration (FDA) listed reversible cognitive impairment as a possible side effect of statins. This claim is controversial because there have not been many large-scale studies with consistent results regarding statins' impact on neuropsychological conditions.


Risks and Benefits of Statin in Dementia
Statin
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The Hypothesis of Paradoxical Statin Mechanism 

In the brain, cholesterol forms the myelin layer, mitochondrial performance, expression of neurotransmitter receptors, development of synapses, and transport of antioxidants such as coenzyme Q10. Administration of high doses of statins or lipophilic statins can increase the diffusion of these drugs to the central nervous system, reducing cholesterol synthesis. This is thought to cause cognitive impairment.

Dementia has been thought to occur due to large blood vessel disorders and microvascular disorders. Statins' benefits in preventing dementia are thought to occur by preventing strokes, lacunar infarcts, and vascular dementia. Studies in mice have shown that atorvastatin can decrease the ß-amyloid formation and calm neuronal inflammation in Alzheimer's disease. This condition is found in lipophilic statins because it is easier to cross the blood-brain barrier.

Statins also have a protective effect regardless of their function of lowering cholesterol, namely reducing brain ischemia by improving endothelial function, reducing low-density lipoprotein (LDL) oxidation, maintaining the stability of atherosclerotic plaque, and inhibiting platelet aggregation.



Study Regarding Statins and Reversible Cognitive Disorders

Continuous observational studies document transient and reversible cognitive impairment with statin use. The main symptom reported was short-term memory impairment that appeared several months after starting statin therapy and was directly proportional to the dose increase. This cognitive impairment is reversible due to cognitive resolution after stopping statin consumption and recurrence when statin therapy is restarted.

Based on the Adverse Event Reporting System (AERS) calculation, the reversible cognitive impairment risk is 0.1–1% of the total population taking statins. Some reports suggest that patients who take simvastatin show minor cognitive impairment on neuropsychiatric tests but experience major impairments in daily functioning. Consuming potent lipophilic statins (such as atorvastatin and simvastatin) causes cognitive dysfunction more frequently than hydrophilic statins (such as rosuvastatin and fluvastatin).

The FDA states that cognitive impairment as side effects of statin use is not severe and is reversible. The FDA also states that the benefits of statins in cardiovascular disease far outweigh the risk of possible side effects, so this drug is still used.



Study Regarding Statins Decrease Dementia Risks

Statins' protective effect against all dementia types and Alzheimer's disease has been extensively studied in clinical trials and meta-analyzes. Patients who were taking statins had a lower risk of dementia than those not taking statins. Some studies also suggest that in addition to preventing dementia, statins can slow the progression of Alzheimer's disease.

Studies link high total cholesterol in middle age with dementia and Alzheimer's disease risks later in life. Increased cholesterol has an association with decreased executive function, attention, memory, and speed of thought. However,  in elderly patients, the analysis did not find this association.

The existing study's results are not supported by sufficient evidence. The Cochrane meta-analysis also suggests no solid evidence base regarding statins' ability to prevent dementia. Another Cochrane meta-analysis also showed that statins did not improve the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-Cog) and Mini-Mental State Examination (MMSE).



Conclusion
Statins are thought to prevent dementia and slow Alzheimer's disease progression, but they also risk causing cognitive impairment. The strength of existing scientific evidence is inefficient due to limited data, lack of sample size, and high research bias.

Because the existing studies' results are still inconsistent, statins cannot treat dementia. Indications for using statins that are always a global reference are hyperlipidemia and preventing cerebrovascular disease. Doctors should be able to detect changes in cognitive function in patients taking statins when they occur.